Received: 16 September 2017

DOI: 10.1002/nau.23457
| Accepted: 2 November 2017

ORIGINAL CLINICAL ARTICLE

Prevalence, management, and prognosis of bladder cancer in

patients with neurogenic bladder: A systematic review

Salima Ismail MD1 | Gilles Karsenty MD, PhD2 |

Emmanuel Chartier-Kastler MD, PhD1 | Olivier Cussenot MD, PhD3,5 |
Eva Compérat MD, PhD4,5 | Morgan Rouprêt MD, PhD1,5 | Véronique Phé MD, PhD1,5

1 Department of Urology, Pitié-Salpêtrière

Academic Hospital, Assistance Publique-
Hôpitaux de Paris, Pierre et Marie Curie
Medical School, Sorbonne Universités,
Paris, France
2 LaConception Hospital, Department of
Urology, Assistance Publique-Hôpitaux de
Marseille, Marseille, France
3 Department of Urology, Tenon Academic
Hospital, Assistance Publique-Hôpitaux de
Paris, Pierre et Marie Curie Medical
School, Sorbonne Universités, Paris, France
4 Department of Pathology, Tenon
Academic Hospital, Assistance Publique-
Hôpitaux de Paris, Pierre et Marie Curie
Medical School, Sorbonne Universités,
Paris, France
5 Groupe de recherche clinique—UPMC n°
5, Oncotype-Uro, Institut Universitaire de
Cancérologie de l'UPMC, Pierre and Marie
Curie Medical School, Sorbonne
Universités, Paris, France
Correspondence
Véronique Phé, MD, PhD, Department of
Urology, Pitié-Salpêtrière Academic
Hospital, 47-83 Boulevard de l’Hôpital,
75651 Paris, Cedex 13, France.
Email: veronique.phe@aphp.fr
Aim: To perform a systematic review of the literature regarding epidemiology,
diagnosis, management and prognosis of bladder cancer in the neuro-urological
patient population, in order to serve as a basis for future recommendations and
research.
Methods: A systematic review was performed according to the PRISMA-Preferred
Reporting Items for Systematic Reviews and Meta-Analyzes Statement. Embase was
searched for studies providing data on epidemiology, diagnosis, management and
prognosis of bladder cancer in neuro-urological patients.
Results: After screening 637 abstracts, 15 studies (13 retrospective and 2 prospective
studies) were included in this study. We identified 332 patients (0.3%) who were
diagnosed with bladder cancer. This mostly affected mostly men (59.3%) and spinal
cord injured patients (98.8%). Mean age at diagnosis was 56.1 years. Bladder cancer
occurred after a long period of evolution of the neurological disease (24.9 years).
Gross hematuria was the predominating presenting symptom (31.6% of cases).
Indwelling urethral or supra-pubic catheters were used in 44.5% of patients. The most
frequent histological subtype of bladder cancer was transitional cell carcinoma
(53.1%), followed by squamous cell carcinoma (33.5%). Muscle-invasive bladder
cancer was reported in 67.7% of patients. The mean cancer-specific mortality rate was
of 47.1%.
Conclusions: The prevalence and high mortality rate of bladder cancer in neuro-
urological patients underlines the importance of long-term follow-up in this specific
population. This highlights the necessity of further studies in this field.

