Circulating tumor DNA dynamics and response to immunotherapy in colorectal cancer.

Abstract

Circulating tumor DNA (ctDNA) is increasingly being investigated as a tool to detect minimal residual disease in resected, stage I-III colorectal cancer. Recent ctDNA studies have indicated that detection of ctDNA following surgery for resectable colorectal cancer confers a significantly higher risk of recurrence than those with negative ctDNA postoperatively. In those with postoperative ctDNA positivity, clearance of minimal residual disease with adjuvant chemotherapy is a positive prognostic indicator. Lastly, ctDNA has demonstrated superior sensitivity to the conventional blood tumor marker carcinoembryonic antigen (CEA) and can offer median lead times of up to 11 months for radiographic detection of recurrence during the surveillance of resected, stage I-III colorectal cancer. In metastatic colorectal cancer (mCRC), there is growing evidence to suggest that plasma ctDNA can be used to monitor tumor response to conventional chemotherapy as well. The present case series demonstrated that plasma ctDNA is a predictor of tumor response to immunotherapy in patients with mCRC that are microsatellite stable or microsatellite instability high. Plasma ctDNA could serve as a dynamic marker of immunotherapy response even in colorectal tumors that were CEA non-producers. Overall, these findings add to ongoing efforts to establish the role of plasma ctDNA in monitoring response to immunotherapy in CRC.