Background: Gastrointestinal tumors are among the most common cancer types, and early detection is paramount to improve their management. Cell-free DNA (cfDNA) liquid biopsy raises significant hopes for non-invasive early detection.

Aim: To describe current applications of this technology for gastrointestinal cancer detection and screening.

Methods: A systematic review of the literature was performed across the PubMed database. Articles reporting the use of cfDNA liquid biopsy in the screening or diagnosis of gastrointestinal cancers were included in the analysis.

Results: A total of 263 articles were screened for eligibility, of which 13 articles were included. Studies investigated colorectal cancer (5 studies), pancreatic cancer (2 studies), hepatocellular carcinoma (3 studies), and multi-cancer detection (3 studies), including gastric, oesophageal, or bile duct cancer, representing a total of 4824 patients. Test sensitivities ranged from 71% to 100%, and specificities ranged from 67.4% to 100%. Pre-cancerous lesions detection was less performant with a sensitivity of 16.9% and a 100% specificity in one study. Another study using a large biobank demonstrated a 94.9% sensitivity in detecting cancer up to 4 years before clinical symptoms, with a 61% accuracy in tissue-of-origin identification.

Conclusion: cfDNA liquid biopsy seems capable of detecting gastrointestinal cancers at an early stage of development in a non-invasive and repeatable manner and screening simultaneously for multiple cancer types in a single blood sample. Further trials in clinically relevant settings are required to determine the exact place of this technology in gastrointestinal cancer screening and diagnosis repeatable manner and screening simultaneously for multiple cancer types in a single blood sample. Further trials in clinically relevant settings are required to determine the exact place of this technology in gastrointestinal cancer screening and diagnosis.