Circulating Tumor DNA Guides Chemotherapy Decisions in Colorectal Liver Metastases

A blood test based on the detection of circulating tumor DNA (tDNA) could become a tool for personalizing treatment for patients with colorectal cancer and liver metastases after surgery. Results from the phase II GALAXY study, presented at the ESMO Gastrointestinal Cancers Congress 2026, show that patients with detectable tDNA after resection of liver metastases derive a significant benefit from adjuvant chemotherapy, while those with negative results have a good prognosis regardless of whether or not they receive additional treatment.

The data reinforce the potential of circulating tumor DNA as a biomarker to detect minimal residual disease and guide therapeutic decisions in a clinical scenario where there is still uncertainty about which patients really need chemotherapy after surgery.

Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer death. The liver is the primary site of metastasis, and although surgery offers the best chance of long-term survival, the persistence of microscopic disease after the procedure means that adjuvant chemotherapy is administered relatively widely, even though the benefit is not uniform among all patients.

Specifically, the goal of the GALAXY study was to evaluate whether the presence of circulating tDNA after surgery can identify those patients at higher risk of relapse and, at the same time, select who truly benefits from subsequent chemotherapy.

The research, led by Hyogo Medical University (Japan) in collaboration with other international centers, including the University of Oxford, included 298 patients who underwent surgery for liver metastases from colorectal cancer . All of them underwent a personalized analysis of circulating tumor DNA between two and ten weeks after the procedure.

The researchers divided the participants into two distinct groups. A total of 191 patients underwent surgery directly, while another 107 had previously received neoadjuvant chemotherapy before surgery. This separation allowed them to analyze the impact of prior treatment on the prognostic value of circulating tDNA and on the effect of the chemotherapy administered subsequently.

tDNA: A marker of residual disease and prognosis

The results showed that, among patients initially undergoing surgery, the detection of circulating tDNA after the intervention was associated with a clearly unfavorable prognosis .

Specifically, these patients had a risk of recurrence more than four times higher than those who tested negative, and a risk of death more than nine times higher.

These data support the role of circulating tumor DNA as a marker of minimal residual disease , capable of identifying the persistence of microscopic tumor cells that cannot be detected by conventional imaging techniques.

The most significant finding of the study was the difference observed in the effect of adjuvant chemotherapy based on blood test results. Among patients with detectable circulating tDNA after initial surgery, those who received chemotherapy experienced a highly significant improvement in both survival and disease control.

At four years of follow-up, overall survival reached 65% in patients treated with chemotherapy , compared to 33% in those who did not receive it. Similarly, disease-free survival was 38% versus 7%, respectively.

Furthermore, the treatment was associated with a 93% reduction in the risk of cancer recurrence, suggesting that chemotherapy administration is particularly effective when circulating tDNA analysis detects residual disease after surgery.

Conversely, patients whose analysis was negative showed a favorable evolution regardless of having received adjuvant treatment, a result that points to the possibility of avoiding unnecessary chemotherapy in some patients.

However, the behavior was different in the group of patients who had received chemotherapy before surgery. Although circulating tDNA continued to demonstrate important prognostic value in predicting both recurrence and survival, the administration of additional chemotherapy after surgery did not result in improved clinical outcomes , regardless of whether the biomarker was positive or negative.

Researchers believe that prior treatment can modify both tumor biology and the clinical interpretation of circulating tumor DNA , so this scenario requires specific studies.

tDNA blood test: Towards more personalized medicine

The clinical interest of these results lies in the possibility of adapting the treatment to the biological characteristics of each patient.

Currently, many patients receive chemotherapy after surgery as a preventive measure, although only a relatively small proportion obtain a real benefit, while virtually all are exposed to toxicities such as neuropathy, fatigue, hematological disorders or gastrointestinal complications.

In this context, Professor Per Pfeiffer, an oncologist at Odense University Hospital (Denmark), who was not involved in the study, pointed out that “only about one in ten patients is cured thanks to adjuvant therapy, while almost all experience treatment-related side effects,” so having a biomarker capable of better selecting candidates would represent a significant advance in clinical practice.

Despite the interest of the results, experts stress that the routine use of circulating tumor DNA to decide on chemotherapy administration cannot yet be considered a standard of care .

Pfeiffer himself noted that the findings are “promising” because they could allow doctors to identify which patients will truly benefit from treatment and avoid unnecessary therapies in those at low risk of relapse. However, he cautioned that current evidence is not yet sufficient to incorporate this strategy into routine clinical practice.

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(Featured image by Trnava University via Unsplash)

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First published in GACETA MEDICA. A third-party contributor translated and adapted the article from the original. In case of discrepancy, the original will prevail.

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