The Search for the Optimal Immunotherapy Sequencing in the Perioperative Setting of RCC

Based on the S-TRAC study, sunitinib was approved as adjuvant therapy for high-risk renal cell carcinoma after nephrectomy; however, the role of perioperative immunotherapy is less clear. Multiple immunotherapy combinations have shown clinical benefit superior to sunitinib in metastatic renal cell carcinoma, but their role in localized or locally advanced renal cell carcinoma still remains controversial. The importance of neoadjuvant immunotherapy in patients with locally advanced RCC is currently under investigation in a large phase 3 clinical trial (PROSPER RCC) and other phase 2 studies investigating PD-1 inhibitors with or without CTLA-4 inhibitors. Multiple ongoing clinical trials (IMmotion010, KEYNOTE-564, and CheckMate 914) are evaluating the adjuvant role of immunotherapy. For the majority of patients with synchronous metastatic renal cell carcinoma, combinations with immunotherapy are now the preferred initial treatment compared to upfront cytoreductive nephrectomy. The timing and benefit of consolidative nephrectomy following immunotherapy combinations are under investigation. Over the next 5 years, these trials will further elucidate optimal timing of immunotherapy in the perioperative setting.