Despite our modern perioperative therapies, many patients with gastrointestinal cancer relapse after surgery. Novel strategies to identify and treat patients at high risk of relapse are needed to improve cancer outcomes. Circulating tumour DNA (ctDNA) is a promising, non-invasive biomarker with the potential to identify the earliest signs of cancer relapse. The presence of tumourspecific DNA in the blood in the absence of visualized tumour is suggestive of minimal residual disease and forebodes measurable relapse. Genomic sequencing techniques have advanced over the past few decades, and we have become better able to detect significantly low levels of DNA circulating in the blood from low-volume disease. Numerous studies using various technologies have established ctDNA as a powerful prognostic biomarker for relapse and survival in gastrointestinal cancers. ctDNA has the potential to risk-stratify patients in the postoperative, post-adjuvant and longitudinal settings for therapeutic escalation or de-escalation strategies. It may also capture early tumour dynamics in response to therapeutic intervention. As the multifaceted potential of ctDNA is attracting the attention of researchers, clinicians and patients, many questions remain regarding its use, interpretation and limitations. Here, we discuss the current understanding of ctDNA for minimal residual disease evaluation in gastrointestinal cancers and potential future directions.
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