KEYWORDS
bladder cancer, incidence, neurogenic bladder, review, systematic

The study was performed at the Pitié-Salpêtrière Academic Hospital,

Department of Urology, Assistance Publique-Hôpitaux de Paris, Pierre et
Marie Curie Medical School, Sorbonne Universités, Paris, France. 1 | INTRODUCTION
Systematic review registration number: CRD42017055802.
John Heesakkers led the peer-review process as the Associate Editor A variety of neurological conditions induce a neurogenic
responsible for the paper. bladder dysfunction. With the advancement for treatment and
Neurourology and Urodynamics. 2017;1–10. wileyonlinelibrary.com/journal/nau © 2017 Wiley Periodicals, Inc. | 1
2
| ISMAIL
follow-up care, it is only to be expected that life expectancy of
patients with neurogenic bladder, that is, neuro-urological
patients will increase. As they live longer, they will inevitably
be exposed to a higher risk of developing other serious
diseases such as bladder cancer.1
While the overall risk of bladder cancer may not be greater
than the risk in the general population,1–3 the mortality rate is
definitely higher. Although bladder cancer is the third most
frequent cause of cancer death among spinal cord injury
patients (SCI),4 it is only the ninth in the US general
population.5 More specifically, a recent study by Nahm et al6
showed that patients with spinal cord injury are 6.7 times
more likely to die of bladder cancer compared to the general
population. This can be explained by the higher rate of
squamous cell carcinoma (SCC) in neuro-urological
patients.1,2,7 This specific bladder cancer histological subtype
is associated with chronic infections, stones and indwelling
catheters,8–13 which explains why this subtype is more
prevalent in patients with neurogenic bladder dysfunction. It
is also known to be an aggressive and often infiltrating tumor,
possibly because of the nature of the tumor itself and also
because of the delay in diagnosis.12,13 Squamous cell
carcinoma of the bladder has a limited response to
chemotherapy and radiotherapy. To improve prognosis, an
early surgical approach is recommended.13,14
Despite the fact that bladder cancer is more morbid in
neuro-urological patients, bladder screening and management
recommendations are mainly based on expert opinions and
lack consensus.1,6,15,16 Indeed, all current management
guidelines are dedicated to transitional cell carcinomas and
non neuro-urological patients. The aim of the current study
was to perform a systematic review of the literature and a
meta-analysis regarding epidemiology, diagnosis, manage-
ment and prognosis of bladder cancer in the neuro-urological
patient population, in order to serve as a basis for future
recommendations and research.
2 | METHODS
2.1 | Data sources and searches
This systematic review was performed according to the Preferred
Reporting Items for Systematic Reviews and Meta-Analyze
(PRISMA) Statement (see Supplementary Material 1).17
We performed a systematic search in Embase in order to retrieve
all published papers regarding bladder cancer and neurogenic
bladder up to July 2017. We additionally searched the reference
lists of all included studies and relevant review articles. No
language nor date restrictions were applied. Medical subject
heading (MeSH) terms used were: neurogenic bladder, neuro-
genic detrusor overactivity, spina bifida, meningomyelocele,
multiple sclerosis, and spinal cord injury. Each of these key words
was crossed with bladder cancer.
ET AL.
2.2 | Study selection
Study selection was performed according to the PICo method
for qualitative studies. We included all original studies that
reported the epidemiology (specifically the incidence and/or
prevalence), risk factors, clinical presentation, histological
details, and management and prognosis of bladder cancer
among neuro-urological patients. Studies on bladder aug-
mentation, case reports, case studies, commentaries, reviews;
studies not published as full-text; and those not discriminating
between non neuro-urological and neuro-urological patients
were excluded. All identified abstracts were imported into a
bibliography management software (Zotero 4.0.28.8; Center
for History and New Media, George Mason University,
Fairfax, VA) and sorted into inclusion and exclusion folders
by drag and drop. Abstracts of all identified studies were
independently reviewed by two authors (SI and VP). Studies
reporting on bladder cancer among neuro-urological patients
were reviewed in full text.
2.3 | Data extraction, risk of bias assessment,
and data synthesis
The variables assessed included year of publication, type of
study, and bladder cancer prevalence. Relevant data regarding
population characteristics and clinical presentations were also
retrieved: population size, age, type of neurological disorders,
presenting symptoms (gross hematuria and other urinary
symptoms), urodynamic parameters, upper urinary tract
assessment, risk factors (bladder stones, smoking, recurrent
urinary tract infections [UTI]), bladder drainage method, and
duration of neuro-urological disease at the time of bladder
cancer diagnosis. We also assessed bladder cancer histopath-
ological data (histological subtype, stage, and grade) and type
of management (intravesical treatment, cystectomy, chemo-
therapy, and radiation therapy). Mean/median follow-up and
survival times as well as rates of cancer-free survival, overall
survival, cancer-specific mortality, other causes of mortality,
and overall mortality were assessed. Finally, the level of
evidence of each study was determined according to the
Oxford Centre for Evidence-Based Medicine (2011). Data
from eligible reports were extracted in duplicate (SI and VP)
and discrepancies were resolved by a third reviewer (MR).
Risk of bias in non-comparative studies cannot be assessed
with Cochrane Risk of Bias Assessment tool used for RCTs.18
Therefore, concern was extended in non-comparative studies
to address external validity by assessing whether specified
confounding factors were reported. A list of the six most
important potential confounders was identified. For each
study, we asked whether each confounder was considered and
whether, if necessary, the confounder was controlled for in
analysis. The potential confounding factors were underlying
neurological disease (eg, spinal cord injury, multiple sclerosis,
ISMAIL ET AL.
etc.), gender, tumor stage, type of treatment, voiding mode, and
duration of the neurological disease since onset.
Overall means and rates were calculated for each variable
whenever possible.
3 | RESULTS
3.1 | Search results
The PRISMA flow diagram of the literature search and results
is shown in Figure 1. After screening 637 abstracts, 15
studies1,7–9,15,19–28 published between 1981 and 2017 were
included in a narrative synthesis (Tables 1–4): 13 retrospec-
tive studies and 2 prospective studies.
3.2 | Study and patient characteristics
Among the 15 included studies, we identified 332 patients with
bladder cancer: 197 men (58.3%) and 15 women (4.5%). In 120
patients (36.1%), gender was unreported. The mean age at
diagnosis was 56.1 years. Patients suffered from spinal cord
injury (SCI) (n = 328; 98.8%), spina bifida (n = 1; 0.3%),
multiple sclerosis (n = 2; 0.6%), or familial paraplegia
(n = 1; 0.3%). The overall incidence of bladder cancer was
0.3%, ranging from 0.1% to 7.4% (Table 1). History of bladder
FIGURE 1 Preferred reporting items for systematic reviews and meta-analyses flow diagram
| 3
stones and smoking ranged between 20.8-45.5% and 12.5-70.0%
, respectively. Recurrent UTIs were taken into account in only 2/
15 (13.3%) studies. Thirty-one percent of patients voided
spontaneously or by reflex voiding. Intermittent catheterization
was practiced in 16.8% of patients. The presence of indwelling
urethral or supra-pubic catheters was the method of choice in
44.5% of patients. Mean time between neurological disease and
bladder cancer diagnosis was 24.9 years (Table 2).
3.3 | Diagnosis of bladder cancer in neuro-
urological patients
Gross hematuria was one of the presenting symptoms in
31.6% of patients. Very scarce data were available regarding
urodynamic parameters and upper urinary tract assessment
(Table 2).
The most frequent histological subtype of bladder cancer
was transitional cell carcinoma (TCC) (53.1%), followed by
squamous cell carcinoma (SCC) (33.5%). Non-muscle invasive
bladder cancer was reported in 31.0% of patients compared to
67.7% muscle-invasive bladder cancer. Treatment care varied
widely ranging from endoscopic management ± intravesical
therapy (27/105, 25.7%) to palliative care (4/87, 4.6%). The
majority of patients were treated by endoscopic resection
followed by cystectomy (107/156, 68.6%) (Table 3).
 4
|

