Colorectal cancer: using a blood test (ctDNA) to guide immunotherapy after surgery

What happened, in summary

A 43-year-old man was hospitalized with severe symptomatic anemia and a hemoglobin level of 3.6 g/dL. CT showed irregular thickening in the ascending colon with nearby inflammation and enlarged right-sided lymph nodes. Colonoscopy found an obstructing mass, and biopsy showed moderately differentiated mucinous adenocarcinoma. No cancer was seen in the chest.

He underwent surgery that began laparoscopically but was converted to an open right hemicolectomy. Pathology showed poorly differentiated Stage IIIC ascending-colon cancer, pT4bN1a. The tumor was mismatch-repair deficient and MSI-high. Germline testing found a pathogenic MLH1 variant, confirming Lynch syndrome.

After recovery, he began adjuvant CAPOX and had circulating tumor DNA measured through follow-up. Instead of falling, the ctDNA rose significantly after 3 cycles, suggesting persistent molecular disease despite chemotherapy. His treatment was therefore changed to pembrolizumab.

On immunotherapy, the ctDNA fell to a near-undetectable level. Interval CT scans showed no visible disease. By cycle 10, about 6 months after starting pembrolizumab, he remained on treatment with no radiographic evidence of recurrence. He developed mild, symptom-free thyroid inflammation around cycle 6. This was monitored without medication and did not require pembrolizumab to be stopped. His current status was ongoing immunotherapy with near-negative ctDNA and clear imaging.

The operation removed the visible tumor, and staging showed no distant metastases. His CEA level remained low and was not useful for monitoring. The ctDNA trend therefore provided additional information when routine tumor-marker testing and interval CT scans did not show recurrence. At cycle 10, he remained on pembrolizumab with clear imaging and near-undetectable ctDNA.