Adjuvant Aspirin in Colorectal Cancer: The Lancet Gastroenterology & Hepatology | July 2026

Introduction: Although aspirin has long been investigated as adjuvant therapy for colorectal cancer (CRC), the overall ASCOLT trial showed no improvement in disease-free survival (DFS). This translational analysis evaluated whether specific molecular biomarkers could identify patients most likely to benefit from aspirin.

Why was this study needed?

• The overall ASCOLT trial failed to demonstrate a survival benefit with adjuvant aspirin.
• Biomarker-guided use of aspirin may identify responsive patient subgroups.
• Previous studies suggested that PIK3CA mutations could predict aspirin benefit.
• The predictive value of COX-2 overexpression remained uncertain.
• Precision medicine approaches are needed to optimize adjuvant treatment in CRC.

Results:

• Within the ASCOLT translational cohort, adjuvant aspirin did not significantly improve disease-free survival in patients with PIK3CA-mutated, PTEN-mutated, or COX-2-overexpressing colorectal cancers.
• However, a meta-analysis combining all three randomized trials demonstrated a significant improvement in disease-free survival among patients with PIK3CA exon 9 or exon 20 mutations, supporting these mutations as potential predictive biomarkers.
• COX-2 overexpression alone was not associated with improved outcomes, suggesting it should not be used independently to guide aspirin therapy.

Clinical Impact:

These findings strengthen the concept of biomarker-guided adjuvant aspirin therapy in colorectal cancer. Rather than prescribing aspirin routinely for all patients, PIK3CA exon 9/20 mutations may identify the subgroup most likely to derive clinical benefit. Larger prospective biomarker-driven studies are needed before widespread implementation.

Bottom Line:

Routine adjuvant aspirin is not supported for all colorectal cancer patients. The greatest evidence of benefit appears to be confined to patients with PIK3CA exon 9 or exon 20-mutated tumours, while COX-2 overexpression alone is not a reliable predictive biomarker.