Risk Stratification in Renal Cell Carcinoma: A Narrative Review

Renal cell carcinoma (RCC) accounts for the majority of kidney cancers, with approximately 80,000 new diagnoses and over 14,000 deaths annually in the United States. Risk stratification is essential for prognostication, treatment selection, and clinical trial design across all disease stages. In localized and locally advanced RCC, pathological stage, histology, and grade remain the primary prognostic factors, while the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria serve as the standard risk stratification tool in the metastatic setting. However, current models rely predominantly on clinical and pathologic variables that act as indirect surrogates of tumor biology and do not account for the molecular heterogeneity inherent to RCC. This narrative review synthesizes and compares established and emerging risk stratification and prognostic models across all stages of RCC. Established models such as the IMDC criteria and the stage, size, grade, and necrosis (SSIGN) score demonstrate robust prognostic performance but are limited by their reliance on clinical and pathologic variables alone. Emerging biomarkers-including circulating tumor DNA, methylated DNA, artificial intelligence-based radiomics, and tissue-based molecular signatures-show promise for improving risk discrimination. The molecular heterogeneity of RCC underscores an urgent need for integrated molecular-clinical-pathologic prognostic tools tailored to specific histologic subtypes to enable more precise, individualized care.