Review

Systematic review of the oncological and

functional outcomes of pelvic organ-preserving
radical cystectomy (RC) compared with standard
RC in women who undergo curative surgery and
orthotopic neobladder substitution for bladder
cancer
€ e* , Yann Neuzillet†, Mathieu Rouanne†, Steven MacLennan‡ ,
Erik Veskima
Thomas B. L. Lam‡, Yuhong Yuan§, Eva Compé rat¶, Nigel C. Cowan**,
Georgios Gakis††, Antoine G. van der Heijden‡‡, Maria J. Ribal§§, Johannes Alfred
Witjes‡‡ and Thierry Lebré t†
*Department of Urology, Tampere University Hospital, Tampere, Finland, †Department of Urology, Hospital Foch,
University of Versailles Saint-Quentin-en-Yvelines, Suresnes, France, ‡Academic Urology Unit, University of Aberdeen,
Aberdeen, UK, §Department of Medicine, Health Science Centre McMaster University, Hamilton, ON, Canada,
¶ ^ pital Tenon, UPMC Paris VI, Paris, France, **Department of Radiology, Queen Alexandra
Department of Pathology, Ho
Hospital, Portsmouth, UK, ††Department of Urology, Eberhard-Karls University, Tu € bingen, Germany, ‡‡Department of
Urology, Radboud University Medical Center, Nijmegen, The Netherlands, and §§Department of Urology, Hospital Clinic,
University of Barcelona, Barcelona, Spain

Context including additional domains based on confounder

Pelvic organ-preserving radical cystectomy (POPRC) for
women may improve postoperative sexual and urinary
functions without compromising the oncological outcome
compared with standard radical cystectomy (RC).
Objective
To determine the effect of POPRC on sexual, oncological and
urinary outcomes compared with RC in women who undergo
standard curative surgery and orthotopic neobladder
substitution for bladder cancer.
Evidence acquisition
Medline, Embase, Cochrane controlled trials databases and
clinicaltrial.gov were systematically searched for all relevant
publications. Women with bladder cancer who underwent
POPRC or standard RC and orthotopic neobladder
substitution with curative intent were included. Prospective
and retrospective comparative studies and single-arm case
series were included. The primary outcomes were sexual
function at 6–12 months after surgery and oncological
outcomes including disease recurrence and overall survival
(OS) at >2 years. Secondary outcomes included urinary
continence at 6–12 months. Risk of bias (RoB) assessment
was performed using standard Cochrane review methodology
assessment.
Evidence synthesis
The searches yielded 11 941 discrete articles, of which 15
articles reporting on 15 studies recruiting a total of 874
patients were eligible for inclusion. Three papers had a
matched-pair study design and the rest of the studies were
mainly small, retrospective case series. Sexual outcomes
were reported in seven studies with 167/194 patients (86%)
having resumed sexual activity within 6 months
postoperatively, with median (range) patients’ sexual
satisfaction score of 88.5 (80–100)%. Survival outcomes
were reported in seven studies on 197 patients, with a
mean follow-up of between 12 and 132 months. At 3 and
5 years, cancer-specific survival was 70–100% and OS was
65–100%. In all, 11 studies reported continence outcomes.
Overall, the daytime and night-time continence rates were
58–100% and 42–100%, respectively. Overall, the self-
catheterisation rate was 9.5–78%. Due to poor reporting
and large heterogeneity between studies, instead of
subgroup-analysis, a narrative synthesis approach was used.
The overall RoB was high across all studies.
Conclusion
For well-selected patients, POPRC with orthotopic neobladder
may potentially be comparable to standard RC for oncological

© 2017 The Authors

BJU Int 2017; 120: 12–24 BJU International © 2017 BJU International | doi:10.1111/bju.13819
wileyonlinelibrary.com Published by John Wiley & Sons Ltd. www.bjui.org

