Using ctDNA to Guide Adjuvant Therapy in Stage II Colorectal Cancer

David J. Kerr, CBE, MD, DSc


December 08, 2022

This transcript has been edited for clarity.

I'm David Kerr, professor of cancer medicine from University of Oxford. Let's talk about a lovely paper that's been published by Jeanne Tie and colleagues in The New England Journal of Medicine. It's a clever study that looks at the role of circulating tumor (ct)DNA in the adjuvant setting.

We've talked about this many times, but we know that for stage II colorectal cancer, there's still a degree of controversy as to whether we should offer adjuvant chemotherapy or not. In this study, patients were randomized in a ratio of 2 to 1 to receive chemotherapy based on standard clinicopathologic features or on the presence of ctDNA positivity at 4 or 7 weeks after the operation. It's a 2-to-1 randomization in favor of the ctDNA test.

If you were ctDNA positive, then you got dealer's choice chemotherapy, either oxaliplatin-based or single-agent fluoropyrimidine. The primary endpoint of the study was to look at 2-year relapse-free survival. A second endpoint was usage of chemotherapy. Was there a difference, a diminution, or a different pattern of delivery of adjuvant chemotherapy in the ctDNA group?

There were 450 patients randomized, which was a reasonable number. The results showed that while maintaining a very similar degree of efficacy, the 2-year disease-free survivals were 92% to 93% in both arms, but significantly less chemotherapy was used in this ctDNA group. Only 15% of patients received chemotherapy there compared with around 30% in the conventionally managed arm.

This was a lovely result and a very interesting one in terms of using the positive predictive value of ctDNA to discriminate use of adjuvant chemotherapy. I think that we could perhaps still be a bit better. If we start to merge tissue prognostic biomarkers with ctDNA, we might be able to do better to identify those patients who might benefit further.

Wouldn't it be nice if we had some predictive biomarkers that would allow us better selection of drugs? Should it be fluoropyrimidine on its own? Should it become combination therapy with oxaliplatin?

I'm sure that we'll see this evolve, but this was a very well-designed study with very interesting results. As we've said before, there's no question that, for colorectal cancer, using ctDNA as a biomarker of minimal residual disease is going to be very useful, and one would hope, increasingly available in the clinical arena.

Have a look at the paper. I'd be interested in any comments that you might have. For the time being, as always, thanks for listening, Medscapers. Over and out. Thank you.

David J. Kerr, CBE, MD, DSc, is a professor of cancer medicine at the University of Oxford. He is recognized internationally for his work in the research and treatment of colorectal cancer and has founded three university spin-out companies: COBRA Therapeutics, Celleron Therapeutics, and Oxford Cancer Biomarkers. In 2002, he was appointed Commander of the British Empire by Queen Elizabeth II.

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