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