outcomes, whilst improving sexual and urinary function
outcomes. However, in women undergoing RC, oncological
and functional data regarding POPRC remain immature and
require further evaluation in a prospective comparative setting.
Introduction
Bladder cancer is a common disease in women, with
~100 000 newly diagnosed cases each year and >35 000
deaths per year worldwide [1]. Two main aetiological factors
for developing bladder cancer in women are tobacco smoking
and the occupational exposure to chemicals accounting for
about half of all cases [2,3]. About 25% of the cases are
muscle-invasive bladder cancer (MIBC) with a high risk of
cancer-specific mortality. Radical cystectomy (RC) is the ‘gold
standard’ management for high-risk urothelial carcinoma of
the bladder (UCB). Standard RC for women includes removal
of the bladder, urethra and adjacent vagina, uterus, distal
ureters, and regional lymph nodes [4].
Sexual dysfunction is prevalent after standard RC, and
especially for younger patients, this is an important concern.
Interest in patients’ health-related quality of life (HRQoL) has
promoted the trend towards pelvic organ-preserving
techniques [5]. Better imaging methods, increased knowledge
of the function of the pelvic structures, and improved surgical
techniques have enabled less radical operative techniques for
treating women with bladder cancer who need cystectomy.
These less radical techniques involve preserving the
neurovascular bundle, vagina, uterus or variations of any of
the stated techniques. These modifications are collectively
called pelvic organ-preserving techniques. Sexual function-
preserving techniques could potentially result in better
HRQoL outcomes for sexual and urinary function after RC.
However, even if such benefits are obtained, it would be
important for oncological outcomes not to be compromised.
The objective of the present systematic review was to
compare pelvic organ-preserving RC (POPRC) with standard
RC in women who undergo curative surgery for bladder
cancer, in terms of sexual, oncological, and urinary function
outcomes. The review was commissioned and undertaken by
the European Association of Urology (EAU) Muscle-invasive
Bladder Cancer (MIBC) Guideline Panel, as part of its
guideline update for 2016.
Evidence Acquisition
Search Strategy and Selection Criteria
The protocol for the systematic review has been published
elsewhere [6]. A systematic literature search was performed
Oncological and functional outcomes of POPRC in women
Keywords
radical cystectomy, urinary bladder neoplasms, urinary
incontinence, sexual function, #BladderCancer, #blcsm
up to 31 May 2016. The search strategy is described in
Appendix 1. In brief, Medline (from 1946), Embase (from
1974), Cochrane controlled trials databases and
clinicaltrial.gov (from 2000) were searched for all relevant
publications. Both medical subject heading (MeSH) and free
text terms, as well as variations of root word were searched.
Key terms related to ‘bladder cancer’ or ‘transitional cell
carcinoma’ were combined using the set operator ‘AND’ key
terms related to ‘cystectomy’. Animal studies, case reports
and editorials were excluded. Due to the expected paucity of
available studies, all study types, including randomised
controlled trials (RCTs), non-randomised comparative studies
(NRCS) and non-comparative studies (e.g., single-arm case
series) without size limitation were included. No language
restrictions were imposed. Studies published as conference
abstracts only were also included. The search was
complemented by additional sources, including the reference
lists of included studies and a panel of experts (EAU MIBC
Guideline Panel).
Types of participants
Women with MIBC or high-risk non-MIBC [UCB or
squamous cell carcinoma (SCC) up to T3b, N1/Nx, M0]
undergoing RC with curative intent (with or without
neoadjuvant chemotherapy and adjuvant treatment) in the
primary setting were included. Populations excluded were
women with metastatic disease (all M sub-stages according to
TNM criteria), salvage cystectomy, previous pelvic
radiotherapy, and non-RC (e.g. partial cystectomy). If any of
these excluded characteristics were present in the population,
studies would still be included if they constituted <10% of the
study population.
Types of interventions
The experimental intervention was RC with any pelvic-organ
preserving technique (i.e. POPRC), including the following:
neurovascular bundle-preserving, vagina-preserving or
genitalia-sparing variations of any of the stated techniques; or
any other sexual function-preserving technique as described
by the trialists. The control or comparator intervention was
standard RC. To minimise clinical heterogeneity the
reconstructive intervention was orthotopic neobladder
substitution in both experimental and control groups. Studies
© 2017 The Authors
BJU International © 2017 BJU International 13
Review

that performed POPRC combined with urinary diversion

instead of orthotopic neobladder substitution were excluded.
Types of outcomes measures
The primary outcomes were:
1 Sexual function (as defined by the trialists, based on
preoperative and postoperative assessment), measured by
the use of standardised questionnaires, measured at 6–
12 months;
2 Oncological outcomes, including disease recurrence (local
or metastatic), measured at >2 years and reported as a
point estimate or as disease-free interval; and overall
survival (OS) at >2 years.
The secondary outcomes were:
1 Urinary function (as defined by the trialists, including the
following measures: need for self-catheterisation, pad usage,
incontinence questionnaires, night vs day continence, etc.),
measured immediately postoperatively and at 6–12 months;
2 Additional oncological outcomes, including pathological
outcomes, such as stage and grade, and positive margins of
the surgical specimen.
Data Collection and Data Extraction
The Preferred Reporting Items for Systematic Reviews and
Meta-analyses (PRISMA) process [7] was followed for
reporting included and excluded studies (Fig. 1). Abstracts
and full texts were reviewed independently by at least two
reviewers (E.V., Y.N., or M.R.) for relevance to the defined
inclusion and exclusion criteria. Disagreement was resolved
by discussion or reference to an independent third party (T.L.
or T.B.L.L.). The references cited in all full-text articles were
also assessed to identify additional relevant articles. A data
extraction form was developed a priori to collect information
on study design, participant characteristics, characteristics of
interventions, and outcome measures. Two reviewers
independently extracted data relating to the pre-specified
outcomes.
Assessment of Risk of Bias (RoB)
The RoB of each included study was assessed independently
by at least two reviewers. RoB in NRCS was performed using
a modified version of the Cochrane RoB tool for RCTs that
included additional items to assess confounding bias. This

Figure 1 Flowchart of the systematic review.

Identification

Records identified through Additional records identified

database searching through hand search
n = 11937 n=4

Records screened after duplicates

removed
n= 9636
Screening

Records screened
n = 9636
Records excludedin
titles screening
n = 9620
Eligibility

Full-text articles
assessed for eligibility Full-text articles
n = 16 excluded
n=1
Reason:
- paper retracted
Included

