Would you consider circulating DNA assay in resected node-negative deficient MMR colon cancer off-trial to guide your treatment?

Hello. It appears you are asking about a stage II MMR deficient/MSI-High colon cancer. The recurrence rate for stage II mismatch repair deficient (dMMR) colon cancer is generally lower than that for mismatch repair proficient (pMMR) tumors. Studies have shown that the 5-year recurrence rate for stage II dMMR colon cancer ranges from approximately 10% to 15%, compared to 20% to 25% for pMMR tumors. This improved prognosis is attributed to the high immunogenicity of dMMR tumors, which leads to a more robust immune response against the cancer cells. In addition, chemotherapy appears to have less benefit for these patients. I would probably NOT test ctDNA.

The adjuvant treatment would need to be Oxaliplatin based given that adjuvant 5FU alone i...

I do not use ctDNA in these cases outside of a clinical trial. The predictive ability of ctDNA has not been confirmed (yet). A recent study (COBRA) was halted early because it met its pre-specified stopping rules. COBRA was a phase II/III study designed to compare 2 adjuvant treatment strategies in the care of patients with T3N0 resected colon cancer. The first strategy is standard care which is surveillance. The second is ctDNA-based where chemotherapy is given for a positive test result after surgery and not given for a negative result. The ctDNA assay used was not tumor-informed (this might ultimately prove to be an important detail). Of the first 7 patients with a positive test result in the control arm, 3 patients spontaneously cleared...

Updated 5-year results from the DYNAMIC study of stage II colon cancer who were randomized to either ctDNA-guided management or standard management showed that recurrence free survival (RFS) rates were 88% and 87% and 5-year overall survival (OS) rates were 93.8% and 93.3% for ctDNA-guided versus standard management, respectively. (Tie et al., Journal of Clinical Oncology 2024) In the GALAXY observational arm from the ongoing CIRCULATE-Japan study, analysis of presurgical and postsurgical ctDNA in 1,039 patients with stage II-IV resectable colon cancer postsurgical ctDNA positivity at 4 weeks was associated with a higher recurrence risk (HR, 10.0; P < .0001) and identified patients with stage II or III CRC who derived a benefit from adjuvan...

Yes, I would offer baseline ctDNA and monitoring if the patient understands it could change the cadence of scans and perhaps increase the chance for early (curative) surgery. This assumes they have at least a 5-year expected baseline survival and would be a surgical candidate, etc.

The analysis by Dr. @Dr. First Last is quite nuanced and recognizes many of the issues here. In addition, the combined analysis by Dan Sargent from the ACCENT data base suggested use of 5FU may be detrimental for MMRd colon cancer (Sargent et al., JCO 2014 and previous) but in the end, concluded that the prognosis was 90% survival in stage II and adjuvant chemotherapy effects were attenuated. In stage III FOLFOX, seems effective and is the control arm for the ATOMIC trial. Given the prognostic power of ctDNA assays in the setting of adjuvant colon cancer as documented in the studies already mentioned, it is clear the risk for ctDNA+ stage II colon cancer is at least as high as stage III and possibly higher. Therefore, I would suggest that t...

One must make a recommendation based on the known data in 2024. In this setting, I would tell the patient that positive ctDNA probably suggests a higher risk of recurrence even though the patient is MSI high. If the patient were to ask me what I would do, I would offer FOLFOX adjuvant with the hope that I am increasing the chance of cure. I look at this recommendation as "the art" of oncology, possibly deviating from the lack of published data.