Adjuvant Therapy in Renal Cell Carcinoma: Current Status and Future Directions

Abstract

In recent years, incredible progress has been made in the treatment of metastatic renal cell carcinoma, with a paradigm shift from the use of cytokines to tyrosine kinase inhibitors, and more recently, immune checkpoint inhibitors (ICIs). Despite advances in the metastatic setting, effective therapies in the adjuvant setting are a largely unmet need. Currently, sunitinib (Sutent, Pfizer) is the only therapy for the adjuvant treatment of RCC included in the National Comprehensive Cancer Network guidelines, which was approved by the FDA based on the improvement in disease-free survival (DFS) seen in the S-TRAC trial. However, improvement in DFS has not translated into an overall survival (OS) benefit for patients at high-risk of relapse post-nephrectomy, illustrating the need for more effective therapies. This manuscript will highlight attributes of both historical and current drug trials and their implications on the landscape of adjuvant therapy. Additionally, we will outline strategies for selecting patients in whom treatment would be most beneficial, as optimal patient selection is a crucial step towards improving outcomes in the adjuvant setting. This is especially critical, given the financial cost and pharmacological toxicity of therapeutic agents. Furthermore, we will review the design of clinical trials including the value of utilizing OS as an endpoint over DFS. Finally, we will discuss how the incorporation of genomic data into predictive models, the use of more sensitive imaging modalities for more accurate staging, and more extensive surgical intervention involving lymph node dissection, may impact outcomes.