Abstract
BACKGROUND: Gastrointestinal cancers remain a leading cause of cancer-related morbidity and mortality worldwide, with surgery being central to curative treatment. Tumour-targeted fluorescence-guided surgery (tFGS) has emerged as a promising approach to improve intraoperative visualisation and oncological precision. METHODS: We conducted a systematic review of preclinical and clinical studies on tFGS in gastrointestinal oncology, registered in PROSPERO (ID: 558994) and following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches of PubMed and Embase identified 133 eligible studies. RESULTS: Nine tracers have currently been evaluated in clinical trials, targeting the following biomarkers: carcinoembryonic antigen, vascular endothelial growth factor, epidermal growth factor receptor, folate receptor α and/or β, integrin αvβ3, 5-aminolevulinic acid and acidic tumour microenvironment. Clinical trials demonstrated that tracers like SGM-101 and panitumumab-IRDye800CW can achieve high tumour-to-background ratios (TBRs) up to 6.1 ex vivo and alter surgical strategy in up to 35% of cases. Preclinical research identified additional promising targets, including mucins, epithelial cell adhesion molecules, urokinase receptors, tumour-associated glycoproteins, gamma-glutamyl transferase, organic anion transporting polypeptides, human epidermal growth factors 1/2 and Lewis antibodies, with TBRs frequently exceeding three. Despite encouraging feasibility and safety data, translation into routine practice is hampered. Confirmation from early health technology assessments is needed to advance tFGS. Besides, standardisation of protocols and phase III confirmatory trials are required to establish clinical benefit and support regulatory approval. CONCLUSION: tFGS holds considerable potential to transform surgical oncology in GI cancers by enabling more precise resections and guiding organ-preserving strategies. Future innovations in multimodal tracers, NIR-II fluorophores and theranostics may further enhance the precision and therapeutic potential of tFGS. KEY POINTS: Tumour-targeted fluorescence-guided surgery (Ttfgs) enhances intraoperative precision in gastrointestinal cancer treatment. Translation of (Ttfgs) into clinical practice is limited by heterogeneity, regulatory hurdles, biomarker variability and absence of phase III trials. Innovations such as multimodal tracers and theranostic agents may further enhance the precision and therapeutic potential of Ttfgs.