TABLE 1 Epidemiology of bladder cancers in the included studies

Gender Neurologic disorder

Median
Year of Sample BC Female Male N/S agea SB SCI MS FP
References publication Type of study LOE size cases Incidence (%) (%) (%) (%) (mean) (%) (%) (%) (%)

Pannek7 2002 Retrospective 3 43 561 48 48/43 561 (0.1) 8/37 (21.6) 29/37 (78.4) 11/48 (22.9) N/S (53.3) 0/48 48/48 (100) 0/48 0/48
1
Parra et al 2007 Retrospective 3 1825 8 8/1825 (0.4) 2/8 (25.0) 6/8 (75.0) 0/8 61.0 (58.8) 1/8 (12.5) 4/8 (50.0) 2/8 (25.0) 1/8 (12.5)

Groah et al19 2002 Prospective 3 3670 21 24/3670 (0.7) — — 21/21 (100) N/S (48.0) 0/21 21/21 (100) 0/21 0/21

Subramonian 2004 Retrospective 3 1324 4 30.7 per 100 000 1/4 (25.0) 3/4 (75.0) 0/4 N/S (58.7) 0/4 4/4 (100) 0/4 0/4
et al20 person-yrs

Sugimara 2008 Retrospective 3 149a 1 1/149 (0.7) — — 1/1 (100) N/S (N/S) 0/1 1/1 (100) 0/1 0/1
et al21

Chao et al22 1993 Retrospective 3 81 6 6/81 (7.4) — — 6/6 (100) N/S (N/S) 0/6 6/6 (100) 0/6 0/6

Kalisvaart 2010 Retrospective 3 1319 32 32/1319 (2.4) — — 32/32 (100) N/S (N/S) 0/32 32/32 (100) 0/32 0/32
et al15

Bickel et al9 1991 Retrospective 4 2900 8 8/2900 (0.3) 0/8 8/8 (100) 0/8 55.5 (56.0) 0/8 8/8 (100) 0/8 0/8

Broecker 1981 Retrospective 4 1052 10 10/1052 (1.0) — — 10/10 (100) 48.0 (N/S) 0/10 10/10 (100) 0/10 0/10
et al23

Bejany et al8 1987 Retrospective 4 300 11 7/300 (2.3) — — 11/11 (100) 50.0 (N/S) 0/11 11/11 (100) 0/11 0/11

El-Masri 1981 Retrospective 3 6744 25 25/6744 (0.4) — — 25/25 (100) N/S (N/S) 0/25 25/25 (100) 0/25 0/25
et al24

West et al25 1999 Retrospective 3 33 565 130 130/33 565 (0.4) 1/130 (0.8) 129/130 (99.2) 0/130 N/S (57.3) 0/130 130/130 (100) 0/130 0/130

Katsumi 2010 Retrospective 3 179a 3 3/179 (1.7) — — 3/3 (100) N/S (N/S) 0/3 3/3 (100) 0/3 0/3
et al26

Sammer 2015 Prospective 3 129 1 1/129 (0.8) 0/1 1/1 (100) 0/1 59.0 (59.0) 0/1 1/1 (100) 0/1 0/1
et al27

Bothig et al28 2017 Retrospective 3 6599 24 24/6599 (0.4) 3/24 (12.5) 21/24 (87.5) 0/1 54.5 (57.7) 0/24 24/24 (100) 0/24 0/24

OVERALL 1981-2017 Retrospective: 3-4 103 397 332 332/102 073 15/332 (4.5) 197/332 (59.3) 120/332 (36.1) 54.7 (56.1) 1/332 (0.3) 328/332 (98.8) 2/332 (0.6) 1/332 (0.3)
(15) 13 (0.3)
Prospective: 2

Age at bladder cancer diagnosis; BC, bladder cancer; LOE, level of evidence N/S, not specified; N/A, not applicable; SB, spina bifida; SCI, spinal cord injury; MS, multiple sclerosis; FP, familial paraplegia.
a
All with supra-pubic catheter/indwelling urethral catheters.
ISMAIL
ET AL.
TABLE 2 Presenting symptoms and risk factors of bladder cancers
ISMAIL

Bladder drainage
ET AL.

