A clinical trial has found that a single blood test after colon cancer surgery can predict the risk of recurrence and adjust the intensity of chemotherapy. The study is seen as the starting point of precision medicine that tailors treatment to the risk of cancer recurrence, moving beyond the era of standard care in which most patients received the same chemotherapy.
A team led by Professors Jeanne Tie and Peter Gibbs at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Australia said in Nature Medicine on the 20th (local time) that a circulating tumor DNA (ctDNA) test can determine the risk of colon cancer recurrence and adjust chemotherapy use accordingly.
The results were also presented the same day at the European Society for Medical Oncology (ESMO) in Germany. ESMO is considered one of the world's three major cancer societies, along with the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR).
ctDNA is tiny fragments of genetic material that enter the bloodstream as cancer cells die. If these fragments are detected in a patient's blood after surgery, it likely means cancer cells remain in the body. If they are not detected, it is largely considered that the cancer has been removed.
The researchers conducted a phase 2/3 clinical trial involving 968 patients with stage 3 colon cancer. All patients had blood drawn for a ctDNA test 5 to 6 weeks after surgery, and treatment decisions were based on the results. One group received standard chemotherapy, while the other had chemotherapy intensity adjusted according to their ctDNA results.
About 70% (702 people) showed no ctDNA after surgery. With cancer largely absent, 87% of these patients remained recurrence-free for three years after surgery. For these patients, the team reduced the intensity of chemotherapy.
After adjusting cycles, combinations, and treatment duration, the use rate of the representative drug oxaliplatin dropped to less than half, from 88.6% in the standard-care group to 34.8% in the de-escalation group. Even so, recurrence-free survival showed little difference between the standard-care group (88.1%) and the de-escalation group (85.3%). This confirmed that patients with little residual cancer after surgery do not necessarily need aggressive chemotherapy.
De-escalated treatment also reduced side effects. The proportion of patients requiring hospitalization fell from 13.2% in the standard-care group to 8.5% in the de-escalation group, and reductions in chemotherapy-related side effects such as nerve damage and fatigue improved patients' quality of life.
By contrast, the outlook was clearly worse for 266 patients who showed ctDNA after surgery. Their three-year recurrence-free survival was 49%, far lower than the 87% among ctDNA-negative patients. In particular, the top 25% with the highest ctDNA levels had a three-year recurrence-free survival of just 23%.
The team applied intensified treatment to patients with detectable cancer DNA by increasing chemotherapy intensity, but the effect on suppressing recurrence was limited. Two-year recurrence-free survival in the intensified group was 51%, actually lower than the 61% in the standard-care group.
Patients who continued to show ctDNA even after intensified treatment had an even worse outlook. Their three-year recurrence-free survival was only 14%. By contrast, the group whose ctDNA disappeared after treatment reached 79%, a large difference. The researchers said, "Patients with detectable cancer DNA need new treatment strategies rather than existing chemotherapy."
Tie said, "Until now, most patients with stage 3 colon cancer received chemotherapy of similar intensity, but now there is a way to adjust treatment intensity based on recurrence risk." Tie added, "Reducing unnecessary chemotherapy can lessen side effects such as nerve damage and improve patients' quality of life," and said, "ctDNA will be a key tool to realize precision medicine in colon cancer treatment."
About 2 million people worldwide are diagnosed with colon cancer each year. Among them, 20% to 40% eventually experience recurrence or metastasis. The team predicted these results will provide important evidence to shift colon cancer care from uniform treatment to risk-based personalized therapy.
References
Nat Med (2025), DOI: https://doi.org/10.1038/s41591-025-04030-w