Aspirin as a possible therapy for the prevention of colon cancer recurrences

A first large phase III study investigated whether aspirin can reduce the risk of recurrence after colorectal cancer and completed standard therapy – with unexpected results.

"ASCOLT" questions aspirin's use in secondary prevention

Until now, there has been no international randomized trial on the efficacy of aspirin after standard adjuvant treatment for colorectal cancer. This changed with the "ASCOLT" study, published in March 2025.1,2 This study was conducted at 66 centers in 11 countries in the Asia-Pacific region where the incidence of colorectal cancer is increasing (Australia, China, India, Indonesia, Malaysia, New Zealand, Saudi Arabia, Singapore, Sri Lanka, South Korea, and Taiwan).

1,587 patients with high-risk colon or rectal cancer (mean age 57 years; 58% male) were included. They received either 200 mg of aspirin daily or a placebo for three years after standard adjuvant chemotherapy and were followed up for five years.

Disease-free survival (DFS) at 5 years was not significantly improved by aspirin: it was 77% versus 74.8% in the placebo group (p = 0.38). A comparable number of safety events occurred in both groups, with fewer heart attacks and strokes reported in the aspirin group, but slightly more gastrointestinal bleeding.

Study authors express disappointment over lack of benefit

Since the introduction of oxaliplatin into adjuvant colon cancer therapy two decades ago, there have been no new effective adjuvant therapies. Therefore, there is a continued need for effective and portable treatment options to increase cure rates.

The exact mechanism of aspirin's potential antineoplastic effect remains unclear. However, it is thought to be related to the inhibition of cyclooxygenase-2 (COX-2) at higher doses. COX-2 is associated with tumor-promoting inflammation, while at lower doses it acts as an irreversible COX-1 inhibitor.

Practical Conclusion

The study failed to demonstrate any relevant benefit of aspirin for recurrence prevention in colorectal cancer patients. "A key conclusion from our study is that aspirin should not be used in an unselected colorectal cancer population to reduce the risk of recurrence after standard treatment," summarizes lead author Prof. Toh Han Chong from the National Cancer Centre Singapore.3

Regarding the term "unselected": The smaller ALASCCA study, published almost simultaneously, found that biomarkers could play a role in further research on this topic. The study shows that taking aspirin for up to three years can significantly reduce the risk of colorectal cancer recurrence.

Specifically, in 314 patients with a PIK3CA mutation, the risk was reduced by an impressive 50% compared to placebo, while 312 patients with other mutations in the pathway were studied.

Sources
  1. Thornber, K. Aspirin Does Not Significantly Improve Disease-Free Survival in Patients with Colorectal Cancer. European Medical Journal https://www.emjreviews.com/oncology/news/aspirin-does-not-significantly-improve-disease-free-survival-in-patients-with-colorectal-cancer/ (2025).
  2. Chia, J. W. K. 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 10, 198–209 (2025).
  3. Aspirin after adjuvant therapy does not improve colorectal cancer outcomes. https://www.healio.com/news/hematology-oncology/20250304/aspirin-after-adjuvant-therapy-does-not-improve-colorectal-cancer-outcomes.