Adjuvant Therapy Options in Renal Cell Carcinoma: Where Do We Stand?

Adjuvant therapy for non-metastatic renal cell carcinoma (RCC) remains controversial. Of the four reported randomized controlled trials evaluating adjuvant vascular endothelial growth factor (VEGF) inhibition, only one met its primary endpoint. The S-TRAC study demonstrated a statistically significant improvement in disease-free survival (DFS) of greater than 1 year with adjuvant sunitinib compared to placebo in patients with high-risk localized RCC and earned it FDA approval. However, the larger ASSURE study which reported first did not find a difference in DFS or overall survival between 1 year of adjuvant sunitinib or sorafenib compared to placebo. Given the discordant results of the two sunitinib studies, two other negative studies of adjuvant targeted therapy with pazopanib and axitinib, the lack of definite overall survival benefit in any study, and the high incidence of treatment-related adverse events with sunitinib, we do not recommend the routine use of adjuvant sunitinib. The decision to offer adjuvant sunitinib should be considered on an individual basis after an informed discussion of the potential toxicities and the risk/benefit ratio. Despite numerous efforts and recently published works, there is a paucity of prognostic and predictive molecular biomarkers in RCC. Further investigation is needed to discover new tools that can enhance the identification of patients who are most likely to benefit from adjuvant treatment beyond pathologic stage. Immune checkpoint inhibitors have great potential to significantly improve outcomes in high-risk localized RCC. Building on their established efficacy in the metastatic setting, several ongoing clinical trials are evaluating their value as single agents or in combination in the neoadjuvant and adjuvant settings. At this time, we recommend participation in clinical trials as the preferred therapeutic option for patients with high-risk, non-metastatic RCC planned for nephrectomy.