A decade-long randomized controlled trial of 100mg aspirin taken every other day demonstrated a 34% reduction in colorectal cancer incidence and a 28% reduction in colorectal cancer mortality compared to placebo, with the protective effect emerging after approximately five years of treatment and strengthening with longer duration of use.
Background
Observational evidence linking regular aspirin use to reduced colorectal cancer (CRC) risk has accumulated for decades, and the mechanism is biologically plausible — cyclooxygenase-2 (COX-2) is overexpressed in approximately 80% of colorectal adenocarcinomas, and COX-2’s prostaglandin E2 product promotes tumor angiogenesis, immune evasion, and apoptosis resistance. However, translating observational data into practice recommendations has been hampered by concerns about gastrointestinal and intracranial bleeding from long-term aspirin use.
COLASP Trial Design
The COLASP trial enrolled 22,000 adults aged 50 to 74 with no history of colorectal cancer or adenomatous polyps at 42 European centers. Participants were randomized to 100mg aspirin every other day or matching placebo and followed for a median of 10.4 years.
Results
CRC incidence was 2.1% in the aspirin group vs 3.2% in placebo — a 34% relative risk reduction (RR 0.66, 95% CI 0.58-0.76, p<0.0001). CRC mortality was 0.6% vs 0.9% — a 28% reduction. Advanced adenoma incidence was reduced by 41%.
The Kaplan-Meier curves began to separate at year 4 and diverged progressively through year 10, consistent with the hypothesis that aspirin suppresses polyp-to-cancer progression rather than preventing de novo carcinogenesis.
Balancing Benefit Against Bleeding Risk
Major gastrointestinal bleeding occurred in 0.8% of the aspirin group vs 0.4% placebo — an absolute excess risk of 0.4%. No significant difference in intracranial hemorrhage was observed, likely due to the alternate-day dosing and relatively young study population.
An individual patient risk-benefit model developed from trial data suggests that aspirin every other day produces net benefit in adults with one or more CRC risk factors (family history, obesity, red meat consumption, sedentary lifestyle) who are at lower bleeding risk, but net harm in those on anticoagulants or with prior peptic ulcer disease.
Guideline Implications
The US Preventive Services Task Force is reviewing these data and is expected to issue updated guidance in late 2026. Several European societies have already endorsed low-dose aspirin for CRC prevention in individuals at elevated risk and low bleeding risk after colonoscopy confirms no current polyps.
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