Mean time
Upper between
Gross Other urinary UDS tract History of Active or History of Other or disease and
hematuria symptoms harameters assessment bladder stones previous recurrent SV/RV IC IUC/SP multiple bladder
References n (%) (%) (%) (%) (%) smoker (%) UTIs (%) (%) (%) (%) (%) cancer (yrs)
Pannek7 48 N/S N/S N/S N/S N/S 12/37 (32.4) 24/37 (64.9) 18/37 (48.7) 12/37 (32.4) 7/37 (18.9) 0/37 22.6
Parra et al1 8 4/8 (50.0) D: 1/8 (12.5) N/S N/S N/S 1/8 (12.5) N/S 1/8 (12.5) 3/8 (37.5) 4/8 (50.0) 0/8 28.3
U: 1/8 (12.5)
Groah et al19 21 N/S N/S N/S N/S N/S N/S N/S 3/21 (14.3) N/S 15/21 (71.4) 3/21 (14.3) 20.0
Subramonian 4 3/4 (75.0) N/S N/S N/S 1/4 (25.0) N/S N/S 1/4 (25.0) 0/4 3/4 (75.0) 0/4 N/S
et al20
Sugimara 1 N/S N/S N/S N/S N/S N/S N/S 0/1 0/1 1/1 (100) 0/1 N/S
et al21
Chao et al22 6 N/S N/S N/S N/S N/S N/S N/S 2/6 (33.3) 0/6 3/6 (50.0) 1/6 (16.7) 25.7
Kalisvaart 32 7/19 (36.8) N/S N/S N/S N/S 21/30 (70.0) N/S N/A N/A N/A N/A 34.0
et al15
Bickel et al9 8 6/8 (75.0) UTI: 5/8 (62.5) DH: 8/8 DU: 2/8 N/S 5/8 (62.5) N/S 3/8 (37.5) 1/8 (12.5) 4/8 (50.0) 0/8 17.6
(100) (25.0)
ESD: 5/8 HN:2 /8
(62.5) (25.0)
Broecker 10 N/S N/S N/S N/S N/S N/S N/S 2/7 (28.6) N/S 4/7 (57.1) 1 /7 (14.3) 18.0
et al23 (median)
Bejany et al8 11 N/S N/S N/S VUR: 5/11 5/11 (45.5) N/S N/S 2/11 (18.2) 0/11 7/11 (63.6) 2 /11 (18.2) 16.3
(45.5)
El-Masri 25 15/25 (60.0) F/DU: 5/25(20.0) N/S N/S 11/25 (44.0) N/S N/S N/A N/A N/A N/A 23.0
et al24 BP: 4/25(16.0)
D: 2/25(8.0)
West et al25 130 N/S N/S N/S N/S N/S N/S N/S 8/42 (19.1) 8/42 (19.5) 26/42 (61.9) 0/42 23.9
Katsumi 3 N/S N/S N/S N/S N/S N/S N/S 0/3 0/3 3/3 (100) 0/3 N/S
et al26
Sammer 1 N/A N/S N/S N/S N/S 0/1 N/S 0/1 1/1 (100) 0/1 0/1 33.0
et al27
Bothig et al28 24 N/S N/S N/S N/S 5/24 (20.8) N/S 10/24 (41.7) 13/24 (54.2) 4/24 (16.7) 0/24 7/24 (29.2) 29.8
Total average 332 31/56 (31.6) 53/173 (30.6) 29/173 (16.8) 77/173 (44.5) 14/173 (8.1) 24.9

BP, bladder pain; D, dysuria; DH, detrusor hyperreflexia; DU, distal ureterectasis; ESD, external sphincter dysynergia; F/DU, frequency/dirty urine; HN, hydronephrosis; IUC/SP, indwelling urethral catheter/supra-pubic catheter;
LUTS, lower urinary tract symptoms; N/A, not applicable; N/S, not specified; SV/RV, spontaneous voiding/reflex voiding; U, urgency; UDS, urodynamic study; UTI, urinary tract infection; UVJO, ureterovesical junction obstruction;
VUR, vesico-ureteral reflux.
a
Data available for two patients.
|
5
6
| ISMAIL
3.4 | Prognosis of bladder cancer in
neuro-urological patients
Data on median/mean follow-up and survival times were very
scarce. Median follow-up and survival times ranged from 19.5
to 48.0 and from 11.5 to 13.0 months, respectively. The mean
overall survival and overall mortality rates were of
42.4% (96/226) and 57.5% (130/226) respectively. The mean
cancer-specific mortality rate was of 47.1% (73/155) (Table 4).
3.5 | Risk of bias and confounding
We had identified a list of the six most important potential
confounders (Figure 2): underlying neuro-urological disease,
gender, voiding mode, duration of the neurological disorder,
tumor stage, and treatment type. Less than 50% of the included
studies reported a gender ratio. Of all 15 included studies, only one
was considered potential confounders in its data analysis. Groah
et al19 calculated a relative risk of 1.9 for bladder cancer in males
and a relative risk of 0.5 in patients with a cervical level of SCI.
4 | DISCUSSION
4.1 | Principal findings
In this present systematic review, we attempted to identify
papers from the multiple different neurogenic bladder
populations; however, the vast majority of the literature
(98.8%) came from the SCI population. Bladder cancer was
reported in 0.3% of the included population and mostly
affected men (59.3%). The mean age at diagnosis was 56.1
and bladder cancer occurred after a long period of evolution of
the neurological disease (24.9 years). Gross hematuria was
definitely the predominant presentation, being reported in
31.6% of cases. Among the risk factors, indwelling urethral or
supra-pubic catheters were used by 44.5% of patients. The
most frequent histological subtype of bladder cancer was
TCC (53.1%), followed by SCC with a rate of 33.5%. The
majority of bladder cancers were muscle-invasive (67.7%)
and radical cystectomy was the treatment of choice in 68.6%
of patients. The overall cancer-specific mortality rate of
47.1% for an overall median follow-up ranged between 19.5
and 48.0 months. Only one study out of 15 was considered
confounders in their data analysis with conflicting results.
4.2 | Findings in the context of existing
evidence
It is well-known by physicians managing patients with a
neurogenic bladder that this population may develop bladder
cancer in the long run due to various risk factors, including
smoking, chronic inflammation of the bladder secondary to the
presence of catheters, bladder stones, and UTIs. However, a
ET AL.
synthesis of all evidence in order to provide recommendations
was not available. To the best of our knowledge, we present the
first systematic review of the literature on bladder cancer that
attempts to include all neuro-urological patients. Previous
reviews of the literature related to the topic were published over
the last decade but these were not systematic and focused only
on SCI patients.2,29 However, despite our efforts, 98.8% of the
patients included in this current study are SCI patients because
of the very limited bladder cancer data available in the
literature regarding other neuro-urological populations.
In our study, the majority of neuro-urological patients
with bladder cancer were men (59.3%), considering the
gender was not specified in 36.1% of patients. The male
predominance can be explained by the fact that the adult male-
to-female ratio of traumatic SCI has been reported to be at
least of 2:1.30 Another explanation are the smoking and
occupational habits of men.31 The incidence of bladder cancer
in the general population is also much higher in men (4.5%)
compared to women (1.5%).32
The overall bladder cancer prevalence in our study
population was 0.3%, which is consistent with the rates that
Welk et al. reported in their review regarding patients with SCI
(0.1-10%).29 In men less than 75 years of age in the general
population, bladder cancer prevalence is also comparable (2 to
4%).31,33 As previously reported and now confirmed once again
in this current study, the rate of SCC (33.5%) is higher in patients
with neurogenic bladder dysfunction compared to the general
population (2-7%).14,29 Bladder cancers in our study population
were more aggressive, as they tended to be muscle invasive, as
SCCs are known to be.12,13 Welk et al29 also reported that the
rate of muscle invasive bladder cancer was significantly higher
in patients with spinal cord injury compared to the general
population. The aggressivity of bladder cancer in patients with
neuro-urological diseases explains why SCI patients are 6.7
times more likely to die of bladder cancer compared to the
general population.6
4.3 | Implications for research
With the advancement of medicine and technology, life
expectancy of patients with neurological disease has
increased, to a state where they are now facing the same
medical diseases as the general population. Bladder cancer
in patients with a neurogenic bladder is much more
aggressive and is responsible of death in about 50% of
cases. Besides the fact that the prevalence of SCC is higher
in these patients, there must be other bladder cancer features
that are specific to patients with neurogenic bladder and may
contribute to its aggressiveness. Identifying these factors
could allow us to improve the diagnosis and treatment
options in these patients. This may also require the study of
the urothelial carcinogenesis in this specific patient
population. Also, future prospective studies regarding the
TABLE 3 Histopathological findings of bladder cancer
ISMAIL

