A ctDNA-Guided Approach to Adjuvant Therapy for Stage II Colon Cancer

Retrospective patient series indicate that a positive test for circulating tumor DNA (ctDNA) after surgery for stage II colon cancer is highly predictive of early disease recurrence, and a negative test correlates with low risk for recurrence. Patient selection for adjuvant therapy based on ctDNA testing is the subject of ongoing clinical trials.

In the current trial, patients with resected stage II colon cancer were randomized 2:1 to treatment with adjuvant chemotherapy based on either standard high risk pathologic criteria or ctDNA results on tests performed 4 and 7 weeks after surgery. Patients with positive ctDNA results received clinician's choice of single-agent fluoropyrimidine or oxaliplatin-based chemotherapy; those with negative results did not receive adjuvant chemotherapy.

Of 441 patients, 40% had high risk features, including T4 disease in 15% and bowel obstruction in 10%. Testing for ctDNA was successful in 99% of patients. Among patients treated with adjuvant therapy, single-agent fluoropyrimidine was used in a higher percentage of the standard-care group than the ctDNA-guided group (90% vs. 38%). Nearly all ctDNA-positive patients (98%) received adjuvant chemotherapy. Of 86 patients with mismatch repair protein-deficient tumors, only 9% received adjuvant therapy.

The primary endpoint, recurrence-free survival (RFS) at 2 years, was noninferior in the ctDNA group compared with the standard-care group (93.5% vs. 92.4%; hazard ratio, 0.96). A lower percentage of patients received adjuvant therapy in the ctDNA-guided group than the standard-care group (15% vs. 28%; relative risk, 1.82). Three-year RFS was 92.5% in ctDNA-negative patients and 86.4% in ctDNA-positive patients. Among ctDNA-positive patients, 3-year RFS trended better with oxaliplatin-based chemotherapy compared to fluoropyrimidine monotherapy (92.6% vs. 76.0%).