Liquid Biopsy in Advanced Prostate Cancer.

Liquid biopsy has emerged as a transformative tool in oncology, enabling minimally invasive and dynamic characterization of tumor biology. In prostate cancer, marked by high heterogeneity and frequent bone metastases, tissue biopsy is often challenging, highlighting the clinical value of circulating biomarkers. Circulating tumor DNA (ctDNA) is the most clinically advanced analyte, supporting detection of actionable alterations such as BRCA1/2 and ATM mutations, guiding targeted therapies, and enabling real-time monitoring of treatment response and resistance. Circulating tumor cells (CTCs) and extracellular vesicles (EVs) provide complementary insights into tumor biology and disease progression. However, challenges remain, including limited sensitivity in low tumor burden and biological confounders such as clonal hematopoiesis (CH), which can lead to false-positive findings. Emerging approaches, including fragmentomics and methylation profiling, offer improved tumor specificity and may help overcome these limitations. Together, these advances support the integration of liquid biopsy into clinical practice for personalized management and longitudinal monitoring in prostate cancer.