Perioperative Immune Checkpoint Inhibitors Combined with Radical Cystectomy: A Rapid Systematic Review and Meta-analysis

Background and objective: Perioperative immune checkpoint inhibitors (ICIs) combined with radical cystectomy (RC) represent an emerging paradigm for optimizing outcomes in muscle-invasive bladder cancer (MIBC). Our aim was to synthesize current evidence regarding the efficacy and safety of perioperative ICIs in this setting. Methods: In this rapid review and meta-analysis (CRD420251145050), we searched the MEDLINE, Embase, and Web of Science databases and the European Society for Medical Oncology 2025 abstract book for randomized controlled trials (RCTs) evaluating perioperative ICIs in patients undergoing RC. Meta-analyses were conducted using random-effects models for survival outcomes and to pool proportions of grade ≥3 adverse events (AEs). Risk of bias was assessed using the Cochrane RoB2 tool. Key findings and limitations: Of 1613 individual records screened, we included five RCTs evaluating ICIs in MIBC; three trials assessed adjuvant-only ICIs, while two assessed perioperative (neoadjuvant + adjuvant) ICIs. In adjuvant-only trials, there was evidence of better disease-free survival for patients with lower tract urothelial carcinoma (LTUC; hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.58-0.92). Perioperative ICIs showed evidence of benefits in terms of event-free survival (HR 0.53, 95% CI 0.32-0.87) and overall survival (HR 0.70, 95% CI 0.51-0.96) for patients with LTUC. Grade ≥3 treatment-related AEs occurred in 16-26% of patients in adjuvant-only trials and 41-71% in perioperative trials. High heterogeneity in treatment regimens, endpoint definitions, and follow-up durations limits interpretability of pooled estimates. Conclusion and clinical implications: Perioperative ICIs show promising efficacy in patients with MIBC undergoing RC. However, substantial heterogeneity in trial design, treatment strategies, and endpoint definitions limits definitive interpretation. Careful optimization of patient selection, treatment sequencing, combination strategies, and molecular profiling will be critical to maximizing the impact of multimodal therapy in MIBC. Patient summary: We reviewed studies in patients with muscle-invasive bladder cancer who received immunotherapy around the time of surgery. The results suggest that combining immunotherapy with surgery may offer a benefit, but further research is needed to determine which patients benefit the most and the best timing and combinations of these treatments.