Role of Circulating Tumor DNA in Guiding Adjuvant Therapy in Colon Cancer

Adjuvant chemotherapy after resection of stage III colon cancer appears to improve outcomes, but many patients are treated to benefit a few. The data in patients with stage II disease are controversial, and efforts to select those with clinical features that increase the risk of recurrence have not led to definitive answers about who should and who should not receive adjuvant therapy.

Tie and colleagues (2022) have reported on 455 patients with stage II colon cancer who were randomized 2:1 to ctDNA-guided management or standard management and followed for a median of 3 years. Operationally, patients in whom tumor DNA was detected in the blood received adjuvant chemotherapy and those who were negative for tumor DNA were observed. In the standard care arm, the decision to use adjuvant therapy was made on the basis of the presence of certain clinical and pathologic risk factors. The factors indicating increased risk were the presence of mismatch repair proficiency, T4 extension, poor cellular differentiation, lymphovascular invasion, a surgical yield of fewer than 12 lymph nodes, tumor perforation of the bowel, and bowel obstruction.

A total of 28% of patients on the standard management arm received adjuvant chemotherapy compared with 15% in whom the decision was ctDNA-guided. Two-year recurrence-free survival was 93.5% for the ctDNA-guided arm and 92.4% for the standard arm, an outcome that was noninferior to implementing adjuvant therapy on the basis of clinical risk factors. Yet that goal was achieved with reducing the number of patients treated by nearly 50%. The data provide strong support for making the decision to use adjuvant therapy in patients with stage II colon cancer based on the presence or absence of ctDNA.