Chin Clin Oncol. 2026 Apr;15(2):38. doi: 10.21037/cco-2025-aw-135.

ABSTRACT

BACKGROUND AND OBJECTIVE: Hepatopancreatobiliary (HPB) cancers, including pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA), are among the deadliest malignancies due to late-stage diagnosis and limited curative options. Conventional tissue biopsies are often invasive and insufficient for longitudinal monitoring. This review synthesizes the current available literature on liquid biopsy, a minimally invasive approach that uses analysis of circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) in serum, plasma, or bile, to enable better early detection, surveillance, and treatment monitoring of HPB cancers.

METHODS: A search of PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Google Scholar identified peer-reviewed studies published between April 2016 and July 2025 using the key terms "liquid biopsy", "ctDNA", "cfDNA", "pancreatic", "hepatobiliary", "liver", "cholangiocarcinoma", and "gallbladder", combined with "early detection", "screening", "surveillance", "minimal residual disease", and "monitoring". Preprints, conference abstracts, and editorials were excluded, and no language restrictions were applied. Fifty-eight studies met the inclusion criteria.

KEY CONTENT AND FINDINGS: Recent studies report strong diagnostic performance for early-stage disease, with sensitivities ranging from 63% to 91% and area under the curve (AUC) values often exceeding 0.90 using next-generation sequencing (NGS), methylation profiling, and fragmentomics. Liquid biopsy has also demonstrated improved identification and detection of cancer-specific gene markers. Significant improvements in early detection and prognostication have been shown for PDAC with KRAS, TP53, SMAD4, and cfDNA methylation panels, and for CCA with FGFR2, IDH1/2, and BAP1 mutations detected in bile-derived cfDNA. In HCC, alterations in TERT promoter, TP53, CTNNB1, along with methylation markers such as RASSF1A, APC, and GSTP1, have predicted early disease and recurrence. Longitudinal ctDNA profiling further enables monitoring of minimal residual disease (MRD) and therapeutic resistance.

CONCLUSIONS: Liquid biopsy provides a powerful, minimally invasive tool for early detection, MRD assessment, and real-time disease monitoring in HPB cancers. Despite promising results, broader clinical adoption is limited by assay variability and the need for standardization and prospective validation. Continued innovation and large-scale studies may establish liquid biopsy as a transformative tool for early detection and personalized management of HPB cancers.

PMID:42145022 | DOI:10.21037/cco-2025-aw-135