Histological subtype Pathological stage

ET AL.

Endoscopic
resection Chemo
only Radical +radical
TCC SCC Other NMI MI pTx ± intraves cystectomy cystectomy Chemo Rad only
References n (%) (%) (%) (%) (%) (%) tx (%) (%) (%) only (%) (%) Other (%)
Pannek7 48 30/37 (81.0) 7/37 (19.0) 0/37 15/37 (40.5) 22/37 (59.5) 0/37 N/S 14/19 (73.7) 4/19 (21.1) 1/19 (5.3) N/S N/S
Parra et al1 8 4/8 (50.0) 3/8 (37.5) 1/8 (12.5) 1/8 (12.5) 7/8 (87.5) 0/8 2/8 (25.0) 6/8 (75.0) 0/8 0/8 0/8 0/8
19
Groah et al 21 N/S N/S N/S N/S N/S N/S N/S N/S N/S N/S N/S N/S
Subramonian 4 1/4 (25.0) 2/4 (50.0) 1/4 (25.0) 0/4 4/4 (100) 0/4 1/4 (25.0) 2/4 (50.0) 0/4 0/4 0/4 Refused treatment:
et al20 1/4 (25.0)
Sugimara 1 1/1 (100) 0/1 0/1 1/1 (100) 0/1 0/1 1/1 (100) 0/1 0/1 0/1 0/1 0/1
et al21
Chao et al22 6 4/6 (66.7) 1/6 (16.7) 1/6 (16.7) N/S N/S N/S 0/6 6/6 (100) 0/6 0/6 0/6 0/6
Kalisvaart 32 10/32 (31.3) 15/32 (46.9) 7/32 (21.9) 9/32 (28.1) 23/32 (71.9) 0/32 N/S 27/32 (84.4) N/S N/S N/S N/S
et al15
Bickel et al9 8 6/8 (75.0) 2/8 (25.0) 0/8 1/8 (12.5) 7/8 (87.5) 0/8 1/8 (12.5) 4/8 (50.0) 1/8 (12.5) 0/8 1/8b (12.5) Lap+PalC: 1/8 (12.5)a
Broecker 10 4/7 (57.1) 2/7 (28.5) 1/7 (14.3) 2/7 (28.5) 5/7 (71.4) 0/7 N/S N/S N/S N/S N/S N/S
et al23
Bejany et al8 11 1/11 (9.1) 9/11 (81.8) 1/11 (9.1) 0/11 11/11 (100) 0/11 0/11 7/11d (63.6) 2/11 (9.1) 1/11 (9.1) 0/11 Lap+PalC: 1/11 (9.1)a
El-Masri 25 8/25 (32.0) 11/25 (44.0) 6/25 (24.0) 1/25 (4.0) 22/25 (88.0) 2/25 (8.0) N/S N/S N/S N/S N/S N/S
et al24
West et al25 130 23/42 (54.8) 14/42 (33.3) 5/42 (11.9) N/S N/S N/S 17/42 (40.5) 25/42 (59.5) N/S N/S N/S N/S
Katsumi 3 0/3 0/3 3/3 (100) N/S N/S N/S N/S N/S N/S N/S N/S N/S
et al26
Sammer 1 0/1 0/1 1/1 (100) 0/1 1/1 (100) 0/1 0/1 1/1 (100) 0/1 0/1 0/1 0/1
et al27
Bothig et al28 24 19/24 (79.2) 4/24 (16.7) 1/24 (4.2) 19/24 (79.2) 5/24 (20.8) 0/24 5/24c (20.8) 15/24 (62.5) 0/24 2/24 (8.3) 0/24 Pall ureterocutaneoastomy:
1/24 (4.2)
PalC: 1/24 (4.2)
Overall 332 111/209 70/209 (33.5) 28/209 (13.4) 49/158 (31.0) 107/158 2/158 27/105 107/156 (68.6) 7/82 (8.6) 4/82 (4.9) 1/63 (1.6) 4/87 (4.6)
average (53.1) (67.7) (1.3) (25.7)