Studies included in
narrative synthesis
n = 15

© 2017 The Authors

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was a pragmatic approach informed by the methodological
literature pertaining to assessing RoB in NRCS [8,9]. A list of
the five most important confounders for harm and benefit
outcomes were identified a priori by the EAU MIBC
Guideline Panel and included age, clinical and pathological
stage, performance status, type of intervention, and body
mass index (BMI). RoB in single-arm case series was assessed
using the following domains: selection bias (i.e. whether study
participants were selected consecutively or were they
representative of a wider patient population), attrition bias,
selective outcome reporting, and whether an a priori protocol
was available (i.e. indicating prospective study design) [10,11].
Data Analysis
A narrative synthesis of the evidence was performed. Meta-
analysis was considered inappropriate because of the expected
heterogeneity of populations, interventions, outcomes, and
study designs. Descriptive statistics were used to summarise
baseline characteristic data. For time-to-event data (e.g.
survival analysis), estimates such as median survival or the
percentage event-free (e.g. recurrence-free survival rate) at the
pre-specified times points were extracted, if available.
Adjusted and unadjusted hazard ratios (HRs) to estimate the
size of intervention differences were extracted, if available.
For categorical data, point estimates reported as proportions
(%), risk ratios or odds ratios with 95% CIs were extracted, if
available. For continuous outcomes, the mean difference with
corresponding 95% CIs, and mean  SD, or
median  interquartile range were extracted, if available. To
explore the potential impact of clinical heterogeneity on
outcomes, subgroup and/or sensitivity analyses were planned
on the following variables: menopausal status, age, BMI, types
of interventions, neoadjuvant chemotherapy, co-morbidities
or performance status (or factors which can influence sexual
function), pathological stage, grade, or carcinoma in situ
(CIS), adjuvant treatment, and postoperative continence
status.
Evidence Synthesis
Quantity of Evidence Identified
The study selection process is summarised in the PRISMA
flow diagram (Fig. 1). In all, 11 937 articles were identified
and screened; of these, 16 articles were eligible for full-text
screening and 15 met the inclusion criteria [12–26].
Characteristics of the Included Studies
Data were available for 874 patients from the 15 studies.
Table 1 [12–26] outlines the baseline characteristics of the
included studies, including the exclusion criteria reported
by the authors. Common practice in studies was to exclude
patients with bladder tumour involving the trigonal area or
Oncological and functional outcomes of POPRC in women
bladder neck. There were no RCTs. Three were
retrospective NRCS with a matched-pair design [12,15,16].
Bhatt Dhar et al. [16] compared groups that did not differ
by means of age, clinical and pathological stage. In an
abstract by Large et al. [12], comparison between standard
RC and vaginal-sparing RC was done. Patients undergoing
the sparing technique were younger (69.1 vs 73.4 years)
and had both a more favourable clinical T stage (≥cT2
64.9% vs 78.9%) and pathological stage ≥T3 (44.7% vs
78.9%). Ali-El-Dein et al. [15] included sexually active
patients with clinical stage ≤T2. They did not report any
characteristics of the group with standard RC, only
urodynamic outcomes and Female Sexual Function Index
(FSFI) score were compared.
We reviewed 12 retrospective case series [13,14,17–26]. The
largest study recruited 86 patients [13], whilst the smallest
study recruited three patients only [17]. Six case series
assessed vaginal-sparing RC [13,14,21–24]. The age of the
patients ranged from 60.8 to 68 years and the pathological
stage was ≥T3 in 19-42% of the study population. Nerve-
sparing RC was assessed by Nesrallah et al. [20]. The age of
patients ranged from 42 to 77 years and the pathological
stages were not reported. A third group of studies reported
the results of genital-sparing RC [17–19,25,26]. There was a
large variation in the age of the patients (20–80 years) and
pathological bladder ≥T3 stage (7.7–100%).
RoB and Confounding Assessment
Figure 2 [12,15,16] presents the RoB assessment for the
NRCS, and Fig. 3 [13,14,17–26] for single-arm case series.
The overall RoB for the NRCS was high or unclear, with all
studies judged to have high confounding bias across most
confounders. Conversely, the overall RoB for case series was
low, with most domains being judged to be at low RoB
except for an a priori protocol. Postoperative voiding
outcomes were mainly appropriately measured and reported.
In most studies, sexual function outcome was assessed by
interviewing patients, which is more prone to bias.
Comparisons of Interventions Results
Table 2 [12–26] presents a summary of findings for all
effectiveness outcomes.
Pathological outcomes
In all, 143 patients (34%) of all patients that underwent
POPRC had ≥ pT3 and 52 (14%) had lymph node positivity
(Table 2). CIS was found in 23 (7%) bladder specimens. The
rate of positive surgical margins was reported in seven studies
ranging from zero to 13.7%. In all, 13 studies reported the
template of lymph node dissection (LND); 11 of these series
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Review

Table 1 Baseline characteristics and design of the study.

© 2017 The Authors

References Study Total No. of Exclusion Recruitment Duration of follow-up, Age of patients, years, Outcomes measured
design number patients criteria period months, mean (range) mean (range) or mean (SD)
of cases with or mean (SD)
preserving
technique Entire study Intervention Control Entire Intervention Control Functional Oncological
study

Vaginal-sparing RC
Large et al. [12] Retrospective 113 94 NR 2005–2009 27.7 20.6 69.1 73.4 LRFS

