Prognostic Factors of Trimodal Therapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND

OBJECTIVE

Trimodal therapy (TMT)-comprising transurethral resection of the bladder tumor, chemotherapy, and radiotherapy-offers a bladder-preserving alternative to radical cystectomy for selected patients with muscle-invasive bladder cancer (MIBC). However, the optimal criteria for patient selection and prognostication remain inadequately defined. A systematic review and meta-analysis was conducted to optimize the selection of MIBC patients who are likely to have better survival outcomes from TMT.

METHODS

A systematic literature search was conducted in MEDLINE, Embase, and Web of Science in February 2025. Eligible studies examined prognostic factors for overall or cancer-specific survival in patients with MIBC undergoing TMT. To reduce the impact of confounding, only multivariable-adjusted estimates were included in the meta-analysis. Pooled hazard ratios (HRs) were calculated using a random-effect model. The risk of bias was evaluated using the Quality In Prognosis Studies (QUIPS) tool (CRD42025641514).

KEY FINDINGS AND LIMITATIONS: A total of 31 studies, including 9416 patients treated with TMT for MIBC, met the inclusion criteria. Older age (per year increase; HR: 1.03, 95% confidence interval [CI]: 1.01-1.05), poor performance status (Eastern Cooperative Oncology Group ≥2 vs 0-1; HR: 2.47, 95% CI: 1.78-3.43), impaired renal function (HR: 1.47, 95% CI: 1.12-1.92), presence of hydronephrosis (HR: 1.65, 95% CI: 1.17-2.34), advanced T stage (HR: 1.47, 95% CI: 1.23-1.77), nodal involvement (HR: 1.90, 95% CI: 1.10-3.30), and concomitant carcinoma in situ (HR: 1.81, 95% CI: 1.02-3.20) were independently associated with worse overall survival. Limitations included heterogeneity in treatment protocols and potential residual confounding across studies.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Specific patient- and tumor-related factors are significantly associated with prognosis in patients undergoing TMT for MIBC. These findings may aid in refining patient selection and risk stratification for TMT-based bladder-preserving approaches.