A daily clinical practice decision-making overview for the present metastatic renal cell carcinoma (mRCC) management...

Renal cell carcinoma (RCC), originating from renal tubular epithelial cells, represents approximately 80 % of all primary kidney tumors. Roughly 30 % of cases are diagnosed at an advanced stage, and a similar proportion experience recurrence after surgery for localized disease. This recurrence rate may improve with the recent introduction of an effective adjuvant immunotherapy.

This work aims to assess the current therapeutic landscape of metastatic RCC (mRCC), with a focus on immunotherapy-based combinations, and to offer expert, real-world insights into clinical decision-making and adverse event (AE) management.

Six oncologists specialized in mRCC completed a structured survey covering four key areas: (1) overall survival, (2) safety of IO-IO and IO-TKI combinations, (3) treatment selection, and (4) sequential strategies. Responses were reviewed in a virtual meeting, with agreement defined as concurrence by at least five of the six participants. Any areas without unanimous agreement were addressed through subsequent discussion rounds until a final agreement was reached.

Nivolumab plus ipilimumab provides durable responses and long-term survival, especially in intermediate- and poor-risk patients. TKI-based combinations, including cabozantinib and lenvatinib, achieve strong disease control, while axitinib offers a greater dosing flexibility due to its short half-life. Toxicity profiles differ by regimen, requiring careful management of immune-related and TKI-associated adverse events. Relapse risk after adjuvant pembrolizumab should guide first-line therapy choice for advanced disease, while metastasis-directed treatments should be considered by multidisciplinary teams.

Optimal first-line treatment for mRCC requires consideration of patient characteristics, clinical and molecular prognostic factors, treatment tolerability, all of these parameters should be evaluated during a multidisciplinary team discussion.