Efficacy of adjuvant anti–PD-1/anti–PD-L1 immunotherapy in resected renal cell carcinoma (RCC): An updated systematic review and meta-analysis.

Abstract

e16508 Background: To systematically review and meta-analyze randomized controlled trials (RCTs) evaluating adjuvant immunotherapy (atezolizumab, pembrolizumab, ipilimumab plus nivolumab, or nivolumab alone) in patients with locally advanced, non-metastatic clear cell renal cell carcinoma (RCC). Adjuvant immunotherapy aims to reduce recurrence risk in high-risk RCC post-nephrectomy, but conflicting trial results necessitate synthesis. Methods: We searched MEDLINE, EMBASE, LILACS, and CENTRAL up to December 2025. Overall survival (OS) and disease-free survival (DFS) were assessed. Effect estimates were pooled as hazard ratios (HR) or risk ratios (RR) with corresponding 95% confidence intervals (95% CI), using fixed- and random-effects models as appropriate. Results: Of 49 records screened, 5 RCTs (IMmotion010, KEYNOTE-564, CheckMate 914 [part A], CheckMate 914 [part B], and PROSPER) comprising 4,232 patients status post nephrectomy were included. Adjuvant immunotherapy improved DFS versus placebo/observation (fixed effect: HR=0.85, 95% CI=0.76 to 0.94; p=0.002), with moderate heterogeneity (Chi2=5.43, df=4 [p=0.25]; I2=26%). A random-effects model yielded consistent results (HR=0.86, 95% CI=0.76 to 0.97; p=0.02). In subgroup analyses, immunotherapy was associated with longer DFS among patients with PD-L1 expression (≥1% IHC SP142 or combined positive score ≥1 IHC 22C3) (fixed effect: HR=0.73, 95% CI=0.62 to 0.87; p=0.0004), without heterogeneity (Chi2=1.58, df=2 [p=0.45]; I2=0%). Patients with sarcomatoid features also derived DFS benefit (fixed effect: HR=0.62, 95% CI=0.45 to 0.83; p=0.002), without heterogeneity (Chi2=3.75, df=4 [p=0.44]; I2=0%). OS data were immature, with no statistically significant difference between groups (fixed effect: HR=0.88, 95% CI=0.71 to 1.08; p=0.23). Conclusions: This is the first meta-analysis to include all five available RCTs of adjuvant immunotherapy in resected RCC. Adjuvant immunotherapy significantly improved DFS overall. In subgroup analyses, patients with PD-L1 expression or sarcomatoid features experienced DFS benefit without heterogeneity. These findings support adjuvant immunotherapy in selected high-risk subgroups, pending mature OS data.