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

follow-up care, it is only to be expected that life expectancy of 2.2 | Study selection
patients with neurogenic bladder, that is, neuro-urological
Study selection was performed according to the PICo method
patients will increase. As they live longer, they will inevitably
for qualitative studies. We included all original studies that
be exposed to a higher risk of developing other serious
reported the epidemiology (specifically the incidence and/or
diseases such as bladder cancer.1
prevalence), risk factors, clinical presentation, histological
While the overall risk of bladder cancer may not be greater
details, and management and prognosis of bladder cancer
than the risk in the general population,1–3 the mortality rate is
among neuro-urological patients. Studies on bladder aug-
definitely higher. Although bladder cancer is the third most
mentation, case reports, case studies, commentaries, reviews;
frequent cause of cancer death among spinal cord injury
studies not published as full-text; and those not discriminating
patients (SCI),4 it is only the ninth in the US general
between non neuro-urological and neuro-urological patients
population.5 More specifically, a recent study by Nahm et al6
were excluded. All identified abstracts were imported into a
showed that patients with spinal cord injury are 6.7 times
bibliography management software (Zotero 4.0.28.8; Center
more likely to die of bladder cancer compared to the general
for History and New Media, George Mason University,
population. This can be explained by the higher rate of
Fairfax, VA) and sorted into inclusion and exclusion folders
squamous cell carcinoma (SCC) in neuro-urological
by drag and drop. Abstracts of all identified studies were
patients.1,2,7 This specific bladder cancer histological subtype
independently reviewed by two authors (SI and VP). Studies
is associated with chronic infections, stones and indwelling
reporting on bladder cancer among neuro-urological patients
catheters,8–13 which explains why this subtype is more
were reviewed in full text.
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
2.3 | Data extraction, risk of bias assessment,
because of the delay in diagnosis.12,13 Squamous cell
and data synthesis
carcinoma of the bladder has a limited response to
chemotherapy and radiotherapy. To improve prognosis, an The variables assessed included year of publication, type of
early surgical approach is recommended.13,14 study, and bladder cancer prevalence. Relevant data regarding
Despite the fact that bladder cancer is more morbid in population characteristics and clinical presentations were also
neuro-urological patients, bladder screening and management retrieved: population size, age, type of neurological disorders,
recommendations are mainly based on expert opinions and presenting symptoms (gross hematuria and other urinary
lack consensus.1,6,15,16 Indeed, all current management symptoms), urodynamic parameters, upper urinary tract
guidelines are dedicated to transitional cell carcinomas and assessment, risk factors (bladder stones, smoking, recurrent
non neuro-urological patients. The aim of the current study urinary tract infections [UTI]), bladder drainage method, and
was to perform a systematic review of the literature and a duration of neuro-urological disease at the time of bladder
meta-analysis regarding epidemiology, diagnosis, manage- cancer diagnosis. We also assessed bladder cancer histopath-
ment and prognosis of bladder cancer in the neuro-urological ological data (histological subtype, stage, and grade) and type
patient population, in order to serve as a basis for future of management (intravesical treatment, cystectomy, chemo-
recommendations and research. 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,
2 | METHODS and overall mortality were assessed. Finally, the level of
evidence of each study was determined according to the
2.1 | Data sources and searches Oxford Centre for Evidence-Based Medicine (2011). Data
This systematic review was performed according to the Preferred from eligible reports were extracted in duplicate (SI and VP)
Reporting Items for Systematic Reviews and Meta-Analyze and discrepancies were resolved by a third reviewer (MR).
(PRISMA) Statement (see Supplementary Material 1).17 Risk of bias in non-comparative studies cannot be assessed
We performed a systematic search in Embase in order to retrieve with Cochrane Risk of Bias Assessment tool used for RCTs.18
all published papers regarding bladder cancer and neurogenic Therefore, concern was extended in non-comparative studies
bladder up to July 2017. We additionally searched the reference to address external validity by assessing whether specified
lists of all included studies and relevant review articles. No confounding factors were reported. A list of the six most
language nor date restrictions were applied. Medical subject important potential confounders was identified. For each
heading (MeSH) terms used were: neurogenic bladder, neuro- study, we asked whether each confounder was considered and
genic detrusor overactivity, spina bifida, meningomyelocele, whether, if necessary, the confounder was controlled for in
multiple sclerosis, and spinal cord injury. Each of these key words analysis. The potential confounding factors were underlying
was crossed with bladder cancer. neurological disease (eg, spinal cord injury, multiple sclerosis,
ISMAIL ET AL.
