Bricker vs néovessie de substitution : laquelle offre la meilleure qualité de vie après cystectomie radicale? Une revue systématique de littérature et méta-analyse

25 avril 2018

Auteurs : I. Ziouziou, J. Irani, J.T. Wei, T. Karmouni, K. El Khader, A. Koutani, A. Iben Attya Andaloussi
Référence : Prog Urol, 2018, 5, 28, 241-250




 




Introduction


There has been an increasing interest on the quality of life in uro-oncology field in the last years. Several new tools were developed to evaluate the health-related quality of life (HR-QoL) especially in bladder cancer (BC) patients: EORTC-QLQ-BLS24, FACT-Bladder, FACT Vanderbilt Cystectomy Index, Bladder Cancer Index [1, 2, 3, 4].


After radical cystectomy (RC), several techniques of urinary diversions (UD) are possible: ureterostomy, ileal conduit (IC), orthotopic neobladder (ONB), etc. The two most commonly practiced techniques are IC and ONB. Patient and surgeon preferences, health status, disease stage, and targeted QoL should all be considered in the selection of UD [5].


Two meta-analyses have been published by Yang et al. and Cerruto et al. in 2016 and 2017 respectively [6, 7]. The main methodological concern with these meta-analyses was the inclusion of studies using different tools of HRQoL measurement with various specificities to BC, which was a source of significant biases. Indeed, while Cerruto et al. concluded to an advantage of ONB compared to IC in terms of HR-QoL, Yang et al. reported a comparable HR-QoL after radical cystectomy after either ONB or IC. Therefore it is still unclear after RC which UD offers the best HR-QoL for patients.


The objective of our study was to compare HR-QoL in patients undergoing ONB and IC after RC.


We performed a systematic review of literature and meta-analysis of studies comparing HR-QoL in patients undergoing ONB and IC after RC and using the BCI-questionnaire in the assessment of HR-QoL. We have chosen the BCI as a single tool of measurement in order to overcome the limitation of heterogeneity encountered in the previous meta-analyses.


Material and methods


Search strategy


We performed a computerized bibliographic search on different databases: PubMed, ScienceDirect, CochraneLibrary and ClinicalTrials.Gov using the following keywords: "Bladder cancer", "Cystectomy", "Orthotopic neobladder", "Ileal conduit", "Quality of life", "Bladder cancer index", and "BCI" in September 2017. Afterwards a complementary search in Google Scholar was made. We used the software Zotero (www.zotero.org/) version 4.0.29.17, for the management of bibliography. A "Preferred Reporting Items for Systematic Reviews and Meta-Analyzes" (PRISMA) chart has been developed to describe the procedure of selecting studies.


Inclusion criteria


According to the PRISMA guidelines, we used the PICO approach to define study eligibility.


The clinical question was formulated according to the PICO criteria (population, intervention, control, outcome):

population: patients undergoing radical cystectomy (Radical cystectomy);
intervention: orthotopic neobladder;
control=ileal conuit;
outcomes=Bladder Cancer Index subdomains.



"Ileal conduit vs orthotopic neobladder: which one offers the best health-related quality of life according to the Bladder Cancer Index questionnaire in patients undergoing radical cystectomy?"


Inclusion criteria were the following:

comparative studies reporting long-term results with a follow-up ≥3 years;
population: Patients undergoing radical cystectomy;
intervention: orthotopic neobladder (ONB);
control: ileal conduit (IC);
outcomes Bladder Cancer Index subdomains' scores:
∘
urinary function (UF),
∘
urinary bother (UB),
∘
bowel function (BF),
∘
bowel bother (BB),
∘
sexual function (SF),
∘
sexual bother (SB).


One exclusion criterion was applied: language other than English or French.


No restriction in time was used.


Systematic review process


Two authors (IZ and JI) reviewed the articles. We performed a systematic review of literature with meta-analysis according to the recommendations of the "Cochrane Handbook for Systematic Reviews of Interventions" and "Preferred Reporting Items for Systematic Reviews and Meta-Analyzes" (PRISMA) [8, 9].


Quality of data assessment


The studies were evaluated according to the criteria of "Oxford Center for Evidence-Based Medicine" [10].


Data extraction


For each study selected, the following data were extracted: year, country, journal, type of study, total number of patients, number of patients "ONB", number of patients "IC", age, percentage of stage less or equal to pT2 in each group, follow-up (months), means and standard deviations of the BCI sub-domains' scores (function and bother).


Statistical analysis


Statistical methods followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions [8].


Continuous outcomes were compared using weighted mean differences, with 95% confidence intervals.


The I 2 tests were used to evaluate the heterogeneity of the studies for each outcome, with the Chi2 tests: heterogeneity was considered significant if I 2 greater than 50% with P <0.10.


In the case of significant heterogeneity with an I 2 value greater than 50%, a random effect model was applied. Otherwise, in the case of non-significant heterogeneity, a fixed effect model was used. The missing values (mean and standard deviations of continuous outcomes when they were not published or reported) were calculated using the Wan formula [11]. The presence of publication bias was examined by funnel plots. The analyzes were performed using ReviewManager 5.3 (version 5.3.5).


