ISSN 2051-4158

JCU

Journal of Clinical Urology

Volume 14  Issue 4  July  2021

Journal of
Clinical Urology
Formerly British Journal of Medical and Surgical Urology

An official publication of The British Association of Urological Surgeons Editor: Ian Pearce

  Volume 14  Issue 4  July 2021

Highlights include:
•  The reflective urologist
•  Point of technique: Limited anterior scrotectomy and scrotoplasty for multiple epidermoid cysts of the scrotum
•  Early outcomes of robot-assisted radical prostatectomy following completion of a structured training curriculum:
a single surgeon cohort study

URO_14_4_cover.indd 1 25/06/2021 8:06:38 PM

 Journal of
Clinical Urology
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 Volume 14  Number 4  July 2021

Contents
Editorial
Editorial237
Ian Pearce

Cohort Study
Urethral recurrence after radical cystoprostatectomy: Experience from a high-volume tertiary referral centre 238
Karl H Pang, Francesco Esperto, Catherine Sproson, Maidie Yeung, Susan L Morgan, Alison P Downey, Christopher J Hillary,
James WF Catto, Derek J Rosario and Aidan P Noon
Early outcomes of robot-assisted radical prostatectomy following completion of a structured training curriculum:  246
a single surgeon cohort study
Arjan S Sehmbi, Ashwin N Sridhar, Kanagasabai Sahadevan, Bhavan P Rai, Pamela Nwangwu, Anna Mohammed, Alex Freeman,
Alexandre Mottrie, Mats J Olsson, N Peter Wiklund, M Senthil Nathan, Timothy P Briggs, John D Kelly and Prabhakar Rajan 
A prospective study on the association between post-voiding residual volume and quality of life during bacille  255
Calmette-Guérin (BCG) instillation therapy for non–muscle-invasive bladder cancer
Daichi Kikuchi, Yoichiro Kato, Misato Takayama, Seiko Kanzaki, Akito Ito, Daiki Ikarashi, Shigekatsu Maekawa, Renpei Kato,
Takashi Seo, Yukihisa Owari, Tatsuru Nozawa, Kazumasa Isurugi, Hiromitsu Fujisawa, Takashi Ujiie, Mitsugu Kanehira,
Ryo Takata and Wataru Obara
A cut above? Inferior vena cava resection without reconstruction: a dual-centre experience 262
Jonathan P Noël, Sarah Yu Weng Tang, Nana Aishatu Liman Muhammad, David Nicol and Roger C Kockelbergh

Case Series
Short-changed during the bacillus Calmette–Guérin shortages? 268
Kenneth R MacKenzie, Sidney D Parker , Dawn Watson and Joanne Cresswell

Cross-sectional Study
The role of intraoperative kidney mucosal biopsy on screening of squamous cell carcinoma of the kidney in nephrolithiasis  275
patients with stones larger than 20 mm
Tri Sunu Agung Nugroho, Ferry Safriadi and Bambang Sasongko Noegroho
A single-centre experience of the management of inguinal lymph nodes associated with penile squamous-cell carcinoma 282
Amit Sharma, Sandesh Parab, Gaurav Goyal, Ajit Patel, Mukund Andankar and Hemant Pathak

Case Report. Infection in Urology

Emphysematous prostatitis as a result of urethral injury: A case report 288
Verónica Hernández-Nájera, Eduardo Barrera-Juárez and Roberto González-Oyervides

Case Report. Oncology (Renal)

Renal carcinoid: A case report of a rare primary renal tumour 290
Michael Y Chen, Jonathan Cho and Rachel Esler

Literature Review
Different clinical presentations of xanthogranulomatous prostatitis: A case series and review of the literature 293
Supun De Silva, Lalani De Silva, Shyamini Sooriyaarchchi, Harshima Wijesighe, Gayani Ranaweera, Susantha De Silva and Chandu De Silva

Systematic Review
The reflective urologist 300
Tim Terry and Anthon Simon Bates

Point of Technique
Point of technique: Limited anterior scrotectomy and scrotoplasty for multiple epidermoid cysts of the scrotum 306
Sally J Deverill, Richard Menzies-Wilson and Rowland W Rees

00_URO 14(4) TOC.indd 233 06/07/2021 12:32:17 PM

 Editor
Ian Pearce
Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK

Associate Editors
Vincent Gnanapragasam
University of Cambridge, Cambridge, UK
Erik Mayer
Imperial College London, London, UK
Bhaskar Somani
University Hospital Southampton NHS Foundation Trust
Sri Sriprasad
Journal of Darent Valley Hospital, Dartford, UK
Clinical Urology Andrew Thorpe
Freeman Hospital, Newcastle, UK

Social Media Editor

Vaibhav Modgil
Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK

Editorial Board Kathleen Kobashi

Virginia Mason Medical Center, Seattle, USA
Anuruddha Abeygunasekera
Colombo South Teaching Hospital, Dehiwala, Sri Lanka Carlos Llorente
Maarten Albersen Hospital Universitario Fundacion Alcorcon, Madrid, Spain
University Hospitals Leuven, Leuven, Belgium
Graeme MacLennan
Marcio A. Averbeck University of Aberdeen, UK
Head of Neuro-Urology, Videourodynamics Unit, Moinhos
de Vento Hospital Porto Alegre, Brazil Anna Mainwaring
Morriston Hospital, Swansea, UK
Rachel Barratt
University College London, UK Kim L Moretti
The Queen Elizabeth Hospital, Adelaide, Australia
Rupesh I Bhatt
University Hospitals Birmingham NHS Foundation Trust, Katia Noyes
UK University of Rochester Medical Center, Rochester, USA
Chris Blick Teng Aik Ong
Royal Berkshire Foundation Trust, Reading, UK University of Malaya Medical Centre, Kuala Lumpur,
Jose Dominguez Malaysia
Instituto Valenciano de Oncologia, Valencia, Spain
Juan Pablo Valdevenito
Garrett Durkan Hospital Clinico Universidad de Chile, Chile
University Hospital Galway, Galway, Ireland
Nicholas Rukin
Michael S Floyd (Jr) Metro North Hospital, Brisbane, Australia
St Helens & Knowsley NHS Trust, UK
Néha Sihra
Mikkel Fode
London Deanery, UK
Roskilde Hospital, Roskilde, Denmark
Peter Grice Andrew Sinclair
East Midlands Deanery, UK Stepping Hill Hospital, Stockport, UK

Chris Harding Tim Terry

Freeman Hospital & Newcastle University, Newcastle, UK Nottingham City Hospital, UK
Dickon Hayne Pedro Vendeira
University of Western Australia, Perth, Australia Clínica do Dragão - Saúde Atlântica, Porto, Portugal

00_URO 14(4) TOC.indd 234 06/07/2021 12:32:17 PM

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1030107 URO Journal of Clinical UrologyEditorial

Editorial

Journal of Clinical Urology

Editorial
2021, Vol. 14(4) 237
© British Association of
Urological Surgeons 2021
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/20514158211030107
https://doi.org/10.1177/20514158211030107
journals.sagepub.com/home/uro

Welcome to what has tradi- clarity and appreciation of reflection that this paper seeks
tionally been the “BAUS to inform and explain. I suspect others may be drawn to it
Issue” of the JCU, which as a welcome deviation from clinical manuscripts but
under normal circumstances whatever your motive for reading, I can assure you it will
would have been available not disappoint in any way.
on the SAGE stand in the Maintaining the wide appeal, we have an excellent
exhibition hall for the dura- point of technique from Sally Jane Deverill, Richard
tion of the annual meeting. Menzies-Wilson, Rowland Rees in Southampton, looking
Now, the journal has evolved at anterior scrotectomy and scrotoplasty for the treatment
into an established digital of multiple epidermoid cysts. Definitely one to remember
format which I hope you are for the future.
all enjoying to the full with Curriculum changes are a current hot topic so it is
its outstanding portability, timely to have the paper by Sehmbi et al assessing the
and the meeting once again will be entirely virtual. 2022 early outcomes of robotic-assisted radical prostatectomy
will be different and a face to face BAUS is certainly the following completion of a structured training curriculum.
anticipation and aspiration. This report from a single institution is both enlightening
This issue of your journal is brimming with widely and extremely well written and I’m sure will be of interest
appealing articles of amazing quality – a true credit to both to all in the field.
authors and reviewers. Once again, it remains for me to thank you all for your
Perhaps I could begin by highlighting a personal favour- ongoing support for the journal during this most difficult
ite of mine, the article on reflective practice by Tim Terry of times, I hope you all have a relaxing summer and look
and Anthony Bates. Why did I find this piece so appeal- forward to your continued engagement with the JCU
ing? I think it is because we spend an awful lot of time All best wishes
talking about reflection, maybe even assessing reflective
pieces for others, or committing our own reflections to Ian Pearce
paper/digital documents but without having the complete Editor in Chief

01_URO1030107.indd 237 25/06/2021 2:35:18 PM

920519 URO Journal of Clinical UrologyPang et al.

Cohort Study

Journal of Clinical Urology

Urethral recurrence after radical

2021, Vol. 14(4) 238­–245
© British Association of
Urological Surgeons 2020
cystoprostatectomy: Experience from a Article reuse guidelines:
sagepub.com/journals-permissions

high-volume tertiary referral centre DOI: 10.1177/2051415820920519

https://doi.org/10.1177/2051415820920519
journals.sagepub.com/home/uro

Karl H Pang1$ , Francesco Esperto2$, Catherine Sproson3,

Maidie Yeung4, Susan L Morgan4, Alison P Downey3,
Christopher J Hillary3, James WF Catto1,3, Derek J Rosario1,3
and Aidan P Noon3*

Abstract
Objectives: To report our urethral surveillance programme and urethral cancer recurrence rate following radical
cystoprostatectomy (RC).
Patients and methods: A retrospective analysis of clinical and histopathological data of men who underwent RC and
urethral surveillance, between January 2011 and October 2016.
Results: RC was performed for 491 men; 31 and 19 men had a synchronous (malignancy, n = 10, 32.3%) and interval
(malignancy, n = 6, 31.6%) urethrectomy, respectively. The remaining 441 men underwent surveillance; 183 (41.5%) men
had at least one urethroscopy, 14 (3.2%) urethrectomies were performed and 12 (2.7%) specimens confirmed urethral
recurrence (UR). Within the URs, 7/12 (58.3%) men presented symptomatically and 5/12 (41.7%) were detected through
surveillance. At a median (interquartile range) follow-up of 21.8 (9.7–36.7) months, the 2-year disease-specific survival
in men who had synchronous urethrectomy was 71.4% (versus no urethrectomy (84.6%) interval urethrectomy (92.9%)
and urethrectomy for recurrence (83.8%)).
Conclusion: UR following RC is low in men without risk factors for urethral disease. Annual urethroscopy and urine
cytology may not be feasible and appropriate in all men after RC, and does not appear to impact survival at 2 years. A
risk-adapted approach may allow the avoidance of annual urethroscopy in asymptomatic men post RC.
Level of Evidence: 3b

Keywords
Urethral recurrence, urothelial cell carcinoma, urethrectomy, urethral surveillance, urethroscopy

Date received: 18 November 2019; accepted: 6 March 2020

Introduction
Radical cystoprostatectomy (RC) and pelvic lymph node
dissection is the gold-standard treatment for men with
muscle-invasive bladder cancer (MIBC) and high-risk
non-muscle invasive bladder cancer (NMIBC).1 The inci-
dence of urethral recurrence (UR) following radical RC is
estimated to be between 1 and 8% in men.2,3 Factors asso-
ciated with UR include RC for NMIBC, tumour multifo-
cality, type of bladder substitution, involvement of the
bladder neck or prostate, and previous history of NMIBC
recurrence.3–5 The management of the urethra at the time
1
Academic Urology Unit, University of Sheffield, UK
2
Department of Urology, Campus Biomedico, University of Rome,
Rome, Italy
3
Department of Urology, Royal Hallamshire Hospital, Sheffield, UK
4
Department of Histopathology, Royal Hallamshire Hospital, Sheffield, UK
$European Society of Residents in Urology
*On behalf of the European Association of Urology Young Academic
Urologists Urothelial Cancer Working Party
Corresponding author:
Aidan Noon, Department of Urology, Royal Hallamshire Hospital,
Glossop Road, Sheffield, S10 2JF, UK.
Email: a.noon@sheffield.ac.uk

02_URO920519.indd 238 25/06/2021 8:13:30 PM

 Pang et al. 239
of RC historically has depended on patient and oncological
factors. Some patients undergo synchronous urethrectomy
at the time of RC (cystoprotatourethrectomy) or undergo
an interval urethrectomy. Some patients will be deemed at
higher risk of UR based on adverse pathological risk fac-
tors from the cystectomy specimen (i.e. multifocal disease
and prostate/prostatic urethral involvement)5,6 and these
patients may elect to undergo an interval urethrectomy.3
However, the increased use of orthotopic bladder recon-
struction and the uncertain survival benefits of prophylac-
tic urethrectomy have changed practice in some centres.
Evidence is conflicted regarding improved outcomes
following asymptomatic detection on surveillance com-
pared with symptomatic self-presentation.1,4,7 Level I evi-
dence involving follow-up protocols for asymptomatic
men is limited. The UK National Institute for Health and
Care Excellence (NICE) Guidelines recommend annual
urethral cytology and/or urethroscopy for 5 years post
RC,8 with the European Association of Urology and
American Urological Association Guidelines also advo-
cating urethral wash and urine cytology in men at high risk
of UR.1,9
Our centre adopts a risk-stratified approach whereby
high-risk patients undergo synchronous or interval ureth-
rectomy. Patients with preserved urethrae are enrolled into
a surveillance programme that consists of annual flexible
urethroscopy and urethral wash cytology, performed by
our centre and district general hospitals. It is unknown
whether this approach is clinically feasible or cost-effec-
tive. Here, we evaluate the effectiveness of our urethral
surveillance strategy following RC.
Patients and methods
Patients
The Royal Hallamshire Hospital (RHH) provides the
only urological service for the city of Sheffield, UK
(approximately 580,000 people). Patients from this com-
munity attend and remain under the care of this hospital
for treatment and surveillance of urological diseases.
Within South Yorkshire, patients outside Sheffield
(Barnsley, Chesterfield, Doncaster and Rotherham)
requiring RC (following a central multidisciplinary team
(MDT) meeting) are referred to the RHH. Any disease
recurrences (urethral, local or distant) are referred back
to Sheffield through the MDT for further discussion of
management.
For the purposes of the current analysis, patients who
underwent urethrectomy were grouped as follows: (a)
‘synchronous’ urethrectomy (performed at the time of
RC), (b) ‘interval’ urethrectomy (planned following recov-
ery from RC due to disease factors known prior to RC or
when RC histology was available) and (c) ‘recurrence’
(patients who developed recurrent disease in their urethra
after RC). Men undergoing RC for urothelial cell
02_URO920519.indd 239
carcinoma between January 2011 and October 2016 were
identified from our prospective database.10 Case notes, and
histology and cytology reports were reviewed. Men
deemed to be high risk for UR were those with widespread
carcinoma in situ (Cis) or those with disease involving the
prostate, prostatic urethra or prostatic ducts, or a positive
urethral margin. If identified as high risk prior to RC, men
were offered a ‘combined’ RC and urethrectomy. If there
were concerns regarding their fitness, there were adverse
intraoperative findings or they were identified as high risk
from the RC histology specimen, patients were offered an
‘interval’ urethrectomy. In men with preserved urethrae,
surveillance involved annual urethroscopy and urethral
wash cytology. Patients were also advised to report any
penile bleeding or discharge, which would lead to an
urgent urethroscopy.
Suspected UR was detected by urethroscopy and/or
urine cytology either through symptomatic presentation or
asymptomatic surveillance. Actual UR was confirmed on
biopsy/urethrectomy.
Prepubic and perineal urethrectomy
Simultaneous urethrectomy during RC was performed pre-
pubically, as first described in 1989 by Van Poppel et al.11
In brief, following mobilisation of the bladder and pros-
tate, and control of the deep vein complex, retropubic dis-
section of the membranous urethra is performed. The
prepubic space is exposed, and prepubic dissection of the
penile and distal urethra from the corpus spongiosum
down to the glans is performed. The whole urethra is
mobilised proximally, bulbar arteries are controlled and
the cystoprotatourethrectomy specimen is removed en
bloc.11–13 Perineal urethrectomy was performed as per
standard.13,14
Statistical analysis
Non-parametric continuous data were analysed using the
Mann–Whitney U test, and categorical data were analysed
using chi-square and Fisher’s exact tests. UR-free survival
and disease-specific survival were plotted using the
Kaplan–Meier method, and were calculated from the date
of RC. Independent predictors of UR were determined by
multivariable analysis and logistic regression.
Results
Patients
A total of 491 men underwent RC between January 2011
and October 2016. Orthotopic neobladder formation
Studer pouch15 was performed in 50 men with negative
intraoperative frozen section of the urethral margin at RC.
Synchronous and interval urethrectomy was performed in
31 and 19 patients, respectively (Figure 1). Malignancy
25/06/2021 8:13:30 PM
 240 Journal of Clinical Urology 14(4)

Figure 1.  Flow chart of the urethrectomy outcome of men analysed in this cohort.
A total of 50 prophylactic urethrectomies were performed. Out of the 441 patients with a preserved urethra, 14 underwent urethrectomy for
suspected urethral recurrence.
UR: urethral recurrence.

was confirmed in 10 (10/31, 32.3%) and 6 (6/19, 31.6%) Table 1.  Urethral management of patients who underwent
of the synchronous and interval urethrectomy histologies, radical cystoprostatectomy.
respectively. The median (interquartile range) time to
n (491) %
interval urethrectomy was 4.6 (3.7–8.0) months. There
were 441 patients with preserved urethrae enrolled into Age (years)
urethral surveillance. The median follow-up was 21.8 (9.7-
36.7) months (Table 1). Median (IQR) 71.4 40.7–87.6

Urethral Mx  
URs Synchronous urethrectomy 31 6.3
Urethrectomy for subsequent recurrence was performed Interval urethrectomy 19 3.9
in 14/441 (3.2%) men. Of these, final histology con-
firmed cancer in 12/441 (2.7%, (12/14, 85.7%)) (Figure Surveillance 441 89.8
1). The median time to suspected UR was 21.4 (11.9–  Urethrectomy 14 3.2
32.4) months and the median time to urethrectomy from
suspected UR was 2.7 (1.6–3.2) months. UR was not   Confirmed UR 12 2.7
detected in the 50 patients with a neobladder. Out of the Follow-up (months)
12 confirmed URs, 5 (41.7%) were detected by surveil-
lance while 7 (58.3%) were detected by symptomatic Median (IQR) 21.8 9.7–36.7
presentation. Of note, three asymptomatic patients did Synchronous urethrectomy was performed at the time of radical
not have any visible disease at urethroscopy but urine cystoprostatectomy.
cytology was suggestive of disease (Table 2). Kaplan– via the prepubic approach. Patients who had high-risk features on post-
Meier plots estimated UR-free rates of 99.0 and 87.6% at operative specimens were offered an interval urethrectomy.
IQR: interquartile range; UR: urethral recurrence; Mx: management.
2 and 5 years, respectively (Figure 2).
There were no significance differences in age and sur-
vival in the UR and non-UR groups. However, all men or had positive lymph nodes. Positive urethral margins
who had UR had NMIBC on transurethral resection of (Cis) was seen in one patient. Multivariable analysis
bladder tumour (TURBT) and RC histologies. None of the (logistic regression) revealed no significant predictors for
patients who had UR received neoadjuvant chemotherapy UR (Supplementary Table 1).

02_URO920519.indd 240 25/06/2021 8:13:30 PM

 Pang et al. 241
Figure 2.  Kaplan–Meier estimate of urethral recurrence.
At a median follow-up of 21.8 (9.7–36.7) months, urethral recurrence within this series was 2.7%. The 2- and 5-year urethral recurrence-free rates
were 99.0 and 87.6%, respectively.
UR: urethral recurrence; Yr: years.
Survival outcomes
The 2-year disease-specific survival (DSS) was 84.6,
71.4, 92.9 and 83.9% in men who did not have an ureth-
rectomy, and those who had synchronous, interval ureth-
rectomy and urethrectomy for recurrence, respectively
(Figure 3) (Log-rank, p = 0.02). During a median fol-
low-up of 21.8 months, 340 (79.6%), 17 (54.8%), 17
(89.5%) and 12 (85.7%) men were alive in the no ureth-
rectomy, and synchronous, interval and recurrence ure-
threctomy groups, respectively (p = 0.01). Pathological
T2+ disease in RC specimens was detected in 36.2, 42,
10.6 and 0% in the no urethrectomy, synchronous, inter-
val and recurrence urethrectomy groups respectively
(p < 0.001) (Table 3).
Surveillance programme
Following RC, patients with preserved urethra were sub-
ject to annual urethroscopy, and urethral washings and
urine cytology. However, urgent urethroscopy was per-
formed if patients presented with symptoms such as visible
haematuria prior to their annual urethroscopy. Out of the
02_URO920519.indd 241
441 men in surveillance programme, 183 (41.5%) men
underwent at least one urethroscopy, of which 160 (87.4%)
had consecutive annual urethroscopies (complete surveil-
lance) and 23 (12.6%) had intermittent annual urethrosco-
pies (incomplete surveillance).
Discussion
The rate of confirmed UR within our centre is low (2.7%)
and is in keeping with the range presented in the literature
(1–8%).2,3 The UR-free rate is 99.0% at 2 years and 87.6%
at 5 years. There was no UR in those who had an ortho-
topic bladder and this was partly due to the fact that ure-
thral frozen sections were taken to ensure negativity prior
to proceeding with an orthotopic. Our low UR rate may be
due to a risk-stratified approach to management, with
patients at high risk of UR undergoing synchronous or
interval urethrectomy, as our data showed that urethral
cancer was found in around one-third of men who under-
went synchronous (32.3%) and interval (31.6%) urethrec-
tomy. The relatively short follow-up and those who did not
undergo check urethroscopies may have underestimated
the rate of UR. UR occurred only in those who had NMIBC
25/06/2021 8:13:31 PM
 242

02_URO920519.indd 242
Table 2.  Patients undergoing urethrectomy for suspected urethral recurrence.

Radical cystectomy details Cytology Urethral surveillance and urethrectomy details Mor-
tality
RC Prostatic Urethral Number of Ure- Visible Time to recur- Urethrectomy
Age (years) RC histology urethra margin throscopies disease Symptoms rence (months) histology

79 2011 G3pTis Clear Negative High-grade 3 No No 49.6 Cis  

disease

74 2011 G3pTa + Cis Clear Negative Suspicious 1 No No 29.0 Cis  

66 2011 G3pT1 Clear Negative 1 Yes No 33.2 G3pTa  

78 2012 G3pTis Cis Positive Cis 2 No No 214 Cis  

74 2012 G3pTa G3pTa Negative 1 Yes Blood PU 12.2 G3pT2 Yes

ducts

75 2012 T0 N/A Negative 1 Yes Blood PU 50.6 G2pTa  

58 2012 G3pT1 + Cis Clear Negative 1 Yes No 18.8 G2pT1  

71 2012 G3pTa + Cis Clear Negative 2 Yes Blood PU Benign  

75 2012 G3pTa + Cis Clear Negative Atypical cells 3 Yes Blood PU 31.7 G3pTa  

64 2013 T0 N/A Negative 1 Yes Blood PU Free-floating high-  

grade tumour

80 2013 G3pTa Clear Negative 1 Yes Blood PU 11.5 G3pTa  

75 2014 G3pT1 + Cis Cis Negative 1 Yes Blood PU 8.5 Cis Yes

69 2015 G3pT1 + Cis Cis Negative 1 Yes Blood PU N/A Benign  

76 2015 G3pT1 + Cis Clear Negative 1 Yes Blood PU 10.9 G3pT1  

Urethrectomy was performed in 14 men with suspected urethral recurrence, and all had RC specimens showing high-risk non-muscle invasive bladder cancer or T0 disease. All patients who presented
symptomatically had visible disease at urethroscopy. The three asymptomatic patients who had non-visible disease at urethroscopy had positive urine cytology.
Cis: carcinoma in situ; G3, grade 3; N/A: not applicable; PU: per urethra; RC: Radical cystectomy.
Journal of Clinical Urology 14(4)

25/06/2021 8:13:31 PM
 Pang et al. 243

Figure 3.  Kaplan–Meier estimate of survival stratified by type of urethrectomy.

The (a) overall and (b) disease-specific survival is lower in the group who had synchronous urethrectomy. There are no differences in 2-year survival
in men who had interval urethrectomy, urethrectomy for urethral recurrence and those who did not have a urethrectomy.

on TURBT and RC histology. The reason is not entirely
clear, and it may be because these men survive longer
compared to muscle-invasive disease.
Survival analysis showed that the DSS rate was the
lowest in the synchronous urethrectomy group and when
looking at the RC histology, this group had the highest
rate of T3+ disease (32.3%), which may explain the
lower DSS rate. There was no statistical difference in
DSS between those who had an interval urethrectomy,
urethrectomy for suspected recurrence and those who did
not have a urethrectomy.
Although our surveillance programme consists of
annual urethroscopy/cytology, just under one-half
(183/441, 41.5%) of men with a preserved urethra were
followed-up for urethroscopy, and not all had urethrosco-
pies on a consecutive annual basis. This suggests that
annual review may not be feasible and that the majority of
the ‘missed’ surveillance opportunities were from district

02_URO920519.indd 243 25/06/2021 8:13:32 PM

 244 Journal of Clinical Urology 14(4)

Table 3.  Histopathological outcomes from different types of urethrectomy.

Non Synchronous Interval Recurrence p-value

  n % n  % n % n  %

Urethrectomy 427 87.0 31 6.3 19 3.9 14 2.9  

RC stage < 0.001

 T0 110 25.8 4 12.9 0 0.0 2 14.3  

 Ta–1 95 22.2 10 32.3 11 57.9 10 71.4  

 Tis 57 13.3 4 12.9 6 31.6 2 14.3  

 T2 59 13.8 3 9.7 1 5.3 0 0.0  

 T3–4 100 23.4 10 32.3 1 5.3 0 0.0  

Unknown 6 1.4 0 0.0 0 0.0 0 0.0  

Death

 Total 87 20.4 14 45.2 2 10.5 2 14.3  

 BCa 61 14.3 11 35.5 1 5.3 2 14.3 0.01

BCa: bladder cancer; Non: no urethrectomy; RC: Radical cystectomy.

general hospitals. A search of our radiotherapy database
showed that none of the studied patients received palliative
or treatment dose radiation to the urethra.
Out of the 12 patients with confirmed UR, 5 (41.7%)
were asymptomatic and detected by surveillance, whilst 7
(58.3%) presented symptomatically despite annual ure-
throscopy. It appears that urethral wash cytology was not
routinely performed. However, of the five patients detected
by surveillance, three were detected by cytology alone
without visible disease.
It is feasible that urethral wash cytology may detect UR
earlier than urethroscopy. Cytology also offers a cheaper,
more convenient method for surveillance compared with
annual urethroscopy. Although the EAU1 and AUA9 guide-
lines recommend urethral wash cytology in high-risk
patients, time interval and duration of follow-up are not
mentioned, and only the NICE guidelines mention annual
follow-up with urethroscopy/cytology for 5 years.8 The
role of wash cytology is controversial and results are often
dependent on the skill of the cytologist. Further analysis of
the role of wash cytology compared with urethroscopic
surveillance involving a large patient cohort is necessary.
In addition, cost-effectiveness analysis will be important
to evaluate the role of surveillance in general compared
with symptomatic self-presentation of UR. The use of
wash cytology is not routine and is performed according to
surgeon preference. The number of patients undergoing
cytology is consequently low and it is thus difficult to draw
strong conclusions regarding its role.
It is possible that some URs have not been captured
within these data, such as those treated conservatively
or those lost to follow-up. It is also difficult to gain an
accurate picture of the follow-up received by those
patients followed up in other hospitals. However, any
detected UR in the peripheral hospitals within South
Yorkshire would be referred back to us.
Since our data suggest that the majority of URs were
detected through symptomatic presentation (all had visible
disease at urethroscopy) and almost two-thirds of men
with non-visible disease at urethroscopy who were asymp-
tomatic had positive urine cytology, it may be clinically
and cost-effective to investigate those who are sympto-
matic with urethroscopy, and offer urine cytology to high-
risk men who do not want or cannot have synchronous or
interval urethrectomy.
Conclusion
The incidence of UR following RC is low in men with-
out risk factors for urethral disease. Routine urethral
surveillance appears unnecessary for such men and does
not impact their survival at 2 and 5 years. The use of a
risk-adapted strategy may allow the safe avoidance of
routine urethroscopy in asymptomatic men after RC.
Conflicting interests
The authors declare that there is no conflict of interest.
Funding
The authors received no financial support for the research,
authorship and/or publication of this article.

