Omega-3 EPA tied to longer survival after liver surgery for bowel cancer spread

Patients scheduled for surgery to remove colorectal cancer that had spread to the liver lived longer when they took high-dose eicosapentaenoic acid, an omega-3 fatty acid known as EPA, before and after their operation, according to results of the phase 3 EMT2 trial presented at the ESMO Congress 2026. In the randomised, double-blind, placebo-controlled study, estimated five-year overall survival was 62.0% among patients assigned to EPA compared with 45.1% among those assigned to placebo, a difference that emerged as the trial’s key secondary endpoint.

The EMT2 trial enrolled 418 patients at 13 UK hepatobiliary surgery centres, all of whom were scheduled for liver resection with curative intent. Participants were assigned to receive 4 g daily of EPA, supplied as high-purity prescription icosapent ethyl, or a mineral oil placebo. Treatment began at least one day before surgery and was planned to continue for two to four years, even after cancer progression. Other cancer treatments were broadly comparable between the groups, with 20% of patients in each arm receiving adjuvant chemotherapy.

EPA was associated with a 32% lower hazard of death, with a hazard ratio of 0.68 and a 95% confidence interval of 0.48 to 0.96, reaching statistical significance at p=0.03. Median overall survival had not been reached in the EPA group, compared with 59.0 months in the placebo group. The survival benefit was consistent in the per-protocol analysis, which showed a hazard ratio of 0.60 with a 95% confidence interval of 0.36 to 0.99, and it remained consistent after adjustment for diabetes, which was more common at baseline in the EPA group at 16% versus 8%, as well as in other sensitivity analyses.

However, the trial’s primary endpoint was not met. Median progression-free survival was similar between the two groups, at 13.5 months with EPA versus 12.9 months with placebo, corresponding to a hazard ratio of 0.89 with a 95% confidence interval of 0.70 to 1.13 and p=0.33. EPA was nevertheless well tolerated, with no excess adverse events, bleeding or atrial fibrillation compared with placebo, and no negative impact on quality of life.

Surgery to remove colorectal cancer that has spread to the liver offers the possibility of long-term survival, but recurrence remains common. Preclinical and observational studies have previously suggested that EPA may have activity against colorectal cancer, and an earlier phase 2 trial had indicated a possible survival benefit, providing the rationale for the larger phase 3 study.

Lead author Professor Mark Hull, of the Leeds Institute of Medical Research at the University of Leeds, said the overall survival benefit seen with EPA in EMT2, if confirmed in other studies, would be clinically meaningful for patients who have had surgery for bowel cancer spread to the liver, in whom the cancer frequently comes back. He noted that this is particularly relevant because EPA is well tolerated and safe, even when other cancer treatments are needed. Hull suggested the survival benefit might reflect effects on the body’s response to cancer, including cachexia, which can involve weight loss, reduced appetite and fatigue. He observed that longer overall survival without a significant improvement in progression-free survival has also been seen in trials of cancer immunotherapy, and said more research is needed to work out whether EPA works by improving the body’s immune response to cancer.

Dr Chiara Cremolini of the University of Pisa, Italy, who was not involved in the study, described the results as definitely intriguing from both a biological and a clinical point of view. She cautioned that the lack of concordance between the progression-free survival and overall survival results requires careful interpretation, noting that progression-free survival is a less established indicator of overall survival after surgery for liver metastases than after surgery for early-stage bowel cancer. She added that additional data would help, including the treatments patients received after their cancer came back and the pattern of spread at the time of progression.

Cremolini said confirmatory results are likely needed before incorporating this treatment option into daily clinical practice, pointing out that patients having surgery for liver metastases vary widely in the biological and molecular characteristics of their cancer and in their previous treatment, factors that future trials could take into account. She also acknowledged the difficulty of conducting clinical trials, and especially academic research, in this setting, and said the authors should be highly congratulated for their successful effort.

The findings suggest a possible role for EPA in care around and after liver surgery for colorectal metastases, but the trial’s investigators and independent commentators agree that further trials are needed before routine use can be recommended. Until such confirmatory evidence is available, the divergence between a significant overall survival benefit and a neutral primary endpoint of progression-free survival remains the central question raised by the EMT2 results.

Subject of Research: Phase 3 trial of omega-3 EPA supplementation around liver surgery for colorectal cancer metastases

Article Title: Omega-3 EPA linked to longer survival after surgery for colorectal cancer liver metastases

Article References: Omega-3 EPA linked to longer survival after surgery for colorectal cancer liver metastases. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: EPA, omega-3, colorectal cancer, liver metastases, EMT2 trial, overall survival, progression-free survival, liver resection, ESMO Congress 2026, icosapent ethyl, phase 3 trial, cachexia