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

[BACKGROUND] 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.

[OBJECTIVE] 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.

[METHODS] 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.

[RESULTS] 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.

[CONCLUSIONS] 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.