Abstract
BACKGROUND: Colorectal cancer (CRC) remains a significant health concern in the world. The existing standard of care guidelines for CRC surveillance fall short of effectively and timely detecting recurrence or metastasis. RECENT FINDINGS: In recent years, circulating tumor DNA (ctDNA) has emerged as a promising material for minimal residual disease (MRD) detection. In this article, we provide an exhaustive review of the methods utilized for MRD detection via ctDNA, present evidence supporting the potential of ctDNA MRD as a valuable biomarker in clinical applications, and engage in a discussion regarding ongoing ctDNA MRD-based clinical trials in CRC. Finally, we offer insights into future prospects of ctDNA-based MRD methodological advancements and clinical research. CONCLUSION: It is foreseeable that more sensitive, flexible, and economical MRD detection methods will emerge with the deeper research on cell-free DNA (cfDNA) genomics, fragmentomics, methylomes, and nucleosome imprinting. At the same time, MRD-guided intervention studies will evolve for revolutionizing the treatment paradigm of CRC.