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

## TL;DR

This study identifies a subgroup of kidney cancer patients with very favorable outcomes, suggesting more precise treatment strategies could improve care.

## Contribution

The study introduces a 'very favorable' risk subgroup within favorable-risk metastatic renal cell carcinoma patients, enhancing prognostic stratification.

## Key findings

- Very favorable patients had significantly longer progression-free and overall survival compared to favorable-risk patients.
- Very favorable classification remained an independent prognostic factor for overall survival in multivariate analysis.
- The findings suggest refined risk models could improve personalized treatment decisions in metastatic renal cell carcinoma.

## Abstract

Metastatic renal cell carcinoma is an aggressive malignancy that requires accurate risk stratification to guide treatment decisions and predict patient outcomes. Existing classification models categorize patients into favorable-, intermediate-, and poor-risk groups; however, they may not fully capture the heterogeneity within the favorable-risk category. This study aims to refine prognostic stratification by distinguishing a “very favorable” subgroup within the favorable-risk cohort. Through retrospective analysis, we demonstrate that patients classified as very favorable exhibit significantly longer survival and improved treatment responses compared to those in the favorable group. These findings suggest that a more nuanced risk classification could enhance clinical decision-making by optimizing therapy selection, minimizing overtreatment, and improving individualized patient management. Our study contributes to the evolving landscape of precision oncology and supports the need for further validation of refined prognostic models in metastatic renal cell carcinoma.

Background/Objectives: 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. Methods: 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 (n = 29) and favorable (n = 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). Results: Patients in the very favorable group demonstrated significantly longer median PFS (22.8 vs. 13.8 months, HR: 0.55, p = 0.020) and OS (74.4 vs. 42.7 months, HR: 0.38, p = 0.013) compared to the favorable group. In multivariate analysis, very-favorable-risk classification remained an independent prognostic factor for OS (p = 0.014) but not for PFS (p = 0.071). Conclusions: 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.