The promise of molecular residual disease (MRD) testing for patients with colorectal cancer.

Molecular residual disease (MRD) assays using circulating tumor DNA (ctDNA) have the potential to detect colorectal cancer recurrence earlier than current standard-of-care surveillance techniques, such as carcinoembryonic antigen measurement and follow-up with computed tomography. Residual cancer cells that increase the risk of disease recurrence and the ctDNA released from these cells into the bloodstream are not detectable through standard imaging but can be detected with MRD tests. Two types of MRD assays developed for use in oncology are tumor-informed, which detect mutations specific to a patient's tumor, and tumor-naive, which detect known ctDNA sequences that are not specific to a patient's tumor genomics. The tumor-informed MRD test has high sensitivity but requires tumor sequencing that takes longer to process, whereas the tumornaive MRD test has a shorter turnaround time but a lower sensitivity. In prospective studies of these tests, patients with ctDNA-positive results were more likely to experience disease recurrence after surgery or definitive therapy than patients with ctDNA-negative results. Multiple platforms are already in clinical use or being developed as part of research studies. One such platform using the Oncodetect MRD test has confirmed the value of ctDNA testing and its association with recurrence-free survival at multiple timepoints (postsurgical, post-definitive therapy, and surveillance) in patients with colorectal cancer.