Metastatic clear cell RCC first-line treatment selection

Authored by Toni Choueiri, published on 2026-02-23 01:00:42.0

Algorithm for selection of first-line treatment for patients with metastatic clear cell RCC. The National Comprehensive Cancer Network, European Association of Urology, and European Society of Medical Oncology guidelines recommend alternative approaches. axi = axitinib; cabo = cabozantinib; IMDC = International Metastatic RCC DatabaseConsortium; ipi = ipilimumab; lenva = lenvatinib ; Nivo = nivolumab; Pembro = pembrolizumab; RCC = renal cell carcinoma; SBRT = stereotactic body radiotherapy; TKI = tyrosine kinase inhibitor.Multidisciplinary tumor board discussion should include, but not be limited to, patient preferences and goals, review of images and pathology, need for referral to a high-volume center, potential inclusion in clinical trials, and requirements for additional supportive care interventions.First and Second-line Treatments in Metastatic Renal Cell Carcinoma, European Urology, Volume 87, Issue 2, 2025, Pages 143-154, https://doi.org/10.1016/j.eururo.2024.10.019.

  1. Metastatic clear cell RCC
    • Multidisciplinary tumor board discussion*
      • Oligometastatic RCC
        • Yes
          • Observation, SBRT, metastasectomy +/- pembrolizumab (<1y from nephrectomy) In select cases: cytoreductive nephrectomy
        • No
          • Sarcomatoid features
            • Yes
              • Nivo+ipi
            • No
              • IMDC risk group
                • Favorable risk
                  • Pembro+axi, nivo+cabo or pembro+lenva In select cases: nivo+ipi or TKI monotherapy
                • Intermediate and poor risk
                  • Need for rapid disease-control
                    • No
                      • Physician’s preference: nivo+ipi, pembro+axi, nivo+cabo or pembro+lenva In select cases: TKI monotherapy
                    • Yes
                      • Pembro+axi, nivo+cabo or pembro+lenva In select cases: nivo+ipi or TKI monotherapy
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