Introduction: Radical nephrectomy is the standard management for locoregional renal cell carcinoma (RCC); however, patients with adverse pathological features are at increased risk of recurrence. IMmotion010 and KeyNote 564 trials investigated the adjuvant role of ICI for high-risk clear cell RCC (ccRCC) and have yielded conflicting results. We aimed to investigate real-world survival outcomes associated with the adjuvant use of ICI in high-risk ccRCC using the National Cancer Database. Methods: In this nationwide contemporary cohort study, patients with newly diagnosed non-metastatic high-risk clear cell RCC undergoing radical nephrectomy between 2015-2019 were included. High-risk RCC was defined as cT2 with Fuhrman grade 4 or cT3a with Fuhrman grade 3/4 or cT3b/T3c/T4 with any grade, or TxN+ any grade. Patients receiving adjuvant ICI were classified as Group A and patients who did not receive adjuvant ICI were classified as Group B. Inverse probability weighting (IPW)-adjusted Kaplan Meier curves were utilized to compare overall survival (OS) between the groups and cox proportional hazard models were utilized to identify the predictors for OS. Results: Overall, 768 patients met the inclusion criteria; 270 patients in Group A and 498 patients in Group B. The mean age was 60.5(10.6) years, and 70.8% of patients were males. 88.4% were Caucasians and 8.5% were Hispanics. The use of ICI in the adjuvant setting for high-risk RCC increased from 17.4% (29 of 167) in 2015 to 61.8% (68 of 110) in 2019. The 5-year overall survival was 36.8% (95%CI, 25.9% -52.4%) for Group A while 50.1% (44.1%-56.4%) for Group B (p=0.30). (Figure 1a) The 5-year OS remained similar between the two groups, even after IPW-adjusted cohort analysis (39.4% in Group A vs 47.9%, p=0.17). ( Figure 1b) The use of adjuvant ICI did not appear to be an independent predictor for OS on multivariable cox regression analysis (HR=1.14, p=0.31) Conclusions: Adjuvant ICI therapy in non-metastatic high-risk ccRCC might not be associated with a benefit in overall survival. SOURCE OF Funding: None
