Low-dose aspirin cuts colorectal cancer recurrence in patients with PI3K mutation, Nordic trial finds

A large randomized trial led by researchers at Karolinska Institutet and Karolinska University Hospital found that daily low-dose aspirin reduced the risk of colorectal cancer recurrence by about half in patients whose tumors carried somatic alterations in the PI3K signaling pathway after surgical removal of tumors. The ALASCCA trial followed more than 3,500 patients treated at 33 hospitals in Sweden, Norway, Denmark and Finland. Participants were randomly assigned to receive 160 milligrams of aspirin daily or a placebo for three years. After the three-year follow-up, recurrence risk was 55% lower in the aspirin arm than in the placebo arm, and the benefit was observed in tumors with PI3K pathway alterations, including mutations in PIK3CA.

"The ALASCCA trial shows for the first time in a randomized setting that low-dose aspirin significantly reduces recurrence in colorectal cancer patients with somatic PI3K pathway alterations," said Anna Martling, M.D., Ph.D., professor at the Department of Molecular Medicine and Surgery at Karolinska Institutet and senior consultant surgeon at Karolinska University Hospital. "This applies to more than one-third of all patients with resected colorectal cancer." The findings were published in the New England Journal of Medicine.

The study also notes that the aspirin effect appeared stronger in women, though the researchers cautioned that more work is needed to understand sex differences in response. Martling emphasized that testing for PI3K pathway alterations should be considered in colorectal cancer patients after surgery, so that clinicians can discuss potential benefits and risks of aspirin therapy with patients.

Aspirin is a widely available, inexpensive drug originally used to relieve pain and reduce inflammation and to prevent blood clots. Low-dose regimens have been studied for cancer prevention and adjuvant therapy for years, and the current trial adds randomized evidence to prior observational data. The researchers and outside experts stressed that aspirin is not universally appropriate and that decisions should be made in consultation with treating physicians.

Common side effects of aspirin include stomach problems and an increased tendency to bleed. It should not be used by people with stomach ulcers, bleeding disorders or asthma. Those taking other blood-thinning medicines or consuming substantial amounts of alcohol should use aspirin with caution. The investigators acknowledged limitations, including that the study was not powered for detailed subgroup analyses and that patients aged 80 or older were not included. Longer follow-up is needed to determine effects on overall survival.

If broadly implemented, the regimen could prevent thousands of cancer recurrences and save lives each year, particularly in settings where access to expensive targeted therapies is limited. The authors argued that the results are immediately relevant for clinicians and guideline committees and should prompt consideration of PI3K pathway alteration testing after surgery. They noted that while aspirin is inexpensive globally, its risks must be weighed against potential benefits on an individual basis until formal guidelines are updated. The trial was funded in part by the Swedish Research Council and the Swedish Cancer Society.

Further follow-up will be required to confirm long-term outcomes, including overall survival, and to determine which patients derive the most benefit from adjuvant aspirin therapy after colorectal cancer resection. In the meantime, researchers urged careful patient selection and shared decision-making to navigate the balance of potential recurrence reduction against possible adverse effects.