| 3

etc.), gender, tumor stage, type of treatment, voiding mode, and stones and smoking ranged between 20.8-45.5% and 12.5-70.0%
duration of the neurological disease since onset. , respectively. Recurrent UTIs were taken into account in only 2/
Overall means and rates were calculated for each variable 15 (13.3%) studies. Thirty-one percent of patients voided
whenever possible. 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
3 | RESULTS
44.5% of patients. Mean time between neurological disease and
bladder cancer diagnosis was 24.9 years (Table 2).
3.1 | Search results
The PRISMA flow diagram of the literature search and results
3.3 | Diagnosis of bladder cancer in neuro-
is shown in Figure 1. After screening 637 abstracts, 15
urological patients
studies1,7–9,15,19–28 published between 1981 and 2017 were
included in a narrative synthesis (Tables 1–4): 13 retrospec- Gross hematuria was one of the presenting symptoms in
tive studies and 2 prospective studies. 31.6% of patients. Very scarce data were available regarding
urodynamic parameters and upper urinary tract assessment
(Table 2).
3.2 | Study and patient characteristics
The most frequent histological subtype of bladder cancer
Among the 15 included studies, we identified 332 patients with was transitional cell carcinoma (TCC) (53.1%), followed by
bladder cancer: 197 men (58.3%) and 15 women (4.5%). In 120 squamous cell carcinoma (SCC) (33.5%). Non-muscle invasive
patients (36.1%), gender was unreported. The mean age at bladder cancer was reported in 31.0% of patients compared to
diagnosis was 56.1 years. Patients suffered from spinal cord 67.7% muscle-invasive bladder cancer. Treatment care varied
injury (SCI) (n = 328; 98.8%), spina bifida (n = 1; 0.3%), widely ranging from endoscopic management ± intravesical
multiple sclerosis (n = 2; 0.6%), or familial paraplegia therapy (27/105, 25.7%) to palliative care (4/87, 4.6%). The
(n = 1; 0.3%). The overall incidence of bladder cancer was majority of patients were treated by endoscopic resection
0.3%, ranging from 0.1% to 7.4% (Table 1). History of bladder followed by cystectomy (107/156, 68.6%) (Table 3).

FIGURE 1 Preferred reporting items for systematic reviews and meta-analyses flow diagram
 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
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| ISMAIL ET AL.

3.4 | Prognosis of bladder cancer in synthesis of all evidence in order to provide recommendations
neuro-urological patients was not available. To the best of our knowledge, we present the
first systematic review of the literature on bladder cancer that
Data on median/mean follow-up and survival times were very
attempts to include all neuro-urological patients. Previous
scarce. Median follow-up and survival times ranged from 19.5
reviews of the literature related to the topic were published over
to 48.0 and from 11.5 to 13.0 months, respectively. The mean
the last decade but these were not systematic and focused only
overall survival and overall mortality rates were of
on SCI patients.2,29 However, despite our efforts, 98.8% of the
42.4% (96/226) and 57.5% (130/226) respectively. The mean
patients included in this current study are SCI patients because
cancer-specific mortality rate was of 47.1% (73/155) (Table 4).
of the very limited bladder cancer data available in the
literature regarding other neuro-urological populations.
