Very Favorable vs. Favorable Risk Groups in Metastatic Renal Cell Carcinoma: A Step Toward Personalized Treatment

<b>Background/Objectives</b>: Metastatic renal cell carcinoma (mRCC) is a heterogeneous disease requiring precise risk stratification for optimal treatment selection. The International Metastatic RCC Database Consortium (IMDC) model classifies patients into favorable-, intermediate-, and poor-risk groups; however, emerging evidence suggests that the favorable-risk category encompasses patients with distinct prognoses. This study aims to evaluate whether subclassifying favorable-risk mRCC into "very favorable" and "favorable" subgroups improves prognostic accuracy and informs treatment strategies. <b>Methods</b>: This retrospective cohort study analyzed 189 patients diagnosed with mRCC at a single tertiary center between 2017 and 2023. Based on IMDC criteria, 75 patients were classified as favorable risk and included in the final analysis. These patients were further stratified into very favorable (<i>n</i> = 29) and favorable (<i>n</i> = 46) groups based on time from diagnosis to systemic therapy, Karnofsky performance status, and presence of metastases at specific sites. Kaplan-Meier analysis and Cox proportional hazards regression models were used to assess progression-free survival (PFS) and overall survival (OS). <b>Results</b>: Patients in the very favorable group demonstrated significantly longer median PFS (22.8 vs. 13.8 months, HR: 0.55, <i>p</i> = 0.020) and OS (74.4 vs. 42.7 months, HR: 0.38, <i>p</i> = 0.013) compared to the favorable group. In multivariate analysis, very-favorable-risk classification remained an independent prognostic factor for OS (<i>p</i> = 0.014) but not for PFS (<i>p</i> = 0.071). <b>Conclusions</b>: Stratifying favorable-risk mRCC patients into very favorable and favorable subgroups enhances prognostic assessment, potentially guiding more tailored treatment strategies. These findings highlight the need for refined risk models to improve personalized management in mRCC.