02_URO920519.indd 244 25/06/2021 8:13:32 PM

 Pang et al. 245
Ethical approval
Ethical approval was not sought for the present study because of
its retrospective nature. This study was completed in accordance
with the Helsinki Declaration as revised in 2013.
Informed consent
Informed consent was not sought for the present study because of
its retrospective nature.
Guarantor
AN.
Contributorship
KHP: project development, data collection, data analysis, manu-
script writing and editing. FE: data collection, data analysis and
critical review of the manuscript. CS: data collection and analysis.
MY: data collection. SLM: data collection and critical review of
the manuscript. APD: data collection and critical review of manu-
script. CJH: data collection and critical review of the manuscript.
JWFC: project development, manuscript editing and critical
review of the manuscript. DJR: project development, manuscript
editing and critical review of the manuscript. APN: project devel-
opment, manuscript editing and critical review of the manuscript
Acknowledgements
The authors would like to acknowledge the medical and nursing
staff within the Departments of Urology and Histopathology
at Sheffield RHH, Doncaster Royal Infirmary Hospital,
Chesterfield Royal Hospital, Rotherham General Hospital and
Barnsley Hospital.
ORCID iD
Karl H Pang https://orcid.org/0000-0001-5703-2319
Supplemental material
Supplemental material for this article is available online.
References
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2. Soukup V, Babjuk M, Bellmunt J, et al. Follow-up after sur-
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outcomes of urethral recurrence following radical cystec-
tomy. Eur Urol 2011;60: 1266–1272.
6. Tobisu K, Tanaka Y, Mizutani T, et al. Transitional cell
carcinoma of the urethra in men following cystectomy for
bladder cancer: multivariate analysis for risk factors. J Urol
1991; 146: 1551–3; discussion 1553–1554.
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definitive therapy of invasive bladder cancer. Can Urol
Assoc J 2009; 3: S237–S242.
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552–559.
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mentation of enhanced recovery after surgery protocols to
radical cystectomy. Eur Urol 2018; 73: 363–371.
11. Van Poppel H, Strobbe E and Baert L. Prepubic urethrec-
tomy. J Urol 1989; 142: 1536–1537.
12. Van Poppel H, Joniau S and Groen A. Surgery illustrated
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13. Joniau S, Shabana W, Verlinde B, et 
al. Prepubic
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14. Elshal AM, Barakat TS, Mosbah A, et al. Complications of
radical cysto-urethrectomy using modified Clavien grad-
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938176 URO Journal of Clinical UrologySehmbi et al.

Cohort Study

Journal of Clinical Urology

Early outcomes of robot-assisted radical

2021, Vol. 14(4) 246­–254
© British Association of
Urological Surgeons 2020
prostatectomy following completion of a Article reuse guidelines:
sagepub.com/journals-permissions

structured training curriculum: a single DOI: 10.1177/2051415820938176

https://doi.org/10.1177/2051415820938176
journals.sagepub.com/home/uro

surgeon cohort study

Arjan S Sehmbi1 , Ashwin N Sridhar2,

Kanagasabai Sahadevan3, Bhavan P Rai4, Pamela Nwangwu2,
Anna Mohammed2, Alex Freeman5, Alexandre Mottrie6,7,
Mats J Olsson8,9, N Peter Wiklund8,9,10, M Senthil Nathan2,
Timothy P Briggs2, John D Kelly2,11 and Prabhakar Rajan1,2,12 

Abstract
Objective: Technical skills in robot-assisted radical prostatectomy (RARP) are not mandated by the Intercollegiate
Surgical Curriculum Programme. The European Association of Urology Robotic Urology Section (ERUS) developed
a structured curriculum; however, surgeons’ outcomes data from subsequent independent practice are limited. We
describe the initial post-ERUS curriculum RARP outcomes for a United Kingdom (UK)-based surgeon.
Patients and methods: This was a prospective single surgeon cohort study of 272 patients who underwent RARP
between February 2016 and October 2019 in a high-volume UK centre and who were followed up at approximately
3 and 12 months. Positive surgical margins (PSMs), and 3- and 12-month continence rates were obtained and used to
generate learning curves, with point of plateau estimated from logarithmic trendlines.
Results: Overall (⩾3 mm) PSM rate for pT2 was 14.9% (5.4%) and pT3 was 22.6% (3.2%). Where data were available,
70.5% (of n=251) and 95.5% (of n=154) patients achieved social continence (0–1 pads) at 3 and 12 months, respectively.
PSM and 3-month social continence rates plateaued at ~175 and ~100 cases, respectively.
Conclusion: Following completion of the ERUS RARP curriculum, early oncological and functional outcomes consistent
with published standards are rapidly achievable in independent practice. These data exemplify the potential value of a
standardised RARP training curriculum to mitigate possible compromises in outcomes.
Level of evidence: IV

1
 entre for Cancer Cell and Molecular Biology, Barts Cancer Institute,
C 8
Department of Urology, Karolinska University Hospital, Stockholm,
Cancer Research UK Barts Centre, Queen Mary University of Sweden
London, UK 9
Department of Molecular Medicine and Surgery, Division of Urology,
2
Department of Uro-oncology, University College London Hospitals Karolinska Institutet, Stockholm, Sweden
NHS Foundation Trust, UK 10
Department of Urology, Icahn School of Medicine at Mount Sinai
3
Department of Urology, South Tyneside and Sunderland NHS Health System, New York, USA
Foundation Trust, UK 11
Division of Surgery and Interventional Sciences, University College
4
Department of Urology, Newcastle-upon-Tyne Hospitals NHS London, UK
Foundation Trust, UK 12
Department of Urology, Barts Health NHS Trust, London, UK
5
Department of Histopathology, University College London Hospitals
NHS Foundation Trust, UK Corresponding author:
6
ORSI Academy, Melle, Belgium Prabhakar Rajan, Centre for Cancer Cell and Molecular Biology, Barts
7
Division of Urology, Onze-Lieve-Vrouw Hospital, Aalst, Belgium Cancer Institute, Cancer Research UK Barts Centre, Queen Mary
University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Email: p.rajan@qmul.ac.uk Twitter: @urosplice

03_URO938176.indd 246 25/06/2021 8:23:01 PM

 Sehmbi et al. 247
Keywords
Robot-assisted surgery, prostatectomy, modular training, curriculum, learning curve, prostate cancer, treatment
outcomes
Date received: 28 March, 2020; accepted: 1 June, 2020
Introduction
Robot-assisted radical prostatectomy (RARP) is the stand-
ard-of-care surgical treatment of localised prostate cancer
(PCa), the commonest male-specific malignancy in
Europe.1 Despite widespread adoption of the technique in
the United Kingdom (UK), technical skills in RARP are
not mandated during training by the Intercollegiate
Surgical Curriculum Programme2 and there is no formal
credentialling process for established surgeons.3
The European Association of Urology (EAU) Robotic
Urology Section (ERUS) developed a structured curriculum4
based on expert consensus5 consisting of key modalities with
demonstrated validity:6–8 (a) web-based e-learning; (b) an
intensive week of structured, simulation-based training at
ORSI Academy incorporating virtual reality simulators and
dry and wet laboratory simulation (synthetic and animal);
and (c) supervised modular training at home institutions,
which involved progressive, proficiency-based training
through surgical steps with increasing levels of complexity
as part of a mini-fellowship programme. However, there is a
paucity of information on surgeons’ outcomes data from sub-
sequent independent practice.9,10
Here, we describe the initial independent experience of
a single UK-trained surgeon with no laparoscopic and lim-
ited (<10 case) open radical prostatectomy (ORP) experi-
ence, who completed the ERUS RARP curriculum.
Patients and methods
Patients, interventions and follow-up
In this single UK centre cohort study, data was collected
prospectively for all patients undergoing RARP for newly
diagnosed Gleason score11 ⩾ 6 cT1–cT3 N0 M0 PCa with
prostate-specific antigen (PSA) <50 ng/ml between
February 2016 and October 2019, and followed up at
approximately 3 and 12 months. Using established opera-
tive techniques,12,13 RARP procedures were performed
independently by a single surgeon who had completed the
ERUS curriculum4 (modular training details are given in
Supplementary Table S1). An experienced surgeon (⩾200
cases) was available on site for the first ~50 cases (details
of assistance are given in Supplementary Table S2), as
cases were unselected from a pooled waiting list.
Patient demographic and clinicopathological data were
prospectively collected which included pre-operative (age,
body mass index (BMI), PSA, Gleason score, clinical
tumour stage (cT)), peri-operative (date of surgery, nerve
03_URO938176.indd 247
sparing (NS), bladder neck reconstruction (BNR), blood
loss and transfusion, Clavien–Dindo complications,14
length of stay (LOS)) and post-operative (Gleason score,
pathological tumour stage (pT), size and location of posi-
tive surgical margin (PSM), continence) characteristics.
RARP specimens were processed as previously described15
and evaluated by a specialist uropathologist.
Patients were followed up by clinicians at approxi-
mately 6 weeks, and subsequently at other referring cen-
tres. Continence status, as determined by pad usage, was
assessed at 3 and 12 months by telephone consultation
using the validated International Consultation on
Incontinence Questionnaire – Urinary Incontinence Short
Form.16 Hence, 3- and 12-month continence outcomes
were available until September 2019 and January 2019,
respectively. Complete continence was defined as use of 0
pads per 24 h and social continence was defined as use of
⩽1 pad per 24 h.17,18
Operative times were not recorded. In view of a known
high level of subjectivity bias for NS reporting,19 infor-
mation on grades and laterality of NS is not given.
Despite EAU PCa guideline recommendations,20 the role
of pelvic lymph node dissection (PLND) is unclear,21
hence data on PLND was excluded. Pre- and post-opera-
tive sexual function, as determined by the International
Index of Erectile Function questionnaire,22 and overall
quality of life outcomes were not available. Long-term
oncological outcomes could not be assessed due to a
short follow-up period.
Clinical data and statistical analyses
All patient data were prospective and stored in an institu-
tionally approved secure database, and the study protocol
was approved prior to data analysis. Patient characteristic
and clinicopathologic data were reported as median and
interquartile range (IQR), excluding missing cases where
detailed. The primary study outcomes were PSM and 3-
and 12-month continence outcomes. For PSM, the point of
plateau for the learning curve (LC) was estimated using
logarithmic trendline of the cumulative PSM rate. Due to a
large number of missing data points for continence out-
comes, the LC point of plateau was estimated from cumu-
lative PSM rate alone. Graphical outputs were created
using Microsoft Excel 365 ProPlus. All data presented are
rounded to the nearest decimal place where appropriate.
Kruskal–Wallis and χ2 tests were used to determine differ-
ences between groups. Statistical analysis was conducted
25/06/2021 8:23:01 PM
 248 Journal of Clinical Urology 14(4)

Table 1.  Patient pre-operative characteristics. Table 2.  Patient peri-operative characteristics.

Pre-operative Median (IQR) Patients Peri-operative Overall cohort (n=272)

characteristics n (%) characteristics

Age at surgery (years) 63 (58–69) 272 (100)   Median (IQR) Patients n (%)

Body mass index (kg/m²) 28 (25–30) 272 (100) Year of surgery

Prostate-specific antigen 7.5 (5.4–10.5)    2016 60 (22.1)

(ng/ml)
 2017 75 (27.5)
 0–10 198 (72.8)
 2018 91 (33.5)
 10–20 58 (21.3)
 2019 46 (16.9)
  >20 16 (5.9)
Nerve sparing 203 (74.6)
Gleason score
Bladder neck 48 (17.6)
  ⩽6 11 (4.0) reconstruction

 3+4 159 (58.5) Blood loss (ml) 250 (150–400) 270 (99.3)a

 4+3 61 (22.4) Transfusion (units) 2 (0.7)

  ⩾8 41 (15.1)  1 1 (0.4)

Clinical T stage (cT)  2 1 (0.4)

  ⩽2 173 (63.6) Complications 21 (7.7)

(Clavien–Dindo)
 3a 94 (34.6)
 I 11 (4.0)
 3b 5 (1.8)
 II 3 (1.1)
IQR: interquartile range.
 IIIa 4 (1.5)

using SPSS® version 26 (SPSS, Chicago, Illinois, USA)  IIIb 3 (1.1)

with p<0.05 taken to indicate statistical significance. Inpatient time (days)

Results and discussion
Demographic and clinicopathologic summary statistics for
the study cohort are reported in Tables 1 to 3. A total of 272
consecutively completed RARP procedures were included
in the study over a period of 44 months, with an average
institutional volume of ~500 cases per annum for the study
period.23 Using a linear model, the case accumulation rate
was 17 cases per quarter (Figure 1(a)), varying from 3 per
quarter in the first 3 months to 24 per quarter in the last 6
months of 2018 (Figure 1(a)). The mean weekly case accu-
mulation rate was 1.43 cases.
The median age of the cohort was 63.0 (IQR=58.0–
69.0) years, the median pre-operative PSA was 7.5
(IQR=5.4–10.5) ng/ml, and the median BMI was 28
(IQR=25–30) kg/m². NS and BNR (as a surrogate indica-
tor of bladder neck sparing) were performed in 74.6%
(n=203) and 17.6% (n=48) cases, respectively. By plot-
ting NS and BNR rates for sequential subgroups of 50
cases, we observed a fall in BNR rate from 30.6% in
cases 0–49 to 9.6% in cases ⩾200 (Figure 1(b)). The NS
 1 217 (79.8)
 2 38 (14.0)
  ⩾3 17 (6.2)
a
Two missing data points.
IQR: interquartile range.
rate increased from 57.1% in cases 0–49 to 90.0% in
cases 150–199, but fell to 76.7% in ⩾200 cases subgroup
(Figure 1(b)). Consistent with published data,24 we
observed low median blood loss (median=250 ml;
IQR=150–400), with only 2 (0.7%) patients receiving
blood transfusions, and a low grade III Clavien–Dindo
complication rate (2.6%) (details given in Supplementary
Table S3). The one-day inpatient LOS rate was lower
than expected at 79.8% (n=217); however, the majority
(73.2%) cases were performed on a Friday, which can
increase LOS for elective surgery.25
The overall PSM rate was 18.4% (n=50). The pT2 and
pT3 PSM rates of 14.9% and 22.6%, respectively, were

03_URO938176.indd 248 25/06/2021 8:23:01 PM

 Sehmbi et al. 249

Table 3.  Patient post-operative pathological characteristics. better than UK national averages (pT2 PSM=17.5% and
pT3 PSM= 42.3%).26 Other studies of post-ERUS RARP
Pathological characteristics Overall cohort (n=272) curriculum outcomes have reported overall PSM rates of
  Patients n (%) 10–24%,9,10 but were limited in surgeon volume (<120
cases)9 or excluded high risk PCa.10 We observed very
Gleason score low rates of ⩾3 mm/multifocal PSMs for pT2 (5.4%) and
  ⩽6 2 (0.7) pT3 (3.2%) disease, which have the greatest impact on
long-term oncological outcomes.27 The majority of PSMs
 3+4 166 (61.0) were either apical (24.0%), basal (26.0%) or anterior
 4+3 81 (29.8) (24.0%).
Post-operative continence data at 3 and 12 months was
  ⩾8 23 (8.5) available for 251 (92.3%) and 154 (56.6%) patients,
respectively (Table 4 and Figure 1(c) and (d)). Missing
Pathological tumour stage (pT)
data were due to an inability to contact patients, who had
 2a 15 (5.5) been discharged to referring centres. The 3-month com-
plete and social continence rates were 43% (n=108) and
 2b 2 (0.7)
70.5% (n=177), respectively, with 30% (n=74) using more
 2c 131 (48.2) than 1 pad per day. The 12-month complete and social con-
tinence rates were 87% (n=134) and 95.5% (n=147),
 3a 94 (34.6)
respectively with 5% (n=7) using more than 1 pad per day.
 3b 30 (11.0) Others reported continence rates of 86–93%; however,
continence definitions were less stringent and complete
Positive surgical margin (PSM) 50 (18.4)
continence rates were not reported.9,10
 Positive: ⩽1 mm 28 (56.0) The true RARP LC is unclear, with a number of studies
reporting different findings,28 including a PSM rate pla-
 Positive: >1 and ⩽3 mm 10 (20.0)
teau as early as 50 cases.29 An individual surgeon’s LC is
 Positive: >3 mm/multifocal 12 (24.0) multifactorial and influenced by technical ability and
familiarity of other prostatectomy approaches.30 The larg-
pT stratified PSM est single surgeon RARP LC study identified a plateau
 pT2 22 (14.9) point for urinary symptoms beyond 1500 cases31 for an
operator with significant ORP experience.
 Positive: ⩽1 mm 12 (8.1) We estimated the LCs by plotting the cumulative PSM
 Positive: >1 and ⩽3 mm 2 (1.4) and continence rates by number of cases completed
(Figure 2(a) to (c)). We observed a PSM rate of ~50% for
 Positive: >3 mm /multifocal 8 (5.4) the first 6 cases which rapidly fell to ~30% by case 25,
 pT3 28 (22.6) and more slowly to ~20% by 200 cases (Figure 2(a)). The
cumulative PSM rate continued to decline beyond 200
 Positive: ⩽1 mm 16 (12.9) cases to below 19.0% for the final 30 cases. Using a loga-
 Positive: >1 and ⩽3 mm 8 (6.5) rithmic trendline, we identified a plateau point in the
cumulative PSM rate at ~200 cases. By plotting PSM
 Positive: >3 mm/multifocal 4 (3.2) rates for sequential subgroups of 50 cases, we observed an
PSM location
increase in PSM rates from groups 0–49 (20.4%) to 50–99
(38.0%) (Figure 2(a)). This trend may be due to an
 Apex 12 (24.0) increase in the proportion of pT3 cases (Supplementary
Table S4) or attempts at technically challenging NS pro-
 Base 13 (26.0)
cedures (Figure 1(b)) causing pT2 PSMs (Supplementary
 Anterior 12 (24.0) Table S4). We observed similar PSM rates for groups
100–149, 150–199 and ⩾200 (12.0%, 10.0% and 13.9%
 Posterolateral 8 (16.0)
respectively) (Figure 2(a)). Excluding the first 100 cases,
 Multiple 5 (10.0) the PSM rate was 12.2%, indicating that a <10% PSM
rate may be achievable in <1600 cases contrary to a pre-
Pathological node stage (pN) 73 (26.8)
vious report.32
 pN1 10 (13.7) By plotting cumulative continence rate by number of
cases completed, we estimated plateaus in 3-month social
 pN0 63 (86.3)
and full continence rates after ~120 cases and ~140 cases,

03_URO938176.indd 249 25/06/2021 8:23:01 PM

 250 Journal of Clinical Urology 14(4)

Figure 1.  Accumulation of robot-assisted radical prostatectomy cases and continence outcomes. (a) Proportion of cases (total
n=272) over time. (b) Proportion of nerve sparing (NS) and bladder neck reconstruction (BNR) procedures performed across
subgroups of cases. (c) and (d) Continence status, as determined by pad usage per 24 h, at 3 and 12 months including (c) and
excluding (d) missing data points.

respectively (Figure 2 (b) and (c)), which is consistent In view of the recognised trade-off between cancer con-
with published data.30 Trends in 12-month cumulative con- trol and functional outcomes,33 we explored the relation-
tinence rates were more difficult to estimate due to missing ship between 3- and 12-month continence rates and PSM
values (Figure 2(b) and (c)). rates stratified by case number (Figure 2(d) and (e)). For

03_URO938176.indd 250 25/06/2021 8:23:03 PM

 Sehmbi et al. 251

Table 4.  Continence outcomes.

Follow-up Complete continence Social continence Number of responders

(0 pads/24h), n (%) (⩽1 pads/24h), n (%) (% of total)

3 months 108 (43.0) 177 (70.5) 251 (92.3)

12 months 134 (87.0) 147 (95.5) 154 (56.6)

Figure 2. (Continued)

03_URO938176.indd 251 25/06/2021 8:23:05 PM

 252 Journal of Clinical Urology 14(4)

Figure 2.  Learning curve for robot-assisted radical prostatectomy cases across the complete cohort. (a) Cumulative positive
surgical margin (PSM) rate across the complete cohort. A logarithmic trendline of cumulative PSM rate is shown as a red dotted
line. PSM for subgroups of cases (0–49, 50–99, 100–149, 150–199, ⩾200) are shown as a bar chart. (b) and (c) Cumulative
continence rates at 3 (black line) and 12 (red line) months for (b) social (⩽1 pads/24h) and (c) complete (0 pads/24h) continence.
(d) and (e) Scatter plot of continence and PSM rates within subgroups of cases (0–49, 50–99, 100–149, 150–199, ⩾200) at (d) 3 and
(e) 12 months. Each circle represents a single subgroup, and the size of the circle correlates with the number of cases.

3-month continence outcomes, we observed a worsening
of results between 0–49 and 50–99 case subgroups (Figure
2(d)), which was largely driven by an increase in PSM
rates (Figure 2(a)) but also a fall in 3-month continence
rates. For subsequent subgroups, both PSM and continence
rates fell within a ~15% margin. For 12-month continence
outcomes, a similar worsening of results was seen between
0–49 and 50–99 case groups, again largely driven by an
increase in PSM rates. However, for the 150–199 and
⩾200 case subgroups, both PSM and continence rates fell
within a <10% margin (Figure 2(e)). For patients in the
⩾200 case subgroup, 12-month social and full continence
rates were close to 100% with overall PSM rates of <15%
(Figure 2(e)). The observed improvement in oncological
and continence outcomes did not appear to be due to case
selection of patients with favourable characteristics in later
subgroups (Supplementary Table S4). Although there was
an increase in the proportion of cT2 cases in the latter sub-
groups, this did not translate into a difference in the pro-
portion of pT2 cases.
Our study has several limitations. This was a single sur-
geon single high-volume institution observational cohort
study, and therefore the generalisability of findings to
other surgeons who have and have not completed the
ERUS curriculum is unclear. Continence outcomes were
prioritised for analysis, and pre- and post-operative sexual
function was not examined. Continence data were obtained
via telephone consultation and 12-month outcomes were
only available on 56.6% of the cohort, which may result in
a reporting bias. Finally, due to the short follow-up period,
we did not report on longer-term oncological outcomes
such as biochemical recurrence-free survival.
Conclusions
We report the largest experience of a single surgeon who
completed the ERUS RARP curriculum, demonstrating that
a surgeon with limited prostatectomy experience can rapidly
achieve outcomes consistent with UK national data. Prior to
commencement of the study, the surgeon had not completed
an unsupervised independently performed RARP, hence our
data are a true representation of post-ERUS curriculum out-
comes. Our findings exemplify the potential value of a
standardised RARP training curriculum to mitigate possible
compromises in outcomes during early independent experi-
ence. Since the LC can be influenced by operative frequency
and volume,34 we believe that the rate of accumulation of
cases may be important, as well as institutional volume to
share colleague experience. Future studies should consider
these and other surgeon- and patient-specific variables for
multiple surgeons at multiple institutions and include penta-
fecta outcomes35 in LC analyses to define a clear point
where measured outcomes may cease to vary.
Conflicting interests
A Mottrie is the Chief Executive Officer of ORSI Academy and
proctor for Intuitive Surgical Inc. NPW is a proctor for and has
received a research grant from Intuitive Surgical Inc.
Funding
The authors disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: PR
is funded by a joint Royal College of Surgeons of England/
Cancer Research UK Clinician Scientist Fellowship in Surgery
(C19198/A15339) and supported by the Barts Charity, the Orchid
Charity, the Urology Foundation and the John Black Charitable
Foundation.
Ethical approval
Not applicable.
Informed consent
The study protocol was registered as a clinical audit by the
Quality and Safety Department at University College London
NHS Foundation Trust.
Guarantor
PR.
Contributorship
ASS, BPR, and PR conceived and designed the study. ANS, PN,
A Mohammed, AF, and PR undertook data collection. ASS and
PR analysed the data and drafted the manuscript. ANS, KS, BPR,
AF, A Mottrie, MJO, NPW, MSN, TPB, and JDK critically
revised the manuscript for important intellectual content. All
authors approved the final version of the manuscript. PR super-
vised the study.
Acknowledgements
We are grateful to our patients without whom this work would
not have been possible. We thank staff at University College
London Hospital NHS Foundation Trust and organisations
within the North Central and East London Cancer Alliance
for their assistance with patient referrals, care, and data
collection.

03_URO938176.indd 252 25/06/2021 8:23:05 PM

 Sehmbi et al. 253
ORCID iDs
Arjan S Sehmbi   https://orcid.org/0000-0002-7697-3445.
Prabhakar Rajan   https://orcid.org/0000-0001-8064-9878.
Supplemental material
Supplemental material for this article is available online.
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950847 URO Journal of Clinical UrologyKikuchi et al.

Cohort Study

Journal of Clinical Urology

A prospective study on the association

2021, Vol. 14(4) 255­–261
© British Association of
Urological Surgeons 2020
between post-voiding residual volume Article reuse guidelines:
sagepub.com/journals-permissions

and quality of life during bacille DOI: 10.1177/2051415820950847

https://doi.org/10.1177/2051415820950847
journals.sagepub.com/home/uro

Calmette-Guérin (BCG) instillation

therapy for non–muscle-invasive
bladder cancer

Daichi Kikuchi1, Yoichiro Kato1 , Misato Takayama2, Seiko Kanzaki3,

Akito Ito4 , Daiki Ikarashi1, Shigekatsu Maekawa1, Renpei Kato1, Takashi Seo2,
Yukihisa Owari5, Tatsuru Nozawa6, Kazumasa Isurugi3, Hiromitsu Fujisawa7,
Takashi Ujiie4, Mitsugu Kanehira1, Ryo Takata1 and Wataru Obara1

Abstract
Objectives: The aim of this study was to investigate the relationship between quality of life (QOL) and residual urine
volume in patients undergoing bacille Calmette-Guérin (BCG) therapy.
Methods: Patients requiring BCG therapy, including those with carcinoma in situ, were enrolled prospectively. The
urine volume collected through urethral catheterization was measured as post-voiding residual volume (PVR) during
BCG therapy. Patients were divided into two groups: small PVR (SPVR), with PVR less than 30 ml, and large PVR (LPVR),
with PVR greater than or equal to 30 ml. QOL status was assessed using the European Organisation for Research
and Treatment of Cancer (EORTC) QLQ-C30 system before and after BCG therapy. Moreover, some patients were
assessed by International Prostate Symptom Score (IPSS) at the same time as assessment with the EORTC QLQ-C30
system. The primary end point was the evaluation of QOL during BCG therapy.
Results: Among the 69 patients with non–muscle-invasive bladder cancer included in this study, 43 were in the SPVR
group and 26 were in the LPVR group. The proportions of women and analgesic use in the SPVR group were higher than
that in the LPVR group; however, medication use for dysuria in the SPVR group was less than that in the LPVR group.
In the QOL analyses, cognitive function and emotional function in the functional scale and fatigue, nausea/vomiting, and
dyspnoea in the symptomatic scale were worse in the SPVR group than in the LPVR group. In the multivariate analysis,
fatigue was worse in the SPVR group than in the LPVR group.
Conclusions: During BCG therapy, patients in the SPVR group had worse QOL, especially fatigue, than those in the
LPVR group.
Level of evidence: Not applicable for this multicentre audit.

