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Liquid Biopsy in Hepatobiliary and Pancreatic Malignancies: Current Evidence and Implications for Surgical Practice
by
, , , , and
Silvio Caringi
1,*
,
Antonella Delvecchio
1,2,
Annachiara Casella
1,
Valentina Ferraro
1,
Matteo Stasi
1,
Nunzio Tralli
1,
Tommaso Maria Manzia
3
,
Riccardo Inchingolo
2,4,
Michele Tedeschi
1,2 and
Riccardo Memeo
1,2 1
Unit of Hepato-Biliary and Pancreatic Surgery, “F. Miulli” General Hospital, 70021 Acquaviva Delle Fonti, Italy
2
Department of Medicine and Surgery, LUM University, 70010 Casamassima, Italy
3
Transplant and HPB Unit, Department of Surgery Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
4
Unit of Interventional Radiology, F. Miulli Hospital, 70021 Acquaviva Delle Fonti, Italy
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(20), 3349; https://doi.org/10.3390/cancers18203349
Submission received: 1 September 2026
/
Revised: 13 October 2026
/
Accepted: 16 October 2026
/
Published: 16 October 2026
(This article belongs to the Special Issue Clinical Treatment and Outcomes of Gastrointestinal Cancer)
Simple Summary
Patients with hepatobiliary and pancreatic malignancies present a challenge for early diagnosis and carry a high recurrence rate even after potentially curative surgery. Liquid biopsy is a minimally invasive method of examination of tumor biomarkers circulating in the blood, which includes circulating tumor DNA, circulating tumor cells, and extracellular vesicles. These biomarkers can give additional information about the biology of tumors other than traditional radiologic and biochemical tests. In the course of surgical treatment, liquid biopsy can be used to assess the risk of recurrence prior to treatment and especially to detect minimal residual disease after surgery before its detection using imaging techniques. This review provides the currently available data on the use of liquid biopsy in pancreatic, liver, and biliary cancer, highlighting its possible significance for surgical practice. While promising results have been shown, currently available data support only its role in prognosis, but there is still insufficient data to use liquid biopsy alone for patient selection for surgery or changes in their therapy. Further prospective studies are needed before the introduction of liquid biopsy into clinical practice.
Abstract
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.