BJU International © 2017 BJU International

– – –
matched pair
Chang et al. [14] Retrospective 21 21 CIS, tumour in bladder 1/1994–12/2001 12 (1–36) 12 (1–36) – 68 (38–76) 68 (38–76) – UF LR
case series neck or trigone
Granberg et al. [22] Retrospective 59 59 Positive urethral margin 1995–2006 29.2 (1–141) 29.2 (1–141) – 62 (20–82) 62 (20–82) – UF RFS, CSS, OS
case series
Neymeyer et al. [13] Retrospective 86 86 NR 10/2003–4/2008 36 36 – – – – SF –
case series
Anderson et al. [21] Retrospective 51 51 Tumour in bladder neck, 1996–2011 37.2 37.2 – 60.8 (11.5) 60.8 (11.5) – UF –
case series invasion to vaginal
wall
Rouanne et al. [23] Retrospective 46 46 Tumour in bladder neck, 2000–2011 68 (6–204) 68 (6–204) – 64.8 (43–86) 64.8 (43–86) – SF, UF OS
case series urethra or in vaginal
wall
Gross et al. [24] Prospective 73 73 NR – 64 (12–227) 64 (12–227) – 61.7 61.7 – UF –
case series (34.7–78.5) (34.7–78.5)
Nerve-sparing RC
Nesrallah et al. [20] Retrospective 29 29 Tumour in bladder neck 2/1995–3/2001 37.5 (14–96) 37.5 (14–96) – 62 (42–77) 62 (42–77) – UF PFS, OS
case series
Bhatt Dhar et al. Retrospective 13 6 Tumour in bladder neck 2002–2004 – 13.2 (12–14) 27.3 – 55.9 (52–59) 56.7 SF –
[16] matched pair or trigone (22–34) (54–62)
Genital-sparing RC
Ali-El-Dein et al. Retrospective 305 15 Basal, multifocal, locally 1/1995–12/2010 – 72 (37–99) – – 43 (25–54) NR SF, UF RFS, PFS, CSS, OS
[15] matched pair advanced tumour
Horenblas et al. Prospective 3 3 Tumour in bladder neck 1994–1998 42 (24–72) 42 (24–72) – 55 (38–71) 55 (38–71) – SF, UF RFS
[17] case series or trigone
Koie et al. [18] Retrospective 30 30 Positive urethral margin 4/1997–5/2008 41 (4–98) 41 (4–98) – 71.2 (45–80) 71.2 (45–80) – SF, UF RFS, PFS, CSS
case series
Kulkarni et al. [19] Retrospective 14 14 CIS, tumour in bladder 1997–2002 24.5 (12–65) 24.5 (12–65) – 64.5 (45–72) 64.5 (45–72) – UF RFS, PFS
case series neck
Wishahi et al. [25] Prospective 13 13 CIS, tumour in trigonal 1995–2006 132 (60–180) 132 (60–180) – 37 (20–54) 37(20–54) – SF, UF RFS, CSS, OS
case series area
Moursy et al. [26] Prospective 18 18 >T3, multifocal, tumour 1/2006–1/2010 70 (39–95) 70 (39–95) – 37.8 (32–43) 37.8 (32–43) – SF, UF LR, DM, OS
case series in bladder neck or in
posterior wall

DM, distant metastasis; LR, local recurrence; LRFS, local recurrence-free survival; PFS, progression-free survival; SF, sexual function; UF, urinary function.

Figure 2 RoB summary: review authors’ judgements about included comparative studies.
Random sequence generation (selection bias)
Ali-El-Dein et al. [15]
Bhatt Dhar et al. [16]
Large et al. [12]
followed so-called standard pelvic LND [13–15,17–24] and
two an extended LND template up to common iliac artery
[15,25].
The final histology was mostly well reported (Table 2). The
oncological outcomes were reported for 850 patients and 80%
(679 patients) had UCB. For 124 (15%) patients the histology
was not specified but the pT-stage was given, 37 patients
(4%) had a malignancy other than UCB, and 10 patients were
operated with benign bladder disease.
Information about chemotherapy was poorly reported.
Granberg et al. [22] and Moursy et al. [26] reported that
three and two patients, respectively, received adjuvant
chemotherapy. Neoadjuvant chemotherapy was described in
studies by Horenblas et al. [17] and Koie et al. [18]. There
were a small number of patients receiving chemotherapy
without any adjustments.
Oncological Outcomes
In all, 11 studies [12,14,15,17–20,22,23,25,26] reported
oncological outcomes of POPRC in women. Only the study
reported by Large et al. [12] had a comparative design; the
rest were small, single-arm case series.
Blinding of participants and personnel (performance bias): Oncological outcomes
Allocation concealment (selection bias)
- -
- -
- -
Oncological and functional outcomes of POPRC in women
Blinding of participants and personnel (performance bias): Urinary function
Blinding of participants and personnel (performance bias): Sexual outcomes
Blinding of outcome assessment (detection bias): Oncological outcomes
Blinding of outcome assessment (detection bias): Urinary function
Blinding of outcome assessment (detection bias): Sexual outcomes
Incomplete outcome data (attrition bias): Oncological outcomes
Incomplete outcome data (attrition bias): Urinary function
Incomplete outcome data (attrition bias): Sexual outcomes
Selective reporting (reporting bias)
Confounder: Performance status
Confounder: Intervention
Confounder: Stage
Confounder: BMI
Confounder: Age
Other bias
? - ? + - ? + ? ? ? ? - - - - ?
? - ? ? - ? ? + ? ? - + - - + +
+ ? ? + ? ? ? ? ? ? - + - - + +
Cancer-specific Survival (CSS) and OS
Survival outcomes for the 197 patients that underwent a
POPRC, were available (Table 2). Oncological outcomes were
available at a mean follow-up of between 12 and 132 months.
Only seven of 11 studies reported a mean follow-up of
>36 months. Only one NRCS reported survival outcomes
[15]. Ali-El-Dein et al. [15] reported 5-year CSS and OS
outcomes only for genital-sparing RC without showing the
outcomes of standard RC. In the discussion of this study,
they mentioned that oncological results between the two
groups were comparable.
Six surgical series [18,20,22,23,25,26] reported mean survival
outcomes. Both 5-year CSS and OS were similar to NRCS
70–88% and 65–83%, respectively. Worse oncological
outcomes were associated with unfavourable pathological
stage or lymph node involvement in several studies.
Local and Metastatic Recurrence
In NRCS, Large et al. [12] found no difference in the local
recurrence rate between vaginal-sparing and standard RC
groups (11.7% vs 10.5%, P = 0.88). Metastatic recurrence
rates were not reported.
© 2017 The Authors
BJU International © 2017 BJU International 17
Review

Figure 3 RoB summary: review authors’ judgements about included

single-arm case series (n = 12). Urinary Function Outcome
Table 3 [14,15,17–21,23–26] presents the urinary function

Outcome appropriately measured (outcome measurement bias)? Oncological

outcomes for POPRC in women. Data from 11 studies

Outcome appropriately measured (outcome measurement bias)? Voiding

Outcome appropriately measured (outcome measurement bias)? Sexual

[14,15,17–21,23–26] recruiting a total of 321 patients were
included.
Follow-up for continence evaluation ranged widely from 1 to
227 months. Continence outcome assessment and
measurement were heterogeneous. Some used objective
Incomplete outcome data (attrition bias): Oncological

Incomplete outcome data (attrition bias): Voiding

measures such as number of daily pads, whereas others used
Incomplete outcome data (attrition bias): Sexual patient reported outcomes. Only Rouanne et al. [23] used a
validated anonymous questionnaire to evaluate continence
Total population or consecutive patients?

(Contilife). Nevertheless, definition of complete continence

was common for nine studies, regardless of assessment
Selective reporting (reporting bias)

methods, consisting of complete dryness.

Only one study was a NRCS that recruited 13 patients and
compared internal genital organ-sparing RC with anterior
pelvectomy [15], whilst 10 studies were case series. Ali-el-
A priori protocol?

Dein et al. [15] retrospectively compared the urodynamic test

Anderson et al. [21]
Chang et al. [14]
Granberg et al. [22]
Gross et al. [24]
Horenblas et al. [17]
Koie et al. [18]
Kulkarni et al. [19]
Moursy et al. [26]
Nesrallah et al. [20]
results of 110 women having pelvic exenteration to 13 women
that underwent POPRC. Urodynamic variables were similar
in both groups. The NRCS reported day- and night-time
continence rates in women receiving POPRC of 100% and
- + - + ? - - + ? 92%, respectively [15]. The continence outcomes of standard
- + + + +
RC were not reported.
? ? ? ?
Day-time continence was reported in 10 case series [14,17–
- + + + ? + + + ? 21,23–26] and night-time continence in seven case series
- + ? + ? - ? + ? [17–21,23,26]. In the vaginal-sparing group, day- and night-
time continence ranged from 59% to 71% and 42–71%,
+ + ? - - ? + + - respectively [14,21,23,24]. In the nerve-sparing technique,
Nesrallah et al. [20] reported 97% day-time continence and
- + + + + + +
? ? 86% night-time continence. Data from five genital-sparing
- + + + ? + + + case series showed day- and night-time continence rates of
?
64–100% and 50–89%, respectively [17–19,25,26].
- + + + ? ? + ? ?
Eight case series studies reported self-catheterisation rates
- + + + ? + + + ? ranging from zero to 30.7% [14,19–21,23–26].

Neymeyer et al. [13] + + + - +

In all, 10 studies were single-centre retrospective cohorts.
- ? ? +
Only three studies, with 94 cases, prospectively collected data.
Rouanne et al. [23] - + + + + ? ? + + There was heterogeneity in patient selection, methods of data
collection, and outcome assessment. For instance, patient
Wishahi et al. [25] + + ? + + ? ? + + selection was related to oncological status, excluding tumours
located in the bladder neck or patients with diffuse CIS.
Conversely, preoperative continence status, that may affect
In case series, local recurrence ranged from zero to 13% functional outcome, was not used as a selection criterion.
[14,18,22,26] and metastatic recurrence 9.5–24% [14,18,20,22]. Moreover, preoperative continence was not accurately
Time to local recurrence ranged from a median of assessed in most studies. Only Anderson et al. [21] collected
6–8 months in three studies [14,18,22]. Large et al. [12] data on preoperative continence. Gross et al. [24] assessed the
reported on 42 patients with ≥pT3 with 11.7% local urethral pressure profile preoperatively, and then analysed it
recurrences and found that compared with ≥pT3 patients that as an outcome criterion, as an indirect measure of
underwent standard RC, there was no difference in local continence. Postoperatively continent patients had a longer
recurrence-free survival (P = 0.61). preoperative functional urethral length compared with

© 2017 The Authors

18 BJU International © 2017 BJU International
 Table 2 Pathological characteristics and oncological outcomes of patients that underwent preserving techniques.

