Aspirin Fails to Prevent Colorectal Cancer Recurrence in Trial

Colorectal cancer remains a global health challenge, ranking as the third most prevalent cancer, with nearly 2 million new cases annually. Despite decades of research, new adjuvant treatments have yet to significantly improve cure rates since oxaliplatin’s introduction. Aspirin, a widely available and cost-effective COX-1 and COX-2 inhibitor, has long been considered a candidate for secondary prevention. However, its efficacy in this role has remained inconclusive.

To address this uncertainty, the ASCOLT trial, the largest randomized study to date on this topic, aimed to determine whether aspirin could reduce the recurrence of colorectal cancer following standard adjuvant therapy.

Key Findings from the Aspirin ASCOLT Trial

• Study Design:
  Conducted across 66 centers in 11 countries, the study enrolled 1,587 adults with high-risk Dukes’ B or C colorectal cancer who had completed surgical resection and chemotherapy. Participants were randomized to receive either 200 mg of aspirin daily or a placebo for three years, with follow-ups lasting five years.
• Primary Outcomes:
  • Disease-Free Survival (DFS):
    • Aspirin Group: 77.0%
    • Placebo Group: 74.8%
    • Hazard Ratio (HR): 0.91 (95% CI: 0.73–1.13)
  • Overall Survival (OS):
    • Aspirin Group: 91.4%
    • Placebo Group: 88.9%
    • HR: 0.75 (95% CI: 0.53–1.07)

  These results suggest no statistically significant difference in disease recurrence or survival rates between the aspirin and placebo groups.

• Subgroup Analysis:
  A potential benefit was observed in patients who did not receive oxaliplatin-based chemotherapy. However, this observation did not reach statistical significance after adjustments for multiple comparisons.

Implications of the Findings

1. Rule-Out for Large Benefits:
   The trial effectively rules out any large-scale benefits of aspirin in the secondary prevention of colorectal cancer recurrence.
2. Potential for Modest Effects:
   While no significant overall outcomes were observed, the trial does not exclude the possibility of modest benefits in specific patient subsets.
3. Biomarker Research:
   Subgroups with particular genetic mutations, such as PIK3CA mutations or COX-2 overexpression, may respond differently to aspirin therapy. Biomarker studies within the ASCOLT trial are ongoing to identify such populations.
4. Meta-Analysis in Progress:
   Future meta-analyses, incorporating data from similar trials, may provide a clearer understanding of aspirin’s role in colorectal cancer management.

Strengths and Limitations of the Aspirin ASCOLT Trial

Strengths:

• Largest randomized trial to assess aspirin’s role in secondary colorectal cancer prevention.
• Comprehensive follow-up and robust methodology.

Limitations:

• Results were not stratified by molecular markers, limiting insights into biomarker-driven effects.
• Subgroup analyses lacked statistical power to confirm modest benefits in specific populations.

Future Directions

The ASCOLT trial underscores the importance of precision medicine in cancer care. Ongoing research into biomarkers could unlock targeted strategies for aspirin use. Meanwhile, patients and clinicians should rely on established therapies for colorectal cancer recurrence prevention.

Takeaway

While aspirin remains a promising candidate for cancer prevention due to its affordability and accessibility, the ASCOLT trial demonstrates that its role in preventing colorectal cancer recurrence is limited without further biomarker identification. For now, aspirin’s use should remain reserved for individuals with confirmed indications based on other health needs.

More Information:

John W K Chia et al, Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial, The Lancet Gastroenterology & Hepatology (2025). DOI: 10.1016/S2468-1253(24)00387-X

Seohyuk Lee et al, Adjuvant aspirin therapy and colorectal cancer survival, The Lancet Gastroenterology & Hepatology (2025). DOI: 10.1016/S2468-1253(24)00393-5