When is immunotherapy too much? The case of favorable-risk metastatic renal cell carcinoma

Crit Rev Oncol Hematol. 2026 May:221:105238. doi: 10.1016/j.critrevonc.2026.105238. Epub 2026 Feb 28.

Abstract

Combination therapies integrating immune checkpoint inhibitors (ICIs) with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), or dual ICI regimens, currently represent the standard of care for advanced clear cell renal cell carcinoma (ccRCC). However, in most favorable-risk patients according to the IMDC classification-particularly those with a low disease burden and without disease-related symptoms-first-line monotherapy with VEGFR-TKIs remains a valid option. This review summarizes the preclinical and clinical evidence supporting this approach, with the aim of guiding oncologists in personalizing therapy while minimizing overtreatment and toxicity.

Keywords: Favorable-risk; Immunotherapy; Metastatic; Renal cell carcinoma.

Publication types

  • Review

MeSH terms

  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / immunology
  • Carcinoma, Renal Cell* / pathology
  • Carcinoma, Renal Cell* / therapy
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy* / methods
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / immunology
  • Kidney Neoplasms* / pathology
  • Kidney Neoplasms* / therapy
  • Neoplasm Metastasis
  • Protein Kinase Inhibitors / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors

Substances

  • Immune Checkpoint Inhibitors
  • Protein Kinase Inhibitors
  • Receptors, Vascular Endothelial Growth Factor