References No of Follow-up, Histology, Pathological Extension Pathological Pathological Positive Local Time to l Metastatic Deaths to DSS, % OS, %
patients months, n (%) or n/N bladder of LND node CIS, surgical recurrence, ocal recurrence, bladder
with mean stage ≥ T3, positive n (%) or margins, n (%) or recurrence, n (%) or cancer,
preserving (range) or n (%) or disease, n/N n (%) or n/N months, n/N n (%) or
technique mean (SD) n/N n (%) or n/N median n/N
n/N (range)

Vaginal-sparing RC
Large et al. 94 27.7 UCB 94 (100) 42 (44.7) NR 25 (26.6) NR 8 (8.5) 11 (11.7) NR NR NR NR NR
[12]
Chang et al. 21 12 (1–36) UCB 17 (80) 4 (19) Pelvic 1 (5) 3 (14) 1 (5) 1 (5) 6 2 (9.5) 2 (9.5) NR NR
[14] ACA 1 (5)
LMS 1 (5)
SCCA 1 (5)
SCC 1 (5)
Granberg 53 29.2 (1–141) UCB 47 (80) T3 18 (34); Pelvic 11 (21) 7 (13) 1 (2) 7 (13) 8 (2–36) 8 (15) 2 (8) 5 years, 5 years,
et al. [22] SCC 3 (5) T4 1 (2) 88 83
SCCA 2 (3)
LMS 1 (2)
benign 6 (10)
Neymeyer 86 36 NR NR Pelvic NR NR NR NR NR NR NR NR NR
et al. [13]
Anderson 49 37.2 (37.2) UCB 48 (94) T3 12 (24) Pelvic 2 (3.9) 10 (19.6) 7 (13.7) NR NR NR NR NR NR
et al. [21] ACA 2 (4)
SCC 1 (2)
Rouanne et al. 46 68 (6–204) UCB 46 (100) pT3 13 (42) Pelvic 3 (10) NR NR NR NR NR NR NR 5 years,
[23] 79
Gross et al. 73 64 (12–227) UCB 69 (95) pT3 21 (28.8); Pelvic NR NR NR NR NR NR NR NR NR
[24] benign 4 (5) pT4 3 (4)
Nerve-sparing RC
Nesrallah 29 37.5 (14–96) NR NR Pelvic 2 (7) NR NR NR NR 7 (24) 2 (7) 3 years, 3 years,
et al. [20] 76 65
Bhatt Dhar 6 13.2 (12–14) NR 0 Pelvic 0 NR NR NR NR NR NR NR NR
et al. [16]
Genital-sparing RC
Ali-El-Dein 15 72 (37–99) UCB 5 (33) 15 (100) Iliac 1/15 (6.7) NR NR 1/15 (6.7) NR 2/15 (13) 3/15 (20) 5 years, 5 years,
et al. [15] SCC 5 (33) 80 80
ACA 4 (27)
LMS 1 (7)
Horenblas 3 42 (24–72) NR 1/3 Pelvic 0 1/3 NR 0 NR 0 0 NR NR
et al. [17]
Koie et al. 30 41 (4–98) UCB 29 (97) 10 (33.3) Pelvic NR NR 0 1 (3.3) <7 5 (16.7) 9 (30) 5 years, NR
[18] LMS 1 (3) 70
Kulkarni et al. 14 24.5 (12–65) UCB 14/14 - Pelvic 5/14 NR NR 1/14 NR 1/14 2/14 NR NR
[19]
Wishahi et al. 13 132 (60–180) UCB 13/13 pT3a 3/13 Iliac 0 0 0 NR NR NR NR 5 years, 5 years,
[25] 100; 100;
10 years, 10 years,
62 62
Moursy et al. 18 70 (39–95) UCB 5 (28) NA NR 2 (11) NR 0 0 NA 3 (17) 2 (11) 5 years, 88 5 years, 88
[26] SCC 13 (72)

SCCA, small-cell carcinoma; ACA, adenocarcinoma; LMS, leiomyosarcoma.

BJU International © 2017 BJU International

© 2017 The Authors
19
Oncological and functional outcomes of POPRC in women
Review

postoperatively incontinent patients, at a median of 35 and

40 mm, respectively.
catheterisation
rate, %
Self-

Sexual Outcome

30.6

30.7
Table 4 [13,15–17,23,25,26] presents the sexual function

NR
NR

NR
9.5

29
10

29

22
0
outcomes of POPRC in women. Data from seven studies
reporting on 168 patients were included, two of them were
continence
Night-time

NRCS [15,16] and five were case series [13,17,23,25,26].

rate, % or
n/N

At the time of surgery, the mean patient age ranged from

12/13

7/14

42.9
71.0
NR

NR
NR
2/3

37.9 to 64.8 years across studies. The mean duration of

80

86

89
postoperative follow-up varied from 13.2 to 132 months.
There was a minimum postoperative period of 6 months for
continence
rate, % or
Daytime

sexual activity assessment across studies. However, baseline

n/N)

sexual function evaluation was lacking in most studies. Only

13/13

9/14
93.3

57.1
64.5
58.9
69.3
100

Bhatt Dhar et al. [16] collected data at baseline and during

2/3
71

97

follow-up.
At the date of analysis, a range of 58–100% of patients had
measurement

resumed sexual activity. Satisfaction related to patients’

Type of

sexuality was mentioned in five of the seven studies and the

Self-impression
Self-impression

Self-impression

Self-impression

Self-impression

reported rates ranged from 80% to 100%. Only one study

Pad-test

Pad-test
Pad-test

Pad-test
Pad-test

Pad-test

reported the postoperative delay (6 weeks) to regain sexual

activity. Definition of sexual activity included either sexual
intercourse and/or vaginal manipulation.
Duration of

mean (SD)
(range) or

(12–227)
(60–180)

Most studies (four) used validated standardised questionnaires

follow-up,

(37–99)
(24–72)

(12–65)

(6–204)

(39–95)
months,

(14-96)
(1–36)

(4–98)
mean

(37.2)

to assess sexual function (i.e. the FSFI and the Contilife). In

these studies, the mean FSFI score ranged from 18/36 to 23.7/
12
72
42
41

68
64
132
70
24.5
37.5
37.2

36. In the other three studies, sexual function was evaluated

by a physician interview. Sexual outcome that was evaluated,
was based on postoperative vaginal lubrication/normal
analysed,
months

orgasm [17], patient’s satisfaction of ‘feeling of femininity’

Time

3, 6, 12

[13] or unchanged sexual life with related dyspareunia [26].

