Colorectal cancer: using a blood test (ctDNA) to guide immunotherapy after surgery — Case 1

What happened, in summary

A 54-year-old man underwent colonoscopy, which found an obstructing mass in the descending colon about 50 cm from the anal verge. The lesion caused severe narrowing of the bowel. Biopsy showed moderately-to-poorly differentiated adenocarcinoma. Tumor testing found a KRAS G13D mutation, a tumor mutational burden of 11 mutations per megabase, and loss of MLH1 and PMS2, indicating mismatch-repair deficiency and MSI-high disease. A broad inherited-cancer panel was negative, and staging found no distant metastases.

About 6 weeks after diagnosis, he underwent laparoscopic left colectomy. Pathology showed Stage IIIC disease, pT4aN2a, with clear surgical margins. Cancer was found in 6 of 25 lymph nodes, and both lymphovascular and perineural invasion were present.

He began adjuvant CAPOX while also having blood-based circulating tumor DNA monitoring. He completed 4 CAPOX cycles, then received 2 cycles of capecitabine alone because oxaliplatin was not tolerated. Despite surgery and chemotherapy, the ctDNA remained positive and continued to rise, suggesting that a small amount of cancer remained even though scans did not show it.

Because the tumor was MSI-high, treatment changed to pembrolizumab. The ctDNA cleared within about 3 months. He completed 1 year of immunotherapy without immune-related side effects. At the latest follow-up, ctDNA remained negative and surveillance CT showed no evidence of disease.

His CEA level stayed low and was not useful for monitoring. The blood-based ctDNA test therefore gave an early warning that chemotherapy had not eliminated molecular disease before recurrence was visible on scans.