Risk-Adapted Use of Adjuvant Systemic Therapy After Nephrectomy for Renal Cell Carcinoma: A Population-Based Study in the Post-approval Era

BACKGROUND: Real-world adjuvant systemic therapy (AST) use for eligible renal cell carcinoma (RCC) patients remains insufficiently characterized in the contemporary treatment era. In particular, it is unclear whether treatment allocation reflects established high-risk tumor characteristics. METHODS: In the Surveillance, Epidemiology, and End Results (SEER) database, the study identified patients eligible for AST after nephrectomy (2018-2022). Temporal trends in AST use were assessed. Multivariable logistic regression models tested associations between histopathologic high-risk features (T4 stage, tumor grade 4, and N1-2 stage) and AST use. RESULTS: Of 6,497 eligible patients, 1,163 (18%) received AST. Annual proportions of AST increased from 13% in 2018 to 36% in 2022. Higher AST use was independently predicted by T4 stage (33% vs. 18%; odds ratio [OR], 1.68; p = 0.006), tumor grade 4 (28% vs. 15%; OR, 1.94; p < 0.001), and N1-2 stage (36% vs. 17%; OR, 2.57; p < 0.001). Patients who had any of these three high-risk features were more likely to receive AST than those who did not (28% vs. 14%; OR, 2.27; p < 0.001). Moreover, a stepwise increase in AST use was observed with an increasing number of high-risk features (one: 26% [OR, 2.09; p < 0.001], two: 37% [OR, 3.56; p < 0.001], three: 40% [OR, 4.04; p = 0.014]). CONCLUSIONS: Only a minority of eligible RCC patients received AST after nephrectomy. However, the proportion of AST use increased over time. Use of AST was strongly associated with adverse tumor characteristics. A stratification according to the number of high-risk features showed a dose-response effect. Nevertheless, AST use remained limited even among patients at the highest risk.