Keywords
Bacille Calmette-Guérin (BCG), bladder cancer, catheterization, post-voiding residual volume, quality of life

Date received: 10 May 2020; accepted: 21 July 2020

1 7
Department of Urology, Iwate Medical University, Japan Division of Urology, Iwate Prefectural Central Hospital, Japan
2
Division of Urology, Morioka JRC Hospital, Japan
3
Division of Urology, Iwate Prefectural Chubu Hospital, Japan Corresponding author:
4
Division of Urology, Iwate Prefectural Ofunato Hospital, Japan Yoichiro Kato, Department of Urology, Iwate Medical University,
5
Division of Urology, Iwate Prefectural Miyako Hospital, Japan 2-1-1 Idaidori,Yahaba, Shiwa, Iwate, 028-3695, Japan.
6
Akita Kouseiren Kazuno Kousei Hospital, Japan Email: katoyooo@iwate-med.ac.jp

04_URO950847.indd 255 25/06/2021 2:37:22 PM

 256 Journal of Clinical Urology 14(4)
Introduction
The purpose of bacille Calmette-Guérin (BCG) instillation
therapy is to prevent the recurrence of non–muscle-inva-
sive bladder cancer (NMIBC) after transurethral resection
of bladder tumour (TURBT) and standard treatment for
carcinoma in situ.1,2 It has been reported that the five-year
bladder recurrence rate was 31.0% to 78.0%, and the five-
year muscle layer progression rate was 0.8% to 45.0%
without BCG therapy for NMIBC.3 Cambier et al. sug-
gested that the five-year late recurrence rate could be
reduced to 25.9% to 55.4% and the five-year (muscle
layer) progression rate could be decreased to 2.4% to
18.9% through the induction of BCG therapy.4 However,
total cystectomy is necessary for patients who are refrac-
tory to BCG therapy.5,6 Therefore, BCG therapy has occu-
pied an important position in the treatment of NMIBC. In
general, BCG therapy is the treatment of choice for patients
with intermediate or high risk NMIBC according to the
European Organisation for Research and Treatment of
Cancer (EORTC) and the Club Urológico Español de
Tratamiento Oncológico (CUETO) risk classification.3,7
One of the disadvantages of BCG therapy includes the
high incidence of adverse events. Therefore, studies have
investigated some administration strategies such as low
doses ranging from one-half to one-sixth of BCG.8–10 On
the other hand, there are a few reports describing that uri-
nation status affects NMIBC recurrence rate or intravesical
therapy. A recent study reported that patients with moder-
ate or severe lower urinary tract symptoms (LUTS) have a
high recurrence rate of NMIBC.11 Based on this result, we
hypothesised that the volume of residual urine might affect
the efficacy of BCG therapy and the incidence of compli-
cations because low bladder clearance might increase the
exposure time to BCG.
Therefore, this prospective study was conducted to ver-
ify whether a large amount of residual urine would be a
risk factor for adverse events during BCG therapy.
Materials and methods
Inclusion and exclusion criteria
This multi-centre, prospective, observational study
enrolled patients with NMIBC after TURBT and/or carci-
noma in situ. Inclusion criteria were biopsy-proven carci-
noma in situ; completely resected solitary, multiple,
primary Ta or T1 tumours of the bladder; and carcinoma in
situ associated with any Ta–T1 urothelial carcinoma of the
bladder. Exclusion criteria were patients with recurrence,
upper urinary tract cancers, other malignancies, immuno-
suppression, a score of greater than 2 on the Eastern
Cooperative Oncology Group performance status, active
infection (grade 3 or higher according to the Common
Terminology Criteria for Adverse Events version 4.0), and
a score of 0 on the EORTC recurrence risk assessment.
04_URO950847.indd 256
Patients were divided into the following two groups on the
basis of “initial” post-voiding residual volume (PVR)
before BCG therapy: small amount of PVR (SPVR), in
which the PVR was less than 30 ml, and large amount of
PVR (LPVR), in which the PVR was 30 ml or greater.
Prior to patient recruitment, this clinical trial was
approved by the ethics committee of Iwate Medical
University (Iwate, Japan) and registered with the University
Hospital Medical Information Network (UMIN) Clinical
Trials Registry with number UMIN000035176. The study
was initiated after obtaining written informed consent
from all enrolled patients.
Treatment protocol
After TURBT, informed consent was obtained from eligi-
ble patients, and then 80 mg Immunobladder (Tokyo strain
BCG, Japan BCG Laboratory, Tokyo, Japan) was provided
as infusion therapy (up to 8 times once a week). Before the
administration of BCG, all patients accomplished self-uri-
nation, after which the urine volume collected through ure-
thral catheterisation was measured each time as the residual
urine volume. After this procedure, BCG instillation
induction therapy was performed at a dose of 80 mg sus-
pended in 40 ml of physiological bacteriostatic-free saline
for irrigation. Patients were instructed to retain the suspen-
sion for 2 hours.
The EORTC QLQ-C30 scores for all patients in this
study and IPSS scores for some patients who received
IPSS analysis were assessed before and after BCG instilla-
tion therapy. Patients who dropped out because of an
adverse event were assessed the day of withdrawal. We
also investigated the presence or absence of smoking and
drinking and analgesic and antibacterial drug use during
BCG treatment, and the completion rate.
End points
The primary end point was the evaluation of adverse
events and the quality of life (QOL) during BCG instilla-
tion therapy between the SPVR and the LPVR groups.
Statistical analysis
The EORTC QLQ-C30 scores of all patients and the IPSS of
some patients in this case series were calculated. Especially
on the IPSS score analysis, we divided patients into three
categories as ‘improved: scores decreased’, ‘no change:
score stable’ and ‘worsened: scores increased’ at the same
time as EORTC QLQ-C30 analysis and assessed. Data were
analysed using the JMP 14 (SAS Institute Inc, Cary, NC,
USA) statistical software. The associations between the
SPVR and LPVR groups were analysed using two-tailed
t-tests and χ2 tests. A p value of less than 0.05 was consid-
ered to indicate a statistically significant difference.
25/06/2021 2:37:23 PM
 Kikuchi et al. 257

Table 1.  Patient characteristics.

Total SPVR group LPVR group p

(n = 69) (n = 43) (n = 26)

Mean PVR (range) 24.5 (0–200) 9 (0–29) 52 (30–200) <0.001

Mean age (range), y 72.7 (56–91) 71.9 (56–91) 74.0 (57–89) 0.32

Sex (M/F) 57/12 32/11 25/1 0.024

Grade, % 0.29

 G1 5 (7.2) 3 (7.0) 2 (7.7)  

 G2 46 (66.7) 26 (60.5) 20 (76.9)  

 G3 18 (26.1) 14 (32.5) 4 (15.4)  

CIS, % 27/69 (39.1) 18/43 (41.9) 9/26 (34.6) 0.55

Agents for dysuria, % 15/69 (21.7) 6/43 (14.0) 9/26 (34.6) 0.044

Alcohol, % 37/68 (53.6) 25/43 (58.1) 12/26 (46.2) 0.33

Tobacco, % 33/68 (47.8) 19/43 (44.2) 14/26 (53.9) 0.44

Analgesics, % 7/68 (10.1) 7/43 (16.3) 0/26 (0) 0.0077

Antibacterial drugs, % 16/68 (23.2) 10/43 (23.3) 6/26 (23.1) 0.99

Mean number of treatments a

7.710 ± 1.138 (69) 7.697 ± 1.205 (43) 7.730 ± 1.041 (26) 0.91

EORTC, % 0.30

 0 0 0 0  

 1–4 22 (31.9) 15 (34.9) 7 (26.9)  

 5–9 41 (59.4) 27 (60.5) 15 (57.7)  

 10–17 6 (8.7) 2 (4.6) 4 (15.4)  

CUETO, % 0.83

 0–4 14 (20.3) 10 (23.3) 4 (15.4)  

 5–6 18 (26.1) 10 (23.3) 8 (30.8)  

 7–9 27 (39.1) 17 (39.5) 10 (38.4)  

  >10 10 (14.5) 6 (13.9) 4 (15.4)  

CIS: carcinoma in situ; CUETO: Club Urológico Español de Tratamiento Oncológico; EORTC: European Organisation for Research and Treat-
ment of Cancer; F: female; LPVR: large post-voiding residual volume; M: male; PVR: post-voiding residual volume; SPVR: small post-voiding residual
volume.

Results group consisted of 32 men and 11 women, and the LPVR

Patient characteristics
From June 2018 to August 2019, a total of 72 patients with
NMIBC were enrolled in this study. Among these 72
patients, three were lost to the final assessment of EORTC
QLQ-C30 scores. Ultimately, the remaining 69 patients
were analysed (57 male and 12 female; mean age, 72.7
years; age range, 56–91 years). Table 1 shows the clinical
and pathological characteristics of all patients. The SPVR
group comprised 25 men and only one woman (p = 0.024).
The use of therapeutic agents for dysuria was higher in the
LPVR group than in the SPVR group (p = 0.044). The rate
of analgesic usage was significantly higher in the SPVR
group than in the LPVR group (p = 0.0077). No signifi-
cant differences were observed between the SPVR group
and the LPVR group in terms of age, pathological factors,
and EORTC or CUETO risk criteria. The frequencies of
smoking and drinking between both groups were also not

04_URO950847.indd 257 25/06/2021 2:37:23 PM

 258 Journal of Clinical Urology 14(4)

Table 2.  Comparison of each mean residual urine volume between the small post-voiding residual volume (SPVR) group and the
large post-voiding residual volume (LPVR) group.

SPVR, ml 95% CI LPVR, ml 95% CI p

1st 11.4 (n = 43) 8.5–14.4 74.2 (n = 26) 55.8–92.5 <0.0001

2nd 25.6 (n = 43) 15.0–36.2 58.6 (n = 26) 39.8–77.4 0.0013

3rd 28.8 (n = 42) 17.7–39.9 51.4 (n = 26) 37.7–65.0 0.012

4th 27.5 (n = 41) 14.2–31.6 53.2 (n = 25) 38.0–68.4 0.00030

5th 26.4 (n = 41) 17.2–35.6 55.5 (n = 25) 40.3–70.8 0.00070

6th 24.3 (n = 41) 17.8–30.9 50.1 (n = 25) 37.5–62.8 0.00010

7th 22.3 (n = 40) 16.0–28.7 57.5 (n = 24) 36.8–78.3 0.00020

8th 23.1 (n = 39) 14.8–31.3 53.8 (n = 24) 36.9–70.7 0.00040

Total 23.1 20.2–26.0 56.9 51.2–62.5 <0.0001

CI: confidence interval.

statistically significant. Antibiotic usage rate was also not
statistically significant between the two groups. The com-
pletion rate of BCG induction therapy was 95.3% in the
SPVR group and 96.1% in the LPVR group, indicating a
high completion rate in both groups compared with the
previous report.12
Post-voiding residual volume status in both
groups
Each fluctuation in the residual urine volume after the sec-
ond BCG intravesical infusion therapy was smaller in the
SPVR group than in the LPVR group; however, at all times
of infusion therapies, the residual urine volumes were sig-
nificantly higher in LPVR than SPVR (Table 2). Four
patients in the SPVR group and two patients in the LPVR
group could not be followed up until the final eighth BCG
instillation therapy. The results of the analysis of 95% con-
fidence intervals of PVR between pre-treatment and the
eighth BCG instillation therapy in the SPVR group
revealed an increasing trend of 8.5–14.4 and 14.8–31.3,
respectively, whereas those in the LPVR group demon-
strated a decreasing trend of 55.8–92.5 and 36.9–70.7,
respectively. As a result, the statistical difference between
the two groups tended to decrease although they main-
tained a significant difference.
Changes in European Organisation for
Research and Treatment of Cancer QLQ-C30
in pre-treatment and post-treatment between
small post-voiding residual volume and large
post-voiding residual volume groups
QOL score tended to decrease overall after BCG instilla-
tion therapy. In the univariate analysis, cognitive function
(p = 0.041) and emotional function (p = 0.0033) in the
functional scale and fatigue (p = 0.0030), nausea/vomit-
ing (p = 0.049) and dyspnoea (p = 0.015) in the sympto-
matic scale were worse in the SPVR group than in the
LPVR group (Table3). In the multivariate analyses, fatigue
was worse in the SPVR group than in the LPVR group
(p = 0.019) (see Table 3).
Changes in International Prostate Symptom
Score in pre-treatment and post-treatment
between small post-voiding residual volume and
large post-voiding residual volume groups
Among 69 patients, 34 patients (24 in the SPVR group
and 10 in the LPVR group) were assessed for IPSS. Total
IPSS in both groups were worsened. However, one of the
urinary symptoms, nocturia, worsened in the SPVR group
but improved significantly in the LPVR group (p =
0.0357) (Table 4). Moreover, urgency had a tendency simi-
lar to nocturia, but not significantly (p = 0.0739) (see
Table 4). Other factors except for nocturia and urgency
were not particular in both groups.
Discussion
Current guidelines recommend an adjuvant intravesical
BCG immunotherapy for intermediate- and high-risk
NMIBC.13,14 However, treatment-related toxicity remains
a clinical problem of BCG. Nieder et al. categorise the
cases as BCG intolerant, and these patients may suffer dis-
ease recurrence because of insufficient treatment due to
side effects.15 To address these problems, administration
methods such as one-half to one-sixth low-dose BCG have
been investigated in BCG induction therapy.9

04_URO950847.indd 258 25/06/2021 2:37:23 PM

 Kikuchi et al. 259

Table 3.  EORTC QLQ-C30 pre-treatment and post-treatment between SPVR and LPVR groups.

Total SPVR group LPVR group Univariate Multivariate

(n = 69) (n = 43) (n = 26)
p Odds ratio (95% CI) p

Functional scale:

  Physical function 1.6 (±2.0) 1.9 (±2.1) 1.1 (±1.6) 0.31  

  Role function 0.42 (±1.1) 0.61 (±1.2) 0.12 (±0.95) 0.18  

  Cognitive function 0.36 (±0.94) 0.56 (±0.85) 0.038 (±1.0) 0.041a 1.4 (0.70–2.7) 0.054

  Emotional function 0.32 (±1.6) 0.72 (±1.5) –0.35 (±1.6) 0.0033a 1.5 (0.97–2.3) 0.35

  Social function 0.35 (±0.98) 0.54 (±1.1) 0.038 (±0.77) 0.063  

  Global QOL –1.3 (±2.8) –1.6 (±2.8) –0.73 (±2.9) 0.21  

Symptomatic scale

 Fatigue 0.49 (±1.9) 1.0 (±1.5) –0.42 (±2.0) 0.0030b 1.6 (1.0–2.5) 0.019

 Nausea/vomiting 0.10 (±0.35) 0.16 (±0.43) 0.0 (±0.0) 0.049b 4.8e+06 (0–.) 0.12

 Pain 0.49 (±1.6) 0.72 (±1.7) 0.12 (±1.4) 0.097  

 Dyspnoea 0.014 (±0.56) 0.14 (±0.47) –0.19 (±0.63) 0.015b 3.2 (0.31–34.0) 0.29

 Insomnia 0.28 (±0.73) 0.30 (±0.83) 0.23 (±0.51) 0.78  

  Appetite loss 0.22 (±0.54) 0.28 (±0.55) 0.12 (±0.52) 0.14  

 Constipation –0.058 (±0.64) 0.047 (±0.58) –0.23 (±0.71) 0.13  

 Diarrhoea 0.10 (±0.52) 0.093 (±0.57) 0.12 (±0.43) 0.76  

  Financial problems 0.058 (±0.45) 0.070 (±0.46) 0.038 (±0.45) 0.78  

CI: confidence interval; EORTC: European Organisation for Research and Treatment of Cancer; LPVR: large post-voiding residual volume; SPVR:
small post-voiding residual volume; QOL: quality of life a: less than 0.05 in Functuional scale; b: less than 0.05 in Symptomatic scale.

Some reports have described the association between
LUTS and the risk of bladder cancer.16,17 Most recently,
Lunney and colleagues reported an association between
dysuria and the recurrence risk of NMIBC.11 They con-
ducted a retrospective survey of NMIBC recurrence
using question indicators and concluded that the presence
of moderate or severe LUTS may be an important prog-
nostic factor for NMIBC. However, to our knowledge, no
studies have investigated the association between urina-
tion status and change in QOL due to BCG therapy. Based
on the background, we hypothesised that patients with
urination disorders have increased residual urine volume
and are more exposed to BCG. Therefore, we divided
patients into two groups based on the difference in resid-
ual urine volume before BCG instillation therapy to con-
duct this prospective study to compare the QOL of
patients before and after BCG therapy. The characteristic
feature in this study is that the amount of urine at the time
of catheterisation performed for each BCG instillation is
the amount of residual urine, so this study is not invasive
for patients.
In terms of QLQ-C30 score, cognitive function and
emotional function in the functional scale and fatigue, nau-
sea/vomiting, and dyspnoea in the symptomatic scale were
worse in the SPVR group than in the LPVR group (see
Table 3). The multivariate analyses revealed that fatigue
was worse in the SPVR group than in the LPVR group (see
Table 3). However, these results contrasted with our
hypotheses. We consider that the magnitude of the effect of
BCG therapy on QOL decline is more susceptible to pol-
lakiuria symptoms than to the exposure time to BCG solu-
tion. This study did not investigate all patients but 34
patients underwent IPSS analysis. The results showed that
the SPVR group suffered from nocturia statistically sig-
nificantly more than the LPVR group (see Table 4). Based
on these results, we consider that the frequency of toilet
use due to frequent urination might have led to fatigue.
Some studies have reported low reproducibility of resid-
ual urine volume.18,19 However, an examination of whether
the differences in residual urine volume between the SPVR
and LPVR groups would change according to the BCG
therapy showed that the differences in the two PVR levels

04_URO950847.indd 259 25/06/2021 2:37:23 PM

 260 Journal of Clinical Urology 14(4)

Table 4.  Differences in pre-IPSS and post-IPSS scores between SPVR and LPVR groups.

SPVR (n = 24) LPVR (n = 10) pa

Improved, No change, Worsened, Improved, No change, Worsened,

% % % % % %

Total IPSS scores 7 (29.2) 1 (4.2) 16 (66.7) 3 (30.0) 2 (20.0) 5 (50.0) 0.3490

1. Incomplete emptying 5 (20.8) 8 (33.3) 11 (45.8) 1 (10.0) 6 (60.0) 3 (30.0) 0.3468

2. Frequency 4 (16.6) 11 (45.8) 9 (37.5) 0 (0) 5 (50.0) 5 (50.0) 0.2154

3. Intermittency 7 (29.2) 8 (33.3) 9 (37.5) 4 (40.0) 3 (30.0) 3 (30.0) 0.8242

4. Urgency 5 (20.8) 11 (45.8) 8 (33.3) 6 (60.0) 3 (30.0) 1 (10.0) 0.0739

5. Weak stream 2 (8.3) 9 (37.5) 13 (54.2) 2 (20.0) 5 (50.0) 3 (30.0) 0.3758

6. Straining 3 (12.5) 9 (37.5) 12 (50.0) 2 (20.0) 6 (60.0) 2 (20.0) 0.2478

7. Nocturia 5 (20.8) 6 (25.0) 13 (54.2) 5 (50.0) 4 (40.0) 1 (10.0) 0.0357

Urination symptoms (1356) 6 (25.0) 3 (12.5) 15 (62.5) 3 (30.0) 2 (20.0) 5 (50.0) 0.7736

Urinary symptoms (247) 6 (25.0) 5 (20.8) 13 (54.2) 3 (30.0) 4 (40.0) 3 (30.0) 0.3811

IPSS: International Prostate Symptom Score; LPVR: large post-voiding residual volume; SPVR: small post-voiding residual volume.
χ test.
a 2

were preserved even during the BCG therapy (see Table 2).
Anticholinergics and β3 stimulants may be effective in
reducing adverse events caused by BCG in patients with
pollakiuria with normal residual urine volume.
This study has some unavoidable limitations. First,
considering the results of previous research,20 we set the
PVR cutoff point as 30 ml because a previous study
reported that the treatment failure rate for LUTS was
significantly high for patients with PVR 30 ml. However,
in the future, it will be necessary to set a more optimal
cutoff point that could distinguish between complications
and treatment effects. This needs to be set with further
accumulation of cases and statistical accuracy. Second,
this prospective study focused on QOL assessment during
BCG treatment using the QLQ-C30 questionnaire but did
not investigate urinary function and its subjective symp-
toms. For this reason, it was impossible to evaluate change
in QOL and actual urination symptoms in a combined
manner. Consequently, only urination function could be
evaluated from the viewpoint of the amount of residual
urine alone, which tended to decrease with treatment pro-
gression, particularly in the LPVR group. Therefore, in the
SPVR group, there was an increase in intravesical compli-
ance due to BCG therapy, and in the LPVR group, there
was a possibility that urinary manipulation with the cath-
eter before treatment could contribute to the decrease in
residual urine volume. Third, because the observation
period was short, we did not evaluate recurrence; there-
fore, it is necessary to evaluate the association between
residual urine volume and recurrence in the future.
In conclusion, we investigated the changes in QOL
caused by the difference in residual urine volume dur-
ing BCG treatment. PVR volume before treatment
demonstrated a relatively high reproducibility, suggesting
that the frequent urinary symptoms in the SPVR group are
associated with the decrease in QOL, especially in terms
of fatigue. In the future, it will be necessary to investigate
how residual urine volume affects the anticancer effect of
BCG treatment.
Conflicting interests
The Authors declare that there is no conflict of interest.
Funding
The authors disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article:
This work was supported by a Keiryokai grant from Iwate
Medical University (grant No. 124).
Ethical approval
The present study was approved by the ethics committee of
Iwate Medical University (Iwate, Japan; register No. MH2018-
060) prior patient recruitment.
Informed consent
Written informed consent was obtained from all patients.
Guarantor
WO.

04_URO950847.indd 260 25/06/2021 2:37:23 PM

 Kikuchi et al. 261
Contributorship
DK and YK performed the experiments, analysed the experimen-
tal data and wrote the manuscript. MT, SK, IA, DI, SM, RK, TS,
YO, TN, KI, HF, TU, MK and RT recruited cases and treated
them according to the protocols. MK was responsible for pre-
serving each patient profile. DK, YK and WO designed the
experiments. WO designed the experiment, interpreted the data
and revised the manuscript.
Acknowledgements
We thank all the urologists of the Iwate Medical University,
Morioka JRC Hospital, Iwate Prefectural Chubu Hospital, Iwate
Prefectural Miyako Hospital, Akita Kouseiren Kazuno Kousei
Hospital, Iwate Prefectural Central Hospital, and Iwate
Prefectural Ofunato Hospital for providing patient samples and
clinical information. The authors also would like to thank Enago
(www.enago.jp) for the English-language review.
ORCID iDs
Yoichiro Kato https://orcid.org/0000-0003-3778-9300
Akito Ito https://orcid.org/0000-0002-6468-5198
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2. Shelley MD, Mason MD and Kynaston H. Intravesical
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947638 URO Journal of Clinical UrologyNoël et al.

Cohort Study

Journal of Clinical Urology

A cut above? Inferior vena cava

2021, Vol. 14(4) 262­–267
© British Association of
Urological Surgeons 2020
resection without reconstruction: Article reuse guidelines:
sagepub.com/journals-permissions

a dual-centre experience DOI: 10.1177/2051415820947638

https://doi.org/10.1177/2051415820947638
journals.sagepub.com/home/uro

Jonathan P Noël1 , Sarah Yu Weng Tang2, Nana Aishatu Liman

Muhammad2, David Nicol1 and Roger C Kockelbergh2,3

Abstract
Objectives: To evaluate outcomes in our patients undergoing inferior vena cava (IVC) resection without reconstruction,
as part of an adrenal/renal cell cancer (RCC) operation.
Methods: British Association of Urological Surgeons (BAUS) Data and Audit System records were obtained for two
operating surgeons, each at geographically separate urological cancer centres. Retrospectively reviewed case notes
of patients who had undergone IVC resection without reconstruction as part of an adrenal/RCC operation, assessing
operative parameters, length of stay, complications and follow-up status.
Results: A total of Twenty-eight patients (20 right-sided tumours, 8 left sided) underwent IVC resection without
reconstruction in May 2013–February 2017. No perioperative or early deaths occurred. Fourteen patients (50%) had
complications: sepsis; pneumonia; congestive cardiac failure; acute kidney injury; symptomatic peripheral deep venous
thrombosis; splenectomy; and significant chyle leak. At a median follow-up of 21 months (range 1–55 months) six
patients (21.4%) have died and two patients (7.1%) progressed to metastatic disease, giving a 71.4% progression-free
survival in this series.
Conclusions: This case series illustrates our experience of IVC resection without reconstruction as an acceptably
safe procedure. This should be considered as an alternative to graft reconstruction, particularly as minimal invasive
approaches are being adopted.
Level of Evidence: 3

Keywords
IVC thrombus, IVC resection, RCC surgery

Date received: 15 April 2020; accepted: 10 July 2020

Introduction
Inferior vena cava (IVC) extension has presented a surgi-
cal challenge for resection of renal cell cancer (RCC) and
adrenal cancer, and involvement of the cava was associ-
ated with a poorer prognosis.1 However, with advancing
surgical techniques which increased the ability to be more
aggressive in a radical resection, it became clearer that it
was not the presence of intracaval extension, but whether
any residual tumour was left, that influenced outcomes.2,3
Intracaval tumour thrombectomy has been a long-
established practice, but tumour adherent to the caval wall
1
Department of Urology, Royal Marsden NHS Foundation Trust, UK
2
Department of Urology, University Hospitals of Leicester NHS Trust,
UK
3
University Hospitals of Leicester NHS Trust, UK
Corresponding authors:
Jonathan P Noël, Department of Urology, Royal Marsden NHS
Foundation Trust, Fulham Road, London, England SW3 6JJ, UK.
Email: dr.jnoel@gmail.com
Twitter: @UroNoel
Roger C Kockelbergh, Professor of Urological Surgery, University
Hospitals of Leicester, Leicester General Hospital, Gwendolen Road,
Leicester, LE7 9GD, UK.
Email: Roger.Kockelbergh@uhl-tr.nhs.uk

05_URO947638.indd 262 25/06/2021 2:38:10 PM

 Noël et al. 263

Table 1.  Existing case series regarding inferior vena cava (IVC) resection.