3.5 | Risk of bias and confounding In our study, the majority of neuro-urological patients
with bladder cancer were men (59.3%), considering the
We had identified a list of the six most important potential gender was not specified in 36.1% of patients. The male
confounders (Figure 2): underlying neuro-urological disease, predominance can be explained by the fact that the adult male-
gender, voiding mode, duration of the neurological disorder, to-female ratio of traumatic SCI has been reported to be at
tumor stage, and treatment type. Less than 50% of the included least of 2:1.30 Another explanation are the smoking and
studies reported a gender ratio. Of all 15 included studies, only one occupational habits of men.31 The incidence of bladder cancer
was considered potential confounders in its data analysis. Groah in the general population is also much higher in men (4.5%)
et al19 calculated a relative risk of 1.9 for bladder cancer in males compared to women (1.5%).32
and a relative risk of 0.5 in patients with a cervical level of SCI. 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
4 | DISCUSSION
(0.1-10%).29 In men less than 75 years of age in the general
population, bladder cancer prevalence is also comparable (2 to
4.1 | Principal findings 4%).31,33 As previously reported and now confirmed once again
In this present systematic review, we attempted to identify in this current study, the rate of SCC (33.5%) is higher in patients
papers from the multiple different neurogenic bladder with neurogenic bladder dysfunction compared to the general
populations; however, the vast majority of the literature population (2-7%).14,29 Bladder cancers in our study population
(98.8%) came from the SCI population. Bladder cancer was were more aggressive, as they tended to be muscle invasive, as
reported in 0.3% of the included population and mostly SCCs are known to be.12,13 Welk et al29 also reported that the
affected men (59.3%). The mean age at diagnosis was 56.1 rate of muscle invasive bladder cancer was significantly higher
and bladder cancer occurred after a long period of evolution of in patients with spinal cord injury compared to the general
the neurological disease (24.9 years). Gross hematuria was population. The aggressivity of bladder cancer in patients with
definitely the predominant presentation, being reported in neuro-urological diseases explains why SCI patients are 6.7
31.6% of cases. Among the risk factors, indwelling urethral or times more likely to die of bladder cancer compared to the
supra-pubic catheters were used by 44.5% of patients. The general population.6
most frequent histological subtype of bladder cancer was
TCC (53.1%), followed by SCC with a rate of 33.5%. The
4.3 | Implications for research
majority of bladder cancers were muscle-invasive (67.7%)
and radical cystectomy was the treatment of choice in 68.6% With the advancement of medicine and technology, life
of patients. The overall cancer-specific mortality rate of expectancy of patients with neurological disease has
47.1% for an overall median follow-up ranged between 19.5 increased, to a state where they are now facing the same
and 48.0 months. Only one study out of 15 was considered medical diseases as the general population. Bladder cancer
confounders in their data analysis with conflicting results. 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
4.2 | Findings in the context of existing
in these patients, there must be other bladder cancer features
evidence
that are specific to patients with neurogenic bladder and may
It is well-known by physicians managing patients with a contribute to its aggressiveness. Identifying these factors
neurogenic bladder that this population may develop bladder could allow us to improve the diagnosis and treatment
cancer in the long run due to various risk factors, including options in these patients. This may also require the study of
smoking, chronic inflammation of the bladder secondary to the the urothelial carcinogenesis in this specific patient
presence of catheters, bladder stones, and UTIs. However, a 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.
| 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
FIGURE 2 Risk of confounding assessment of long-term follow up in this specific population. The
necessity of further studies, especially in the long term and
time of 24.9 (16.3-33.0) years following the neurological disease.
regarding carcinogenesis in this field, is crucial.
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
ACKNOWLEDGMENT
remains controversial due to lack of sensitivity and specific-
ity.15,16,27,39,40 Moreover, cystoscopies in patients with a SCI The authors thank E. Spanudakis for her review of the
above T6 may trigger autonomic dysreflexias and therefore manuscript.
should be performed by specialised urologists or under general
anaesthesia.28
AUTHORS’ CONTRIBUTION
4.5 | Limitations of the study All authors substantially contributed in 1) Conception and design;
Some limitations of the study need to be addressed. First, 2) Drafting and revising the article critically for important
although the objective of our study was to perform a systematic intellectual content; and 3) Final approval of this version.
review that assesses bladder cancer in the neuro-urological
patient population, we were mainly exclusively able to target ORCID
patients with SCI because of the major lack of literature
regarding bladder cancer in other neurological diseases (ie, Salima Ismail http://orcid.org/0000-0001-9203-5136
multiple sclerosis, spina bifida . . .). Another limitation is that the Gilles Karsenty http://orcid.org/0000-0002-9047-3332
included studies were mostly retrospective series. Primary
outcomes and methodology varied widely and this explains why
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