Liquid biopsy in hepatobiliary and pancreatic cancers: A paradigm shift in early detection, prognostic stratification, and perioperative monitoring

BACKGROUND Hepatobiliary and pancreatic cancers are among the most lethal malignancies due to late-stage diagnosis and limited treatment options. Liquid biopsy has emerged as a minimally invasive tool for early cancer detection, prognosis, and therapeutic monitoring. AIM To concise the available data on liquid biopsy and establish its role in hepatobiliary surgeries. METHODS This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. A comprehensive literature search was performed using PubMed, Scopus, Web of Science, and EMBASE for studies published up to March 2025. Studies assessing the role of circulating tumor DNA, circulating tumor cells, exosomes, and other liquid biopsy markers in hepatobiliary and pancreatic cancers were included. The risk of bias was evaluated using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias Tool for clinical trials. RESULTS Liquid biopsy demonstrated significant potential for early cancer detection, perioperative risk stratification, intraoperative surgical decision-making, and postoperative monitoring of minimal residual disease. However, challenges remain regarding standardization, sensitivity, and clinical validation. CONCLUSION Liquid biopsy represents a paradigm shift in hepatobiliary and pancreatic cancer management. Advancements in next-generation sequencing and artificial intelligence may enhance its clinical utility. Further large-scale studies are needed to establish standardized protocols for routine implementation.