Tissue-Based Biomarkers for Fluorescence-Guided Surgery of Pancreatic Ductal Adenocarcinoma: A Systematic Review

Pancreatic ductal adenocarcinoma (PDAC) is an invasive cancer with poor survival outcomes and limited treatment options. This systematic review aimed to identify and evaluate tissue-based biomarkers with potential applications in fluorescence-guided surgery (FGS), an approach that enables real-time intraoperative tumour visualisation to improve surgical precision. A systematic review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD420251056295). A comprehensive literature search was conducted across MEDLINE, Embase, and Cochrane Library databases from 1980 to January 2026 and was updated in March 2026. The EU Clinical Trials Registers were also searched for biomarker-targeted clinical trials. The TASC-T (Theranostic Target Selection Criteria) scoring system was used to assess biomarker suitability. EGFR, MSLN, CEA, and integrin αvβ6 scored highest, reflecting their strong potential as theranostic targets. MUC1 and uPAR also demonstrated high positivity and accessibility for imaging and therapy. While CA19-9 is a widely used serum biomarker, its role as a tissue target appears limited because of its high expression in benign conditions. EGFR and αvβ6 are both undergoing evaluation in phase II clinical trials and have emerged as promising targets for FGS in PDAC. This review highlights the need for standardised protocols and collaborative research to expand the clinical utility of these biomarkers. The methods and scoring criteria used in this review provide a transferable framework for identifying tissue biomarkers in other cancers and disease states.