Chemo, chemotherapy; Endosc, endoscopic; Intraves tx, intravesical therapy; Lap, laparotomy; MI, muscle invasive; NMI, non-muscle invasive; N/S, not specified; PalC, palliative care; pTx, unknown pathological stage; Rad,
radiotherapy; SCC, squamous cell carcinoma; TCC, transitional cell carcinoma.
a
Bladder rupture cases.
b
Patient also had BCG.
c
Four patients had palliative TUR.
d
Four patients also had simultaneous urethrectomy.
|
7
8
| ISMAIL ET AL.

screening for bladder cancer in neuro-urological patients

Overall mortality (%)
could improve the global management of these patients and
their prognosis. The results of such studies may serve as a

130/226 (57.5)
15/37 (40.5)

13/21 (61.9)

23/32 (71.9)

21/25 (84.0)
24/42 (57.1)

15/24 (62.5)
6/11 (54.5)
3/8 (38.0) basis for future specific guidelines regarding screening,

2/4 (50.0)

3/8 (37.5)
5/7 (71.4)
diagnosis, treatment options and follow-up for bladder

N/S
N/S
0/1
0/6
cancer in neuro-urological patients. However, the facts
remain that bladder cancer in neuro-urological patients is
Other cause mortality (%)

uncommon and that current screening methods, whether it

be cystoscopy, urinary cytology or urinalysis, are neither
effective nor cost-effective. For the moment, we should

20/155 (12.9)
avoid screening the general neuro-urological population,
12/21 (57.1)
5/37 (13.5)

2 /8 (25.0)
1/21 (4.8)

and only target patients with signs and symptoms.34

0/25

0/24
N/S
N/S

N/S
N/S
N/S
0/8

0/4
0/1
0/6

4.4 | Implications for practice

Cancer-specific mortality (%)

A number of key concepts can be drawn from this current

systematic review. The simple fact that 44.5% of patients with
neurogenic bladder dysfunction and bladder cancer had either
73/155 (47.1)
10/37 (27.0)

12/21 (57.1)

21/25 (84.0)

15/24 (62.5)
9/21 (42.8)

an indwelling urethral catheter or a supra-pubic catheter as

3/8 (38.0)

2/4 (50.0)

1/8 (12.5)

their longest/most recent method of bladder drainage is

N/S
N/S

N/S
N/S
N/S
0/1
0/6

alarming. To avoid chronic bladder irritation other method of

bladder drainage should be encouraged.
Overall survival (%)

Moreover, gross hematuria in neuro-urological patients may

TABLE 4 Follow-up time, survival, and mortality rates of neuro-urological patients with bladder cancers

often be wrongly considered benign and therefore does not get

96/226 (42.4)
22/37 (59.5)

18/42 (42.9)
8/21 (38.1)

9/32 (28,1)

5/11 (45.5)
4/25 (16.0)

9/24 (37.5)

investigated. In reality, gross hematuria investigations seem to

5/8 (62.5)

2/4 (50.0)

5/8 (62.5)
2/7 (28.5)
1/1 (100)
6/6 (100)

be justified and necessary, since hematuria is the most common

N/S
N/S

presenting symptom of bladder cancer. In contrast, urinary

cytology cannot be considered a useful tool because it has a poor
Median survival (mean) mos.

sensitivity for the detection of SCC1,14 and because it has a

limited ability to distinguish bladder cancer from alterations that
may be due to infections, inflammations and stones.35
The high mortality rate of bladder cancer in neuro-urological
patients calls into question the screening methods for these
12.5 (13.3)

11.5 (22.7)
13.0 (N/S)

patients. A 2015 study by Averbeck and Madersbacher16

N/A
N/S
N/S
N/S
N/S

N/S
N/S

N/S
N/S
N/S
N/S
N/S

investigated the normal follow-up of the neuro-urological patient

in a systematic fashion. Regarding the follow-up of these patients,
they concluded that “there is a lack of high-level evidence studies
Median follow-up (mean) mos.

and guidelines are mainly based on expert opinions”. International

guidelines on neurogenic lower urinary tract dysfunction remain
incomplete on follow-up recommendations due to a lack of solid
data. Among other things, they recommend a urinary tract
19.5 (29.1)

48.0 (48.0)

ultrasound every six months and a “detailed specialist investiga-

N/S (22.3)

N/S (12.3)

N/S (66.0)

tion every 1-2 years and on demand when risk factors emerge”.36
N/S

N/S

N/S
N/S

N/S
N/S
N/S

N/S
N/S
N/S

The Consortium for Spinal Cord Medicine clinical practice

guidelines also state that there are no studies assessing the
130

332

optimum frequency of follow-up investigations.29,37 Moreover,

48

21

32

10
11
25

24
n

4
1
6

3
1

the American Urological Association has not elaborated guide-

Subramonian et al20

lines for neurogenic bladder dysfunction until now. Even for the
Kalisvaart et al15
Sugimara et al21

