Liquid Biopsy in Hepatobiliary and Pancreatic Malignancies: Current Evidence and Implications for Surgical Practice

Liquid biopsy is an emerging approach for the molecular characterization of hepatopancreatobiliary (HPB) malignancies through the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs). These biomarkers may complement conventional imaging and serum markers by providing additional information on tumor biology and disease evolution. This narrative review examines the available evidence concerning the potential applications of liquid biopsy in HPB surgical practice, with particular emphasis on preoperative prognostic assessment, postoperative molecular residual disease detection, recurrence monitoring, and treatment adaptation. Among the different circulating biomarkers, ctDNA currently has the most developed perioperative evidence base. Studies involving pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and biliary tract cancers have demonstrated associations between ctDNA detection and unfavorable oncological outcomes, particularly postoperative recurrence. Nevertheless, the available evidence remains predominantly observational, with considerable heterogeneity in patient populations, sampling protocols, analytical platforms, and outcome definitions. Although the integration of circulating biomarkers with conventional anatomical criteria has generated interest in the concept of “biological resectability”, this framework remains hypothetical and has not been prospectively validated for surgical treatment selection. Similarly, ctDNA-guided modifications of neoadjuvant therapy, adjuvant treatment, or postoperative surveillance have not yet demonstrated clinical benefit in HPB malignancies. Liquid biopsy should therefore currently be regarded as a promising investigational prognostic tool rather than an established determinant of surgical or oncological management. Standardized methodologies and prospective interventional trials are required before its routine clinical implementation.