6–12

6–12
6–12
6–12

6–12
6–12
>12
>12
1–6
NR

Only two of the considered studies had a comparative design.

Table 3 POPRC series in women reporting on continence outcomes.

Bhatt Dhar et al. [16] reported that female sexual function

was preserved in all patients who received neurovascular
Type of diversion

Hautmann neobladder

Hautmann neobladder

Hautmann neobladder
‘U’-shaped neobladder

‘U’-shaped neobladder
‘Z’-shaped neobladder

preservation and declined in patients who underwent non-

‘J’-shaped neobladder

neurovascular preservation. Similarly, Ali-El-Dein et al. [15]

assessed the FSFI parameters in women with genitalia-sparing
Neobladder,
Neobladder

Neobladder

Neobladder

cystectomy (n = 13) and other women with orthotopic

neobladder without genital sparing (n = 110). They found
that the mean FSFI scores in the study group were
significantly higher than in RC women without genital
Case, n

sparing. The authors also report significant differences in

favour of genital sparing cases in all domains of the FSFI.
21
13

30
14
29
51
46
73
13
18
3

Discussion
Ali-El-Dein et al. [15]
Horenblas et al. [17]

Anderson et al. [21]

Nesrallah et al. [20]

Rouanne et al. [23]

Kulkarni et al. [19]

Wishahi et al. [25]

Moursy et al. [26]

RC followed by orthotopic neobladder substitution is now an

NR, not reported.
Chang et al. [14]

Gross et al. [24]

Koie et al. [18]
References

established type of urinary diversion in women. Despite the

fact that first encouraging series of the POPRC were reported
20 years ago, we still consider this approach as experimental.
The main concerns related to the POPRC are a potentially

© 2017 The Authors

20 BJU International © 2017 BJU International
 Oncological and functional outcomes of POPRC in women

higher risk of positive surgical margins, local recurrences at

(mean)
score
the urethra and reproductive organs, as well local invasion or

FSFI
concomitant malignancies in gynaecological organs.

22.3

23.7
NR

NR

NR

NR
18
Satisfaction, %
In the literature, according to single-centre series, the urethral
recurrence rate in women with neobladders ranges between
0.6% and 4.3% [27–29]. The evidence reviewed here suggests
or n/N

that 0–13% of those having preserving techniques will have a

12/12 local recurrence. As shown by Stein et al. [30], patients with
95.3

NR
NR
3/3
5/6

82
an uninvolved bladder neck rarely have urethral involvement
of cancer. More recently, in a multicentre study by Gakis
% or n/N

et al. [29], it was reported that only the final positive surgical
activity,
Sexual

margin was associated with urethral recurrence. In a

12/12

12/13
89.5

100
NR
6/6

univariable analysis, involvement of the bladder trigone and

58

positive nodes were not risk factors for urethral recurrence.

Measure

Interview

Interview

Interview
Contilife

Clinical staging has a remarkable role in avoiding local

FSFI

FSFI

FSFI

invasion of the bladder cancer into the reproductive organs.

Due to the anatomy, the most commonly reported local
invasion occurs from the bladder base to the vagina [31,32].
evaluation
FSFI score
Baseline

In preoperative assessment, it should be taken into account

that risk factors for gynaecological organ invasion include a
24.5
No
No
No

No
No
No

palpable mass, hydronephrosis, and positive lymph nodes

[31]. Evidence from previous studies suggests that the risk of
Duration of follow-
up, months, mean

secondary malignancy of genital organs after RC in women is

low [33].
(range)

(60–180)
(37–99)
(24–72)
(12–14)
(6–204)

(39–95)

According to a multi-institutional database of 888 consecutive

(6–54)

patients undergoing standard RC for bladder cancer, the 5-

36
70
42

68
132
70
13.2

year recurrence-free survival rate was 58% and the CSS was
66% [34]. Recurrence-free survival and OS in a large single-
centre study of 1054 patients was 68% and 66% at 5 years,
Hautmann neobladder

Hautmann neobladder
‘U’-shaped neobladder
Type of diversion

‘Z’-shaped neobladder

and 60% and 43% at 10 years, respectively [35]. In all, 10

studies in the present review reported, besides functional
Neobladder

Neobladder
Neobladder

outcomes, oncological outcomes. Independent of the

preserving-technique, the oncological results were comparable
to the traditional RC and the orthotopic neobladder.
Table 4 POPRC series in women reporting on sexual outcomes.