Results


Included studies


Two hundred and sixty articles were identified following the search in MedLine, ScienceDirect, CochraneLibrary and ClinicalTrials.Gov databases, using the keywords: "Bladder cancer", "Cystectomy", "Orthotopic neobladder", "Ileal conduit", "Quality of life", "Bladder cancer index", and "BCI". After the exclusion of studies that did not meet the inclusion criteria, or with an exclusion criterion, as well as duplicates, four studies were selected: Gellhaus 2017, Goldberg 2016, Huang 2015, Hedgepeth 2010 [12, 13, 14, 15].


Afterwards a complementary search in Google Scholar identified a study, which was not included.


The PRISMA chart illustrates the steps in the selection process (Figure 1).


Figure 1
Figure 1. 

PRISMA flow diagram: review process for meta-analysis.




Characteristics and quality of studies


The characteristics of the selected studies are detailed in the Table 1. IC patients were significantly older than ONB patients in three studies (Goldberg, Gellhaus, Hedgepeth). In the study of Huang et al., there was no significant difference in the age between the two groups.


Statistical analysis


The Bladder Cancer Index sub-domains' scores correspond to Likert scales: the higher the score (whether it is a function score or bother score), the better is clinical status and quality of life.


Outcome: urinary function BCI subdomain score


The BCI score for urinary function was reported by four studies, including a total of 486 patients (Figure 2). The pooled results according to a random effect model demonstrated a significant difference of −18.17 of the BCI score of the urinary function in favor of the ileal conduit (95% CI: −27.49, −8.84, P =0.0001) with significant heterogeneity (Chi2=84.41, df =3, (P <0.00001), I 2=96%).


Figure 2
Figure 2. 

Forest plot: urinary function subdomain score.




Outcome: urinary bother BCI subdomain score


The BCI score of urinary bother was reported by four studies, including a total of 486 patients (Figure 3). The pooled results according to a random effect model demonstrated a significant difference of −3.72 from the BCI score of urinary bother in favor of ileal conduit (95% CI: −6.66, −0.79, P =0.01) with significant heterogeneity (Chi2=11.51, df =3, (P =0.009), I 2=74%).


Figure 3
Figure 3. 

Forest plot: urinary bother subdomain score.




Outcome: bowel function BCI subdomain score


The BCI score of bowel function was reported by two studies, including a total of 187 patients (Figure 4). The pooled results using a fixed-effect model demonstrated a non-significant difference of −0.92 between ONB and IC (95% CI: −4.30, 2.47, P =0.60) with non-significant heterogeneity (Chi2=1.92, df =1 (P =0.17), I 2=48%).


Figure 4
Figure 4. 

Forest plot: bowel function subdomain score.




Outcome: bowel bother BCI subdomain score


The BCI score of bowel bother was reported by two studies including 187 patients (Figure 5). The pooled results of the fixed-effect model showed a non-significant difference of 0.42 between ONB and IC (95% CI, −2.82, 3.65, P =0.80) with non-significant heterogeneity (Chi2=0.06, df =1 (P =0.81), I 2=0%).


Figure 5
Figure 5. 

Forest plot: bowel bother subdomain score.




Outcome: sexual function BCI subdomain score


The BCI score for sexual function was reported by two studies including 187 patients (Figure 6). The pooled results of the fixed-effect model showed a significant difference of 12.7 in favor of ONB (95% CI, 6.32, 19.08, P <0.0001) with non-significant heterogeneity (Chi2=0.00, df =1 (P =1.00), I 2=0%).


Figure 6
Figure 6. 

Forest plot: sexual function subdomain score.




Outcome: sexual bother BCI subdomain score


The BCI score of sexual bother was reported by two studies including 187 patients (Figure 7). The pooled results of the fixed-effect model showed a non-significant difference of −7.08 between ONB and IC (95% CI, −15.13, 0.96, P =0.08) with non-significant heterogeneity (Chi2=1.96, df =1 (P =0.16), I 2=49%).


Figure 7
Figure 7. 

Forest plot: sexual bother subdomain score.




Publication bias


The funnel plots were examined for the six outcomes (Figure 8, Figure 9, Figure 10, Figure 11, Figure 12, Figure 13).


Figure 8
Figure 8. 

Funnel plot: urinary function subdomain score.




Figure 9
Figure 9. 

Funnel plot: urinary bother subdomain score.




Figure 10
Figure 10. 

Funnel plot: bowel function subdomain score.




Figure 11
Figure 11. 

Funnel plot: bowel bother subdomain score.




Figure 12
Figure 12. 

Funnel plot: sexual function subdomain score.




Figure 13
Figure 13. 

Funnel plot: sexual bother subdomain score.





Discussion


Why choosing the BCI as a tool of measurement of HR-QoL?


The Bladder Cancer Index (BCI) was developed and validated by Gilbert et al. in 2010 [4].


It is a reliable and BC-specific instrument to evaluate HR-QoL in patients with localized disease. It was developed in three steps: review of the literature, development of the questionnaire and validation by assessment of consistency and reproducibility [4]. Afterwards many translated versions of BCI were validated in French, Spanish, Hungarian and Arabic languages [16, 17, 18, 19].


