Minimal residual disease testing in gastrointestinal cancers: a US perspective

Gastrointestinal (GI) cancers represent a highly lethal subset of human malignancies. Colorectal cancer (CRC) remains the most prevalent subtype, representing the second-leading cause of cancer death in the USA, with rising incidence in younger adults. To improve outcomes for patients with GI malignancies, use of assays to monitor clinically undetectable molecular residual disease (MRD) via the analysis of circulating tumor DNA has become commonplace. However, rigorous studies evaluating the utility of MRD assays have lagged behind their widespread clinical adoption in the USA. We provide a narrative review of clinical studies characterizing the prognostic performance of MRD assays for patients with non-metastatic CRC and evaluate the evidence supporting use of MRD testing to de-escalate or intensify treatment. We additionally highlight emerging evidence and ongoing studies in populations of special interest, including patients with microsatellite instability-high disease and patients with a targetable molecular alteration. Finally, we summarize emerging MRD data for pancreatic, gastroesophageal, and hepatobiliary malignancies. This review offers a comprehensive evaluation of current MRD evidence for GI malignancies and outlines future pivotal trials that will ultimately inform guidelines and direct patient management.