October 19, 2025

expert reaction to conference abstract on the DYNAMIC-III study on ctDNA-guided adjuvant chemotherapy de-escalation in stage III colon cancer

A conference abstract presented at the European Society for Medical Oncology (ESMO) 2025 meeting looks at adjuvant chemotherapy given in stage III colon cancer.

Prof Andrew Beggs, MRC Senior Clinical Fellow and Consultant Colorectal Surgeon, University of Birmingham, said:

“The study looks at doing a “liquid biopsy” test after surgery to remove the patients cancer. This is to see whether there might be any residual tumour that would be killed by giving doses of chemotherapy after surgery. For many years, with bowel cancer that is “advanced”, we have given chemotherapy to reduce the risk of the cancer coming back.

“They found that the liquid biopsy tests may be able to guide who we give chemotherapy to after surgery. They weren’t conclusively able to say it was “better” in the groups they studied, but showed that in earlier stage cancers that doing a liquid biopsy test may reduce the need for chemotherapy. However, the later stage tumours are the ones we want to target, and so further research is needed.

“It may well be that the test they used was not sensitive enough to pick the right patients for chemotherapy. Liquid biopsy technology is developing very fast, and this study relies on follow-up data that has taken several years to generate.

“In summary, this study adds evidence that it is likely we will be able to better select patients for chemotherapy after bowel cancer surgery, by only selecting those who really need it, removing the side effects for those who are found not to need chemotherapy in the end.”

Prof Marco Gerlinger, Professor of Gastrointestinal Cancer Medicine and Consultant Medical Oncologist, Barts Cancer Institute, St Bartholomew’s Hospital, said:

“Chemotherapy given after the surgical removal of a lymph node positive (Stage 3) colon cancer reduces the risk of the cancer coming back. A major problem in clinical practice is that we overtreat many patients, as 50% have already been cured by surgery alone. Until recently, we had no tests to identify those patients who don’t need chemotherapy. The Phase 3 DYNAMIC-III trial used a state-of-the-art high-sensitivity circulating tumour DNA test, which can detect tiny amounts of DNA that is shed from micrometastases. It then reduced or omitted chemotherapy in patients where the test was negative to avoid this overtreatment.

“The trial is formally negative because the recurrence rate was not statistically similar, but slightly higher, in the group where the circulating tumour DNA was used to de-escalate chemotherapy. This shows that the circulating tumour DNA test alone is insufficient to determine in which patients chemotherapy can be omitted without risking under-treatment. However, a pre-planned subgroup analysis in patients with low-risk Stage 3 tumours, where only up to 3 lymph nodes were positive, the de-escalation strategy may be non-inferior. Although the trial is not practice changing for all Stage 3 colon cancers, it is highly important and will likely influence clinical practice. For low-risk Stage 3 tumours, patients may make an informed decision to omit or reduce chemotherapy intensity if the test comes back negative as the trial showed that this reduces severe side effects. But further trials are needed to confirm these results and to determine how circulating tumour DNA and other risk stratification approaches need to be combined to optimally tailor chemotherapy to the patient’s preferences and recurrence risk. More detailed subgroup analyses of the DYNAMIC-III trial are also important to explore in which patients chemotherapy can be completely omitted and where it should only be reduced.”

The conference abstract ‘ctDNA-guided adjuvant chemotherapy de-escalation in stage III colon cancer: Primary analysis of the ctDNA-negative cohort from the randomized AGITG DYNAMIC-III trial (Intergroup study of AGITG and CCTG)’ by P. Gibbs et al. was presented at European Society for Medical Oncology (ESMO) 2025 meeting. The embargo on the abstract lifted at 23:05 UK time on Sunday 19th October 2025

Declared interests

Prof Andrew Beggs: I am co-inventor and hold a patent for a liquid biopsy assay developed to work on Nanopore sequencing which covers all cancers. I also hold research funding for this from Oxford Nanopore and receive additional funding from Natera.

For all other experts, no reply to our request for DOIs was received.