First author Year published Number of patients Conclusions

Duty16 2009 6 No chronic lower limb oedema

17
Daylami 2010 6 3/6 (50%) lower limb oedema

Ali19 2013 14 Complication rates not specified for the level III tumour thrombus
group

Blair20 2018 3 No significant difference in complication rates than patients who

underwent IVC reconstruction

Theodoraki21 2018 5 3/5 (60%) mild transient lower limb oedema, not affecting quality of
life

presented challenges to completely resect, with associated Materials and methods

risks of residual tumour and/or embolisation from this.
This was addressed by adopting the practice of removal of
the caval wall with the adherent tumour.4
The strategies involved with excision of an affected
segment of VC have turned full circle, since the earliest
reports in the 1950s and 1960s.5–8 These reports describe
resection of the involved caval segment without graft
reconstruction which was the general approach1,2 until the
first report of reconstruction using a polytetrafluoroethyl-
ene (PTFE) graft in 1984.9 This technique of reconstruc-
tion was popularised and widely published in urological
literature. Authors of these series suggested it allowed a
more aggressive resection of tumour burdened segments
of the vessel wall, which translated to superior oncological
and vessel patency outcomes.10,11 However, some surgeons
returned to a notion that reconstruction does not need to be
standard, supported by published scientific scrutiny.12,13
Surgical oncologists’ opinions continue to differ with
respect to the ideal strategy in caval wall surgery. It is
suggested that an all or nothing approach should be dis-
counted, and the decision whether or not reconstruction
is required is undertaken intra-operatively.14 Previous
studies demonstrated that in complete occlusion of the
VC, collateral circulation forms to a degree sufficient to
allow en bloc excision of the affected segment, without
compromising post-operative venous return distal to that
segment.15,16
Despite long periods of data collection, previously pub-
lished series have small patient numbers17,18 as shown in
Table 1. This is likely due to the threshold for suitability to
undergo surgical resection (with or without reconstruc-
tion) of the IVC for tumour thrombus; a well-known series
recruited only 14 patients who had level III tumour throm-
bus (intrahepatic extension).19
In this series, we aimed to analyse data pooled from two
tertiary referral renal cancer centres, to allow for a larger
cohort of patients with the majority having level III tumour
thrombus; which we have defined as thrombus extending
to the main hepatic veins and requiring liver mobilisation
for access.
Prospectively collected British Association of Urological
Surgeons (BAUS) Data and Audit System records were
reviewed for the two senior authors who both perform this
surgery as consultants. Each consultant operates at geo-
graphically separate urological cancer centres which are
region specific tertiary referral sites for advanced upper
urinary tract and retroperitoneal surgery. We reviewed
medical records of patients who had undergone IVC resec-
tion without reconstruction as part of an RCC/adrenal
operation, assessing operative parameters, length of stay,
complications and follow-up status.
Results
In both cancer centres, a total of 77 IVC explorations
were performed between May 2013 and February 2017.
A total of 28 patients, 21/28 (75%) male and 7/28 (25%)
female, underwent IVC resection without reconstruction:
20/28 (71%) of patients had right-sided renal tumours;
8/28 (29%) of patients had left-sided tumours. TNM
Classification for renal tumours was T3 for 25/28 (89.1%)
and T4 3/28 (10.7%). Level III IVC tumour thrombus
was found in 23/28 (82.1%), Level IV in 3/28 (10.7%)
and Level II in 2/28 (7.1%). No patients in either centre
required IVC resection with reconstruction, and all
patients were managed with curative intent.
Presenting symptoms in our cohort of IVC resection
without reconstruction included haematuria 12/28 (42.9%),
anaemia/lethargy 8/28 (28.6%), abdominal pain 7/28 (25%)
and 1/28 (3.5%) lower limb oedema. Their co-morbidities
included hypertension/cardiovascular disease 8/28 (28.6%),
peripheral vascular disease 6/28 (21.4%), chronic renal
failure 2/28 (7.1%) and the remainder having no significant
medical history. No perioperative or early post-operative
deaths occurred, and the patient parameters are summarised
in Table 2. All operations were for renal tumours, there
were no adrenal primary tumours in this series, although
adrenalectomy was performed with nephrectomy in most
cases.

05_URO947638.indd 263 25/06/2021 2:38:10 PM

 264 Journal of Clinical Urology 14(4)
Table 2.  Summary of patient parameters.
Assessed parameter
Patient demographics
Age (years)
Follow-up (months)
Intraoperative parameters
Operative time (min)
Estimated blood loss (l)
Transfused volume
(l, excluding cell saved blood)
Post-operative parameters
Duration of Intensive Care Unit stay (days)
Duration of inpatient stay (days)
Change in serum creatinine (µmol/l)
a
Shortest operative times were within the timeframe of 1–2 h.
Fourteen patients (14/28, 50%) had significant compli-
cations; four (4/28, 14%) had more than one complication.
Complications included intra operative splenectomy
(3/28, 11%), post-operative sepsis (1/28), hospital-acquired
pneumonia (4/28, 14%), congestive cardiac failure, acute
kidney injury (5/28, 18%, all right-sided tumours), venous
thromboembolism (2/28, 7%) and significant chyle leak
(1/28, 3.5%).
In total, 3 patients (3/28, 11%) developed significant
lower limb oedema, however this resolved within a few
weeks for two of these patients. Post-operatively, serum
creatinine worsened transiently, with a median increase of
21. One patient (1/28, 3.6%) required haemodialysis in
the immediate post-operative period. There was no impact
on hepatobiliary function as a result of the operation.
Overall, Clavien-Dindo Classification II = 7 patients and
Classification IVa = 1 patient.
At a median follow-up of 21 months, six patients (6/28,
21.4%) died and two (2/28, 7.1%) developed metastatic
disease. This resulted in a 71.4% (20/28) progression-free
survival in our series (inclusive of one cytoreductive
nephrectomy). Post-operative histopathology was clear
cell RCC 25/28 (89.2%), papillary RCC 2/28 (7.1%) and
leiomyosarcoma 1/28 (3.6%).
Discussion
The case series found in published literature report favour-
able outcomes from a small number of patients.15,22 This
reflects careful selection of suitable patients out of a small
cohort who have a locally advanced cancer burden, yet are
05_URO947638.indd 264
Values
Median Minimum Maximum
66 42 83
21 1 55
210 90a 420
1.4 0.25 6
0.6 0 3
3.5 1 15
9.5 4 32
+21.5 –48 +171
candidates to undergo major surgical resection. As we gain
confidence in the technique of IVC resection without
reconstruction, we have been able to expand our selection
criteria for patients suitable for surgery, with satisfactory
outcomes.
Candidates for IVC resection without reconstruction
have chronic IVC obstruction with development and
established presence of collateral vasculature. This can
subjectively present with a history of bilateral lower limb
swelling which subsequently resolves, and can be objec-
tively demonstrated on cross sectional imaging (Figure1).
All patients underwent staging computed tomography
(CT) chest, abdomen and pelvis, but magnetic resonance
imaging (MRI) was used for clarity on venous system
anatomy. In addition to CT appearance, it is important to
note that the decision to resect the IVC is a combination
of tumour mobility and appearance on intraoperative
ultrasound, and adherence to the caval wall. For patients
without complete or near-complete occlusion of the IVC
by tumour thrombus, IVC resection is still feasible, but
the patient is warned to expect significant swelling of the
legs and genital area in the early post-operative period.
We observed in our series that swelling does reduce in the
longer term, giving a satisfactory cosmetic and functional
outcome. No pre-operative angiography was routinely
performed in our cohort to determine which patients were
at risk of lower limb oedema or renal failure. This is not
dissimilar to patients who for other reasons experience an
acute IVC thrombosis, in whom acute swelling may only
occur in 50%, and collateral circulation may form within
days.23
25/06/2021 2:38:10 PM
 Noël et al. 265
Figure 1.  Coronal view of contrast computed tomography
image showing complete occlusion of the inferior vena cava.
One patient underwent haemodialysis in the immediate
post-operative period, which was due to pre-renal insult to
the solitary kidney of a 5 l intra operative blood loss. One
patient developed chlye leak via their chest drain; this was
managed with delayed removal 10 days post operatively
and a medium chain triglyceride diet. Liver mobilisation
resulted in a transient rise in liver enzymes for some
patients, but there was no long-term impact on hepatobil-
iary function in our cohort.
With respect to technical considerations of surgery,
when the renal or adrenal tumour is fully mobilised, the
venous drainage is left intact; vascular control of the IVC
is obtained with Rummel’s tourniquets and/or vascular
clamps. A level III tumour thrombus is approached by liga-
tion and division of all short hepatic veins and liver mobi-
lisation. This allows access to the superior extent of the
tumour and creates space to apply a vascular stapler to the
IVC. Control of the hepatic inflow is required in some
cases. Division of the IVC and renal vein was achieved
using a vascular stapler.
An important point of technique is to preserve the lum-
bar vein at Vertebral Level 1 where possible, as this allows
drainage directly into the azygous system. It can be tempo-
rarily occluded with a bulldog clamp, allowing ease of
caval clamp placement. Preservation of this usually large
lumbar vein seems logical to maintain venous drainage
and hence reduce post-operative lower limb oedema.
With regards to patient selection, right-sided tumours
are surgically less challenging than left-sided tumours
owing to the closer proximity of the IVC, and the ability of
the left renal vein to drain via collaterals: lumbar, gonadal
05_URO947638.indd 265
and adrenal veins. In contrast to the left kidney’s venous
drainage, the right kidney has little collateral venous drain-
age and will not usually survive if the renal vein is divided
and occluded at the IVC level. However, in our series of
left-sided tumours, the right renal vein will drain if it
remains in continuity with or is re-anastomosed to the
remaining infrarenal IVC. Therefore, reconstruction of the
IVC should be considered in left-sided primary renal
tumours with infrarenal extension of tumour thrombus that
is adherent to the wall of the VC.
Our results are broadly comparable with a larger UK
series of 50 patients who had similar levels of tumour
thrombus and underwent excision of the thrombus rather
than IVC resection.19 The patients in this series included
those with significant intrahepatic tumour thrombus (with
two exceptions). Our median blood loss of 1.4 l and no
perioperative mortality associated with, on average, high
levels of tumour thrombus, therefore suggests acceptable
morbidity levels associated with this operative technique.
Comparing our results to those of IVC resection with
reconstruction, we suggest that we are avoiding the poten-
tial complications of graft usage, without significant dif-
ferences in the outcomes that the graft reconstruction aims
to improve.20 Biological grafts (e.g. bovine pericardial or
autologous peritoneo-fascial) have been proposed as alter-
natives to synthetic grafts, citing a reduced risk of infec-
tion and improved long-term patency.24 This highlights the
need to explore the use of techniques other than synthetic
graft material. We therefore suggest that these risks would
be further eliminated by removing a reconstructive step,
where appropriate. This would add simplicity to an already
complex operation, potentially reducing blood loss and
overall surgical risk.
A series analysing the outcome of reconstructed cava
have stated their graft thrombosis rate is in the region of
12%.25 Venous thromboembolism risk can be higher with
reconstructed cava than the 7% risk in our experience of
IVC resection-only approach; a larger series of IVC recon-
struction quoted a 22% VTE rate and notably, over half of
these were pulmonary emboli.26 In our selected patients
with IVC obstruction, they are likely to have coexisting
iliofemoral thrombosis preoperatively and therefore we
would suggest that IVC reconstruction in these patients
could carry an even higher risk of pulmonary embolism
given the presence of existing downstream thrombus.
A weakness of our paper is the short follow up in our
data, however long-term survival outcomes (with the
adjunct of a Kaplan-Meir curve) would be meaningful to
our series. This is challenging in a centralised specialist
service where the data on long-term follow up rests with
referring hospitals, often due to geographical convenience
for the patient.
This retrospective study seeks to inform and update
renal surgeons on our practice, and the message would be
25/06/2021 2:38:10 PM
 266 Journal of Clinical Urology 14(4)
wider when a comparison between IVC resection with or
without reconstruction can be carried out as a randomised
controlled trial (RCT). However, prospective studies with
these patients can be challenging as they are high risk and
small in number; the pool of surgeons who perform this is
also small but is growing. An RCT would be foreseeable at
present in the National Health Service/UK. Finally, with
the advent of robotic/minimally invasive approaches to
caval tumour surgery,27 the consensus on optimal open
approaches will become increasingly valuable in the tran-
sition to minimal invasive techniques of the future.
Conclusion
This case series illustrates our experience of IVC resection
as an acceptable, safe option. Our preference is now to
resect the IVC and only proceed with reconstruction if this
is required to maintain drainage of the remaining contralat-
eral renal vein. Our post-operative complications were
neither specific to, nor worsened by, resection without
reconstruction. This can be considered as an alternative to
graft reconstruction of the IVC in selected cases. We wel-
come an RCT to compare no reconstruction with recon-
struction. The urology community should also consider
that IVC resection without reconstruction will allow sig-
nificant advantage to the adoption of minimally invasive
approaches of the future.
Acknowledgements
We would like to thank Yang Sun for his assistance in data
collection.
Conflicting interests
The author(s) declare that there is no conflict of interest.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
Ethical approval
Not applicable.
Informed consent
Not applicable.
Guarantor
JN
Contributorship
JN, ST, NM and RK collected the data; JN and ST wrote the
paper, with senior review from DN and RK.
05_URO947638.indd 266
ORCID iD
Jonathan P Noël https://orcid.org/0000-0003-3404-993X
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941780 URO Journal of Clinical UrologyMacKenzie et al.

Case Series

Journal of Clinical Urology

Short-changed during the bacillus

2021, Vol. 14(4) 268­–274
© British Association of
Urological Surgeons 2020
Calmette–Guérin shortages? Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/2051415820941780
https://doi.org/10.1177/2051415820941780
journals.sagepub.com/home/uro

Kenneth R MacKenzie, Sidney D Parker  , Dawn Watson

and Joanne Cresswell

Abstract
Objective: Intravesical bacillus Calmette–Guérin (BCG) is the first-line treatment of choice for high-risk non-muscle-
invasive bladder cancer (NMIBC). Our aim was to evaluate the long-term impact of BCG shortages on oncological
outcomes.
Methods: All patients undertaking an initial course of intravesical BCG for intermediate or high risk NMIBC at a single
UK cancer centre between August 2012 and August 2014 were evaluated. Compliance was defined as completing 12
doses of BCG within the first year following diagnosis.
Results: Due to BCG shortages, 25/114 (22%) patients were compliant with planned maintenance treatment. Compared
to the compliant cohort, the non-compliant due to BCG shortages cohort had a higher rate of disease recurrence (35.3%
vs. 24%), required more additional intravesical treatments (14.7% vs. 12%) and had a higher rate of radical cystectomy
(11.8% vs. 4%). Disease-free survival was superior in the compliant cohort at two years (88% vs. 79.5%) and at 4.5 years
(72% vs. 56.1%). There was no statistically significant difference, likely due to the sample size.
Conclusions: The consequences of undertreatment due to BCG shortages can impact long-term cancer outcomes.
Increased vigilance, robust long-term surveillance and alternative treatment strategies are required for NMIBC patients
affected by shortages in BCG supplies.
Level of evidence: Level 2b

Keywords
Bacillus Calmette–Guérin, BCG, shortage, bladder, cancer, non-muscle

Date received: 3 March 2020; accepted: 9 June 2020

Introduction reducing recurrence-free and progression-free survival.

Intravesical bacillus Calmette–Guérin (BCG) therapy is a
recommended treatment for intermediate- and high-risk
non-muscle-invasive bladder cancer (NMIBC) following
transurethral resection of bladder tumour.1,2 Dosage and
duration have been evaluated, with consensus that a six-
week induction course followed by maintenance for at
least one year is required for superiority over intravesical
chemotherapies.1–3 Optimal duration of maintenance was
identified by the Southwest Oncology Group (SWOG),
with regular maintenance for three years significantly
However, compliance was challenging due to multiple
factors, and only 16% successfully completed the full
treatment course.4
Department of Urology, James Cook University Hospital, South Tees
NHS Foundation Trust, UK
Corresponding author:
Sidney D Parker, Department of Urology, James Cook University
Hospital, Marton Road, South Tees NHS Foundation Trust,
Middlesbrough TS4 3BW, UK.
Email: Sidney.parker1@nhs.net

06_URO941780.indd 268 25/06/2021 2:38:36 PM

 MacKenzie et al. 269
Figure 1.  Outcomes of patients completing induction bacillus Calmette–Guérin.
To reduce treatment toxicity, the European Organisation
for Research and Treatment of Cancer (EORTC) investi-
gated reduced dose and duration of BCG therapy.5,6 There
was a significant reduction in recurrence for three years of
full-dose maintenance compared to one year of full dose.
However, there was no significant difference in progres-
sion-free survival or mortality.5,6 As a consequence, the
recommendation from the European Association of
Urology (EAU) and the National Institute of Health and
Care Excellence (NICE) is a minimum of one year of
maintenance for intermediate disease and one to three
years of maintenance for high risk disease.1,2
In addition to varied opinion of dose and duration, there
became significant worldwide issues with supplies of
intravesical BCG.7 Both suppliers, Merck and Sanofi, had
significant issues, and the urological community were left
without a consistent supply from 2012 to 2014. Sanofi
ceased production altogether. In the UK, the British
Association of Urological Surgeons (BAUS) provided a
consensus statement with a variety of management strate-
gies, including one year of full-dose maintenance BCG
only or one year of reduced dose therapy.8 More recently,
concern has been raised again due to Merck, the only
Medicines and Healthcare Products Regulatory Agency–
approved supplier, warning that supplies may again falter.9
The aim of this study is to evaluate the ‘real-world’ effect
of BCG shortages on long-term oncological outcomes
within a UK cancer centre.
Methods
All patients with intermediate- and high-risk NMIBC with
a multidisciplinary team (MDT) recommendation to initi-
ate intravesical BCG in a UK cancer centre from August
2012 to August 2014 were included. Re-resection was
06_URO941780.indd 269
offered in accordance with NICE guidance.1 Induction
consisted of one instillation of intravesical BCG for six
consecutive weeks, with maintenance occurring following
induction with one installation for three consecutive
weeks. Although the EAU recommendation is for one year
of maintenance with instillations at 3, 6 and 12 months,
there were limitations to the delivery of such an intense
schedule. As a consequence, within the department, main-
tenance was delivered at 6 and 12 months following the
start of induction. Despite this ‘real-world’ application of
maintenance, a further cohort was undertreated due to
BCG shortages. Therefore, compliance to our departmen-
tal BCG protocol was defined as completing 12 doses of
BCG within the first 12 months of initiating treatment. A
full dose of OncoTICE® was used throughout. Cystoscopy
and urine cytology was repeated every three months for
the first two years then every six months thereafter in
accordance with NICE guidance.1 Recurrence or progres-
sion was demonstrated with histological confirmation in
all cases.
Figure 1 describes the variety of reasons patients were
deemed non-compliant with the protocol. Those that were
non-compliant due to a shortage of intravesical BCG
were included as a comparative cohort and named ‘failed
by health care’ (FbH). The treatment groups were com-
pared on a primary end point of disease-free survival.
Disease recurrence and disease progression were evalu-
ated, although cancer-specific death could not be reliably
identified. Both cohorts had rigid cystoscopies and bladder
biopsies following completion of induction BCG, and we
included all initial responders (patients who responded to
treatment and had negative biopsies at their first check
cystoscopy). Disease recurrence was defined as any dis-
ease histologically confirmed after initial response.
Disease progression was defined as any upgrading in the
25/06/2021 2:38:36 PM
 270 Journal of Clinical Urology 14(4)
tumour pathological stage. Time to recurrence was from
initial histological diagnosis to recurrence event. Regular
upper-tract follow-up was recommended for all patients as
per EAU guidance. However, on evaluation, this was
inconsistently performed, and each patient in both cohorts
received an average of 2.3 (range 0–6) computed tomogra-
phy scans during their follow up. Chi-square testing was
used to evaluate significance in oncological outcomes
between the two cohorts, with a p-value of <0.05 regarded
as clinically significant. Disease-free survival was calcu-
lated using the Kaplan–Meier method and a two-sided log-
rank test.
Results
A total of 114 patients initiated an induction course of
intravesical BCG. Figure 1 provides a description as to the
reasons why patients became non-compliant with the
planned schedule. At 12 months, 25 (21.9%) patients were
compliant. Thirty-four (29.8%) patients were not compli-
ant due to FbH. Twenty-eight (24.6%) patients had BCG
failure, most commonly due to persistence of disease, and
required additional treatment.
Table 1 provides the demographics of the overall, com-
pliant and FbH cohorts. The median age of the total cohort
was 75.5 years (interquartile range 68–81 years). The
majority of patients in both cohorts had primary high-risk
disease (Table 1).
The trend for disease-free survival in the compliant
cohort was better at two years (88% vs. 79.5%, p=0.38)
and 4.5 years, although this did not reach statistical signifi-
cance (72% vs. 56.1%, p=0.09; Figure 2). Disease progres-
sion occurred in one patient in each cohort. The overall
mortality rate for the total cohort was 35/114 (30%).
The median follow-up for the compliant cohort was
longer compared to the FbH cohort (71 vs. 60 months).
The FbH cohort had a higher rate of disease recurrence
(35.3% vs. 24%, p=0.61), although the median time to
recurrence was similar (24.5 vs. 22.5 months) compared to
the compliant BCG cohort. The FbH cohort had a higher
rate of cystectomy (11.8% vs. 4%, p=0.35), with a median
time to cystectomy (29 vs. 21 months) along with a higher
number of patients requiring further treatment of any type
(29.4% vs. 20%, p=0.40; Table 2). Radical cystectomy
was performed for disease relapse or disease progression.
Discussion
The study provides an evaluation of the delivery of BCG
therapy during a period of shortages and the impact on
oncological outcomes. In an era of intermittent BCG short-
ages, the results indicate that the majority of patients suit-
able for BCG were not administered the standard treatment
recommendations. Although there was no significant dif-
ference, the FbH cohort showed a persistent trend towards
06_URO941780.indd 270
a higher disease recurrence, rate of cystectomy and
requirement for additional treatments
The BCG supply was particularly affected from 2012 to
2014 due to a worldwide difficulty in production and the
loss of one of the two main suppliers (Sanofi).7,10 The pre-
carious supply again appears to be in difficulty with Merck
(the single supplier), stating a production warning and a
new consensus document from the American Urological
Association (AUA) on managing patients during the BCG
shortage.9 In a period where shortages are likely to reoc-
cur, our study provides up-to-date evidence of the practical
implication of BCG shortages for patients.
In our study, there was limited use of alternative options.
During the shortage, EAU and BAUS recommended the
usage of one year of intravesical BCG or intravesical
chemotherapy.8,11 The recommendation from our MDT
was for all patients with high-grade grade 2 disease to
undergo one year of intravesical BCG due to its superior
oncological benefits compared to intravesical chemother-
apy.5 This series reflects common practice in 2012, three
years prior to NICE guidance in 2015, when high-grade
grade 2 disease was frequently treated similarly to grade 3
disease.1 However, considering current guidance, 20% of
our historical cohort had intermediate disease and could
have been treated with intravesical chemotherapy,
allowing greater utilisation of limited BCG resources.
Furthermore, device-assisted therapies were an emerging
technology for NMIBC.12 Chemohyperthermia was avail-
able in our unit during the shortages and, as an experimen-
tal therapy, was primarily utilised in the setting of clinical
trials. Data about its effectiveness were limited at the time
of this cohort. One patient received chemohyperthermia
following BCG failure as a part of the HYMN trial.13 More
recent data support the use of chemohyperthermia as an
effective alternative to BCG. A recent RCT by Ardens
et al. randomised 190 patients to either chemohyperther-
mia with MMC or BCG.14 The chemohyperthermia cohort
had a superior recurrence-free survival (78.1% vs. 64.8%,
p=0.08) for patients with intermediate- and high-risk
NMIBC at 24 months and provides evidence of a tolerable
and effective alternative to BCG should further shortages
occur.14
In the UK, there is a yearly incidence of 10,000 bladder
cancers, of which approximately 7500 (75%) are non-mus-
cle invasive.2,15,16 Of these, an estimated 2250 (30%)
patients are recommended BCG due to their high recur-
rence rate and a 20–25% lifetime risk of progression to
muscle-invasive disease.17 In this cohort, 29.8% of patients
requiring BCG treatment did not receive adequate treat-
ment. Therefore, a significant percentage of patients per
year in the UK are potentially being undertreated because
of shortages of BCG. In this cohort, the FbH patients had a
worse disease-free survival at 4.5 years, along with a
greater number of additional treatments. Furthermore,
there was an increased rate of radical cystectomy (11.8%)
25/06/2021 2:38:36 PM
 MacKenzie et al. 271

Table 1.  Demographics of compliant, FbH cohort and overall cohorts.

Compliant cohort, N=25 FbH cohort, N=34 Total cohort, N=114

Age (years), median (IQR) 69 (63–75) 77 (66–82) 75.5 (68–81)

Sex, n (%)

 Male 19 (76) 31 (91) 97 (85)

 Female 6 (24) 3 (9) 17 (15)

Type of cancer, n (%)

 Primary 20 (80) 30 (88) 94 (82)

 Recurrent 5 (20) 4 (12) 20 (18)

Size, n (%)

  <3 cm 7 15 41

  >3 cm 3 5 17

 Unknown 15 14 56

Grade, WHO 1973, n (%)

 G1 0 0 0

 G2 12 (48) 21 (62) 47 (41)

 G3 11 (44) 11 (32) 57 (50)

  CIS only 2 (8) 2 (6) 10 (9)

T category, n (%)

 Ta 14 (56) 22 (65) 65 (57)

 T1 9 (36) 10 (29) 39 (34)

  CIS only 2 (8) 2 (6) 10 (9)

CIS present, n (%)

 Yes 15 (60) 14 (41) 58 (51)

 No 10 (40) 20 (59) 56 (49)

Variant tumour, n (%)

 Yes 1 (4) 1 (3) 2 (2)

 No 24 (96) 33 (97) 112 (98)

Re-resection, n (%)

 Yes 14 (56) 15 (44) 56 (49)

 No 11 (44) 19 (56) 58 (51)

Risk group (CIS included), n (%)

 Intermediate 4 (16) 11 (32) 23 (20)

 High 21 (84) 23 (68) 91 (80)

FbH: failed by health care; BCG: bacillus Calmette–Guérin; IQR: interquartile range; WHO: World Health Organization; CIS: carcinoma in situ.

06_URO941780.indd 271 25/06/2021 2:38:36 PM

 272 Journal of Clinical Urology 14(4)

Table 2.  Four-and-a-half year outcomes of compliant and FbH

cohorts.

Outcome Compliant FbH cohort,

cohort, N=25 N=34

Follow-up (months) 71 (58–77) 60 (55-68)

Died 3 (12%) 6 (17.6%)

Recurrence 6 (24%) 12 (35.3%)

Time to recurrence 22.5 (17–62) 24.5 (11–56)

(months)

Progression 1 (4%) 1 (2.9%)

Time to progression 62 32
(months)

Further treatment

Radical cystectomy 1 (4%) 4 (11.8%)

Time to cystectomy 21 (n/a) 29 (17–45)

(months)

Radiotherapy  0  0

Re-challenged with BCG 2 (8%) 4 (11.8)

Mitomycin C  0 1 (2.9%)

Thermotherapy 1 (4%)  0

Palliative care due to 1 (4%) 1 (2.9%)

metastatic disease
Figure 2.  Disease-free survival over years demonstrated by
a Kaplan–Meier curve – complete (compliant) cohort versus No further treatment 20 (80%) 24 (70.6%)
failed by health care (FbH) cohort.
Data shown are median (range) or n (%).

compared to both the compliant cohort (4%) and the

EORTC 20911 trial (4.2%).5 This demonstrates the
increased risk to the FbH cohort and the importance of an
enhanced surveillance protocol. It is important to exercise
duty of candour when counselling patients at times of
treatment shortages.18
Additionally, with the potential threat of another world-
wide BCG shortage, this may be an opportunity for the UK
to create a prospective data registry of patients with inter-
mediate- and high-risk NMIBC. A registry could provide a
UK-wide evaluation of management, identifying varia-
tions in each patient’s decision for alternative treatments,
as well as observational data about outcomes.
The study has limitations. The cohort size limits the
interpretation of statistical significance, although the
trends are apparent that the FbH cohort does have a lower
disease-free survival and an increased requirement for fur-
ther intervention. This difference may become significant
over a longer follow-up period.
Although the cohorts appear to be similar, we cannot
rule out the potential for bias in determining which
patients received maintenance treatment. Ostensibly, this
was simply a matter of whether supplies were available.
However, this is clearly not randomised and is a potential
confounding factor.
For patients to receive the recommended schedule of
BCG is challenging due to many factors. In our cohort,
only 51.7% of patients were deemed suitable to receive
maintenance. Oddens et al. reported a completion rate of
61.8% for one year of BCG maintenance.6 The rate of
BCG failure is likely higher due to two factors. First, in our
cohort, any disease recurrence within the first 12 months
was defined as a BCG failure and treatment changed
accordingly, whereas in Oddens et al., patients continued
maintenance until a second recurrence or disease progres-
sion.6 Second, 7% of patients had a positive biopsy for car-
cinoma in situ on their first check cystoscopy at three
months and were re-challenged with a further induction
course of BCG. Kamat et al. advocate waiting until six
months post induction to define patients as truly BCG
refractory due to a 25–67% response after their first main-
tenance course.19 Our study cohort was treated prior to
widespread adoption of definitions of BCG failure.

