Concurrent radiosensitising regimens for bladder-preserving radiotherapy in non-metastatic muscle-invasive bladder cancer: a systematic review and structured evidence synthesis with exploratory network meta-analysis.

PURPOSE: To synthesise randomised comparative and prospective evidence on concurrent radiosensitising regimens used with bladder-preserving radiotherapy for non-metastatic muscle-invasive bladder cancer and determine whether the available evidence supports a regimen hierarchy. METHODS: PubMed/MEDLINE, Embase, Web of Science Core Collection, and Cochrane CENTRAL were searched till May 14, 2026. Randomised trials formed the comparative evidence backbone. A frequentist random-effects network meta-analysis was restricted to connected early-response data; safety, cystectomy, and long-term oncological outcomes were summarised descriptively. Prospective non-randomised and protocol-based studies were organised as an evidence map. RESULTS: Six randomised or randomised phase II/III trials formed the comparative evidence base. Only early response produced a connected network and no active regimen was statistically superior to radiotherapy alone. Numerical estimates were highest for radiotherapy plus paclitaxel/cisplatin (odds ratio 2.81, 95% confidence interval 0.85-9.34), followed by cisplatin-based chemoradiotherapy (1.96, 0.86-4.45); the gemcitabine-based estimate was imprecise (0.71, 0.19-2.64). The most mature randomised signal came from BC2001, in which 5-fluorouracil/mitomycin C improved locoregional control. The prospective component included 28 studies and 1690 patients; 24 studies involving 1114 patients comprised the main regimen-level map. Complete response rates ranged from 60.0% to 94.0% (median 75.6%). CONCLUSION: Concurrent radiosensitisation is important in bladder-preserving radiotherapy, but evidence does not support a definitive cross-regimen hierarchy. Regimen selection should reflect evidence maturity, fitness, availability, toxicity, and patient preferences.