Adjuvant immunotherapy for locally advanced renal cell carcinoma

Locally advanced renal cell carcinoma (RCC) presents a therapeutic challenge due to 20-40% relapse risk post-nephrectomy. There has been substantial interest in utilizing immunotherapy interrupting the PD-1/PD-L1 axis in the perioperative space, especially in the adjuvant setting, in order to minimize such risk.

We conducted a PubMed search using the terms 'adjuvant' and 'RCC.' We begin by examining landmark studies in the postoperative space for locally advanced RCC, with special emphasis on immunotherapeutic biologics. Important considerations are outlined in an effort to explain the conflicting data on the benefit of adjuvant immunotherapy as well as to adequately assess the magnitude of potential benefit of the recently approved adjuvant pembrolizumab. Relevant contemporary challenges and opportunities as well as future directions of the field are also discussed.

Systemic immunotherapy with monoclonal antibodies targeting the PD-1/PD-L1 axis likely holds promise, either alone or potentially in combinations, in minimizing recurrence risk for locally advanced RCC. However, emphasis on post-protocol care, robust endpoint selection, and continued work and validation on predictive biomarkers are needed to confidently select those patients that may benefit the most and minimize biologic and financial toxicity.