The present systematic review reports daytime continence,

mean (range)

night-time continence, and self-catheterisation rates of 57.1–

Age, years

42 (25–54)
55 (38–71)
55.9 (52–59)
64.8 (43–86)
37.9 (20–54)
37.8 (32–43)

100%, 42.9–100%, and 0–30.7%, respectively. By way of

comparison, in a recent review of functional results of
NR

orthotopic neobladder in women, Hautmann et al. [36]

reported daytime continence, night-time continence, and self-
catheterisation rates of 77–97%, 66–86%, 10–61%,
assessed, n/N
No. patients

respectively. Hence, these functional results are somewhat

disappointing in the setting of a surgical procedure designed
to improve them. However, one plausible explanation is that
86/86
12/15

31/46
13/13
17/18
6/13
2/3

inclusion in the included studies was based on oncological

criteria without regard to preoperative continence status. It is
Ali-El-Dein et al. [15]

Bhatt Dhar et al. [16]

possible that the results are influenced by an impaired

Horenblas et al. [17]
Neymeyer et al. [13]

Rouanne et al. [23]

Wishahi et al. [25]
Moursy et al. [26]

continence of the included population at baseline. It is

References

recommended that that future studies report baseline and

change from baseline data for continence outcomes.
Moreover, continence was defined heterogeneously across the
studies, and the follow-up duration was inadequate.

© 2017 The Authors

BJU International © 2017 BJU International 21
Review
Performing evaluation at 6–12 months, as reported in the
included studies, may also lead to underestimation of the
definitive continence rate. In summary, heterogeneity in the
included populations continence outcome definition and
measurement time-point means that it remains uncertain as
to whether there is an improvement in continence outcomes
linked to the POPRC.
Despite major pelvic surgery, Rouanne et al. [23] reported
that most sexually active women were interested in preserving
a good quality of sexual life. This response rate confirmed
that overall HRQoL and sexual function in particular
continue to be major issues for patients with cancer and
cancer survivors. Although poorly identified, impaired sexual
function has been recognised as the primary source of self-
assessed distress among patients undergoing RC [37–39].
Indeed, several anatomical factors have been identified to
decrease postoperative sexual dysfunction: nerve-sparing
cystectomy with conservation of the neurovascular bundles on
the lateral walls of the vagina, preservation of the anterior
vaginal wall, and vascularisation of the clitoris.
Ali-El-Dein et al. [15] hypothesised that preservation of the
whole vagina and its freedom of any suture line was possibly
the reason for early regaining of sexual activity, compared
with those without genitalia preservation. Similarly, the
authors reported significant differences in favour of genital-
sparing cases in all domains evaluated by the FSFI.
However, we recommend that prospective multicentre studies,
reporting baseline and postoperative data with validated
questionnaires, are needed to assess the relationship between
postoperative sexual outcomes and POPRC in women.
Limitations of the Study
This is the first systematic review of the evidence base for
POPRC in women. Our comprehensive search strategy
involving both female and male patients to avoid missing
combined studies yielded only 15 studies. Most studies were
retrospective and non-comparative with small numbers of
investigated patients, meaning that any estimates are
uncertain and likely to be biased. Furthermore, the optimal
baseline and change from baseline measurements for the
sexual and urinary function outcomes were mostly absent.
Some of the studies did not report the final histology because
they focused only on the functional outcomes. Included
studies that did report the histology had included mostly
patients with UCB and a few patients with SCC. Planned
subgroup-analysis was not possible due to lack of
information.
From the results of the present systematic review, none of the
POPRC techniques (neurovascular bundle-preserving, vagina-
preserving or genitalia-sparing) can be recommended over the
© 2017 The Authors
22 BJU International © 2017 BJU International
others due to the lack of studies comparing different
operation techniques. The nature of the comparison is bound
to be biased, although it is the best that we can do using the
available data, which has been systematically reviewed.
Heterogeneity in outcome definition, measurement and
reporting hampers the usefulness of the current evidence
base. A core outcome set, using the methodology outlined by
the Core Outcome Measures in Effectiveness Trials (COMET)
initiative [40] is needed to ensure that future studies address
the outcomes that are important for decision-making for
patients, clinicians, policy makers and healthcare funders, and
are defined and measured consistently.
Conclusion
In women with high-risk bladder cancer, oncological and
functional data from POPRC followed by reconstruction of
the neobladder remains immature and requires prospective
research to make comparisons with standard RC. However,
for well-selected patients, sparing female reproductive organs
during RC appears to be oncologically safe and provides
improved functional outcomes. The overall quality of the
evidence was low as the included studies were underpowered
with a significant RoB and confounding. For the same reason
it is difficult to define a preserving technique that performs
better than others.
Conflicts of Interest
None.
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Correspondence: Erik Veskim€ae, Department of Urology,
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Finland.
e-mail: erikveskimae@gmail.com
© 2017 The Authors
BJU International © 2017 BJU International 23
Review

Abbreviations: BMI, body mass index; CIS, carcinoma in situ;
CSS, cancer-specific survival; EAU, European Association of
Urology; FSFI, Female Sexual Function Index; HR, hazard
ratio; HRQoL, health-related quality of life; LND, lymph node
dissection; MIBC, muscle-invasive bladder cancer; NRCS,
non-randomised comparative studies; OR, odds ratio; OS,
overall survival; PRISMA, Preferred Reporting Items for
Systematic Reviews and Meta-analyses; (POP)RC, (pelvic
organ-preserving) radical cystectomy; RCT, randomised
controlled trials; RoB, risk of bias; RR, risk ratio; SCC,
squamous cell carcinoma; UCB, urothelial carcinoma of the
bladder.
Supporting Information
Additional Supporting Information may be found in the
online version of this article:
Appendix S1. Search strategy of the systematic review.

© 2017 The Authors

24 BJU International © 2017 BJU International