Practical integration of ctDNA-defined minimal residual disease in gastrointestinal cancers: testing windows and evidence-aligned management frameworks.

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker of minimal or molecular residual disease and real-time tumor burden in gastrointestinal cancers, but its clinical integration remains uneven across disease settings. This narrative review summarizes current evidence in colorectal, gastroesophageal, pancreatic, and biliary cancers, with emphasis on practical testing windows, assay selection, and evidence-aligned interpretation. The strongest data support ctDNA use in resected colon cancer, particularly stage II disease, where postoperative ctDNA refines recurrence risk assessment and has enabled treatment de-escalation in selected prospective settings. In rectal, upper gastrointestinal, pancreatic, and biliary cancers, current evidence is mainly prognostic and less practice-defining. Serial ctDNA may support postoperative risk stratification, surveillance prioritization, and trial selection, but treatment escalation or de-escalation should preferably remain within prospectively studied contexts. Key barriers include assay standardization, false-positive calls, turnaround time, reimbursement, and the need to distinguish prognostic validity from proven clinical utility.