Metastatic Renal Cell Carcinoma: Which Patients Have the Best Outlook?

Cancer research · Renal cell carcinoma

Patients with metastatic renal cell carcinoma who fall into a very favorable risk subgroup experience longer overall survival with vascular endothelial growth factor (VEGF) therapies and worse outcomes when treated with immune‑oncology combinations that use two immune checkpoint inhibitors.

A retrospective cohort analysis of 641 patients with metastatic renal cell carcinoma (mRCC) identified a very favorable risk subgroup (tier 1) defined by high Karnofsky performance status, long interval from diagnosis, and absence of brain, bone, or liver metastases. Compared with standard favorable‐risk (tier 2) patients, tier 1 patients showed significantly longer overall survival when treated with VEGF‑targeted therapies, whereas those receiving dual immune checkpoint inhibitor combinations (IO‑IO) had poorer survival and lower response rates. Molecular profiling of a subset of tumors from the IMmotion151 trial revealed lower PD‑L1 expression and fewer sarcomatoid features in the very favorable group, suggesting a distinct, less immunogenic, angiogenic phenotype.

The findings refine prognostic stratification in mRCC, indicating that patients in the very favorable subgroup may derive greater benefit from VEGF‑targeted therapy while potentially experiencing inferior outcomes with IO‑IO combinations. This has implications for individualized treatment planning, clinical trial design, and updating practice guidelines.

Evidence level: Állatkísérletes. Állatmodellben vizsgálták.

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