Adjuvant Immune Checkpoint Inhibitors After Radical Surgery for High-Risk Urothelial Carcinoma: A Meta-Analysis
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Background
Patients with high-risk muscle-invasive urothelial carcinoma (MIUC) remain at substantial risk of recurrence following radical surgery. Adjuvant immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have emerged as a potential strategy to reduce recurrence and improve survival outcomes.
Methods
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating adjuvant ICIs versus observation or placebo in high-risk MIUC. Data were extracted for disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS), recurrence-free survival beyond the urothelial tract (RFS-extraUT), and health-related quality of life (HRQoL). Standardized mean differences (SMDs) were used to express effect sizes with 95% confidence intervals (CIs), and pooled using inverse-variance weighting under common- and random-effects models. Heterogeneity and subgroup analyses were performed according to drug class, PD-L1 status, and clinical covariates.
Results
Nine study-level comparisons from four phase III RCTs (CheckMate 274, IMvigor010, AMBASSADOR, and related updates; n > 2,200) were included. Adjuvant ICIs significantly prolonged DFS compared with control (SMD –0.32; 95% CI –0.44 to –0.21; p < 0.001), with consistent benefits across subgroups and low heterogeneity (I² = 25%). OS benefit was emerging, with nivolumab demonstrating significant advantage at extended follow-up (HR 0.76; 95% CI 0.61–0.96), while pembrolizumab and atezolizumab yielded neutral OS results.
Conclusions
Adjuvant PD-1/PD-L1 inhibitors improve DFS and show emerging OS benefits without compromising HRQoL in high-risk MIUC. Nivolumab has demonstrated the most robust long-term survival evidence to date, supporting its role as standard of care. Further biomarker-driven trials are warranted to refine patient selection.
