Trimodality therapy versus radical cystectomy for muscle-invasive bladder cancer: A systematic review and meta-analysis

Background: Radical cystectomy (RC) is the guideline-recommended gold standard of curative treatment for muscle-invasive bladder cancer (MIBC). Trimodality therapy (TMT) has recently emerged as a viable alternative treatment, aiming to improve long term survival and bladder preservation rates. Methods: A systematic literature search was conducted on PubMed, Embase, Scopus and CENTRAL for randomized trials or covariatematched studies comparing RC versus TMT for MIBC. A graphical reconstructive algorithm was used to obtain overall survival (OS) and cancer-specific survival (CSS) of individual patients, which was then pooled under random-effects individual patient data (IPD) meta-analysis using Cox-models to determine hazard ratios (HRs) and 95% CI. Results: Altogether, 11 studies, comprising mostly cT2-T4, node-negative, nonmetastatic MIBC, were analyzed. Across 9 studies (6780 patients), TMT was associated with lower OS versus RC (shared-frailty HR = 1.14, 95% CI, 1.08-1.21, P < 0.001). Estimated OS at 1, 5 and 10 years was 86%, 47% and 18% respectively for TMT, and 86%, 57% and 22% for RC. Across 8 studies (4,776 patients), TMT was associated with lower CSS versus RC (shared-frailty HR =1.09, 95% CI, 1.01-1.18, P = 0.024). Estimated CSS at 1, 5 and 10 years was 92%, 62% and 29% respectively for TMT, and 94%, 72% and 29% respectively for RC. Conclusions: In the absence of large trials, our meta-analysis of studies of the next-highest quality of evidence suggests that RC may still confer OS and CSS benefit over TMT in MIBC. RC should remain the standard of care for nonmetastatic MIBC while TMT remains a valid alternative for carefully selected and informed patients. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data min