Circulating Tumor DNA (ctDNA) Clearance May Predict Treatment Response in Neoadjuvant Colorectal Cancer Management

Background: Circulating tumor DNA (ctDNA) is extracellular DNA released by tumors and has been proposed as a marker of residual disease as well as a predictor of disease recurrence in the adjuvant setting. However, data are lacking on the utility of this biomarker in the neoadjuvant setting. Methods: We performed a retrospective study of stage III and IV colorectal cancer patients receiving neoadjuvant treatment at a single institution. Results: Seventeen patients converted from a positive pre-neoadjuvant ctDNA to a negative ctDNA prior to surgery. Five patients remained persistently positive despite systemic treatment. ctDNA conversion was found to be associated with a higher incidence of favorable treatment effect scores on final surgical pathology. There was no difference in recurrence-free survival in this small population. Furthermore, no added benefit was identified for patients receiving additional neoadjuvant therapy after the time of positive to negative ctDNA conversion. Conclusions: This study highlights the potential utility of ctDNA and the need for prospective trials in the neoadjuvant setting to monitor treatment response and guide decisions on treatment duration.