Aspirin in Colorectal Cancer Care: Who to Treat, When, and Why.

purpose of reviewAspirin is ubiquitous, inexpensive, and mechanistically compelling in colorectal cancer (CRC), yet its clinical role has become more ambiguous with—notwithstanding—new data. Neutral phase III results in unselected disease, biomarker-restricted signals of benefit, and guideline shifts driven by bleeding risk have left clinicians without a consistent, setting-specific approach. This review fills that gap by translating the post-precision aspirin literature into a selection-first framework that specifies who may benefit, when off-trial use is reasonable versus discouraged, and why trial enrolment remains the preferred option in key areas of uncertainty. RECENT

findingsIn prevention, aspirin produces modest reductions in adenoma recurrence in selected high-risk surveillance cohorts and shows delayed cancer-endpoint benefit in Lynch syndrome, highlighting that baseline CRC risk and time horizon are decisive. In older adults and lower-risk settings, the time-to-benefit often does not align with a higher, earlier bleeding liability. After curative-intent treatment, randomised trials now define clear boundaries: routine adjuvant aspirin in unselected resected CRC is not supported, whereas recurrence reduction appears confined to PI3K-pathway / PIK3CA-altered localised disease, supporting biomarker-restricted consideration and rigorous prospective validation. In metastatic CRC, existing signals are largely non-randomised and confounded, precluding anticancer-motivated prescribing outside prospective studies. Aspirin in CRC should be targeted rather than routine. The proposed clinical algorithm integrates setting, absolute risk, PI3K/PIK3CA status, bleeding/antithrombotic context, and expected time horizon to maximise net benefit while reducing avoidable harm, and to prioritise trial enrolment where equipoise persists.