Broecker et al23

Overall average
El-Masri et al24

Katsumi et al26
Sammer et al27

general population, guidelines are only available for transitional

Bothig et al28
Groah et al19

Bejany et al8
Bickel et al9
Chao et al22

West et al25
References

Parra et al1

cell carcinomas of the bladder. This highlights the importance of

Pannek7

prospective studies to investigate disease-specific outcomes. In

our study, bladder cancer was diagnosed after an overall mean
ISMAIL ET AL.
FIGURE 2 Risk of confounding assessment
time of 24.9 (16.3-33.0) years following the neurological disease.
The French speaking group of neuro-urology recommends that a
cystoscopy and urinary cytology be performed fifteen years after
the neurological disease diagnosis.1,38 However, this practice
remains controversial due to lack of sensitivity and specific-
ity.15,16,27,39,40 Moreover, cystoscopies in patients with a SCI
above T6 may trigger autonomic dysreflexias and therefore
should be performed by specialised urologists or under general
anaesthesia.28
4.5 | Limitations of the study
Some limitations of the study need to be addressed. First,
although the objective of our study was to perform a systematic
review that assesses bladder cancer in the neuro-urological
patient population, we were mainly exclusively able to target
patients with SCI because of the major lack of literature
regarding bladder cancer in other neurological diseases (ie,
multiple sclerosis, spina bifida . . .). Another limitation is that the
included studies were mostly retrospective series. Primary
outcomes and methodology varied widely and this explains why
many data were missing. For example, follow-up data were
missing in 10 (66.7%) of the studies. Standard deviations were
only reported in six studies for one or two variables, while the
others did not report any. Data collection for the bladder
drainage method was complicated by the fact that one unique
patient may have been using many different bladder drainage
methods since the diagnosis of his neurological disease. Also,
because included studies were published between 1981 and
2017, the histopathological data regarding bladder cancer grade
and lymph node stage were not reported in a consistent fashion.
Therefore, it was not possible to include these data in our study.
Again, because older studies were also included, bladder cancer
management may have been suboptimal at that time and this
could contribute to the high cancer-specific mortality rate in our
meta-analysis. Finally, the fact that this is a meta-analysis
implies that all the limitations of the included studies are also
limitations to this current study. However, since we aimed to
summarize existing evidence, we consider our approach to be
acceptable. We lack the inclusion of the general population as a
comparator. Moreover, studies were small and outcomes varied
widely. Thus, scarcity of data did not allow for subgroup
analyzes. Finally, the risk of confounding was substantial and
more reliable evidence is urgently required.
| 9
5 | CONCLUSIONS
This review indicates that bladder cancer in neuro-urological
patients, particularly in the SCI population, is as prevalent as
it is in the general population. However, the prevalence of
aggressive bladder cancer and of SCC is higher. The
prevalence, aggressiveness and high mortality rate of bladder
cancer in neuro-urological patients underlines the importance
of long-term follow up in this specific population. The
necessity of further studies, especially in the long term and
regarding carcinogenesis in this field, is crucial.
ACKNOWLEDGMENT
The authors thank E. Spanudakis for her review of the
manuscript.
AUTHORS’ CONTRIBUTION
All authors substantially contributed in 1) Conception and design;
2) Drafting and revising the article critically for important
intellectual content; and 3) Final approval of this version.
ORCID
Salima Ismail http://orcid.org/0000-0001-9203-5136
Gilles Karsenty http://orcid.org/0000-0002-9047-3332
REFERENCES
1. Parra J, Drouin S, Comperat E, et al. Bladder cancer in neurological
patients: analysis of a single-centre series. Prog En Urol J Assoc Fr
Urol Société Fr Urol. 2007;17:1333–1336.
2. Ruffion A, Comperat E, Roupret M, Chartier-Kastler E. Bladder
cancer and neurogenic bladder. Prog En Urol J Assoc Fr Urol
Société Fr Urol. 2007;17:431–435.
3. Lee W-Y, Sun L-M, Lin C-L, et al. Risk of prostate and bladder
cancers in patients with spinal cord injury: a population-based
cohort study. Urol Oncol. 2014;32:1–7.
4. National Spinal Cord Injury Statistical Center, University of
Alabama at Birmingham. 2014 Annual statistical report—complete
public version. Available at: https://www.nscisc.uab.edu/Public
Documents/reports/pdf/2014%20NSCISC%20Annual%20Statisti
cal%20Report%20Complete%20Public%20Version.pdf. Accessed
March 13, 2016.
5. Howlader N, Noone A, Krapcho M, et al. Seer cancer statistics
review, 1975-2012. National Cancer Institute. Available at: http://
seer.cancer.gov/csr/1975_2012/. Accessed March 13, 2016.
6. Nahm LS, Chen Y, DeVivo MJ, Lloyd LK. Bladder cancer mortality
after spinal cord injury over 4 decades. J Urol. 2015; 193:1923–1928.
7. Pannek J. Transitional cell carcinoma in patients with spinal cord
injury: a high risk malignancy? Urology. 2002;59:240–244.
8. Bejany DE, Lockhart JL, Rhamy RK. Malignant vesical tumors
following spinal cord injury. J Urol. 1987;138:1390–1392.
10
| ISMAIL
9. Bickel A, Culkin DJ, Wheeler JS. Bladder cancer in spinal cord
injury patients. J Urol. 1991;146:1240–1242.
10. Locke JR, Hill DE, Walzer Y. Incidence of squamous cell
carcinoma in patients with long-term catheter drainage. J Urol.
1985;133:1034–1035.
11. Kaufman JM, Fam B, Jacobs SC, et al. Bladder cancer and squamous
