Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials

• Published in: European urology 2022-01, Vol.81 (1), p.50-61
• Main Authors: Burdett, Sarah, Fisher, David J., Vale, Claire L., Sternberg, Cora N., Clarke, Noel W., Parmar, Mahesh K.B., Bono, Aldo V., Cognetti, Francesco, Collette, Laurence, Cote, Richard J., Goebell, Peter J., Groshen, Susan, Lehmann, Jan, Rolevich, Alexander I., Sonntag, Roland W., Stockle, Michael, Studer, Urs E., Torti, Frank M., Zhegalik, Alexander G., Tierney, Jayne F.
• Format: Article
• Language: English
• Subjects: Bladder cancer; Chemotherapy; Chemotherapy, Adjuvant; Cisplatin - therapeutic use; Female; Humans; Individual participant data; Male; Meta-analysis; Muscles; Platinum Priority – Review – Bladder Cancer; Randomized Controlled Trials as Topic; Systematic review; Urinary Bladder Neoplasms - drug therapy
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2021.09.028

This systematic review and meta-analysis, based on updated individual participant data, demonstrates that cisplatin-based adjuvant chemotherapy is a valid option for improving outcomes for muscle-invasive bladder cancer. Our prior systematic review and meta-analysis of individual participant data (IPD) suggesting a benefit of adjuvant chemotherapy for muscle-invasive bladder cancer was limited by the number and size of included randomised trials. We have updated results to include additional trials, providing the most up-to-date and reliable evidence of the effects of this treatment. To investigate the role of adjuvant cisplatin-based chemotherapy in the treatment of muscle-invasive bladder cancer. Published and unpublished trials were sought via searches of bibliographic databases, trials registers, conference proceedings, and hand searching. Updated IPD were centrally collected, checked, and analysed. Results from individual randomised controlled trials (RCTs) were combined using a two-stage fixed-effect model. Prespecified analyses explored any variation in effect by trial and participant characteristics. Analyses of ten RCTs (1183 participants) demonstrated a benefit of cisplatin-based adjuvant chemotherapy on overall survival (hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70–0.96, p = 0.02). This represents an absolute improvement in survival of 6% at 5 yr, from 50% to 56%, and a 9% absolute benefit when adjusted for age, sex, pT stage, and pN category (HR = 0.77, 95% CI = 0.65–0.92, p = 0.004). There was no clear evidence that the effect varied by trial or participant characteristics. Adjuvant chemotherapy was also shown to improve recurrence-free survival (HR = 0.71, 95% CI = 0.60–0.83, p