Biomarker-led advances in renal cell carcinoma diagnosis, progression monitoring and therapeutic decision-making

Renal cell carcinoma (RCC) diagnosis and management remain challenging due to asymptomatic presentation and limitations in accurately characterizing small renal masses. Noninvasive liquid biopsy biomarkers, including circulating proteins, metabolites, cell-free DNA, microRNAs, and inflammatory markers, have emerged as promising tools for RCC detection, prognostic stratification, and treatment monitoring. Here we review recent advances in blood- and urine-based biomarkers, highlighting key findings such as the diagnostic accuracy of kidney injury molecule-1 (KIM-1), CA15-3, metabolomic signatures, and urinary protein panels, alongside the prognostic relevance of circulating tumor DNA and systemic inflammatory indices. Despite encouraging analytical and clinical validity, no biomarker has yet demonstrated clinical utility due to biological, methodological, and regulatory challenges. Continued efforts focusing on standardized protocols, prospective validation, and integration with imaging and clinical data are essential to translate these biomarkers into personalized RCC management strategies.