New data published in JAMA Oncology from extended follow-up of the ASPREE and ASPREE-XT studies show that daily low-dose aspirin does not reduce overall cancer incidence in healthy older adults and is associated with a higher risk of cancer-related death. The findings challenge long-standing assumptions about aspirin’s role in cancer prevention and have implications for preventive prescribing in ageing populations.
ASPREE was a randomised, double-blind, placebo-controlled trial that enrolled 19 114 community-dwelling adults aged 70 years or older (or 65 years or older among Black and Latino participants in the United States) who were free of cardiovascular disease, dementia, and independence-limiting physical disability at baseline. Participants were randomly assigned to receive aspirin 100 mg daily or a placebo and were followed for a median of 4.7 years during the trial phase, with additional observational follow-up through the ASPREE-XT extension study, giving a total median follow-up of 8.6 years.
CLINICAL SUMMARY
What was examined
Extended follow-up of a randomised, placebo-controlled trial evaluating the effect of daily low-dose aspirin (100 mg) versus placebo on cancer incidence and cancer-related mortality in healthy older adults.
Key findings
- Aspirin was not associated with a reduction in overall cancer incidence over long-term follow-up (HR = 0.98; 95% CI, 0.92–1.05), including for colorectal cancer.
- Cancer-related mortality was higher in the aspirin group than in the placebo group (HR = 1.15; 95% CI, 1.03–1.29).
- The excess cancer mortality was largely confined to the period of active aspirin treatment, with no evidence of a persistent legacy effect after trial completion.
Clinical implications
- Low-dose aspirin should not be used as a strategy for cancer prevention in healthy older adults.
- The findings support current recommendations against routine aspirin use for primary prevention in this age group and highlight the need for careful, individualised risk–benefit assessment when prescribing aspirin, given the absence of cancer prevention benefit and the observed increase in cancer-related mortality.
In the updated analysis, investigators assessed long-term cancer outcomes, including cancer incidence and cancer-related mortality. Over an extended follow-up, there was no significant difference in overall cancer incidence between the aspirin and placebo groups (hazard ratio [HR] = 0.98; 95% CI, 0.92–1.05), including for colorectal cancer (HR = 1.01; 95% CI, 0.84–1.21). However, cancer-related mortality was higher among participants originally assigned to aspirin. The relative risk of death from cancer was 7.8 events per 1000 person-years in the aspirin group compared with 6.8 events per 1000 person-years in the placebo group, corresponding to an HR of 1.15 (95% CI, 1.03–1.29).
The increase in cancer mortality was observed across several solid tumour types, including colorectal cancer. Importantly, the excess risk was driven largely by outcomes observed during the randomised trial phase, when aspirin exposure was active. In analyses confined to the post-trial observational period, prior randomisation to aspirin was not associated with differences in cancer incidence or cancer-related mortality compared with placebo, suggesting no persistent “legacy effect” after treatment cessation.
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These findings contrast with earlier observational studies and secondary analyses of cardiovascular prevention trials that suggested aspirin might reduce cancer incidence and mortality, particularly for colorectal cancer. One explanation proposed by the authors is that aspirin’s biological effects may differ according to age at initiation, with potential anticancer benefits seen in middle-aged populations not translating to older adults. The authors also noted the possibility that aspirin may influence tumour progression or the clinical expression of existing subclinical cancers in this age group, although this remains speculative.
The trial population consisted of healthy older adults without established indications for aspirin therapy, and the results should not be extrapolated to patients with cardiovascular disease or other conditions for which aspirin is clearly indicated. Nonetheless, the data add to growing evidence that routine aspirin use for primary prevention in older adults offers limited benefit and may carry harm, including bleeding risk and, potentially, increased cancer-related mortality.
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From a clinical perspective, these findings reinforce current guideline trends away from recommending aspirin for primary prevention in older adults and underscore the importance of individualised risk–benefit discussions when considering long-term aspirin use in this population. For oncology, the study provides robust randomised evidence that low-dose aspirin should not be promoted as a general cancer prevention strategy in healthy older individuals.
Paper: Orchard SG et al. Cancer Incidence and Mortality With Aspirin in Older Adults: Follow-Up of the ASPREE Trial. JAMA Oncol. Published online January 29, 2026. Access online here.
