Treatment Selection in Advanced Clear Cell Renal Cell Carcinoma

Dr. Voss and Dr. Serzan discuss factors that inform first-line treatment selection in advanced clear cell renal cell carcinoma (RCC) among established immune checkpoint inhibitor-based regimens. Dr. Serzan explains that IMDC risk remains useful as a prognostic tool and for discussions around expected outcomes, but he does not use it alone to restrict treatment selection because available IO-IO and IO-TKI regimens can be considered across IMDC risk groups. He describes a systematic approach that incorporates tumor pathology, including the presence of sarcomatoid features, radiographic disease burden and sites of metastases, symptoms, comorbidities, and other patient-specific considerations. The discussion then focuses on high-grade disease, particularly sarcomatoid and rhabdoid features. Dr. Voss highlights evidence from CheckMate 214 and retrospective analyses suggesting substantial activity with ipilimumab plus nivolumab in patients with these aggressive histologic features. The experts emphasize the potential for deep and durable responses while recognizing the complexity of treatment selection in patients with high-grade disease and substantial tumor burden.