Adjuvant PD-1 Inhibitors After Radical Surgery for High-Risk Muscle-Invasive Urothelial Carcinoma: A Systematic Review and Meta-Analysis of Phase 3 Trials.

[INTRODUCTION] Patients with high-risk muscle-invasive bladder cancer (MIBC) remain at substantial risk of disease recurrence. Randomized phase 3 trials have evaluated adjuvant programmed cell death 1 (PD-1) inhibitors in this setting, but the magnitude and consistency of benefit across patient subgroups remain incompletely defined.

[METHODS] We performed a systematic review and meta-analysis of randomized phase 3 trials comparing adjuvant PD-1 inhibitors with placebo or observation in patients with resected high-risk MIBC. HRs for disease-free survival (DFS) and overall survival (OS), as well as risk ratios for adverse events, were pooled using random-effects models. Prespecified subgroup analyses were conducted according to PD-L1 (programmed death-ligand 1) expression and prior receipt of cisplatin-based neoadjuvant chemotherapy.

[RESULTS] Two phase 3 trials encompassing patients treated with adjuvant nivolumab or pembrolizumab were included. Adjuvant PD-1 inhibitor therapy significantly improved DFS compared with control (pooled HR <1), with consistent benefit observed across PD-L1-defined subgroups and regardless of prior neoadjuvant cisplatin use. A favorable trend toward improved OS was observed, although survival data remain immature. Treatment was associated with a higher incidence of grade 3 or higher and immune-related adverse events compared with placebo or observation.

[CONCLUSIONS] Among patients with resected high-risk MIBC, adjuvant PD-1 inhibitor therapy significantly improves DFS with an acceptable safety profile. However, owing to the limited number of studies and short follow-up periods, these findings should be considered preliminary, and longer follow-up is required to confirm any potential OS benefit.