06_URO941780.indd 272 25/06/2021 2:38:36 PM

 MacKenzie et al. 273
Finally, patients in the compliant cohort completed
only 12 doses within their first year and, as a result, were
non-compliant, as they received one maintenance course
less than the EAU and SWOG recommendations.2,4
Additionally, the monitoring for upper-tract and meta-
static disease was less frequent than current recommen-
dations.2 Despite these issues, the disease-free survival
for the compliant cohort is comparable to previously
reported literature.5,6 This study provides a realistic
reflection of managing patients in the National Health
Service, highlighting the practical difficulties in ensuring
patients have their checks and maintenance therapies.
Conclusions
A significant number of patients did not receive mainte-
nance BCG therapy due to shortages. It is important when
counselling patients for BCG therapy to explain the poten-
tial of therapy shortages and the potential for worsening of
oncological outcomes as a result of undertreatment.
Further work in the form of a UK registry to follow effected
cohorts in multiple centres may provide beneficial infor-
mation about patient impact and outcomes from alterna-
tive treatment options.
Conflicting interests
K.M. and S.P. are employees of LET Newburn County Durham
and Darlington. Neither has received grants. D.W. and J.C. are
employees of South Tees Hospital NHS Foundation Trust.
Neither has received grants.
Funding
The authors received no financial support for the research,
authorship and/or publication of this article.
Ethical approval
James Cook University Hospital does not require ethical approval
for reporting individual cases or case series.
Informed consent
Written informed consent was obtained from the patients for
their anonymized information to be published in this article
Guarantor
None
Contributorship
K.M. wrote the first draft of the manuscript. All authors reviewed
and edited the manuscript and approved the final version of the
manuscript.
ORCID iD
Sidney D Parker   https://orcid.org/0000-0002-7906-7579
06_URO941780.indd 273
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13. Tan WS, Panchal A, Buckley L, et al. Radiofrequency-
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der cancer following induction or maintenance bacillus
Calmette–Guérin therapy (HYMN): a Phase III, open-label,
randomised controlled trial. Eur Urol 2019; 75: 63–71.
14. Arends TJ, Nativ O, Maffezzini M, et al. Results of
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chemohyperthermia with mitomycin C versus bacillus
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cancer. Eur Urol 2016; 69: 1046–1052.
15. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and
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1 6. Cancer Research UK. Bladder cancer statistics 2019, https://
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936885 URO Journal of Clinical UrologyNugroho et al.

Cross-sectional Study

Journal of Clinical Urology

The role of intraoperative kidney mucosal

2021, Vol. 14(4) 275­–281
© British Association of
Urological Surgeons 2020
biopsy on screening of squamous cell Article reuse guidelines:
sagepub.com/journals-permissions

carcinoma of the kidney in nephrolithiasis DOI: 10.1177/2051415820936885

https://doi.org/10.1177/2051415820936885
journals.sagepub.com/home/uro

patients with stones larger than 20 mm

Tri Sunu Agung Nugroho , Ferry Safriadi and

Bambang Sasongko Noegroho

Abstract
Introduction: Renal pelvic squamous cell carcinoma is a very rare tumor, with a prevalence <1% of all urinary tract
tumors, about 0.5–8% of all kidney tumors, and the average age is 50–70 years. Although the incidence of renal squamous
cell carcinoma is less common than renal cell carcinoma and renal transitional cell carcinoma, due to its more aggressive
nature renal squamous cell carcinoma is often found intraoperatively and is already in an advanced stage or metastasis.
The relevant medical history of squamous cell carcinoma is pyelonephritis, chronic nephrolithiasis, and a history of kidney
stone surgery. Data which was obtained from previous research at Hasan Sadikin Hospital, from January 2014–December
2017, found the incidence of renal squamous cell carcinoma from nephrectomy procedures was 6%.
Methods: This study was a cross-sectional study with a correlative analytic study, samples were taken consecutively
from biopsy of kidney mucosa intraoperatively in hospitalized patients with kidney stones with size larger than 20 mm
at the Department of Urology, Hasan Sadikin Hospital Bandung, which performed open kidney surgery or percutaneous
nephrolithotomy from January–May 2019.
Results: The number of samples in this study were from 30 patients, consisting of 16 males and 14 females. Five patients
underwent open kidney surgery and 25 patients underwent percutaneous nephrolithotomy surgery, with an average of
age of 49.5±11.8 years and 63.3% of patients were aged from 40–60 years. In this study, one patient (3.3%) showed
squamous cell carcinoma of the kidney, a 57-year-old male patient with a left staghorn kidney stone who underwent left
percutaneous nephrolithotomy surgery.
Conclusion: There is a benefit for intraoperative kidney mucosal biopsy as a screening for squamous cell carcinoma of
the kidney in nephrolithiasis patients with stones larger than 20 mm.
Level of evidence: 3

Keywords
Kidney mucosal biopsy, nephrolithiasis, squamous cell carcinoma

Date received: 12 December 2019; accepted: 22 May 2020

Introduction
Kidney cancer accounts for 5% and 3% of all malignancies
in men and women respectively, representing the seventh
most common cancer in men and the 10th most common
cancer in women. Approximately 90% of these account for
renal cell carcinomas (RCCs) of the renal parenchymal
Urology Department, Universitas Padjadjaran, Indonesia
Corresponding author:
Tri Sunu Agung Nugroho, Urology Department, Hasan Sadikin
Hospital, Universitas Padjadjaran, Bandung 40184, Indonesia.
Email: tsunuan@gmail.com

07_URO936885.indd 275 25/06/2021 2:39:30 PM

 276 Journal of Clinical Urology 14(4)
tissue.1,2 Malignancy of the renal pelvis accounts for 10%
of renal carcinomas as urothelial tumors. Primary tumors
arising from the renal collection system are rare, only
accounting for 4–5% of all urothelial tumors of the urinary
tract.3 Renal pelvic squamous cell carcinoma (SCC) is
considered to be a very rare kind of tumor, with a preva-
lence of <1% of all tumors of the urinary tract, 0.5–8% of
all tumors of the kidney, and on average it occurs between
the ages of 50–70 years. Although the incidence of renal
SCC is very rare, because of its aggressive nature renal
SCC is often found intraoperatively in an advanced stage
(locally advanced) or metastasized, thus explaining the
high mortality rate. Renal SCC is also difficult to be diag-
nosed in the early stages due to its non-specific symptoms,
radiological examination findings, and the absence of
tumor markers.3–6
Chronic kidney disease and kidney cancer are consid-
ered to be renal disorders associated with nephrolithiasis. A
study conducted by Keddis and Rule showed that individu-
als with a history of nephrolithiasis may have 2–3 times the
potential to suffer from chronic kidney disease in the
future.7 Shih et al. reported that individuals with nephro-
lithiasis had twice the potential to develop kidney malig-
nancy. The risk of urinary tract tumors increases with the
length of time the patient suffers from urinary tract
stones.4,8,9 Irritation of renal mucosa is related to the size of
the stone and the length of time the patient has suffered
from kidney stones. Some of the studies in the literature
mention that staghorn stones and also large/complex kid-
ney stones with sizes >20 mm are associated with renal
pelvic malignancy. Raghavendran et al. in their study men-
tioned that the average duration of chronic kidney stone
history from 18 patients with renal pelvic malignancy asso-
ciated with kidney stones is 8.8 years (6–11.6 years).10,11
Other studies also mention that chronic irritation,
inflammation, and infection caused by staghorn stones are
believed to induce reactive changes in urothelial or renal
pelvic epithelial cells that lead to the development of neo-
plasia through the process of metaplasia and leukoplakia
and may eventually develop into SCC.3,4,10,12,13 The inci-
dence of SCC accompanied by the presence of urinary
tract stones varies greatly, starting from 18% in the USA to
100% in Hong Kong.4,14
The initial diagnosis of SCC is sometimes difficult,
especially when kidney stones present, since both the
symptoms and radiological features will be obscured by
those of the kidney stones, and the imaging studies will
only reveal the finding of the stones or hydronephrosis due
to obstruction.13–15 Biopsy of the renal pelvic or calix wall
must be considered in chronic cases of large kidney stones,
especially in the case of staghorn stones.16–18 SCC of renal
pelvic may have poor prognosis. The five-year survival
rate of renal pelvic SCC is less than 10% due to the aggres-
sive nature of renal SCC, with the survival rate of renal
SCC patients after surgical treatment being 7 months on
average, much lower when compared with that of renal
07_URO936885.indd 276
transitional cell carcinoma (TCC) patients (50 months).
Early detection of SCC is expected to lead to immediate
treatment and a better prognosis.3,5,6,14,19
Given the potential for renal SCC to occur in patients
with nephrolithiasis larger than 20 mm in size, and the dif-
ficulty of early detection of renal SCC from atypical symp-
toms and radiological features, the diagnostic quality of
renal biopsy is good as one of the modalities for clinical
diagnostic approach to renal malignancy. Further studies
on the usage and role of renal biopsy in patients with neph-
rolithiasis larger than 20 mm as a screening for renal SCC
are necessary.
SCC of the kidney
Uroepithelial cells of the renal pelvocalyceal system can
be affected with malignancies, such as SCC. Carcinoma of
renal squamous cells is considered to be a very rare kind of
malignancy. The incidence of renal pelvic SCC in the lit-
erature is about 0.5–8% of all renal malignancies.5,6,20,21
Compared with other malignancy of the urinary tracts, the
prognosis for SCC is worse. Studies have shown that the
survival rate of kidney SCC patients after surgery is 7
months on average, lower when compared with that of kid-
ney TCC patients (50 months). The five-year survival rate
is less than 10%.5,19,22
Kidney SCC is often associated with kidney stones
or infection, and is usually found at an advanced stage
without any complaints such as pain or palpable mass in
the waist. Chronic irritation such as those caused by
long-standing kidney stones and infections is believed
to induce reactive changes in urothelial cells and trigger
neoplasms through the process of metaplasia and
leukoplakia.4,14 Staghorn stones have been reported to
be the main cause of renal pelvis SCC with poor
prognosis.7,8,23,24 Since there are almost no other effec-
tive therapeutic modalities, the main therapy for kidney
SCC is surgery, such as radical nephrectomy or nephro-
ureterectomy. Adjuvant or concomitant chemotherapy
is administered in cases where the prognosis does not
significantly improve after radical nephrectomy while
radiotherapy is still under consideration.6,12,14
Kidney stones
Urinary tract stone is a common disorder in populations
with an incidence of 8.8–12%, and is the third most com-
mon urological disease in both genders. It is, however,
commonly found in men with the proportion of 2:1 for
men and women, respectively. Urinary tract stone (uro-
lithiasis) is associated with risk factors for malignancy of
the urinary tract.7,8 Kidney stone (nephrolithiasis) is a pre-
disposing factor of non-communicable and chronic dis-
eases of the kidneys. Simple kidney stone is less than 20
mm in size, large/complex kidney stone is larger than 20
mm in size, while staghorn stone refers to large and
25/06/2021 2:39:30 PM
 Nugroho et al. 277
branched stones that partly or completely fill of the pelvo-
calyceal system. This kind of stone is usually unilateral,
associated with urease-producing bacterial infections and,
therefore, known as a struvite infection stone.25,26
Management of kidney stones depends on the size,
location, presence or absence of infection, and kidney
function. Indications of active kidney stone removal
include cases of stone with a low likelihood of spontane-
ous passage, the presence of persistent urinary tract
obstruction, stone size >20 mm, the presence of infection,
and other conditions. The goal of treatment in patients with
kidney stones is to overcome pain, remove blockages,
remove existing stones, and prevent recurrence of stone
formation.27–29 Staghorn stones cause squamous metapla-
sia and uroepithelium dysplasia. Kidney stone coexistence
has been reported in 18–100% of cases of kidney SCC.
Staghorn stones are the main cause of SCC of the renal
pelvis. Clinical manifestations include abdominal or pel-
vic pain, hematuria, and abdominal mass. This is often
involved with hydronephrosis. Elimination of staghorn
stones is necessary to eliminate infection and prevent
squamous metaplasia from kidney epithelium.4,6,7
Renal mucosal biopsy
Renal mucosal biopsy can show the histology of the radio-
logically renal mass. This biopsy must be considered in
patients with masses that are not too large for surveillance
before treatment in order to predict the therapy that can be
used. This procedure is used to determine the characteris-
tics of the renal mass.18,30 The macroscopic findings of the
renal pelvis were different in cases of malignancy so that
the mucosa were hyperemic and thickened. Kidney biopsy
may be performed via open incision or laparoscopic tech-
nique. These methods ensure positive renal identification
for macroscopic diagnosis, and biopsy provides better
samples under direct examination.31 Open kidney biopsy is
considered to be a safe procedure, often performed in
patients with significant comorbidities, and is associated
with significant postoperative morbidity.16 This surgical
procedure allows for the availability of multiple core or
tissue slices and provides the ability to directly visualize
and control any bleeding present.32 Renal pelvis or calix
wall biopsy must be considered in cases with long-stand-
ing or chronic, large kidney stones, especially for staghorn
stones.16,17
Subjects and methods
This was a prospective analytic study which used a cross-
sectional study design. The samples were taken consecu-
tively from patients with large kidney stones (>20 mm)
that underwent surgery, both open surgery or percutaneous
nephrolithotomy (PCNL), in the Urology Department,
Universitas Padjadjaran, Hasan Sadikin Hospital,
Bandung. The inclusion criteria were patients who were
07_URO936885.indd 277
Table 1.  Patients distribution according to gender and age
categories.
Gender and age categories n %
Male 16 53.3
<40 years 3  
40–60 years 9  
>60 years 4  
Female 14 46.7
<40 years 2  
40–60 years 10  
>60 years 2  
admitted to the Urology Department, diagnosed with
nephrolithiasis with stone size larger than 20 mm, and
underwent kidney stone surgery, either open surgery or
PCNL during January–May 2019. The exclusion criteria
were patients with imaging studies or clinical symptoms
(i.e. hematuria) that were suspicious of malignancy. All
patients that were included in this study had given special
informed consent that pelvic renal carcinoma can be
caused by chronic inflammation due to nephrolithiasis and
that a biopsy needed to be performed. Multiple biopsies
were done in each patient, in 2–3 suspected locations. The
sample was taken by a grasper. The complications of renal
biopsy were hematuria, perinephric hematoma, and infec-
tion. Patients that were positive for SCC from biopsy were
planned for radical nephrectomy.
Results
The total of samples in this study were from 30 patients,
consisting of 16 males and 14 females. Five patients under-
went open kidney surgery and 25 patients underwent
PCNL surgery.
Table 1 illustrates the patient distribution according to
gender and age categories. Of 16 male patients, 3 of them
were younger than 40 years; 9 were between 40–60 years;
and 4 were over 60 years. Of 14 female patients, 2 of them
were younger than 40 years; 10 were between 40–60 years;
and 2 were over 60 years. The mean ages of the male and
female patients were 50.3±11 and 48.6±13.1 years,
respectively.
Table 2 illustrates the patient distribution according to
number or types of the stones, and types of surgery con-
ducted. Of the 30 patients studied, the majority of patients
had multiple stones larger than 20 mm in size and staghorn
stones, with each group composed of 13 patients (43.3%).
Most of the patients (25 patients (83.3%)) underwent
PCNL surgery. From 16 male patients, 4 patients under-
went open surgery; while 12 others underwent PCNL
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 278 Journal of Clinical Urology 14(4)

Table 2.  Patients distribution according to number/types of Based on Table 5, from four patients in the group of
the stones, and types of surgery conducted. single stone with size larger than 20 mm, all of their histo-
pathological findings resulted in chronic non-specific
Size of stone(s) Types of surgery n %
inflammation. From 13 patients in the group of multiple
Open surgery PCNL stones with size larger than 20 mm, all of their histopatho-
logical findings also resulted in chronic non-specific
Single stone, >20 0 4 4 13.4 inflammation. From 13 patients in the staghorn stone
mm
group, 1 histopathological finding resulted in SCC, 7 his-
Multiple stones, 3 10 13 43.3 topathological findings resulted in chronic non-specific
>20 mm inflammation and the remaining 5 resulted in nephritis.
Based on Table 6, from 17 patients with duration of ill-
Staghorn stones 2 11 13 43.3
ness less than 1 year, 16 histopathological findings resulted
Total 5 25 30 100 in chronic non-specific inflammation; and 1 resulted in
nephritis. From nine patients with an estimation of dura-
PCNL: percutaneous nephrolithotomy.
tion of illness from 1–5 years, five histopathological find-
ing resulted in chronic non-specific inflammation and the
Table 3.  Patients distribution according to histopathological remaining four resulted in nephritis. From four patients
examination findings. with an estimation of duration of illness over 5 years, one
histopathological finding resulted in SCC and three others
Histopathological findings n % resulted in chronic non-specific inflammation.
Squamous cell carcinoma (SCC) 1 3.3 From the results of histopathological examinations of
30 patients after intraoperative renal mucosal biopsies via
Nephritis 5 16.7 PCNL and open kidney stone surgery, one histopathologi-
cal finding resulted in SCC, a malignancy in the renal pel-
Chronic non-specific inflammation 24 80.0
vis, which was found in a 57-year-old male patient with
Total 30 100.0 staghorn stones. Biopsy samples were taken intraopera-
tively during PCNL surgery and it was known that the
patient had been suffering from the disease for 7 years.
Table 4.  Patients distribution according to the estimation of Using the chi-square test, the relationship between the size
duration of illness. of stones, estimation of duration of illness, and the histo-
pathological examination result was found to have a sig-
Duration of illness n %
nificant value, since the p-value results are less than 0.05
<1 year 19 63.3 (p-value=0.044 based on stone size and p-value=0.009
based on duration of illness). This result means that intra-
1–5 year(s) 7 23.3 operative renal mucosal biopsy can be used as a means of
>5 years 4 13.4 screening for renal pelvic malignancy in patients with
nephrolithiasis. It can be concluded that intraoperative
Total 30 100.0 renal mucosal biopsy may play a role for screening the
occurrence of malignant SCC in patients with nephrolithi-
asis larger than 20 mm in size.
surgery. From 14 female patients, one of them underwent
open surgery; and 13 others underwent PCNL surgery.
Table 3 illustrates the patient distribution according to
Discussion
histopathological examination findings from renal mucosal There were 30 patients included in this study, with a distri-
biopsy. Of 30 patients, the majority of patients (24 patients bution of 16 male patients and 14 female patients, of which
(80%)) showed chronic non-specific inflammation, and 1 5 patients underwent open kidney surgery and 25 patients
patient (3.3%) showed renal pelvic malignancy (SCC) underwent PCNL surgery. All patients that were included
from the histopathological examination findings. in this study had given special informed consent that pel-
Table 4 illustrates the patient distribution according to vic renal carcinoma can be caused by chronic inflamma-
the estimation of duration of illness. Of 30 patients stud- tion due to nephrolithiasis. Multiple biopsies were done in
ied, the majority of patients (19 patients (63.3%)) stated each patient, in 2–3 suspected locations. The sample was
that the estimation of duration of illness was less than 1 then taken by a grasper. The complications of renal biopsy
year, and only 4 patients (13.4%) stated that the estimation were hematuria, perinephric hematoma, and infection. The
of duration of illness was more than 5 years. patient that was positive for SCC from the biopsy was

07_URO936885.indd 278 25/06/2021 2:39:30 PM

 Nugroho et al. 279

Table 5.  Correlation of number/types of the stones with the results of histopathological examination findings from intraoperative
renal mucosal biopsy in patients with nephrolithiasis.

Size of stone(s) Histopathological Finding Total p-Value

Squamous cell Chronic non-specific Nephritis

carcinoma inflammation

Single stone, >20 mm n 0 (0.0%)   4 (100.0%) 0 (0.0%)   4 (100.0%) 0.044

Multiple stones, >20 mm n 0 (0.0%) 13 (100.0%) 0 (0.0%) 13 (100.0%)

Staghorn stone n 1 (7.7%)   7 (53.8%) 5 (38.5%) 13 (100.0%)

Total n 1 (3.3%) 24 (80.0%) 5 (16.7%) 30 (100.0%)

Table 6.  The role of intraoperative renal mucosal biopsy in patients with nephrolithiasis, observed from the correlation of
estimation of duration of illness and the results of histopathological examination findings.

Duration of illness Histopathological finding Total p-Value

Squamous cell Chronic non-specific Nephritis

carcinoma inflammation

<1 year n 0 (0.0%) 16 (94.1%) 1 (95.9%) 17 (100.0%) 0.009

1–5 year(s) n 0 (0.0%) 5 (55.6%) 4 (44.4%) 9 (100.0%)

>5 years n 1 (25.0%) 3 (75.0%) 0 (0.0%) 4 (100.0%)

Total n 1 (3.3%) 24(80.0%) 5 (16.7%) 30 (100.0%)  

planned for radical nephrectomy. From the histopathologi-
cal examination results of 30 patients who had undergone
intraoperative renal mucosal biopsy during open kidney
stone surgery and PCNL, there was one histopathological
finding (3.3%) that resulted in SCC, a malignancy in the
pelvis kidney, which was found in a 57-year-old male
patient with a left staghorn stone. The biopsy sample was
taken intraoperatively during PCNL surgery of the left kid-
ney and it is known that the patient had suffered from kid-
ney stones for 7 years. The macroscopic views of the renal
pelvis were different in the case of malignancy in that the
mucosa was hyperemic and thickened. Imaging studies
were conducted before surgery, no sign of malignancy was
found and no complaints regarding malignancy, such as
hematuria.
A case series of four patients with renal pelvic SCC
reported that the average age of the subject involved in
their study was 60 years, the ratio of the genders of the
subjects was three male to one female, and the ratio of left
to right kidney affected by the disease was 1:1. In 100% of
the cases, staghorn stones were present.9 Other studies
states that the average age of subjects with renal SCC is 56
years, with the same incidence rate between men and
women, and the same occurrence of the sides of involve-
ment of the kidney.19,33,34 Several previous studies have
shown that renal pelvic SCC was a rare kind of tumor, with
the prevalence of less than 1% of all urinary tract tumors,
and 0.5–8% of all kidney tumors. On average, renal pelvic
SCC occurs in those between the age of 50–70 years.4,6,33
The incidence of SCC accompanied by the presence of uri-
nary tract stones varies greatly, starting from 18% in the
USA to 100% in Hong Kong.14,19
Some studies state that chronic irritation which might
be caused by chronic kidney stones, is a risk factor for kid-
ney SCC. Other risk factors are infection, vitamin defi-
ciency, exposure to endogenous and exogenous chemicals,
radiotherapy, and smoking. Other studies state that the
cells and lymphocytes inflammatory mechanisms might be
caused by kidney stones and infection of damaged cells,
and with enough cytokines and chemokines secreted by
lymphocytes, triggering tumor cell growth and squamous
metaplasia which contributes to the onset and progression
of the kidney SCC.14,15,33 In a study conducted by
Raghavendran et al., 18 patients with renal pelvic malig-
nancy associated with kidney stones on average had a his-
tory of chronic kidney stones with a duration of 8.8 years
(6–11.6 years).11
Detection of renal SCC through imaging studies is
usually difficult, since most of the time only kidney
stones and hydronephrosis can be seen, both of which
emerge as a result of the obstruction. The diagnosis of
kidney SCC is usually done postoperatively, after

07_URO936885.indd 279 25/06/2021 2:39:30 PM

 280 Journal of Clinical Urology 14(4)
histopathological examination is performed. Some case
reports used non-invasive procedures with urine cytology
examination to obtain histopathological features, but
confirmation was still performed using histopathological
examination after the surgery. There is neither specific
diagnostic imaging modality nor tumor marker examina-
tion for renal SCC. A study suggested to perform a biopsy
of the renal pelvis/calyces during kidney stone therapy.
This diagnostic modality might assist in the management
of kidney mass.5,13,18,19,30
Biopsy of the renal pelvis or calix wall should be con-
sidered in cases of long-standing/chronic large-sized kid-
ney stones, especially in the case of staghorn stones.16–18
The kidney stones and infections are dangerous since they
might obscure the presence of aggressive kidney malig-
nancies. The researchers emphasize that suspicion in this
type of case should be raised due to the poor prognosis
associated with this aggressive SCC, thus an early diagno-
sis and prompt definitive treatment can be made.3,17
Conclusions
From the results of this study, some conclusions can be
drawn. Intraoperative renal mucosal biopsy can be sug-
gested as a means of screening for the occurrence of malig-
nant SCC in patients with nephrolithiasis larger than 20
mm in size for more than 5 years. Staghorn stone is sus-
pected as one of the risk factors for renal pelvic malig-
nancy, in this case, SCC. The duration for which a patient
suffers from kidney stones (more than 5 years) is thought
to be closely related to chronic irritation that causes urothe-
lial cell metaplasia thus triggering SCC. From this study, it
was found that 3.3% of total incidence of kidney stones
that are larger than 20 mm in size developed into SCC.
Conflicting interests
The authors declare that there is no conflict of interest.
Funding
The authors received no financial support for the research,
authorship, and/or publication of this article.
Ethical approval
Ethical permission was obtained from the Health Research Ethics
Committee and the Director of Human Resources and Education
at Hasan Sadikin Academic Medical Center - Indonesia with reg-
ister number: LB.02.01/X.6.57/74/2019.
Informed consent
Written informed consent was obtained from the patients for
their anonymized information to be published in this article.
Guarantor
Tri Sunu Agung Nugroho.
07_URO936885.indd 280
Acknowledgements
None.
ORCID iD
Tri Sunu Agung Nugroho https://orcid.org/0000-0003-2454
-8161
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939407 URO Journal of Clinical UrologySharma et al.

