Are there any adverse risk factors in stage I colon cancer that would warrant ctDNA testing?

I would not check ctDNA in this setting. If there is an adverse feature of the tumor and the patient is a candidate for further treatment, I would do close surveillance imaging and CEA at the most. A recent publication of a larger cohort study of stage II to IV resected colorectal cancer suggests that ctDNA may add little to good cross-sectional imaging and CEA monitoring (Ji et al., PMID 39729315).

No.

And, what would you do then? Give FOLFOX for stage 1 without real data on risk? CIRCULATE-Japan is inadequate for stage 1 data.

The risk of recurrence for T2N0 colon cancer is around 10–15% after surgery, but it can vary depending on the patient and other factors. Similar to well-described high-risk factors for recurrence in T3 N0 colon cancer (exclusive of those cancers that are MSI-H), such as poorly differentiated/undifferentiated histology, lymphatic or vascular invasion, bowel obstruction, <12 lymph nodes examined, perineural invasion, localized perforation, close, indeterminate, positive margins, or high-tier tumor budding (NCCN), one might consider checking for the same for T2N0 tumors. (Garfinkle et al., PMID 31550095)

Circulating tumor ctDNA has emerged as a useful marker for an elevated risk of recurrence. In a prospective study of patients with stage I-III...

This is a great question and we have limited data.

The best evidence would be from the CIRCULATE-Japan study which included 228 pathological stage I colon cancer patients. The positive rate in this population is extremely low in the MRD window (only 2 positive, means a positive rate of <1%) so it will be a very low yield test. Even in the surveillance window, there were only 7 out of 226 patients who had recurrent disease so continuous monitoring may pick up more cases but still an extremely low yield test (Nakamura et al., PMID 39284954 extended data figure 1). Would not recommend getting tumor-informed ctDNA tests routinely for stage I colon cancer patients. We do not have data for high-risk features in stage I colon cancer but it possibl...