Low-Dose Aspirin Cut Recurrence in PI3K-Altered Colorectal Tumors

CATEGORY: GUT & DIGESTIVE HEALTH

Colorectal cancer patients whose tumors carried alterations in the PI3K signaling pathway and who took a daily low-dose aspirin for three years after surgery saw their cancer return about half as often as those given a placebo, in a randomized trial published in the New England Journal of Medicine.¹ Within three years, cancer recurred in 7.7% of patients taking aspirin versus 14.1% of those taking an identical inactive pill. The PI3K pathway is a chain of growth signals inside cells that, when altered by gene changes in a tumor, can help cancer cells survive and spread—and roughly one in three colorectal cancers carries such an alteration.

ALASCCA Tested 2,980 Tumors, Randomized 626 Patients

The trial, called ALASCCA, ran at hospitals across Sweden, Norway, Denmark, and Finland. Researchers genetically tested the tumors of 2,980 people who had undergone surgery for colon or rectal cancer that had not spread to distant organs, and found PI3K-pathway alterations in 37% of them. Of those, 626 patients were randomly assigned to take either 160 milligrams of aspirin—a typical low “baby aspirin” range dose—or a matching placebo every day for three years. Neither patients nor doctors knew who was taking which. The study then tracked whose cancer returned over those three years, which is how the headline result was determined.

58% Lower Risk in the Second Alteration Group

Among patients with the most common “hotspot” mutations in the PIK3CA gene—the trial’s primary group—recurrence within three years was 7.7% with aspirin versus 14.1% with placebo, a 51% lower risk. In a second group whose tumors carried other alterations in the same pathway, the result pointed the same way: 7.7% versus 16.8%, a 58% lower risk. The consistency across both groups strengthens the finding, and because this was a randomized, placebo-controlled trial—the study design best able to show cause and effect—the result carries more weight than the earlier observational studies that first hinted aspirin might help. At three years, 88.5% of aspirin patients and 81.4% of placebo patients were alive without their cancer returning, a secondary measure whose range still spanned no difference.¹

Severe Adverse Events, 16.8% Versus 11.6% on Placebo

Aspirin was not free of downsides. Severe adverse events—mostly bleeding-related, since aspirin thins the blood—occurred in 16.8% of aspirin users versus 11.6% on placebo. The benefit also applied specifically to tumors with PI3K-pathway alterations, which is why the trial tested every tumor’s genes first; the study does not show whether aspirin helps when those alterations are absent. Researchers noted that tumor gene testing is already routine in many cancer centers, and that aspirin is one of the least expensive medicines in the world—a combination that could make this finding relevant to colorectal cancer care in many countries.

Pooled Trials Found 35% Lower Recurrence or Death

A 2026 pooled analysis of four randomized trials in colorectal cancers with PIK3CA mutations linked aspirin and related anti-inflammatory drugs to a 35% lower risk of recurrence or death—real, but smaller than the halving reported here—with no clear effect on overall survival.² A separate trial’s own PIK3CA subgroup was too small to settle it: among 69 such patients, recurrence or death was equally common on aspirin and placebo.³

Key Takeaways

• In a randomized trial of 626 colorectal cancer patients whose tumors carried PI3K-pathway alterations, a daily 160 mg aspirin for three years roughly halved the risk of the cancer returning: 7.7% versus 14.1% in the primary group.¹
• About one in three colorectal cancers carries a PI3K-pathway alteration, which can be identified by testing the tumor’s genes—the benefit was shown only in tumors with these alterations.
• Severe adverse events, mostly bleeding, were more common with aspirin (16.8% versus 11.6%), so the finding reflects a trade-off between benefit and risk.

References

1. Martling A, Hed Myrberg I, Nilbert M, et al. Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer. New England Journal of Medicine. 2025;393(11):1051–1064. link
2. Blanchard-Cavagis ER, Abrahão Reis PC, Visani FLV, et al. Adjuvant aspirin and cyclooxygenase-2 inhibitors in resected, PIK3CA-mutated colorectal cancer: a systematic review and meta-analysis of randomized controlled trials. Critical Reviews in Oncology/Hematology. 2026;220:105167. link.
3. Segelov E, Li S, Li I, et al. Adjuvant aspirin for colorectal cancer with PIK3CA-mutated and COX-2 overexpressed tumours: the ASCOLT translational research study and meta-analysis. eBioMedicine. 2026;130:106389. link.