Cross-sectional Study

Journal of Clinical Urology

A single-centre experience of the

2021, Vol. 14(4) 282­–287
© British Association of
Urological Surgeons 2020
management of inguinal lymph nodes Article reuse guidelines:
sagepub.com/journals-permissions

associated with penile squamous-cell DOI: 10.1177/2051415820939407

https://doi.org/10.1177/2051415820939407
journals.sagepub.com/home/uro

carcinoma

Amit Sharma , Sandesh Parab, Gaurav Goyal, Ajit Patel,

Mukund Andankar and Hemant Pathak

Abstract
Background: Twenty-two cases of penile carcinoma that were managed at our institution over a 5-year period were
analysed on the basis of inguinal lymph node dissection (ILND), complications and follow-up.
Methods: A total of 22 cases post penectomy were stratified into low risk (T1 G1 or G2 without lympho-vascular
invasion and negative on fine-needle aspiration cytology (FNAC)) and high risk (T1 G3 and above and/or lympho-vascular
invasion). Low-risk patients having palpable lymphadenopathy were given a course of antibiotics. If the lymph nodes
were still palpable, FNAC was done, and patients then underwent superficial ILND (SILND) or even ILND in cases with
positive frozen-section reports. In the high-risk group, all patients underwent SILND, and if required, underwent ILND.
Two patients in the high-risk group were lost to follow-up after 9 months. Histopathology reports were noted, and
patients were followed up for 2 years.
Results: In the low-risk group, seven patients had palpable lymph nodes and underwent SILND. The remaining five
patients were put on surveillance. Amongst the seven who underwent SILND, six were positive at frozen section,
requiring ILND. Nine patients in the high-risk group underwent ILND. Four patients in the ILND group had a minor
wound infection. Lymphoedema was seen in two patients which was managed conservatively, and lymphorrhoea was
seen in one patient. Flap necrosis occurred in one patient. Recurrences were seen in three patients in the high-risk
group. Two who had deep node involvement and who had early nodal recurrence underwent bilateral ILND. One
patient in the high-risk group had late ipsilateral nodal recurrence and underwent ipsilateral ILND. There were no
regional recurrences.
Conclusion: Carcinoma of the penis has high morbidity because of delayed presentation, lack of awareness and poor
compliance. This necessitates staging SILND in all high-risk cases for therapeutic and prognostic purposes.

Keywords
Carcinoma, penis, inguinal lymph node, dissection, metastasis

Date received: 13 December 2019; accepted: 9 June 2020

Introduction
Squamous-cell carcinoma (SCC) of the penis, although rare,
is a potentially fatal malignancy.1 In the Western world, at
diagnosis, tumours are usually localized and can be man-
aged by local excision or circumcision, laser ablation,
brachytherapy, external radiation or partial penectomy.1
Department of Urology, TNMC & BYL Nair Hospital, India
Corresponding author:
Amit Sharma, Department of Urology, TNMC & BYL Nair Hospital,
Mumbai Central, Mumbai, Maharashtra 400008, India.
Email: dramiturology@gmail.com

08_URO939407.indd 282 25/06/2021 2:40:07 PM

 Sharma et al. 283
Table 1.  Pathological staging and grade of primary penile growth and their risk stratification.
Risk stratification Pathological staging
Low risk (N=12) pT1, G1
pT1, G2
High risk (N=10) pT1, G3
pT2, G3
pT3, G3
However, at our set-up, most patients present with advanced
stages (stage T2 and above), and require more radical
management.
The survival of a patient with penile carcinoma is deter-
mined by the presence and extent of inguinal metastases.1–3
In patients with no palpable inguinal adenopathy, the risk
of occult metastases is estimated to be as high as 30% and
is predicted by tumour grade and presence of lympho-vas-
cular invasion.3 In patients with palpable inguinal nodes,
approximately 50% have tumour metastases.1 The progno-
sis for survival in patients with lymph node metastases is
tightly correlated with the number and location of involved
lymph nodes and the presence of extranodal extension.1
The prognostic importance of lymph node metastases
and the potential therapeutic effect of early resection have
led to the widely practiced procedure of staged ilioinguinal
lymph node dissection (ILND).1 We describe our experi-
ence in the management of inguinal nodes in 22 patients
with penile carcinoma.
Methods
Hospital records of patients with penile carcinoma who
were managed at the department of urology over a period
of 5 years between January 2014 and December 2018 were
reviewed, and patients were retrospectively analysed on
the basis of demographics, clinical presentation, manage-
ment, complications, follow-up and outcome. All patients
were admitted and underwent partial/total penectomy after
biopsy confirmation of the penile lesion and fine-needle
aspiration cytology (FNAC) of the palpable inguinal
nodes.
Risk stratification was done as low risk (T1 G1 or G2
without lympho-vascular invasion FNAC negative) and high
risk (T1G3 and above and/or lympho-vascular invasion)
based on the histopathology report of the primary tumour.
Low-risk patients having palpable lymphadenopathy were
given a course of antibiotics. If they were still palpable,
FNAC was repeated followed by superficial ILND (SILND)
and, if required, ILND. All patients in the high-risk group
underwent ILND. Histopathology reports were noted, and all
high-risk patients were referred to the medical oncology
department where they received adjuvant cisplatin-based
08_URO939407.indd 283
Number of patients Total
4 12
8
3 10
4
3
chemotherapy. All patients were followed up for 2 years to
assess for postoperative complications and recurrence.
Recurrence was defined as the presence of a hard inguinal
lymph node at follow-up; early recurrence was defined as
recurrence occurring within a year of surgery. Recurrence
after 1 year was defined as late recurrence.
Follow-up was done at 14 days, then every 3 months for
a year and then biannually. At every follow-up, all patients
were examined clinically for neo-meatus, voiding difficul-
ties, lymphoedema and inguinal nodes. All patients under-
went annual contrast-enhanced computed tomography
(CECT) of the pelvis and bilateral inguinal region. In addi-
tion, patients were referred for CECT and FNAC if, at any
follow-up, hard inguinal lymph nodes were palpable.
Bilateral ILND was done in patients with early recurrence,
and ipsilateral ILND was done in patients with late
recurrence.
Results
A total of 22 patients with penile SCC were managed in the
department during the specified time period. The mean age
at presentation was 56 years. All patients presented with a
fungating growth in the penis. Ten patients had unilateral
palpable inguinal lymph nodes, and four patients had bilat-
eral palpable inguinal nodes. Eight patients did not have
palpable inguinal lymph nodes. There was no history of
associated human papillomavirus or human immunodefi-
ciency virus infection and no history of multiple sexual
partners. All patients were uncircumcised, and none had
phimosis.
All patients underwent surgery: eight underwent partial
penectomy, and 14 underwent total penectomy. Risk strati-
fication was then done based on histopathology report into
low risk (T1 G1 or G2 without lympho-vascular invasion
FNAC negative) and high risk (T1 G3 and above and/or
lympho-vascular invasion). The pathological T staging
and risk stratification is summarized in Table 1. Twelve
patients were in the low-risk category, and 10 patients
were in the high-risk category.
Seven patients in the low-risk group had unilateral pal-
pable inguinal lymph nodes and underwent SILND. The
other five were put on surveillance. Out of the seven who
25/06/2021 2:40:07 PM
 284 Journal of Clinical Urology 14(4)

Table 2.  Clinical presentation and management of patients with inguinal lymph nodes in penile carcinoma.

Clinically palpable lymph nodes FNAC Frozen Frozen ILND

positive positive negative required
  None Unilateral Bilateral at SILND at SILND

Low risk – T1, G1 or G2 5 7 0 6 6 1 6

High risk – T1, G3 or 3 3 4 7 9 1 9

T2 and above with
lymphovascular invasion

Total 8 10 4 13 15 2 15

FNAC: fine-needle aspiration cytology; SILND: superficial inguinal lymph node dissection; ILND: inguinal lymph node dissection.

Table 3.  Final histopathology of inguinal lymph nodes after ILND.

Risk Pathological Total Number of patients Number of Extracapsular Recurrence

stratification staging number of requiring ILND lymph nodes extension
patients (frozen found positive at
positive) histopathology

Low risk (N=12) pT1, G1 4 0 – –  

pT1, G2 8 6 ⩽3 0  

High risk pT1, G3 3 2 ⩽3 0  

(N=10)
pT2, G3 4 4 4–5 2 1

pT3, G3 3 3 >5 2 2

ILND: inguinal lymph node dissection.

underwent SILND, six were positive at frozen section and
underwent ILND.
In the high-risk group (n=10), seven patients had posi-
tive FNAC for inguinal lymph nodes and underwent ILND
(four had bilateral involvement and underwent bilateral
ILND). The other three patients with negative FNAC
underwent bilateral SILND. Of these, two were found to
be positive at frozen section and underwent ILND. One
patient with negative lymph nodes at frozen section was
kept on follow-up. The clinical presentation and the sur-
gery performed is summarised in Table 2. The final histo-
pathology of the lymph nodes after ILND is described in
Table 3.
Postoperatively, patients were catheterized for 5 days,
after which the catheter was removed. Patients were dis-
charged on postoperative day 6 if there were no wound
complications. Superficial surgical site infections were
seen in four patients who underwent ILND. Lymphoedema
was seen in two patients, which was managed conserva-
tively (low-fat diet), and lymphorrhoea was seen in one
patient. Flap necrosis occurred in one patient. The patient
underwent daily dressings until the necrosis became
demarcated. He underwent flap reconstruction when his
wound swab was negative. He was discharged after 21
days following complete wound healing.
At 2 years of follow-up, all 12 patients in the low-risk
group had no recurrence; two patients in the high-risk
group were lost to follow-up. There were no regional
recurrences in the high-risk group. Two patients had early
nodal recurrence (as detected by clinical examination and
computed tomography) and underwent bilateral ILND.
One patient had late ipsilateral recurrence andunderwent
ipsilateral ILND. All patients with recurrence are on regu-
lar follow-up and have no complaints.
Discussion
Sequential penile lymphatic drainage occurs to the ingui-
nal nodes in the superficial (above the fascia lata) and deep
(superior and medial to the sapheno-femoral junction
beneath the fascia lata) regions and then to pelvic lymph
nodes associated with the ipsilateral iliac vessels and obtu-
rator fossa.3–6 Drainage can either be unilateral or bilat-
eral.3 However, visceral metastases are rare.6
It is well known that the presence and extent of inguinal
lymph node metastases are the most important prognostic

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 Sharma et al. 285
factors for survival in patients with penile SCC.2 The lit-
erature suggests that amongst the clinically palpable lymph
nodes present in 28–64% of patients, 47–85% are caused
by metastatic invasion, and the rest are caused by inflam-
matory reactions.2 However, 12–20% of patients without
palpable inguinal lymph nodes are also reported to harbour
cancerous occult tumours.7
Therefore, clinically palpable inguinal lymph nodes
have to be differentiated into reactive adenopathy (due to
infection) and true metastatic disease for appropriate man-
agement.3 An antibiotic course to treat and resolve reactive
nodes raises the specificity of palpable adenopathy to 70–
86%.3,8,9 Routine FNAC of such nodes has also been advo-
cated (false-negative rate: 15%) at the time of or
immediately after penectomy,2,10 the strategy being man-
agement of negative lymph nodes following 4–6 weeks of
antibiotics, repeat FNAC of persistent palpable lymph
nodes and ILND of positive lymph nodes.3
In this study, low-risk patients were managed in the
same way. Patients with persistent palpable FNAC nega-
tive nodes in the low-risk category underwent SILND, and
if positive at frozen section, they underwent ILND.
The classic radical ILND is the procedure of choice in
cases with documented inguinal nodal metastases.3
However, there have been many modifications to avoid the
morbidity associated with classic radical ILND, the com-
plications being lymphoedema, lymphocele or seroma for-
mation, skin flap necrosis and wound infection.11–13 Death
is rare (sepsis or deep-vein thrombosis and subsequent pul-
monary embolism).11,14 Saphenous-sparing modified
ILND is a modification of the extensive radical classic
ILND wherein all superficial and deep inguinal lymph
nodes are removed but the saphenous vein and its branches
are spared.3,11,15,16 In another modification by Catalona, the
lateral extent of the node dissection is limited to the femo-
ral vessels.3,17 In this study, the saphenous-sparing modi-
fied ILND approach was followed. Other strategies to
minimize morbidity include aggressive wound care, mini-
mal intraoperative flap handling, preservation of robust
subcutaneous tissue, early ambulation, use of compression
stockings, wound drains, antibiotic administration and
appropriate use of myo-cutaneous flap cover.3,11,13 In this
study, superficial surgical site infections were seen in three
patients who underwent ILND. Lymphoedema was
observed in two patients, which was managed conserva-
tively. Lymphorrhoea was seen in one patient. Flap necro-
sis occurred in one patient.
Pelvic lymph node metastasis has been reported to
carry a grave prognosis, and 5-year survival rates have
been reported to be <20%.3,6,16 The published literature
states that the presence of more than two positive nodes,
extracapsular extension of the disease and the presence of
high-grade cancer in inguinal nodes are risk factors for
pelvic node metastasis.3,5,8,16,18 It has also been suggested
that pelvic lymphadenectomy may be deferred in patients
08_URO939407.indd 285
with no such negative prognostic factors.3,5,8,16,18 However,
pelvic lymph node dissection is common in managing
patients with penile cancer.3,5,15
The management of contralateral groin in patients with
unilateral disease is one of the issues in risk stratification.
Bilateral ILND should be done in patients with high-risk
primary tumour or an intermediate-risk primary tumour
with other adverse prognostic factors such as lymphatic
and vascular invasion or an infiltrating pattern of invasion
because of the known bilateral nature of penile lymphatic
drainage.3,15
For patients with negative inguinal lymph nodes, the
following risk-stratified approach is suggested in the liter-
ature: very low-, low- and intermediate-risk patients with
stage Tis, Ta, T1G1–2 primary tumours are to be put under
observation, while high-risk patients with stage T2–T4 pri-
mary cancer or vascular invasion or nodular growth pat-
tern on histology should be offered bilateral superficial
inguinal dissection with frozen section, or complete modi-
fied dissection.3,8 Surveillance after management of the
primary tumour recommends groin examinations every 2
months for 2 years, every 3 months for the next year and
every 6 months until year 5.3,15
Various studies suggest that early ILND for clinically
occult metastases carries a significant survival benefit, as
up to 30% of non-palpable inguinal lymph nodes would
harbour occult metastasis, which would be uncovered at
lymph node dissection or may present as palpable adenop-
athy at a later time.3,14,16 Hence, patient identification and
selection is important. Recent studies indicate that dynamic
sentinel node biopsy, especially when combined with
ultrasonography with or without FNAC, can provide high
sensitivity for detecting inguinal metastasis in clinically
N0 cases, with a lower morbidity rate compared with
ILND.3,19 Magnetic resonance imaging with lymphotropic
nanoparticle enhancement and positron emission tomogra-
phy combined with CT have also been shown to have a
high sensitivity and specificity in the detection of occult
nodal metastases.3,20–22
Removing only the superficial inguinal lymph nodes
has also been documented in patients with clinically nega-
tive groins.3 Frozen-section analysis allows determination
of metastatic disease while attempting to minimize mor-
bidity.8 This approach was followed in the present study so
as to detect occult metastases and proceed with contralat-
eral inguinal dissection, thereby decreasing the chances of
recurrences and providing survival benefit.
The grade and stage of the primary tumour, microscopic
presence of vascular invasion, lymphatic invasion and an
infiltrating (rather than pushing) pattern of tumour inva-
sion are independent prognostic factors in the develop-
ment of nodal metastases.3,23,24 On the basis of these
criteria, patients are classified into low-, intermediate and
high-risk groups, as is also adopted by the European
Association of Urology.15,25,26 Solsona et al. reported that
25/06/2021 2:40:07 PM
 286 Journal of Clinical Urology 14(4)
low- risk patients (Ta, Tis or grade 1 disease) are associ-
ated with a <17% of nodal micrometastases.25 High-risk
patients with stage T2 or higher disease and grade 2 or 3
disease are associated with a 68–73% risk of node-positive
disease.25 Ficarra et al. recently published a nomogram for
predicting the likelihood of nodal metastasis using tumour
thickness, growth pattern, grade, lymphovascular inva-
sion, corpus cavernosum invasion, corpus spongiosum
invasion, urethral infiltration and clinical node status.27
It has also been suggested to defer surgery and put all
node-negative patients into an active surveillance protocol
and operate at the advent of clinically palpable lymph
nodes.3 However, several studies have been in favour of
early resection in intermediate or high-risk patients, as pre-
viously defined in prior studies.19,28–30
Adjuvant chemotherapy is offered for N2 disease after
complete surgical treatment of local disease and inguinal
lymph node metastasis.2 Neoadjuvant combination chemo-
therapy containing cisplatin is suggested for patients with
large and immobile inguinal nodal metastasis, after which
surgical consolidation can be considered if the disease
responds or is stable.2 The results of chemotherapy are poor
in advanced penile cancer and unresectable primary tumours
(i.e. T4 disease); fixed, bulky or relapsed inguinal lymph
nodes; and visceral metastasis.2 The available evidence sug-
gests that early ILND confers a better prognosis compared
with surveillance and delayed inguinal dissection.2 In this
study, adjuvant chemotherapy was given to all high-risk
patients. None of the patients received radiotherapy.
To conclude, the presence and extent of inguinal metas-
tases play an important role in the survival of patients with
penile malignancy. Hence, management of inguinal nodal
disease by staging SLND in all high-risk cases for thera-
peutic and for prognostic purpose is essential for optimum
survival of such patients, as was tried in our study. However,
large population-based studies and trials are necessary to
formulate guidelines for management further.
Acknowledgements
None.
Conflicting interests
The authors declared no potential conflicts of interest with respect
to the research, authorship and/or publication of this article.
Funding
The authors received no financial support for the research,
authorship and/or publication of this article.
Ethical approval
Ethical approval was given by the Institutional Ethical
Committee.
08_URO939407.indd 286
Informed consent
Informed consent for publication was given by all patients
involved.
Guarantor
A.S.
Contributorship
The concept, data collection, drafting of the manuscript and edit-
ing were undertaken by A.S. The concept, data collection and
drafting of the manuscript were undertaken by S.P., G.G., and
A.P. Drafting and critical editing of the manuscript and final
approval were done by M.A. and H.R.P.
ORCID iD
Amit Sharma https://orcid.org/0000-0002-8436-5773
References
1. Pagliaro LC and Crook J. Multimodality therapy in penile
cancer: when and which treatments? World J Urol 2009; 27:
221–225.
2. Lau WD, Ong CH, Lim TP, et al. Penile cancer: a local case
series and literature review. Singapore Med J 2015; 56:
637–640.
3. Leveridge M, Siemens R and Morash C. What next?
Managing lymph nodes in men with penile cancer. Can
Urol Assoc J 2008; 2: 525–531.
4. Dewire D and Lepor H. Anatomic considerations of the
penis and its lymphatic drainage. Urol Clin North Am 1992;
19: 211–219.
5. Lont AP, Kroon BK, Gallee MPW, et al. Pelvic lymph node
dissection for penile carcinoma: extent of inguinal lymph
node involvement as an indicator for pelvic lymph node
involvement and survival. J Urol 2007; 177: 947–952.
6. Culkin DJ and Beer TM. Advanced penile carcinoma. J
Urol 2003; 170: 359–365.
7. Heyns CF, Mendoza-Valdés A and Pompeo AC. Diagnosis
and staging of penile cancer. Urology 2010; 76: S15–23.
8. Pettaway CA, Lance RS and Davis JW. Tumors of the
penis. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW
and Peters CA (eds) Campbell–Walsh urology. 10th ed.
Philadelphia, PA: Elsevier Health Sciences, 2011, pp.901–
933.
9. Horenblas S, Van Tinteren H, Delemarre JF, et al. Squamous
cell carcinoma of the penis: accuracy of tumour, nodes and
metastasis classification system, and role of lymphangiogra-
phy, computerized tomography scan and fine needle aspira-
tion cytology. J Urol 1991; 146: 1279–1283.
10. Horenblas S. Lymphadenectomy for squamous cell carci-
noma of the penis. Part 1: diagnosis of lymph node metasta-
sis. BJU Int 2001; 88: 467–472.
11. Bevan-Thomas R, Slaton JW and Pettaway CA.
Contemporary morbidity from lymphadenectomy for penile
squamous cell carcinoma: the M.D. Anderson Cancer
Center experience. J Urol 2002; 167: 1638–1642.
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12. Bouchot O, Rigaud J, Maillet F, et al. Morbidity of inguinal
lymphadenectomy for invasive penile carcinoma. Eur Urol
2004; 45: 761–766.
13. Nelson BA, Cookson MS, Smith JA Jr, et al. Complication
of inguinal and pelvic lymphadenctomy for squamous cell
carcinoma of the penis: a contemporary series. J Urol 2004;
172: 494–497.
14. Ornellas AA, Correia Seixas AL, Marota A, et al. Surgical
treatment of invasive squamous cell carcinoma of the penis:
retrospective analysis of 350 cases. J Urol 1994; 151: 1244–
1249.
15. Solsona E, Algaba F, Horenblas S, et al. European
Association of Urology. EAU guidelines on penile cancer.
Eur Urol 2004; 46: 1–8.
16. Horenblas S. Lymphadenectomy for squamous cell carci-
noma of the penis. Part 2: the role and technique of lymph
node dissection. BJU Int 2001; 88: 473–483.
17. Catalona WJ. Modified inguinal lymphadenectomy for car-
cinoma of the penis with preservation of saphenous veins:
technique and preliminary results. J Urol 1988; 140: 306–
310.
18. Jacobellis U. Modified radical inguinal lymphadenectomy
for carcinoma of the penis: technique and results. J Urol
2003; 169: 1349–1352.
19. Lam W, Alnajjar HM, La-Touche S, et al. Dynamic sentinel
lymph node biopsy in patients with invasive squamous cell
carcinoma of the penis: a prospective study of the long-term
outcome of 500 inguinal basins assessed at a single institu-
tion. Eur Urol 2013; 63: 657–663.
20. Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive
detection of clinically occult lymph-node metastases in
prostate cancer. N Engl J Med 2003; 348: 2491–2499.
21. Tabatabaei S, Harisinghani M and McDougal WS. Regional
lymph node staging using lymphotropic nanoparticle
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in patients with penile cancer. J Urol 2005; 174: 923.
22. Scher B, Seitz M, Reiser M, et al. 18F-FDG PET/CT for
staging of penile cancer. J Nucl Med 2005; 46: 1460–1465.
23. Guimaraes GC, Lopes A, Campos RSM, et al. Front pattern
of invasion in squamous cell carcinoma of the penis: new
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ses. Urology 2006; 68: 148–153.
24. Ficarra V, Zattoni F, Cunico SC, et al. Lymphatic and vas-
cular embolizations are independent predictive variables of
inguinal lymph node involvement in patients with squamous
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25. Solsona E, Iborra I, Rubio J, et al. Prospective validation
of the association of local tumor stage and grade as a pre-
dictive factor for occult lymph node micrometastasis inpa-
tients with penile carcinoma and clinically negative inguinal
lymph nodes. J Urol 2001; 165: 1506–1509.
26. Hungerhuber E, Schlenker B, Karl A, et al. Risk stratifica-
tion in penile carcinoma: 25- year experience with surgical
inguinal lymph node staging. Urology 2006; 68: 621–625.
27. Ficarra V, Zattoni F, Artinai W, et al. Nomogram predictive
of pathological inguinal lymph node involvement in patients
with squamous cell carcinoma of the penis. J Urol 2006;
175: 1700–1705.
28. Kroon BK, Horenblas A, Lont AP, et al. Patients with penile
carcinoma benefit from immediate resection of clinically
occult lymph node metastases. J Urol 2005; 173: 816–819.
29. McDougal WS. Carcinoma of the penis: improved survival
by early regional lymphadenectomy based on the histologi-
cal grade and depth of invasion of the primary lesion. J Urol
1995; 154: 1364–1366.
30. McDougal WS, Kirchner FK Jr, Edwards RH, et al.
Treatment of carcinoma of the penis: the case for primary
lymphadenectomy. J Urol 1986; 136: 38–41.
25/06/2021 2:40:07 PM
812294 URO Journal of Clinical UrologyHernández-Nájera et al.
Case Report. Infection in Urology
Emphysematous prostatitis as a result of
urethral injury: A case report
Verónica Hernández-Nájera1,2 , Eduardo Barrera-Juárez1,2
and Roberto González-Oyervides1,2
Level of evidence: Level 5, case report.
Case report
A 35-year-old male with a history of diabetes presented to
the emergency department with a persistent fever and weak-
ness after discontinuation of insulin therapy. The patient had
a neurogenic bladder and an indwelling transurethral cathe-
ter. His vital signs revealed a diaphoretic febrile male with
hypotension and tachycardia. The physical examination
showed a phimotic penis with periurethral necrosis, and a
nonfunctional Foley catheter in place. Local examination of
the genitalia revealed an oedematous and tender scrotum
with no crepitus to palpation. A Foley catheter replacement
was performed for a three-way catheter to irrigate the blad-
der, obtaining turbid urine output with necrotic debris.
Complete blood count revealed an elevated white blood
cell count, with 85% neutrophils. Blood culture tested posi-
tive for Klebsiella pneumoniae susceptible to carbapenem.
A simple abdominal tomography was performed, finding
the presence of gas in the prostatic tissue (Figure 1).
Broad-spectrum antibiotics were initiated. The patient
underwent a cystoscopy that revealed necrosis of the ure-
thral mucosa and a perforating lesion in the prostatic
region. Because of the extension of necrosis in the urethra
and penile tissues, a penectomy and suprapubic catheter
were performed. After 15 days of broad-spectrum antibiot-
ics, the patient was afebrile with overall clinical improve-
ment. A simple tomography was performed, showing no
evidence of gas within the prostatic region.
Discussion
Emphysematous prostatitis (EP) is a gas-forming infec-
tion. This disease is less prevalent in Western societies
than other parts of the world.1 Predisposing factors for
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these infections are immunosuppressive conditions such as
diabetes, cirrhosis and human immunodeficiency virus.2
As prostatic abscess, the signs and symptoms of EP are
highly variable and nonspecific. Owing to this variability
in symptoms, the diagnosis is challenging in several clini-
cal settings. Rectal examination reportedly includes an
augmented prostate, hyperthermia and pain in up to 75%
of patients.3
Several imaging techniques had been used to aid in the
diagnosis of this unusual and deadly condition; however, a
simple tomography can provide specific anatomic details
and identification of gas in body tissues.4
Because of the low occurrence of this condition, we do
not rely on a treatment algorithm that applies to every single
patient, hence several ways to treat this condition have been
described in the literature through time. Antibiotics should
be started from the early stages of the disease, followed by
surgical treatment. Drainage procedures can be transurethral,
by perineum incision, or percutaneous (transperineum).5
EP is an extremely rare condition with a high mortality
rate, the prognosis of which is better with early diagnosis
and treatment. Often, unspecific and variable symptoms
make the clinical diagnosis of this disease challenging. In
the aforementioned case, the poor control of glycaemic
1Escuela
de Medicina, Tecnologico de Monterrey, Mexico
2Hospital
Metropolitano ‘Dr. Bernardo Sepúlveda’, Secretaría de Salud
de NL, Mexico
Corresponding author:
Verónica Hernández-Nájera, Escuela de Medicina, Tecnologico de
Monterrey, Zambrano Hellion Medical Center, Batallón San Patricio
112, Real de San Agustín, 66278 San Pedro Garza García, N.L.
Mexico.
Email: veronica.hernandez.najera@gmail.com
25/06/2021 8:07:30 PM
 Hernández-Nájera et al. 289
Figure 1.  Sagittal (left), coronal (upper right) and axial (bottom right) computed tomography images of the abdomen with
presence of gas within the prostatic parenchyma.
levels might have made the patient susceptible to bacteriu-
ria with the precipitating factor of a prostatic urethral
injury. Conservative management was not feasible in our
patient because the infected gas-necrosis extended to the
cavernous bodies, glans and urethra, requiring radical
management with phallectomy.
Conflicting interests
The authors declare that there is no conflict of interest.
Funding
This research received no specific grant from any funding agency
in the public, commercial, or not-for-profit sectors.
Ethical approval
The ethics committee of our institution approved this study iden-
tified with the title Emphysematous prostatitis as a result of ure-
thral injury: A case report.
Informed consent
Written informed consent was obtained from the patient for his
anonymised information to be published in this article.
Guarantor
VH.
09_URO812294.indd 289
Contributorship
EB and RG researched the literature. VH wrote the first draft of
the manuscript. All authors reviewed and edited the final version
of the manuscript.
Acknowledgements
We would like to thank Alejandro García-Ramirez, MD, for his
contribution to this research.
ORCID iD
Verónica Hernández-Nájera https://orcid.org/0000-0001-5502-
7030
References
1. Hsu L, Chiang P and Kang C. Emphysematous prostatic
abscess: Rare case and systematic review. J Formos Med
Assoc 2015; 114: 292–293.
2. Wen S, Juan Y, Wang C, et al. Emphysematous prostatic
abscess: Case series study and review. Int J Infect Dis 2012;
16: e344-e349.
3. Tai H. Emphysematous prostatic abscess: A case report and
review of literature. J Infect 2007; 54: e51-e54.
4. Washecka R and Rumancik W. Prostatic abscess evaluated by
serial computed tomography. Urol Radiol 1985; 7: 54–56.
5. Oliveira P, Andrade J, Porto H, et al. Diagnosis and treat-
ment of prostatic abscess. Int Braz J Urol 2003; 29: 30–34.
25/06/2021 8:07:30 PM
814048 URO Journal of Clinical UrologyChen et al.
Case Report. Oncology (Renal)
Renal carcinoid: A case report of
a rare primary renal tumour
Michael Y Chen1,2 , Jonathan Cho1 and Rachel Esler1
Background
Renal carcinoid tumours are rare malignant tumours com-
posed of neuroendocrine cells, also known as enterochro-
maffin cells or amine precursor uptake and decarboxylation
cells. Since they were first described in 1966, there have
been approximately 100 cases of primary renal carcinoid
tumours in the literature.1 There is some inconsistent
nomenclature, with a World Health Organization classifi-
cation grading from 1 to 3 all of which are referred to as
carcinoid, while other papers refer to a spectrum of neu-
roendocrine tumours ranging from well-differentiated car-
cinoid, large cell neuroendocrine carcinoma and small cell
carcinoma.2,3
Case report
A 37-year-old woman presented with several months his-
tory of constipation, abdominal distension and haematuria
on the background of poorly controlled type 2 diabetes. A
large left-sided abdominal mass was palpable. Ultrasound
and computed tomography (CT) showed a 17×12×17 cm
left renal tumour without evidence of renal vein involve-
ment or metastases (Figure 1).
The patient underwent an open left nephrectomy with
an uncomplicated postoperative course. Histology
showed a well-differentiated neuroendocrine tumour,
probably carcinoid type, with clear margins. The patient
had subsequent resolution of her constipation. Further
history revealed preceding intermittent hot flushes and
hypotension. A staging gallium-dotatate positron emis-
sion tomography (PET) scan showed intense uptake in T2
vertebra, left ilium, pelvic soft tissue and the contralat-
eral right kidney. A partial nephrectomy was not consid-
ered in the contralateral kidney given the widespread
metastases. She was managed with a multidisciplinary
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team (MDT) including urology, endocrinology, medical
oncology and nuclear medicine including discussion at a
neuroendocrine MDT meeting. She was initially man-
aged with octreotide but follow-up imaging 6 months
later showed progression of metastases. She was subse-
quently started on lutetium177-dota-octreotate (lutate)
treatment (Figures 2 and 3).
Discussion
This case highlights an uncommon kidney tumour
which is often unsuspected as clinical and radiological
features are similar to other renal neoplasms. Surgery
remains the primary treatment. A review of 29 cases
managed surgically found that at a mean follow-up of
20 months 73.1% of patients had no evidence of dis-
ease.4 Our case appeared to present with symptoms of
carcinoid syndrome, particularly the hot flushes, which
is unusual for renal carcinoids. A review of 56 cases
found symptoms of carcinoid syndrome in only four
patients.5 Metastatic disease was not identified on
standard CT in this case but was present on PET scans.
Approximately 50% of patients with renal carcinoid
will also present with metastasis and the risk is directly
related to the size of the tumour.2 Thus renal carcinoids
are an uncommon malignancy that is difficult to diag-
nose without histology, and patients frequently present
with metastasis.
1Royal Brisbane and Women’s Hospital, Australia
2School of Medicine, University of Queensland, Australia
Corresponding author:
Michael Y Chen, Royal Brisbane and Women’s Hospital, 3/5 Sovereign
St, Indooroopilly, Queensland 4068, Australia.
Email: michaelyuechengchen@hotmail.com
25/06/2021 2:42:08 PM
 Chen et al. 291

