KIM-1 and beyond: emerging biomarkers for adjuvant immunotherapy in clear cell renal cell carcinoma

INTRODUCTION: Adjuvant immunotherapy has transformed the management of high-risk resected ccRCC, with pembrolizumab demonstrating improvements in DFS and OS. However, divergent outcomes across recent phase III trials highlight the limitations of clinicopathologic staging alone for guiding postoperative treatment decisions. A substantial proportion of patients may receive adjuvant therapy without deriving meaningful benefit, underscoring the urgent need for biologically informed risk stratification. AREAS COVERED: KIM-1, a circulating biomarker derived from proximal tubular epithelium, has emerged as a promising candidate in this setting. Elevated postoperative KIM-1 levels are consistently associated with inferior oncologic outcomes and may reflect minimal residual disease. Exploratory analyses from IMmotion010 suggest a potential predictive enrichment effect for adjuvant immunotherapy benefit in patients with high baseline KIM-1. Additional biomarkers including sarcomatoid differentiation, specific genomic drivers (PBRM1, BAP1, VHL), circulating tumor DNA, epigenetic signatures, and systemic inflammatory markers, provide complementary insights into tumor biology and host-tumor interaction. EXPERT OPINION: Although none of these biomarkers are currently validated for routine clinical decision-making, integrative models combining clinicopathologic and molecular features may enable more precise selection of patients for adjuvant immunotherapy and help reduce overtreatment in localized ccRCC.