metaplasia in spinal cord injury patients. J Urol. 1977; 118:967–971.
12. Esrig D, McEvoy K, Bennett CJ. Bladder cancer in the spinal cord-
injured patient with long-term catheterization: a casual relation-
ship? Semin Urol. 1992;10:102–108.
13. Arslan B, Bozkurt IH, Yonguc T, et al. Clinical features and
outcomes of nontransitional cell carcinomas of the urinary bladder:
analysis of 125 cases. Urol Ann. 2015;7:177–182.
14. Manunta A, Vincendeau S, Kiriakou G, Lobel B, Guillé F. Non-
transitional cell bladder carcinomas. BJU Int. 2005;95:497–502.
15. Kalisvaart JF, Katsumi HK, Ronningen LD, Hovey RM. Bladder
cancer in spinal cord injury patients. Spinal Cord. 2010;48:257–261.
16. Averbeck MA, Madersbacher H. Follow-up of the neuro-urological
patient: a systematic review. BJU Int. 2015;115:39–46.
17. Moher D, Liberati A, Tetzlaff J, Altman DG, Group PRISMA.
Preferred reporting items for systematic reviews and meta-analyzes:
the PRISMA statement. Int J Surg Lond Engl. 2010;8: 336–341.
18. Viswanathan M, Ansari MT, Berkman ND, et al. Assessing the risk
of bias of individual studies in systematic reviews of health care
interventions. In: Methods Guide for Effectiveness and Compara-
tive Effectiveness Reviews. AHRQ Methods for Effective Health
Care. Rockville (MD): Agency for Healthcare Research and Quality
(US); 2008. Available at: http://www.ncbi.nlm.nih.gov/books/
NBK91433/. Accessed March 13, 2016.
19. Groah SL, Weitzenkamp DA, Lammertse DP, Whiteneck GG,
Lezotte DC, Hamman RF. Excess risk of bladder cancer in spinal
cord injury: evidence for an association between indwelling catheter
use and bladder cancer. Arch Phys Med Rehabil. 2002;83:346–351.
20. Subramonian K, Cartwright RA, Harnden P, Harrison SCW. Bladder
cancer in patients with spinal cord injuries. BJU Int. 2004;93:739–743.
21. Sugimura T, Arnold E, English S, Moore J. Chronic suprapubic
catheterization in the management of patients with spinal cord
injuries: analysis of upper and lower urinary tract complications.
BJU Int. 2008;101:1396–1400.
22. Chao R, Clowers D, Mayo ME. Fate of upper urinary tracts in
patients with indwelling catheters after spinal cord injury. Urology.
1993;42:259–262.
23. Broecker BH, Klein FA, Hackler RH. Cancer of the bladder in
spinal cord injury patients. J Urol. 1981;125:196–197.
24. El-Masri WS, Fellows G. Bladder cancer after spinal cord injury.
Paraplegia. 1981;19:265–270.
25. West DA, Cummings JM, Longo WE, Virgo KS, Johnson FE, Parra
RO. Role of chronic catheterization in the development of bladder
cancer in patients with spinal cord injury. Urology. 1999;53:292–297.
26. Katsumi HK, Kalisvaart JF, Ronningen LD, Hovey RM. Urethral
versus suprapubic catheter: choosing the best bladder management
for male spinal cord injury patients with indwelling catheters.
Spinal Cord. 2010;48:325–329.
27. Sammer U, Walter M, Knüpfer SC, Mehnert U, Bode-Lesniewska
B, Kessler TM. Do we need surveillance urethro-Cystoscopy in
patients with neurogenic lower urinary tract dysfunction? PLoS
ONE. 2015;10:e0140970.
ET AL.
28. Böthig R, Kurze I, Fiebag K, et al. Clinical characteristics of bladder
cancer in patients with spinal cord injury: the experience from a
single centre. Int Urol Nephrol. 2017;49:983–994.
29. Welk B, McIntyre A, Teasell R, Potter P, Loh E. Bladder cancer in
individuals with spinal cord injuries. Spinal Cord. 2013;51:
516–521.
30. World Health Organization, International Spinal Cord Society, eds.
International Perspectives on Spinal Cord Injury. Geneva,
Switzerland: World Health Organization; 2013.
31. Kirkali Z, Chan T, Manoharan M, et al. Bladder cancer: epidemiology,
staging and grading, and diagnosis. Urology. 2005;66:4–34.
32. Ferlay J, Soerjomataram I, Ervik M, et al. Cancer incidence and
mortality worldwide: IARC Cancer Base No. 11. 2013. Available
at: http://globocan.iarc.fr. Accessed December 19, 2015.
33. Parkin D, Whelan S, Felay J. Cancer incidence in five continents.
Lyon Fr IARC Publ. 2002;VIII
34. Elliott SP. Screening for bladder cancer in individuals with spinal
cord injury. J Urol. 2015;193:1880–1881.
35. Raisi O, Magnani C, Bigiani N, et al. The diagnostic reliability of urinary
cytology: a retrospective study. Diagn Cytopathol. 2012;40:608–614.
36. European Urology Assocation Guidelines. Neurogenic lower urinary
tract dysfunction—update March 2011. 2013. Available at: http://
uroweb.org/wp-content/uploads/20_Neurogenic-LUTD_LR.pdf.
Accessed December 20, 2015.
37. Consortium for spinal cord medicine. bladder management for
adults with spinal cord injury: a clinical practice guideline for
health-care providers. 2006. Available at: http://www.pva.org/atf/
cf/{CA2A0FFB-6859-4BC1-BC96-6B57F57F0391}/CPGBladder
Manageme_1AC7 B4. pdf.
38. Ruffion A, de Sèze M, Denys P, Perrouin-Verbe B, Chartier-Kastler
E. Recommandations du Grouve d’Études de Neuro-Urologie de
Langue Française (GENULF) pour le suivi du blessé médullaire et
du patient spina bifida. Prog En Urol J Assoc Fr Urol Société Fr
Urol. 2007;17:631–633.
39. Austin JC, Elliott S, Cooper CS. Patients with spina bifida and
bladder cancer: atypical presentation, advanced stage and poor
survival. J Urol. 2007;178:798–801.
40. Hamid R, Bycroft J, Arya M, Shah PJR. Screening cystoscopy and
biopsy in patients with neuropathic bladder and chronic suprapubic
indwelling catheters: is it valid? J Urol. 2003;170:425–427.
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How to cite this article: Ismail S, Karsenty G,
Chartier-Kastler E, et al. Prevalence, management,
and prognosis of bladder cancer in patients with
neurogenic bladder: A systematic review.
Neurourology and Urodynamics. 2017;1–10.
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