Abstract
Molecular profiling of biliary tract cancers (BTCs) has paved the way for a broader range of therapeutic options, leading to improved survival outcomes. Given the challenges of tissue evaluation in BTCs, circulating tumor DNA (ctDNA) has emerged as a promising non-invasive biomarker for genomic profiling. Bile has been proven to be a reliable ctDNA source, demonstrating higher concordance with tumor tissue than plasma. More importantly, ctDNA provides valuable insights into both clonal evolution and treatment response, including the detection of resistance mechanisms and mutation clearance, which are often associated with disease control. Although its role in recurrence monitoring remains investigational, early studies suggest that ctDNA detection may precede radiological recurrences. This review examines recent advancements in ctDNA analysis for patients with BTC, highlighting key developments, current clinical implications, and ongoing challenges. Large-scale prospective studies are needed to validate the clinical utility of ctDNA and to support its integration into BTC management.