Circulating tumor DNA (ctDNA) represents a powerful measure of minimal residual disease (MRD) in colorectal cancer (CRC). Although immunotherapy has been widely established in metastatic CRC that is mismatch repair deficient or microsatellite instability-high (dMMR/MSI-H), its role in non-metastatic CRC is rapidly evolving. In resected, dMMR/MSI-H stage II CRC, adjuvant fluoropyrimidine has no benefit and is not recommended. There is growing evidence to suggest diminished benefit from neoadjuvant chemotherapy and chemoradiation in localized CRC that is dMMR/MSI-H. We present two cases of dMMR/MSI-H stage III CRC treated with definitive surgery wherein adjuvant oxaliplatin-based chemotherapy led to a failure to clear postoperative plasma ctDNA levels, prompting a change to immune checkpoint blockade with pembrolizumab and resultant ctDNA clearance. We illustrate that chemotherapy may achieve suboptimal disease control in localized colon cancer that is dMMR/MSI-H, while plasma ctDNA offers a window of opportunity to gauge the efficacy of oxaliplatin-based adjuvant chemotherapy to clear microscopic disease in resected, dMMR/MSI-H stage III colon cancer. These findings are important to contextualize given that relapse is inevitable with failure to clear MRD in the postoperative stage I-III CRC setting whereby chemotherapy remains the standard adjuvant therapy in resected, dMMR/MSI-H stage III colon cancer.
Keywords: Colorectal cancer; adjuvant therapy; ctDNA; immunotherapy; microsatellite instability; mismatch repair deficient.
Circulating tumor DNA (ctDNA) is a blood test that can detect cancer, which is a disease when new cells grow rapidly, even when they are not needed. These cells crowd out other cells. Cancer can occur anyplace in your body. In this report, we provide details of two patients who have colorectal cancer, which is cancer of the large intestine. After undergoing surgery to remove the cancer, we gave both of these patients chemotherapy (a drug that kills cancer cells) to protect them from the colorectal cancer returning or spreading to other parts of the body. We found out that ctDNA blood tests showed that in both patients chemotherapy was not working. We stopped the chemotherapy and switched these patients to receive immunotherapy, which is another drug that kills cancer cells by making the immune system work better. After giving these patients immunotherapy, the ctDNA blood tests showed that the cancer was killed. Our report gives us a good example to use ctDNA blood tests as a new way to detect if cancer is there even after surgery and chemotherapy and to better treat patients with colorectal cancer. In certain patients with a special type of colorectal cancer, immunotherapy may be better than chemotherapy to treat these patients.