Low-dose aspirin does not reduce cancer incidence in older adults and is associated with increased cancer-related mortality, with no evidence of a protective legacy effect after treatment cessation, according to an extended follow-up of the ASPREE randomised clinical trial.
The original Aspirin in Reducing Events in the Elderly (ASPREE) randomised clinical trial enrolled 19,114 community-dwelling adults in Australia and the US aged 70 years or older (≥65 years for US Black and Latino individuals) who were free from overt cardiovascular disease, dementia and independence-limiting physical disability at baseline.
Participants were randomised between 2010 and 2014 to receive daily 100 mg aspirin or placebo for a median of 4.7 years. They were subsequently followed in the observational extension study ASPREE-XT through to 2024.
While previous studies, largely among middle-aged adults, reported that aspirin reduced cancer risk after 10 years, particularly for colorectal cancer, the ASPREE trial found that low-dose aspirin treatment for a median of 4.7 years had no effect on overall cancer incidence but in fact increased risk of incident late-stage cancer and cancer-related mortality.
Long-term follow up of aspirin and cancer risk
Reported in JAMA Oncology, the recent extended follow-up trial examined whether 4.7 years of treatment with low-dose aspirin influenced cancer incidence and mortality in older adults over 10 years of follow-up (median 8.6 years) and assessed the legacy effects of exposure on the association with cancer.
Over the combined randomised and post-randomised periods, 3,448 incident cancers and 1,173 cancer-related deaths occurred. Low-dose aspirin was not associated with overall cancer incidence (hazard ratio [HR] 0.98; 95% CI 0.92–1.05), nor with cancer incidence by stage or type, including colorectal cancer (HR 1.01; 95% CI 0.84–1.21). Incidence rates were comparable across localised, metastatic, haematological and solid tumours.
However, aspirin was associated with a 15% increase in cancer-related mortality over long-term follow-up (HR 1.15; 95% CI 1.03–1.29). Cancer death rates were 7.8 versus 6.8 events per 1,000 person-years in the aspirin and placebo groups, respectively.
The authors noted that this excess mortality likely reflected the 35% increased risk observed at the end of the randomised phase, particularly driven by stage 4 disease.
Results of legacy analyses
Legacy analyses were conducted among 14,907 participants who were cancer-free at the end of the trial and consented to ongoing follow-up. During the post-trial period (median 4.3 years), 1,451 incident cancers and 376 cancer-related deaths occurred.
Original aspirin assignment was not associated with differences in cancer incidence (HR 0.91; 95% CI 0.82–1.01) or cancer-related mortality (HR 1.02; 95% CI 0.83–1.25), suggesting no persistent legacy effect.
The authors noted study limitations including the relatively short median duration of randomised treatment, multiple analyses without adjustment for multiplicity, and potential confounding during the observational phase, including open-label aspirin use.
However, strengths included the large, double-blind RCT design; rigorous adjudication of cancer outcomes; and high retention over extended follow-up.
The authors concluded that the findings do not support the initiation of multiyear low-dose aspirin for cancer prevention in older adults. Further research is now needed for longer-term follow-up to clarify potential delayed effects and to better understand age-related differences in aspirin’s impact on cancer biology, they added.
Reference
Orchard S G et al. Cancer Incidence and Mortality With Aspirin in Older Adults: Follow-Up of the ASPREE Trial. JAMA Oncol 2026 Jan 29:e256196.