Figure 1.  Coronal and axial slices from computed tomography scan showing left sided renal tumour.

Figure 2.  Gallium-dotatate positron emission tomography scan showing uptake in left ilium (a), T2 vertebra (b), contralateral
kidney (c) and pelvic soft tissue (d).

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 292 Journal of Clinical Urology 14(4)
Figure 3.  Macroscopic kidney specimen (a), histology of the
tumour showing ribbon-like appearance (b), vascular invasion
of tumour cells (c).
Conflicting interests
The authors declare that there is no conflict of interest.
10_URO814048.indd 292
Funding
This research received no specific grant from any funding agency
in the public, commercial, or not-for-profit sectors.
Ethical approval
Our institution does not require ethical approval for reporting
individual cases or case series.
Informed consent
Written informed consent was obtained from the patients for
their anonymised information to be published in this article.
Guarantor
MYC.
Contributorship
MYC wrote the first draft of the manuscript. All authors reviewed
and edited the manuscript and approved the final version.
Acknowledgements
None.
ORCID iD
Michael Y Chen https://orcid.org/0000-0001-8294-6876
References
1. Resnick ME, Unterberger H and McLoughlin PT. Renal
carcinoid producing the carcinoid syndrome. Medical Times
1966; 94: 895–896.
2. Korkmaz T, Seber S, Yavuzer D, et al. Primary renal car-
cinoid: treatment and prognosis. Crit Rev Oncol/Hematol
2013; 87: 256–264.
3. Lane BR, Jour G and Zhou M. Renal neuroendocrine
tumors. Ind J Urol: Journal of the Urological Society of
India 2009; 25: 155–160.
4. Omiyale AO and Venyo AK-G. Primary carcinoid tumour
of the kidney: a review of the literature. Adv Urol 2013;
2013: 579396.
5. Lane BR, Chery F, Jour G, et al. Renal neuroendocrine
tumours: a clinicopathological study. BJU Int 2007; 100:
1030–1035.
25/06/2021 2:42:10 PM
945914 URO Journal of Clinical UrologyDe Silva et al.

Literature Review

Journal of Clinical Urology

Different clinical presentations of

2021, Vol. 14(4) 293­–299
© British Association of
Urological Surgeons 2020
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case series and review of the literature DOI: 10.1177/2051415820945914

https://doi.org/10.1177/2051415820945914
journals.sagepub.com/home/uro

Supun De Silva1, Lalani De Silva1 , Shyamini Sooriyaarchchi1,

Harshima Wijesighe2 , Gayani Ranaweera2,
Susantha De Silva3 and Chandu De Silva2

Abstract
Objective: Xanthogranulomatous prostatitis (XGP) is a rare entity that has different clinical presentations. This report
of three cases illustrates the diversity of clinical features of XGP, together with a comprehensive literature review.
Methods: Three elderly male Sri Lankan patients underwent transurethral resection of the prostate for severe lower
urinary tract symptoms. Carcinoma of the prostate was suspected in two patients, and one of them had a very high
prostate-specific antigen level (324 ng/mL), suggestive of metastatic prostate carcinoma. The third patient had a clinically
benign prostate gland. The histology of all three resected prostate chippings revealed XGP.
Results: This case series encompasses two cases of XGP that mimicked carcinoma of the prostate clinically and another
case that had benign clinical features. Patients with XGP can have clinical, radiological and serological evidence of
advanced prostate carcinoma. Other rare modes of presentation of XGP include prostate abscess and haematospermia.
Many concerns of XGP such as aetiology, epidemiology, natural history, risk of malignant transformation and possible
treatment options remain unclear due to the paucity of the literature.
Conclusions: XGP presents with a variety of benign and malignant clinical features. The possibility of encountering XGP
in patients with clinically malignant prostates should not be overlooked.

Keywords
Xanthogranulomatous prostatitis, granulomatous prostatitis, carcinoma of the prostate

Date received: 31 March 2020; accepted: 3 July 2020

Introduction Case presentation

Chronic inflammation of the prostate is caused by various Case 1
infective and non-infective aetiologies. Chronic prostati-
tis due to non-infective aetiologies is relatively rare. A 68-year-old Sri Lankan male presented with lower urinary
Granulomatous prostatitis (GP) is a subset of non-infec- tract symptoms (LUTS) for six months. His International
tive chronic prostatitis. Xanthogranulomatous prostatitis
(XGP) is a much rarer variant of GP. XGP is essentially a 1
 ostgraduate Institute of Medicine, University of Colombo,
P
histopathological diagnosis. Identification of the predom- Sri Lanka
2
Department of Pathology, Faculty of Medicine, University of Colombo,
inance of xanthoma cells, which are lipid-laden mac-
Sri Lanka
rophages in the inflammatory infiltrate, is the histological 3
Urology Unit 2, National Hospital of Sri Lanka, Sri Lanka
hallmark of the disease.1 Significant gaps in the knowl-
Corresponding author:
edge of this specific disease entity persist due to the pro-
Supun De Silva, Postgraduate Institute of Medicine, University of
found inadequacy of the literature. This literature review Colombo, 1485/A/3, Joranis Peris road, Kottawa North, Pannipitiya,
incorporates a series of three cases is an effort to recapitu- Colombo 10, Western Province 80300, Sri Lanka.
late the current knowledge about XGP. Email: supun85@gmail.com

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 294 Journal of Clinical Urology 14(4)
Prostate Symptom Score (IPSS) was 23, and his quality of
life (QoL) score was 4. In the digital rectal examination, the
prostate gland was nodular and stony hard, mainly on the
right side (T2b). A trans-rectal ultrasound scan (TRUS) iden-
tified a 2.7 cm×2.2 cm hypoechoic lesion in the right lobe of
the prostate, which was highly suggestive of carcinoma of
the prostate (CAP), with a prostate size of 45 mL. The post-
voidal residual volume (PVR) was 120/430 mL (27.9%). His
serum prostate-specific antigen (PSA) level was 5.3 ng/mL.
Uroflowmetry gave a maximum flow of 6 mL/s, with a
latency of 45 seconds. Based on these findings, he was
scheduled for a transurethral resection of prostate (TURP).
His cystourethroscopy revealed bilobar occlusive prosto-
megaly with moderate bladder trabeculations. TURP was
performed, and the weight of the resected sample was 35 g.
Case 2
An 82-year-old patient was admitted with the first episode
of acute urine retention (AUR). He had been suffering from
LUTS for three months, for which treatment with tamsulo-
sin had been initiated. There was no family history of pros-
tate carcinoma. He did not experience any perineal pain
suggestive of acute prostatitis. A digital rectal examination
revealed a bilaterally nodular, rock-hard prostate (T2C). His
PSA was 324 ng/mL. TRUS detected bilateral nodules in
the prostate, which were highly suspicious for malignancy,
and the prostate size was 78 mL. A bone scan and regional
X-ray images were negative for bone metastases. He was
offered TURP, and 42 g of prostate was resected. The PSA
declined to 185 ng/mL three months after TURP.
Case 3
A 69-year-old patient was treated and followed up in the
urology clinic for LUTS for two years, with satisfactory
control of symptoms, with an average IPSS score of 12.
The clinical impression of the prostate at the initial presen-
tation was benign, and the PSA value was 1.0 ng/mL. His
LUTS gradually worsened for three months, with a wors-
ening of his IPSS score up to 28 and QoL of 4. His maxi-
mum urine flow rate was 6.8 mL/s and PVR was 180/300
mL. A repeat digital rectal examination of the prostate
revealed the same findings as the initial examination.
Based on these findings, he was offered TURP. Cystoscopy
revealed bilobar occlusive prostomegaly, and 23 g of the
prostate were resected.
Microscopy
The entire tissue was processed and examined in all three
cases. Microscopy of all three patients revealed benign
glandular and stromal hyperplasia, with focal areas of
infarction and acute inflammation. The stroma contained
numerous loosely formed granulomas composed of
11_URO945914.indd 294
epithelioid histiocytes and a prominent collection of foamy
histiocytes (xanthoma cells). The xanthoma cells con-
tained vacuolated cytoplasm. Lymphoid follicles with ger-
minal centres were present in the background. There was
no evidence of high-grade prostate intraepithelial neopla-
sia or malignancy in any of the three cases. These findings
were consistent with XGP. Immunohistochemistry for
pancytokeratin was performed in cases 2 and 3 to exclude
the possibility of disrupted malignant glands or cells within
the inflammatory infiltrate. Immunohistochemistry for
CD-68 was positive in the xanthoma cells and mac-
rophages. These two stains also excluded the possibility of
a high-grade foamy gland carcinoma with sheets of malig-
nant foamy cells. Thus, the findings were consistent with
XGP (Figures 1 and 3). Negative staining with the Zeihl–
Neelsen stain excluded tuberculous inflammation.
Discussion
Xanthogranulomatous inflammation is a disease process
commonly known to affect the kidneys and gallbladder.
The involvement of the prostate gland in xanthogranu-
lomatous inflammation was first described by Tanner
and McDonald in 1943.2 A systematic classification of
GP with particular emphasis on XGP was given by
Symmers in 1950.3 Since then, 26 cases of XGP have
been reported. A summary of all the reported cases of
XGP is given in Table 1, according to the chronological
order of publication.
GP is classified into several types. Epstein et al.
described four main types of GP: specific, non-specific,
allergic and post-surgical.22 Shukla et al. reviewed 22
cases of GP, received over 13 years, and classified them
into non-specific, tuberculous, post-surgical, allergic and
XGP.1 Several other authors have also classified GP in
different ways.23–25 However, there is no worldwide con-
sensus on a universal method to classify GP. The rarity of
the disease entity and the paucity of the literature on cer-
tain types of GP such as XGP are responsible for this
scenario. Despite the controversy in classification, XGP
is recognised as a separate entity in many of these clas-
sification systems.
The aetiology is not identified in many forms of GP,
except for some infective causes such as tuberculosis.
The aetiology of XGP is elusive as well. Many inflamma-
tory and infectious aetiologies have been considered
without a wide-reaching agreement. Most cases of XGP
have been reported from tropical countries. India1,8,13,15
and China12,14,16,18 have reported five cases of XGP each.
Other tropical countries such as Pakistan,6 Morocco,19
Mexico,17 Bahrain,5 Taiwan9 and South Africa21 have
also reported cases of XGP. In this series, Sri Lanka can
further be added to the list, with three cases of XGP.
However, cases of XGP reported from temperate coun-
tries are sparse.4,10,11,20 Thus, the possibility of an
25/06/2021 2:43:09 PM
 De Silva et al. 295

Figure 1.  Microscopic images of case 1. (a) There are collections of foamy histiocytes (arrows) associated with a moderate
lymphoid infiltrate (hematoxylin and eosin (H&E) ×40, arrows). (b) Foamy cells with abundant vacuolated cytoplasm and small
central nuclei. Lymphocytes and a few eosinophils are present in the background (H&E ×400).

Figure 2.  Microscopic images of case 2. (a). Diffuse sheets of large clear cells (xanthoma cells) in the stroma (H&E ×100). (b) The
cells show abundant clear cytoplasm with eccentrically located nuclei, resembling signet ring cells (H&E ×400, arrows). C. AE1/AE3
immunostain is negative in foamy cells.

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 296 Journal of Clinical Urology 14(4)

Figure 3.  Microscopic images of case 3. (a) Focal collections of foamy cells with lymphoid aggregates adjacent to a focus of
necrosis (not shown in the figure; H&E ×100). (b) The foamy cells show large eccentric nuclei (H&E ×400, arrows). (c) CD-68
immunostain shows strong diffuse cytoplasmic staining. (d) AE1/AE3 immunostain is negative in foamy cells.

Table 1.  A summary of cases of XGP so far reported.

Author Number Age Presentation PSA Clinical diag- Specimen Country Year
of cases (ng/mL) nosis

Meikos et al.4 2 58 LUTS N/A BPE Open Poland 1985

prostatectomy

  46 LUTS+UTI N/A BPE TR Bx  

Zaber et al.5 1 63 Fecaluria 2.2 Entero-vesical TURP Bahrain 2004

fistula

Rafique et al.6 1 60 LUTS 150 CAP TURP Pakistan 2006

Min et al.7 1 82 Haematuria 86.8 Prostate TURP South 2011

abscess Korea

Valsangkar et al.8 1 52 AUR – Prostate TURP India 2012

abscess

Lee et al.9 1 74 LUTS 11.74 BPE TRUS Bx Taiwan 2012

Majumdar et al.10 1 65 Sepsis – Prostate TURP UK 2013

abscess

(Continued)

11_URO945914.indd 296 25/06/2021 2:43:11 PM

 De Silva et al. 297

Table 1. (Continued)

Author Number Age Presentation PSA Clinical diag- Specimen Country Year
of cases (ng/mL) nosis

Pastore et al.11 5 Range: Haematospermia Range BPE TURP Italy 2013

51–62 (all patients) 4.8–6.7

Wang et al.12 1 75 LUTS 172.5 CAP TRUS Bx China 2013

Patil et al.13 1 64 LUTS 15 CAP TURP India 2014

Cheng et al.14 2 60 LUTS 6.5 BPE TRUS Bx China 2014

  71 LUTS 5.5 BPE TRUS Bx  

Mane et al.15 1 65 LUTS 40 CAP Open India 2015

Prostatectomy

Wang16 1 56 LUTS – – PVP China 2016

Nayola et al.17 1 47 LUTS 0.9 CAP Open Mexico 2016

Prostatectomy

Xing et al.18 1 75 PR bleeding 172.5 Prosto-rectal TRUS Bx China 2016

fistula

Shukla et al.1 2 65 Dysuria 8.85 CAP TURP India 2017

  69 LUTS – BPE TURP  

Jabbour et al.19 1 59 Sepsis 0.54 Prostate TURP Morocco 2018

abscess

Belga et al.20 1 70 Sepsis – Prostate TURP Canada 2019

abscess

Mukendi et al.21 1 71 LUTS 9.5 CAP TRUS Bx South 2019

Africa

LUTS: lower urinary tract symptoms; BPE: benign prostatic enlargement; UTI: urinary tract infection; AUR: acute urine retention; TURP: transure-
thral resection of prostate; CAP: carcinoma of the prostate; TR Bx: trans-rectal biopsy; TRUS Bx: trans-rectal ultrasound-guided biopsy; PVP: plasma
vaporisation of prostate; PR bleeding: per rectal bleeding.

environmental factor contributing to the pathogenesis of
XGP must be explored. Because of the prevalence of
tuberculosis in many countries where XGP is found, it is
also important to exclude tuberculous prostatitis in every
case of XGP.
Most patients with XGP present with LUTS. Commonly,
subjects are asymptomatic until they experience severe,
bothersome LUTS. When examined clinically, most
patients have hard prostate glands that are suggestive of
carcinoma of the prostate, similar to cases 1 and 2 in this
article. Therefore, the clinical work-up for patients with
XGP is commonly directed towards diagnosing CAP.
Sepsis due to a prostate abscess is also a frequent mode of
presentation.7,8,10,19,20 Further, XGP is found to result in the
formation of fistulae. Cases of an entero-vesical fistula5
and a prosto-rectal fistula18 due to XGP have been reported.
In another interesting case series from Italy, five patients
who presented with haematospermia were eventually
diagnosed with XGP.11 Thus, XGP is a disease with a wide
spectrum of clinical presentations.
XGP can result in a transient elevation of serum PSA
levels. Three cases of XGP were reported with a serum
PSA level >100 ng/mL, which is consistent with meta-
static CAP.6,12,18 The highest PSA value out of the three
cases was 172.5 ng/mL.12,18 The follow-up PSA of all
three patients normalised after a year on average. Case 2
of this series reported the highest-ever PSA level seen in
a case of XGP (324 ng/mL). The PSA of the index patient
dropped significantly at three months from TURP (185
ng/mL) but remained very high for a benign condition
such as XGP. When CAP is histologically excluded, the
presence of a significant remnant prostatic tissue after
TURP and continuation of inflammation of the prostate
are the only possible explanations for this scenario.
However, this patient will be followed up with a repeat
PSA level at the one-year mark.

11_URO945914.indd 297 25/06/2021 2:43:11 PM

 298 Journal of Clinical Urology 14(4)
XGP can produce radiological findings similar to CAP
in TRUS,6 as in case 1 of the series. Therefore, most cases
of XGP are reported to be suspicious of malignancy,
according to TRUS findings. However, the magnetic reso-
nance imaging (MRI) characteristics of XGP are fairly
specific. Iso-intense T1-weighted images, hypo-intense
T2-weighted images, hyper-intense diffusion weighted
images and hypo-intense images in apparent diffusion
coefficient mapping in enlarged bilateral peripheral zones
were the MRI findings which were found to be specific for
XGP.9,14 The Prostate Imaging Reporting and Data System
(PI-RADS) of radiological grading, which is based on
MRI findings of the prostate, differentiates CAP from
XGP and other benign conditions.26 For this reason, MRI
scanning of the prostate has become the standard of care.
Furthermore, an MRI-guided transperineal template
biopsy of the prostate is the recommended method of pros-
tate biopsy at present.27 The diagnosis of XGP can be made
before the treatment is offered according to the standard
imaging and biopsy protocols. However, in cases 1 and 2
of the series, TURP was offered to sample the prostate
ahead of prostate biopsy due to the need to treat the blad-
der outflow obstruction at the same time.
The diagnosis of XGP is essentially histological. The
predominant presence of xanthoma cells is the pathologi-
cal hallmark of XGP. These are foamy histiocytes with a
vacuolated cytoplasm (Figures 1–3). The xanthoma cells
are found inside loosely formed granulomas that are
immersed in an inflammatory infiltrate in the stroma, with
numerous lymphoid follicles. Rarely, XGP can be con-
fused with the foamy gland variant of the CAP. However,
the finding of the normal glandular epithelial components
in the stroma with chronic inflammatory infiltrate, together
with positive staining of xanthoma cells with CD68 and
negative staining with pancytokeratin, excludes any suspi-
cion of co-existing CAP. Negative staining with other
immune markers such as PSA and prostatic acid phos-
phatase can also be used for this purpose.28 In our second
patient who had very high PSA levels, we considered the
possibility of a neoplastic process being masked by the
extensive inflammatory infiltrate. Thus, the entire tissue
specimen was sampled and carefully evaluated to exclude
prostatic intraepithelial neoplasia in surviving glands, and
a pancytokeratin stain was carried out to exclude any epi-
thelial elements within the inflammatory infiltrate.
The management of patients with XGP solely depends
on the symptom profile. No specific treatment is available
for XGP. Corticosteroids and estragon10 have been used in
some isolated patients with XGP, but the value of neither
drug has been sufficiently established for it to be recom-
mended to clinical use. The management of bladder out-
flow obstruction due to XGP is also not different from the
management of bladder outflow obstruction due to BPE.
Although a short-lived improvement of LUTS can be
achieved with α-blockers, most cases of XGP eventually
11_URO945914.indd 298
need TURP, as LUTS tends to worsen with time.
Complicated cases of XGP such as a prostate abscess need
early endourological intervention in the form of TURP.
Thus, it is evident that the histopathological diagnosis of
XGP does not have a significant impact on patient man-
agement and, in most instances, helps the clinician only by
excluding CAP.
There has been only minimal progress in broadening
the knowledge about XGP over the years. Current knowl-
edge about XGP remains at the level of case reports and
case series. The rarity of the disease, benign disease course,
requirement to pay more attention to studies on CAP and
the presence of little clinical significance of the diagnosis
may have resulted in the paucity of the literature about the
disease. Many areas of XGP such as aetiology, epidemiol-
ogy, natural history, risk of malignant transformation and
possible treatment options remain unclear due to this rea-
son. Therefore, more literature is necessary to bridge the
gaps in present-day knowledge about XGP.
Conclusions
XGP mimics CAP clinically, biochemically and radiologi-
cally. The rare possibility of finding XGP in a patient with
a clinically malignant prostate gland should not be over-
looked. The management of XGP is exclusively sympto-
matic, and no specific treatment is available for the same.
In conclusion, it is evident that further research is neces-
sary to make up for the information deficit about XGP.
Conflicting interests
The authors declared no potential conflicts of interest with
respect to the research, authorship and/or publication of this
article.
Funding
The authors received no financial support for the research,
authorship and/or publication of this article.
Ethical approval
National Hospital of Sri Lanka does not require ethical approval
for reporting individual cases or case series
Informed consent
Written informed consent was obtained from the patients for
their anonymised information to be published in this article.
Guarantor
W.S.L.D.
Contributorship
W.S.L.D. wrote the draft of the manuscript. L.J.D., S.S.,
H.D.W. and G.G.R. compiled the figures wrote the pathology
sections of the draft. W.S.L.D. and W.A.S.D. were involved in
25/06/2021 2:43:11 PM
 De Silva et al. 299
patient management. M.V.C.D., G.G.R. and W.A.S.D. edited
the manuscript. All authors reviewed manuscript and approved
the final version of the manuscript.
Acknowledgements
We wish to acknowledge the staff of the Department of Pathology,
Faculty of Medicine, University of Colombo for the assistance
provided in preparing the figures of the article.
ORCID iDs
Lalani De Silva https://orcid.org/0000-0002-8223-6871
Harshima Wijesighe https://orcid.org/0000-0002-2847-1440
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966907 URO Journal of Clinical UrologyTerry and Bates

Systematic Review

Journal of Clinical Urology

The reflective urologist

2021, Vol. 14(4) 300­–305
© British Association of
Urological Surgeons 2020
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/2051415820966907
https://doi.org/10.1177/2051415820966907
journals.sagepub.com/home/uro
Tim Terry1 and Anthon Simon Bates2

Abstract
This paper reviews UK reflective practice in urology from historical and current usage perspectives. While appraisal,
revalidation and annual review of competence progression processes mandate reflective practice its use in everyday
urological practice is not evidenced in the urological literature. With the Covid-19 pandemic changes in urological
care abound and front line NHS staff face being overwhelmed physically and emotionally by their experiences. Regular
personal reflective practice and within teams offers vital support for urologists, their teams and their patients. A model
for daily personal ‘small’ reflective practice and episodic ‘big’ reflective practice is proposed.
Level of evidence: Not applicable.

