Perioperative immune-based treatment for cisplatin-eligible muscle-invasive bladder cancer: a meta-analysis of randomized controlled trials

Purpose: Perioperative immune-based strategies are redefining the treatment landscape of muscle-invasive bladder cancer, but their overall benefit and subgroup effects remain incompletely characterized. The aim of this meta-analysis is to evaluate the efficacy and safety of perioperative immunotherapy-based strategies in cisplatin-eligible muscle-invasive bladder cancer and explore treatment effects across clinically relevant subgroups. Materials and methods: This is a systematic review and meta-analysis of randomized phase III trials assessing perioperative immune-based treatments in muscle-invasive bladder cancer. Hazard ratios for event-free survival and overall survival were pooled using random-effects models. Exploratory subgroup analyses were conducted by age, sex, race, and tumor stage. Safety outcomes were analyzed using risk ratios. Results: Two phase III trials were included. NIAGARA evaluated durvalumab added to cisplatin-based chemotherapy, whereas KEYNOTE-B15 evaluated enfortumab vedotin plus pembrolizumab as a chemotherapy-replacing strategy. The limited quantitative synthesis favored the experimental regimens for event-free survival (HR 0.61, 95% CI 0.48-0.78) and overall survival (HR 0.71, 95% CI 0.59-0.86). Benefit was observed across most subgroups. Numerically larger effects were observed in patients with higher-risk disease (>T2N0), whereas confidence intervals crossed unity in T2N0 disease; this finding is hypothesis-generating and does not establish a stage-treatment interaction. Overall toxicity incidence was similar between groups, although serious adverse events were more frequent in the experimental arms (RR 1.32, 95% CI 1.18-1.49). Differences in treatment exposure and regimen-specific toxicity limit interpretation of a uniform class effect. Limitations include the small number of trials and exploratory subgroup analyses. Conclusions: Available randomized evidence supports the clinical integration of the specific perioperative immune-based regimens evaluated in NIAGARA and KEYNOTE-B15 for cisplatin-eligible muscle-invasive bladder cancer. However, the two regimens should not be considered interchangeable, and the optimal regimen and patients deriving the greatest benefit remain uncertain.