Liquid biopsy for Renal Cell Carcinoma: A comprehensive review of techniques, applications, and future prospects

Liquid biopsy techniques have developed rapidly in recent years and demonstrated success in cancer detection, disease characterization, and ongoing disease monitoring. These components, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and cell-free DNA (cfDNA), offer minimally invasive diagnostic tools that provide valuable insights into the genomic landscape of tumors. Its applications have expanded to include various malignancies, including renal cell carcinoma (RCC). RCC, a heterogeneous malignancy, poses unique diagnostic and therapeutic challenges. Up to 40% of patients experience recurrence or metastasis following initial surgical resection, necessitating the need for precise diagnostic and prognostic tools. The application of liquid biopsy in RCC, particularly through CTCs and ctDNA/cfDNA, holds significant promise. This review first delves into the various methodologies of CTC and cfDNA/ctDNA detection in RCC and highlights their roles in RCC management. Next, we discuss in depth about current existing evidence for the utilization of liquid biopsy in RCC diagnosis, prognosis, treatment outcomes prediction and association with the progression of the disease. Despite advancements, RCC's biological features, including low ctDNA shedding and significant intratumoral heterogeneity, present challenges in the clinical application of liquid biopsy. The review also discusses the limitations of current techniques and emphasizes the need for standardized protocols and further validation in large, diverse cohorts. Future directions include integrating liquid biopsy with advanced imaging techniques and leveraging artificial intelligence to improve RCC diagnostics and patient management. With continued refinement, liquid biopsy could become an essential tool in personalized oncology, improving outcomes for RCC patients.