Keywords
Reflective practice, reflective cycles, Driscoll’s model, Covid-19, patient care, recognition primed decision-making model

Date received: 11 May 2020; accepted: 12 August 2020

Introduction
Reflective practice (RP) is mandated in the professional role
of a urologist and this is evidenced in their annual appraisal
and quintennial revalidation returns. The use of RP by urolo-
gists is informed by publications by the General Medical
Council (GMC), Conference of Postgraduate Medical Deans
(UK) (COPMeD), Academy of Medical Royal Colleges
(AoMRC), Royal Colleges of Surgeons, encouraged by
defence unions and the four nations education arms includ-
ing Health Education England.1–5 Urology trainees are also
required to show participation in RP at their annual review of
competence progression (ARCP) through various work-
based assessments (including reflective case-based discus-
sions and reflective comments sections made available on
most varieties of workplace-based assessments within the
Intercollegiate Surgical Curriculum Programme (ISCP) port-
folio), which include technical and non-technical skills.
Evidence of RP can then be presented in reports from their
clinical and educational supervisors and by trainees.6
So, what is RP, how was it developed,
how is it performed, what are its
with the intention of gaining insight and using the lessons
learned to maintain good practice or make improvements
where possible’.2 RP may occur ‘in practice’ as in thinking
on your feet or more often ‘on practice’ as in thinking after
the event.7 It should be performed regularly as a self-
assessment tool to avoid complacency and to promote per-
sonal and professional development and most importantly
to maintain or enhance best patient care.
The modern history of RP begins with John Dewey
(1859–1952) who was an American professor of phi-
losophy and education. In 1910, he wrote a book enti-
tled How We Think, in which he described critical
thinking as reflective thought, moving reflection beyond
contemplation. He coined the term ‘reflective thought’
stating ‘we do not learn from experience, we learn from
reflecting on experience’.8 He described the first learn-
ing cycle which was later modified and amplified by
Kolb (Figure 1).
1
 epartment of Urology, Nottingham University Hospitals NHS Trust,
D
UK
2
Department of Urology, Aberdeen Royal Infirmary, UK

benefits and how well is it done? Corresponding author:

Tim Terry, Department of Urology, Nottingham University Hospitals
RP is ‘the process whereby an individual thinks analyti- NHS Trust, City Campus, Hucknall Road, Nottingham NG5 1PB, UK.
cally about anything relating to their professional practice Email: grsterry@aol.com

12_URO966907.indd 300 25/06/2021 2:44:22 PM

 Terry and Bates 301
Figure 1.  Kolb’s four-stage learning cycle, 1984.
Kolb (1984) proposed that experiential learning con-
sists of a continuous loop process of four stages moving
from an initial experience, to reflection on that experience
and then learning from that reflection. The fourth stage
involves active experimentation to generate new ideas and
testing them in reality, in essence forming a new paradigm.
This learning cycle can then be repeated in a modus oper-
andi style of trial and error.9
In 1970 Terry Borton, an American school teacher, pub-
lished a model of reflective education as a framework for
RP. Borton described his model as a fluid process in which
no part of it can exclude another – a ‘continuous integrated
flow’ with no beginning or end. He called it the: what
(increasing awareness); so what (evaluating information);
and now what (experimenting with new behaviour).10 His
model was later taken, copied and popularised by Driscoll
(1994) for use in RP in clinical medicine, where it is now
commonly employed.11 Driscoll’s model unsurprisingly
uses the same three self-aimed, sequential questions con-
sisting of what? so what? and now what? (Figure 2).
So how can we apply Driscoll’s model
to RP in urology in a practical sense?
Stage 1 ‘What?’ is a description of the urologist’s self-
awareness and questions the nature of the ‘experience’
or ‘situation’ under focused consideration. It is impor-
tant to use a rich question resource to understand more
fully what has happened. This is best summarised in
Kipling’s serving men ‘What and why and when and
how and where and who’.12
Stage 1 questions include ‘What happened, what did
you expect and what was different? What was the result?
What do you think about it now? How do you feel about
it?’ Reflexivity allows the reflective practitioner to gain an
objective perception of their role in the experience, with a
12_URO966907.indd 301
Figure 2.  Driscoll’s model. 1994.
metacognitive view, akin to a view of themselves on stage
from a seat in the audience. Team RP offers different per-
ceptual positions as in self, another and an observer which
equates to the ‘three pairs of shoes’ in negotiating yourself
through an experience by analysing successful strategies
observed and then applying them, also known as neuro-
linguistic programming.13 In team RP the observer role
should be rotated through a different team member on each
occasion who will feedback their observations in order to
improve team performance.
Stage 2 ‘So what?’ is an evaluation and analysis of the
answers from stage 1 asking the questions ‘Why does this
matter? What was the impact on you, on others?’
Stage 3 ‘Now what?’ is a synthesis of the obtained data
and the formulation of an action plan for transitional or
transformative change where necessary. It asks ‘What will
you do next time? What will you need to do to prepare?
How are you going to measure the impact of these
changes? What difference does it make if you choose to
do nothing?’ (Figure 1).
In 1985 Gary Klein and others began to develop a recog-
nition primed decision-making model which might be
applied to RP. The theory behind recognition primed deci-
sion-making is that in a situation (Driscoll stage 1), the
decision-maker (the reflective practitioner) will pick up
cues and indicators that let them recognise patterns (Driscoll
stage 2). Based on these patterns and the outcome decision
that has to be made, the reflective practitioner will choose a
single course of action called an ‘action script’ which they
consider will achieve the necessary functional outcome.
This action script is first run through a mental simulation
which is based on tacit experiential knowledge. If this script
25/06/2021 2:44:22 PM
 302 Journal of Clinical Urology 14(4)
Figure 3.  Klein’s recognition primed decision-making model in
reflective practice.
is deemed unworkable a second action script is considered
and mentally rehearsed and so on until an action script that
is functionally appropriate is found (Driscoll stage 3). The
more experienced the reflective practitioner is the more
their recognition patterns are enhanced and the more likely
it is that the first action script which they choose will work
(Figure 3). Training such momentary mindfulness in how
we interact as clinicians, especially in pressurised circum-
stances, serves to provide an intuitive and thoughtful strat-
egy to the resolution of conflicting stimuli and subsequent
problem solving.
What Klein and others have postulated with their recog-
nition primed decision-making model is that intuition
takes primacy in the process and analysis is used to verify
that the intuitions are appropriate to the situation.14,15
Donald Schon previously postulated a central role for intu-
ition in reflection by expert practitioners based on the tacit
knowledge that they had acquired over time in the form of
a repertoire of images, metaphors and theories.7 Thinking
‘out loud’ helps us to recognise cues and patterns and to
build up a set of action scripts for things that work, and
things it’s best not to try again! In any decision-making
process it is vital to have a good understanding and be very
clear about the given presenting situation and what you
want to achieve.
Traditionally, RP has focused on ‘What we do’ as out-
lined above but in a complex and volatile world, in unprec-
edented circumstances presented by Covid-19, ‘How we
are’ is just as important as ‘What we do’.16 To do this, the
reflective urologist must look internally for insights into
their thinking, feelings and behaviour about the experience
or event being considered in RP. Such self-awareness pro-
motes open mindedness, being in the moment, being aware
of internal biases, use of active listening and real time
12_URO966907.indd 302
feedback. Significantly, it also checks our mental and emo-
tional status and asks do we need to be doing anything
about ‘How we are’. Importantly, it checks our psycho-
logical safety in a conscious way.
‘How we are’ for urologists was investigated in 2016 by
O’Kelly and colleagues. In their report, nearly half of
respondents – 42% (575/1380) of urologists in UK and
Ireland indicated burnout. In this paper 15% reported using
non-prescription drugs or alcohol to alleviate symptoms,
8% sought professional help, 60% said they would avail
themselves of counselling if it were available and 80% of
respondents said that burnout should be actively evaluated
in their profession.17 This begs enquiry as to when and
how these urologists used RP in their own professional
practice. It certainly invites enquiry as to how the wellbe-
ing issues of the urologists identified in this paper were
managed in real time both by themselves and the institu-
tions in which they were working.
With Covid-19 ‘How are we’ has become a much more
important question regarding coping with stress and tired-
ness or fatigue using our personal resource skills. The like-
lihood of depression, post-traumatic stress disorder and
even suicide with Covid-19 needs proactive thought and
planning for supporting the morale and wellbeing of all
NHS staff. In a recent report by the British Medical
Association into the wellbeing of UK doctors during the
Covid-19 outbreak involving a poll of 6126, 4500
responded to questions about mental health and of these
over 2000 (44%) admitted expressing burnout or suffering
from depression or anxiety relating to or made worse by
their work.18
Developmental mentoring following RP, together with
other helping measures, may mitigate against severe emo-
tional turmoil or distress.19 Urologists who find RP diffi-
cult to use either because of time constraints or the culture
they work in should seek active coaching to import formal
RP into their professional practice.
It is important to recognise that the proper endpoint of
RP is to crystallise the outcome(s) in writing in a journal,
diary, blog, tweet or e-portfolio as this allows subsequent
validation at a later time by a third party, for example at
annual appraisal. This ensures that any newly acquired
learning is not lost, which might be the case if only conver-
sation with a colleague is used. Clearly, thoughts alone
may not endure. Learning happens when thoughts are put
into language, written or spoken. Furthermore, insights
alone are not enough, it is the action you take with newly
acquired insights that matters.20 There is clear scope in the
ISCP for trainees to engage with RP, although little is done
in reality to mandate RP as an activity for each workplace-
based assessment. We would encourage all trainees to per-
form RP routinely for every workplace-based assessment,
as the learning curve towards consultant practice. We sug-
gest this will imbibe RP as routine activity for the next
generation of consultants. For consultants, the availability
25/06/2021 2:44:22 PM
 Terry and Bates 303
Table 1.  When to do RP.2,3,6
•  Clinical uncertainty
•  Missed diagnosis
•  Postoperative complications
•  Adverse postoperative outcome
•  Complaints
•  Complements
•  Complex procedure went well
•  Interesting seminar, paper, research meeting
•  Appraisal, revalidation, ARCPs
ARCP: annual review of competence progression; RP: reflective practice.
Table 2.  How team RP helps with change environment for
Covid-19.
•  M aking complex decisions re service adaptions, scope of
practice, end of life care, protecting workforce
•  Building individual and team resilience
•  Managing new teams
•  Managing distress, fear, anxiety
•  Developing coping and adjustment skills
•  New ways of working and learning with Covid-19 and
post-Covid-19
•  Being prepared for new pandemics
RP: reflective practice.
of an online RP recording system incorporating workplace
activity is still required, and further work to avail a secure,
confidential and preferably non-disclosable portal for con-
sultants in the UK is needed.
When should you use personal RP?
The answer is whenever you feel uncertainty about an
experience or situation or at the end of the day to ask ‘has
all gone well?’ and if not why not. RP may happen several
times a day checking at hand over of care, following out-
patient interactions, reviewing outcomes of surgery either
in-action or more usually on-action and during teaching
episodes.7 It is important to recognise positive experiences
in RP as well as negative outcomes (Table 1).
Covid-19 of course features significantly in current uro-
logical practice and has generated massive transforma-
tional changes within most working domains of this
surgical speciality and continues to do so as a result of for-
mal team RP (Table 2). These procedural changes are
stressful in their own way, but added to this are the emo-
tional stresses arising from managing patients with multi-
organ failure with a high risk of mortality and the possibility
of contracting the disease itself. Personal RP should regu-
larly ask ‘How are we’ and lead to early assessment and
management by a trained third party where necessary.
It is ineluctable that RP in some form should be part of
a urologist’s everyday practice. This brings us to the reality
that formal RP using Driscoll’s model as described above,
12_URO966907.indd 303
Table 3.  Reflective template what, why, how stems for free-
text responses.
•  What do you want to reflect on?
•  Why do you want to reflect on it?
•  What do you hope to get out of this reflection?
•  What reflective model did you use?
•  How will this reflection affect your practice and make
you a better clinician?
•  How do you feel emotionally about this reflection?
Adapted from reference 2.
or indeed any other RP framework model, is not practical
or indeed necessary in most instances. Rather, formal RP,
say using Driscoll’s model, should be prompted by signifi-
cant experiences or situations which are readily character-
ised by the need for remedial endpoint translational or
transformative management and system change. These
situations do generate important new learning and should
be recorded using a standardised template uploaded into an
e-portfolio (Table 3). Most daily RP, however, is actually
done informally, naturally and instinctively, using consid-
ered thought and intuition as proposed by Schon and
Klein.7,15 We might call this ‘small RP’ (informal) as
opposed to ‘big RP’ (formal). Small RP regularly monitors
clinical practice through checking that accepted standards
in all domains are being maintained, and if they are not
then minor process change(s) maybe required and subse-
quently audited. Small RP may need to become big RP if
the situation is not resolved (Table 4).
RP may also entail wearing the ‘six thinking hats’ of Dr
Edward de Bono (1985) to obtain different perspectives of
issues, but one at a time, to avoid confusion from too many
angles. This then allows the individual to challenge
assumptions and patterns of behaviour in the same way as
this technique does in developmental mentoring. Each
‘thinking hat’ represents a different style of thinking with
blue hat – process, white hat – facts, red hat – feelings,
green hat – creativity, yellow hat – benefits and black hat
– cautions. Within a group setting, the colours of the think-
ing hats may combine to provide many aspects of each
individual’s reflections, providing a richness through
group RP that personal reflection alone might not provide.
This might be especially relevant when making group, or
departmental decisions.21
The benefits of RP
The benefits of formal RP for the urologist are those of
improved self-awareness, self-development and the valida-
tion of their professional performance in all domains which
can drive continuing professional development and life-
long learning. Regular informal and formal RP attends to
emotional intelligence and promotes the ability to inspire,
influence and motivate colleagues. Its consistent use also
enhances innovation, good judgement and heightens
25/06/2021 2:44:22 PM
 304 Journal of Clinical Urology 14(4)

Table 4.  Algorithm for RP.

Small RP (informal) Big RP (formal)

Daily routine practice Episodic significant situation

Maintain standards Major change required with audit review

Model not required Reflective model required

Personal journal entry Standardised template e-portfolio

External validation not required Validation required at monthly mortality morbidity or supporting professional activity time

No improvement move to big RP No improvement move to big RP change required and re-audit

RP: reflective practice.

awareness of risk. Through better emotional management
of oneself, we may become more compassionate to others.
Regular review of one’s emotions offers an opportunity for
a urologist to be aware of their resilience and be proactive
in its management when necessary.17,18
Formal RP leads to transparency and honesty in a pro-
fessional setting that is aimed at improving the holistic
environment which translates into higher personal achieve-
ment, a higher performing team and ultimately the end
product – excellence in patient care.
How well do urologists perform
formal RP?
This is a difficult question to answer as there are no histori-
cal data available and also there is no standardised meth-
odology in current use. A developed questionnaire on
formal RP might ask:
•• What triggers formal RP?
•• How often is it performed?
•• Is a formal reflective model used?
•• Are outcomes recorded and if so how and when?
•• Are outcomes validated and if so by whom and are
timely appropriate actions taken?
•• Does the formal RP capture ‘How we are’?
Answers to these questions may then afford the opportu-
nity to generate a taxonomy then to generate a custom-
ised, urology-specific template to record formal RP.
Notwithstanding this, some generic templates for clinical
formal RP are available in the academy and COPMeD RP
toolkit under ‘resources’ what, why, how2 and these seem
suitable for use by urologists (adapted in Table 3).
If it is genuinely believed that formal RP is the foun-
dation of professional development of urologists, a way
of recognising and articulating what we are learning on a
moment by moment basis, then it behoves us to develop
a standardised process of formal RP to capture new learn-
ing in real time. This would necessitate using a bespoke
model for the RP framework and capturing prospective
data using a template uploaded to an e-portfolio to allow
review by a third party for validation. A dedicated App
for RP purposes might also be used in this process. This
would allow any required changes to be put into action in
a timely fashion. It would also collect data for annual
appraisal to be collected prospectively, which presently is
mostly not the case. The important questions to consider
in this process are who should that third party be, how
should they be trained and how often should reviews take
place? As always, this comes down to resources but it
seems logical to suggest that real time appraisal of formal
RP involving team/departmental learning might take
place as part of regular morbidity and mortality meetings,
while leaving annual appraisal to take place as it cur-
rently does with an appointed trained appraiser. Personal
RP situations dealing with complaints or adverse inci-
dents may require dedicated face-to-face meeting with a
trained nominated colleague in supporting professional
activity time.
Conclusion
Personal formal RP is about being self-aware and observ-
ing what is going on around you. It is about asking con-
sidered questions and using critical and creative thinking
to formulate novel ideas and testing them in real life
where change is necessary. Not only will this improve
patient care and the use of NHS resources but it will also
identify urologists whose wellbeing is fragile so that
bespoke helping aides including developmental mentor-
ing could be employed early to avoid burnout.19 The cur-
rent literature suggests that burnout is a condition
endemic in its own right among clinicians and urologists
in particular17 and which has now been exacerbated by
the Covid-19 pandemic.18
Conflicting interests
There are no conflicting interests contained in the submission
‘The reflective urologist’ to JCU.

12_URO966907.indd 304 25/06/2021 2:44:22 PM

 Terry and Bates 305
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
Ethical approval
Not applicable.
Informed consent
Not applicable.
Guarantor
Tim Terry is the guarantor.
Contributorship
TT wrote the paper and AB reviewed iterations and contributed
as a second authour.
Acknowledgements
The authors would like to acknowledge the expert educational
contributions from Mary Rose Brooks.
ORCID iDs
Tim Terry https://orcid.org/0000-0001-9617-8396
Anthon Simon Bates https://orcid.org/0000-0003-3033-1241
Supplemental material
Supplemental material for this article is available online.
References
1. General Medical Council. The reflective practitioner-guidance
for doctors and medical students. [Online]. https://www.gmc-
uk.org/education/standards-guidance-and-curricula/standards-
and-outcomes (accessed 23 June 2020).
2. Academy and COPMeD Reflective Practice Toolkit.
Refelective practice toolkit for reflection by Postgraduate
Deans [Online] August 2018. http://www.aomrc.org.
uk/wp-content/uploads/2018/08/Reflective_Practice_
Toolkit_AoMRC_CoPMED_0818.pdf (accessed 23 June
2020).
3. Reflection in clinical practice. Royal College of
Surgeons (RCS). file:///C:/Users/Anthony/Downloads/
CPD%20Guidance%20for%20Surgeons.pdf (accessed
23 June 2020).
4. MDU. A quick guide to reflective practice. Guidance.
August 2019. https://www.themdu.com/guidance-and-
advice/guides/quick-guide-to-reflective-practice (accessed
23 June 2020).
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5. Statement on doctors in training reflective practice from
HEE. February 2018. https://www.hee.nhs.uk/news-blogs-
events/news/statement-doctors-training-reflective-practice-
hee (accessed 23 June 2020).
6. Intercollegiate Surgical Curriculum Project. Syllabus ISCP
Urology 2016. https://www.iscp.ac.uk/curriculum (accessed
23 June 2020).
7. Schon DA. The reflective practitioner: how professionals
think in action. Aldershot, UK: Ashgate, 1983.
8. Dewey J. How We Think. New York: Health and Co., 1910.
9. Kolb DA. Experiential learning: experience as the source
of learning and development. Vol. 1. Englewood Cliffs, NJ:
Prentice-Hall, 1984.
10. Borton T. Reach, Touch and Teach. US: McGraw-Hill Inc.,
1970.
11. Driscoll J and Teh B. The potential of reflective practice to
develop individual orthopaedic practitioners and their prac-
tice. J Orthopaed Nursing 2001; 5: 95–103.
12. Destination innovation. How to use six serving men as a
problem analysis method. https://www.destination-innova-
tion.com/how-to-use-six-serving-men-as-a-problem-analy-
sis-method/ (accessed 23 June 2020).
13. Knight S. NLP at work, 2nd ed. Chapter 12. London:
Nicholas Brealey, 2002, pp. 196–197.
14. Decision Making Confidence. Recognition primed decision
making model overview. 2006–2019. https://www.decision-
making-confidence.com (accessed 24 June 2020).
15. Klein G. A naturalistic decision making perspective on stud-
ying intuitive decision making. J Appl Res Memory Cognit
2015; 4: 164–168.
16. University of Minnesota. Harrison M. Reflective practice
in uncertain times: how you are is as important as what
you do. March 2020.https://news.cehd.umn.edu/reflective-
practice-in-uncertain-times-how-you-are-is-as-important-
as-what-you-do/ (accessed 23 June 2020).
17. O’Kelly F, Manecksha RP, Quinlan DM, et al. Rates of self-
reported ‘burnout’ and causative factors amongst urologists
in Ireland and the UK: a comparative cross-sectional study.
BJU Int 2016; 117: 363–372.
18. Haynes L. GP Online. Two fifths of doctors suffering burn-
out or depression during COVID-19 outbreak. https://www.
gponline.com/two-fifths-doctors-suffering-burnout-depres-
sion-during-covid-19-outbreak/article/1680883 (accessed
April 2020).
19. Terry T, French G and Redfern N. Mentoring for urologists?
J Clin Urol 2019; 12: 158–162.
20. Egan E. The Skilled Helper. A problem-management and
opportunity-development approach to helping, 10th edn.
Part 1: 3–67. Brooks/Cole Cengage Learning, 2014.
21. Six Thinking Hats – The de Bono Group. https://www.
debonogroup.com/services/core-programs/six-thinking-
hats/ (accessed 24 June 2020).
25/06/2021 2:44:22 PM
927820 URO Journal of Clinical UrologyDeverill et al.
Point of Technique
Point of technique: Limited anterior
scrotectomy and scrotoplasty for
multiple epidermoid cysts of the
scrotum
Sally J Deverill , Richard Menzies-Wilson
and Rowland W Rees
Abstract
Multiple scrotal epidermoid cysts present a difficult challenge. Individual cyst excision for multiple cysts is painstaking,
and there is a high risk of recurrence. If treated conservatively, multiple cysts may cause pain, become infected or cause
problems with self-esteem due to the cosmetic appearance. We present a technique for excision of the anterior scrotal
wall as a treatment for multiple scrotal epidermoid cysts.
Level of evidence: Not applicable.
Keywords
Andrology, reconstruction, epidermoid cysts, scrotum, scrotectomy
Date received: 9 April 2020; accepted: 25 April 2020
Introduction
Epidermoid cysts are common, benign, simple stratified
epithelial lined cysts which can affect any skin with hair
follicles, including in the genital region. They form as a
result of plugging of the follicular orifice and usually have
the hallmark sign of a visible punctum. They typically con-
tain a thick, white material made of keratin which differen-
tiates them from sebaceous cysts which contain sebum.
The finding of multiple epidermoid cysts may be associ-
ated with a history of acne vulgaris or Gardner’s syndrome,
a rare autosomal dominant genetic disorder which is a sub-
type of familial adenomatous polyposis.1
If minimal in number, epidermoid cysts may be
treated conservatively, or they can be individually
excised. The entire cyst wall and its contents need to
be excised in order to prevent recurrence. Indications
for excision include infection, interference with every-
day life (e.g. getting caught in clothing/zips) or psy-
chological issues such as embarrassment, anxiety or
13_URO927820.indd 306
Journal of Clinical Urology
2021, Vol. 14(4) 306­–309
© British Association of
Urological Surgeons 2020
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/2051415820927820
https://doi.org/10.1177/2051415820927820
journals.sagepub.com/home/uro
low self-esteem. A rare but significant complication of
multiple scrotal epidermoid cysts includes infection
progressing to Fournier’s gangrene.2 Multiple scrotal
epidermoid cysts can also rarely lead to scrotal calcino-
sis via dystrophic calcification.3,4
Scrotal epidermoid cysts seem predominantly to affect
the anterior aspect of the scrotal skin, clustering around
the midline raphe, with relative posterior scrotal and per-
ineal sparing, and this pattern has also previously been
described in the literature.5 In our experience of 10
patients, multiple and extensive scrotal cysts have been
associated with an excess of redundant anterior scrotal
skin (Figure 1), which is thought to contribute to cyst
University of Southampton Hospitals Trust, UK
Corresponding author:
Sally J. Deverill, University of Southampton Hospitals Trust,
Southampton, Tremona Road, SO16 6YD, UK.
Email: s.deverill@doctors.org.uk
Twitter @SallyDeverill
25/06/2021 2:45:22 PM
 Deverill et al. 307
Figure 1.  Excess and lax anterior scrotal skin containing
multiple epidermoid cysts.
formation by increasing sweat and moisture, thereby
increasing plugging of the follicular orifices and leading
to epidermoid cyst formation. After excision of this excess
skin with the majority of the cysts, there is rarely recur-
rence of cysts in the rest of the scrotum. Furthermore, due
to the excess and lax scrotal skin, after excision, there
tends to be enough skin to close, but rarely a split skin
graft or skin flap might be required, especially in more
extensive cases.6
Options for removal
1. Individual cyst excision and wound closure: This is
time-consuming and results in multiple irregular
scars and/or unsightly scarring.
2. Total excision of the scrotal wall followed by skin-
flap reconstruction: This is sometimes required in
extensive cases, for example those cases involving
the entire scrotal skin.
3. Partial excision of the anterior scrotal wall (ante-
rior scrotectomy) and scrotoplasty±split skin
graft: This is useful in cases with the majority of
cysts in the anterior scrotum, where there is excess
or lax scrotal skin.
Point of technique
Examination of the patient should confirm multiple scrotal
epidermoid cysts, predominantly affecting the anterior
scrotal skin (see Figure 2). There may be the occasional
cyst outside of this region, which can be individually
excised separately.
13_URO927820.indd 307
Figure 2.  Multiple scrotal epidermoid cysts.
This surgery is best performed in the supine position-
ing, under general anaesthesia. No routine antibiotic
prophylaxis is required.
The anterior scrotal web can be held up using allis
clamps or similar (as demonstrated in Figure 3). Once the
scrotal skin is stretched, the skin to be excised is marked
with care to leave enough scrotal and penile skin to close.
Excision of the marked section scrotal skin is performed
with a combination of scalpel incision to the skin and
monopolar pencil diathermy to the dartos layer for haemo-
stasis. Care is taken not to breach the tunica vaginalis layer.
The wound is then closed, if possible with two layers,
using 3-0/4-0 vicryl to dartos for haemostasis, and with
4-0 vicryl rapide vertical mattress sutures to the skin (see
figure 4).
When consenting the patient for this procedure, in addi-
tion to the standard risks of wound infection, bleeding/
bruising, scrotal haematoma/collection, chronic scrotal
pain, damage to underlying structures, poor cosmesis and
risks of general anaesthesia, it is important to explain that
there will be a change in the scrotal capacity, with a more
compact scrotum (see Figure 5).
Conclusion
Whilst multiple epidermoid cysts of the scrotum is a fairly
rare phenomenon, individual excision of cysts often leads
to recurrence, repeated surgery and poor cosmesis. We
25/06/2021 2:45:23 PM
 308 Journal of Clinical Urology 14(4)

Figure 3.  Redundant excess scrotal skin: marked for anterior scrotectomy incision.

present a simple technique to excise the anterior scrotum in

order to manage multiple cysts with good cosmetic results.

Conflicting interests
The authors declare that there is no conflict of interest.

Funding
The authors received no financial support for the research,
authorship and/or publication of this article.

Ethical approval
Not applicable.

Informed consent
Figure 4.  Wound closure after anterior scrotectomy with
Written informed consent was obtained from all subjects.
vertical mattress sutures.

Guarantor
R.R.

Contributorship
S.D. wrote the first draft of the manuscript. All authors reviewed
and edited the manuscript and approved the final version of the
manuscript.

Acknowledgements
We would like to thank Mr Rowland Rees for his help and sup-
port in developing the manuscript for this point of technique.

ORCID iD
Sally J Deverill https://orcid.org/0000-0001-5389-5600

References
1 . Koh KJ, Park HN and Kim KA. Gardner syndrome
associated with multiple osteomas, intestinal polypo-
sis, and epidermoid cysts. Imaging Sci Dent 2016; 46:
267–272.
2. Angus W, Mistry R, Floyd MS Jr, et al. Multiple large
infected scrotal sebaceous cysts masking Fournier’s gan-
grene in a 32-year-old man. BMJ Case Rep 2012; 2012:
Figure 5.  Scrotal appearance at postoperative follow-up. bcr1120115253.

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 Deverill et al. 309

3. Kuma Y, Reshmar S and Deivanayagam S. Multiple

5. Wollina U, Schönlebe J, França K, et al. Idiopathic scrotal
Epidermal cysts of the scrotum: a rare case report. Int Surg calcinosis – a case report. Open Access Maced J Med Sci
J 2017; 4: 2375–2376. 2018; 6: 108–109.
4. Solanki A, Narang S, Kathpalia R, et al. Scrotal calcinosis: 6. Mohite P and Bhatnagar A. A case of multiple sebaceous
pathogenetic link with epidermal cyst. BMJ Case Rep 2015; cysts over scrotum in a 35 years old male. Internet J Surg
2015: bcr2015211163. 2006; 9: 1–4.

13_URO927820.indd 309 25/06/2021 2:45:24 PM

27_Blanks.indd 156 25/06/2021 3:33:46 PM
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