Aspirin fails to prevent recurrence after colorectal liver metastasis treatment

Daily low-dose aspirin did not lower the risk of cancer returning in patients treated for colorectal cancer that had spread to the liver, according to a randomised trial led by Sheraz Yaqub of the University of Oslo and Oslo University Hospital. Patients given aspirin also had lower overall survival and more serious adverse events than those given placebo. The results appear in The Lancet Gastroenterology & Hepatology.

Why recurrence is the central problem

Around 30% of people with colorectal cancer develop liver metastases at some point. Surgery offers many of them the best chance of a cure, yet the cancer comes back in more than half of those operated on. Metastatic disease, rather than the primary bowel tumour, is usually what threatens life, so any inexpensive way of reducing recurrence would be of considerable interest.

Aspirin has been an appealing candidate. Observational studies have linked its use after colorectal cancer treatment with lower recurrence and better survival. More recent randomised trials have examined the effect in patients whose tumours carry particular molecular alterations. The Oslo team wanted to know whether the same approach would work after treatment of liver metastases.

Design of the ASAC trial

The trial, known as ASAC, was a multicentre, phase 3, randomised, double-blind, placebo-controlled study. It enrolled 466 patients at 14 hospitals in Norway, Sweden and Denmark. All had received treatment with curative intent for colorectal cancer liver metastases, either surgery or local ablation.

Participants were assigned to aspirin at 160 mg daily or an identical placebo for up to three years. Because most recurrences occur within two years of surgery, the follow-up period was designed to cover that window.

What the trial found

Aspirin did not reduce recurrence compared with placebo. Overall survival was lower in the aspirin group, although the researchers say this finding should be interpreted with caution. Serious adverse events were more frequent among patients taking aspirin.

The team also examined molecular changes in tumour tissue. ASAC ran alongside the Scandinavian ALASCCA trial, which found that aspirin reduced recurrence in some patients with localised colorectal cancer whose tumours had specific alterations in the PI3K signalling pathway. In ASAC, no benefit was seen even among patients with the molecular alterations examined.

The authors also point to an earlier registry study by the same group, which linked Norwegian cancer and prescription data and found longer survival among patients taking aspirin. Registry analyses can reveal associations but cannot show that a drug caused the difference, which is the gap randomised trials are designed to fill.

Implications and limits

The authors conclude that aspirin should not be routinely recommended to prevent recurrence after curative-intent treatment of colorectal cancer liver metastases. They stress that results from patients with primary colorectal cancer cannot simply be transferred to those treated for liver metastases, where stage and tumour biology may differ. The reasons aspirin might help some groups and not others remain unclear.

The trial tested starting aspirin after cancer treatment, and patients already taking it were not eligible. The findings therefore say nothing about people who take aspirin for cardiovascular or other medical reasons, who should discuss any change with their doctor.

For researchers, the study is a reminder of how far observational signals can diverge from trial results, and it narrows the field of settings where aspirin is worth testing. Future work is likely to focus on why the effect differs between disease stages and which tumour characteristics, if any, identify patients who could benefit.

Source: Aspirin does not prevent recurrence after treatment for colorectal cancer liver metastases (Medical Xpress, 9 November 2026).

Image: AI-generated illustration.