ctDNA/MRD Testing for Colon Cancer: A Work in Progress or Ready for Prime-Time Standard of Care?

In patients with surgically resectable colon cancer (CC), clinicopathologic characteristics translate into cancer staging and predict recurrence risk. Adjuvant chemotherapy reduces the risk of recurrence and is offered to high-risk patients. However, some patients are inevitably overtreated or undertreated; better risk stratification is necessary to improve outcomes after surgery. Circulating tumor DNA (ctDNA)-based minimum residual disease (MRD) assays sequence plasma cell-free DNA for tumor DNA to predict the presence of otherwise subclinical malignancy. Studies have demonstrated that detectable ctDNA after surgery for CC predicts a high rate of recurrence and improves prognostication. Recent clinical trials show promise for using ctDNA to guide therapy, in particular standard-risk stage II CC. Large, randomized studies evaluating ctDNA-guided adjuvant chemotherapy versus standard of care in stage III CC are ongoing. Current data are insufficient to recommend routine use of ctDNA to guide adjuvant chemotherapy in resectable stage III CC.