Clinical and Molecular Validation of the Very Favorable IMDC Risk Group in Metastatic Renal Cell Carcinoma

Can the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable risk group in metastatic renal cell carcinoma be redefined to identify a biologically and clinically distinct very favorable subgroup with different treatment outcomes?In this cohort study of 641 patients from the IMDC, a very favorable risk subgroup defined by clinical criteria was found to have significantly longer overall survival and distinct treatment benefit compared with patients in the favorable risk group. Molecular validation using tumors from the IMmotion151 trial showed that the very favorable subgroup was enriched for angiogenic features and less immunogenic profiles, with improved outcomes on vascular endothelial growth factor receptor–based therapies and inferior outcomes with 2 immune-oncology regimens.The findings of this study suggest that refining the IMDC favorable risk category identified a biologically distinct subgroup that may benefit from tailored treatment strategies and may inform future clinical trial design.

Corresponding Author: Martin Zarba, MD, Arthur JE Child Comprehensive Cancer Centre, 3395 Hospital Dr NW, Room 10-2366, Calgary, AB T2N 5G2, Canada (martin.zarba@gmail.com).

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