Radical cystectomy with neoadjuvant cisplatin-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC). However, recurrence remains common. Postoperative radiation therapy (PORT) has been explored to improve locoregional control and survival, but evidence remains inconclusive. This systematic review and meta-analysis assessed the role of PORT in MIBC.
PubMed, Embase, and Cochrane were searched through March 2025 (CRD42025632052). Eligible studies included randomized controlled trials (RCTs), prospective nonrandomized studies, and comparative observational cohorts of patients with MIBC undergoing radical cystectomy, with or without PORT. Prospective single-arm studies of PORT were included for safety outcomes. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS); secondary outcomes included locoregional recurrence (LRR) and treatment-related toxicities. Random-effects models were used.
Fifteen studies (5 RCTs, 2 prospective nonrandomized, and 8 retrospective cohorts) were included. A total of 19,033 patients (PORT, 1157) were included in the comparative analysis. PORT was associated with improved OS (hazard ratio, 0.84; 95% CI, 0.71-0.98; P = .026), although these results were not maintained in urothelial-only analysis. LRR was markedly reduced (risk ratio, 0.31; 95% CI, 0.15-0.65; P = .002), a finding maintained in urothelial-only and RCT-only analyses. No RFS benefit was observed in the primary analysis, but sensitivity, urothelial-only, and RCT-only analyses demonstrated significant improvements. Grade ≥3 acute gastrointestinal and genitourinary toxicities occurred in 3.3% and 1.8% of patients, respectively; late toxicities in 4.3% and 0.62%.
PORT reduced LRR across all analyses, improved OS in the overall and RCT-only analysis, and showed RFS benefits in sensitivity, urothelial-only, and RCT-only analyses. PORT may benefit selected high-risk patients, and its integration with contemporary radiation and systemic therapies warrants further prospective evaluation.
Advances in radiation oncology. 2026 May 15*** epublish ***
Rafael Lara Nohmi, Fabricia Cardoso Marques, Heloisa Carneiro Brito, Luciana de Moura Leite, Daniel V Araujo
Universidade de São Paulo (USP), São Paulo, São Paulo, Brazil., Universidade Federal do Ceará (UFC), Fortaleza, Ceará, Brazil., Universidade Federal da Paraíba (UFPB), Joao Pessoa, Paraíba, Brazil., Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo, São Paulo, Brazil., Division of Hematology and Medical Oncology, University of Florida, Gainesville, Florida.