There is a lack of specificity in other HR-QoL instruments as they included common questions on wellbeing for oncologic patients in addition to a specific module for BC.


There are also limitations in the disease stage: EORTC-QLQ-BLS24 and FACT-Bladder questionnaires are applicable only for patients with non-muscle invasive bladder tumors (NMIBT) while FACT Vanderbilt Cystectomy Index is exclusively used for patients with muscle-invasive BC (MIBC) [1, 2, 3]. Results from comparative studies of HR-QoL in mixed patients with BC at different stages may be difficult to interpret using these questionnaires.


The BCI questionnaire overcomes these limitations. It is entirely specific to BC patients and applicable for NMIBT and MIBC patients. In a recent comparative study with the Functional Assessment Cancer Therapy-Vanderbilt Cystectomy Index (FACT-VCI), the BCI was a better tool for assessing and counseling patients on expected treatment-specific changes after RC with UD [20].


The BCI questionnaire provides a robust measure of urinary, bowel and sexual outcomes. It is also sensitive to the differences in treatments, and applicable to both sexes and all the UDs [13]. For these reasons, we have chosen the BCI subdomains' scores (urinary function and bother, bowel function and bother, sexual function and bother) as outcomes in this meta-analysis.


Urinary function and bother


IC patients were older than ONB patients. However, unexpectedly IC patients had significantly better long-term results of UF and UB compared to ONB patients.


This may be explained by voiding problems in ONB patients [4]. In addition, ONB patients have a problem of urinary leakage caused by the loss of reflex micturition and injury to the urethral sphincter [14]. They need a rehabilitation to learn the new urination habit and some exercises such as Kegel Exercise in order to reinforce the urethral sphincter [14].


UB score was also better in IC patients although they may face problems of peristomial urinary leakage from the pouch, skin irritation, foul urine odor, etc. This significant result demonstrates that IC is well tolerated by patients. Stomial issues are often overcome by good self-care and assistance of care providers [14].


Bowel function and bother


There was no difference between IC and ONB patients regarding bowel subdomains. This may be explained by similarities in the use of ileal segment in both UDs (although the length is shorter in IC) and the respect of some specific contra-indications of using bowel in UD such as inflammatory chronic bowel disease.


Sexual function and bother


ONB patients had better SF score than IC patients. This is due to the difference of age: ONB patients were younger than IC patients. There was also no significant difference in sexual bother. Therefore no conclusion can be made from these findings regarding sexual QoL.


Limitations of our study


There were limitations in our study. As the studies included were not randomized, the risk of selection bias was considerable regarding the choice of UD. Indeed the age was higher in IC group. Sexual function was not evaluated or not reported in two studies.


Another limitation was related to the BCI questionnaire: There was no evaluation of the body image by the BCI. Hedgepeth et al. found no significant difference between IC and ONB in terms of body image evaluated by EORTC body image scale [15]. However Huang et al. reported better body image evaluated by the same scale in ONB patients at the short term, but no difference was observed at the long term (>1 year) [14].


Finally, regarding publication bias, Funnel plots were difficult to interpret because of the number of studies included for each outcome (≤4).


Conclusion


This meta-analysis of non-randomized studies demonstrated a better HR-QoL in urinary outcomes in IC patients compared with ONB patients. No conclusion can be made regarding the sexual outcomes because of the age difference between IC and ONB patients. However these results should be confirmed by randomized comparative studies.


Disclosure of interest


The authors declare that they have no competing interest.




Table 1 - Characteristics of included studies.
1st author  Year  Country  Journal  Type of study  Total no of patients (IC/ONB)  % of female patients (IC/ONB)  % of ≤pT2 (IC/ONB)  Age (years)  Follow-up (months)  Quality of the study 
Goldberg  2016  Israel  Urologic Oncology  Retrospective  95 (49/46)  IC=10, ONB 4 (NS)  77.55/76.08  IC=72 (46-85), ONB =61 (44-75) (P =0.0002)  IC 46.6 (mean±20.5)
ONB 44.4 (mean±31.1) 
Gellhaus  2016  US  The Journal of Urology  Retrospective  92(44/48)  21/2.1 (P <0.0001)  68.18/81.25  IC=67.2±9.4, ONB=58.4±9.1 (P <0.0001)  At least 60 months after RC 
Hedgepeth  2010  US  Oncology  Prospective  224 (85/139)  22.4/16.6 (P =0.05)  70.78/77.77  IC=71.09 (mean at surgery±8.23 SD); ONB=60.76 (mean at surgery±9.30 SD) (P <0.001)  Baseline and at 1, 6, 12, 24, 48, 72, 96 months after RC  2b 
Huang  2015  China  BMC Urology  Retrospective  117 (78/39)  12.8/12.8  79.5/84.6  IC=64.0 (mean, range 52.0-74.8) ONB=63.6 (mean, range 51.5-76.0) (P =0.885)  Baseline and at 6, 12, 18, 24, 36, 48, 60 months after RC 



Légende :
NS: non-significant difference.


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