Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline

J Clin Oncol. 2022 Sep 1;40(25):2957-2995. doi: 10.1200/JCO.22.00868. Epub 2022 Jun 21.


Purpose: To provide recommendations for the management of patients with metastatic clear cell renal cell carcinoma (ccRCC).

Methods: An Expert Panel conducted a systematic literature review to obtain evidence to guide treatment recommendations.

Results: The panel considered peer-reviewed reports published in English.

Recommendations: The diagnosis of metastatic ccRCC should be made using tissue biopsy of the primary tumor or a metastatic site with the inclusion of markers and/or stains to support the diagnosis. The International Metastatic RCC Database Consortium risk criteria should be used to inform treatment. Cytoreductive nephrectomy may be offered to select patients with kidney-in-place and favorable- or intermediate-risk disease. For those who have already had a nephrectomy, an initial period of active surveillance may be offered if they are asymptomatic with a low burden of disease. Patients with favorable-risk disease who need systemic therapy may be offered an immune checkpoint inhibitor (ICI) in combination with a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI); patients with intermediate or poor risk should be offered a doublet regimen (no recommendation was provided between ICIs or an ICI in combination with a VEGFR TKI). For select patients, monotherapy with either an ICI or a VEGFR TKI may be offered on the basis of comorbidities. Interleukin-2 remains an option, although selection criteria could not be identified. Recommendations are also provided for second- and subsequent-line therapy as well as the treatment of bone metastases, brain metastases, or the presence of sarcomatoid features. Participation in clinical trials is highly encouraged for patients with metastatic ccRCC.Additional information is available at

Publication types

  • Systematic Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / pathology
  • Humans
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Vascular Endothelial Growth Factor A


  • Angiogenesis Inhibitors
  • Protein Kinase Inhibitors
  • Vascular Endothelial Growth Factor A

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma