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

CATEGORY: GUT & DIGESTIVE HEALTH

Aspirin has long been suspected of holding colorectal cancer at bay, and the ALASCCA trial asked a sharper version of the question: in whose tumors? Researchers screened 2,980 tumors for alterations in the PI3K signaling pathway, then randomized 626 patients who had them. Among those with the most common of the alterations, cancer returned within three years in 7.7% of the patients taking a daily low-dose aspirin, against 14.1% of those taking an identical inactive pill.¹ Roughly half as often, in other words.

One in Three Colorectal Cancers Carries the Alteration

The PI3K pathway is a chain of growth signals inside cells. When gene changes in a tumor alter that chain, cancer cells can survive and spread more easily. Roughly one in three colorectal cancers carries such an alteration. ALASCCA ran at hospitals across Sweden, Norway, Denmark and Finland. The tumors it tested came from people who had undergone surgery for colon or rectal cancer that had not spread to distant organs, and 37% of those tumors carried a PI3K-pathway alteration. Of that group, 626 patients took either 160 milligrams of aspirin, a typical low “baby aspirin” dose, or a matching placebo, every day for three years. Which pill a patient got was decided by lot, and neither patients nor doctors knew. The trial then tracked whose cancer returned over those three years, which is how the headline number was produced.

58% Lower in the Second Alteration Group

The primary group was patients whose tumors carried the most common “hotspot” mutations in the PIK3CA gene: 7.7% recurrence with aspirin against 14.1% with placebo, a 51% lower risk. A second group, with other alterations in the same pathway, pointed the same way. There it was 7.7% against 16.8%, a 58% lower risk. Agreement between the two groups strengthens the finding. Assignment was random and placebo-controlled, the design best able to show cause and effect, so this carries more weight than the 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

Bleeding Was the Cost

Aspirin thins the blood. Severe adverse events, mostly bleeding-related, hit 16.8% of aspirin users against 11.6% on placebo. The benefit applied specifically to tumors with PI3K-pathway alterations, which is why every tumor’s genes were tested first. Whether aspirin helps when those alterations are absent, the trial does not say. Researchers noted that tumor gene testing is already routine at 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 results are more modest. A 2026 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, with no clear effect on overall survival.² One separate trial’s own PIK3CA subgroup was too small to settle anything. Among its 69 such patients, recurrence or death was equally common on aspirin and placebo.³

Key Takeaways

• Among 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% against 14.1% in the primary group.¹
• About one in three colorectal cancers carries such an alteration, identifiable by testing the tumor’s genes. The benefit was shown only in tumors that had one.
• Severe adverse events, mostly bleeding, were more common with aspirin, 16.8% against 11.6%, so the finding describes a trade-off rather than a free gain.

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.