Prevention by Aspirin of Colorectal Adenoma Recurrence: Some Advances and Latest Results of the APACC Trial

In a randomized controlled trial (RCT), 272 patients were assigned to lysine acetylsalicylate 160 mg/day (n = 73) or 300 mg/day (n = 67) or placebo (n = 132). The primary end points were adenoma recurrence and adenomatous polyp burden (APB) at year 1 or 4 (last colonoscopy) and at year 4. At last colonoscopy, APB tended to be lower under aspirin 160 mg or at either dose compared with placebo (P = 0.06 and 0.07, respectively). At year 4, 55 patients had received aspirin 160 mg/d, 47,300 mg/d, and 83 placebo. APB and proportions of patients with at least one recurrent adenoma were similar in both groups. A personal history of adenomas and an initial APB higher than 10 mm predicted recurrence. Among 219 adenomas from 136 patients, 128 adenomas (58%) from 59 patients strongly expressed COX-2 assessed by immunohistochemistry, mainly adenomas larger than 10 mm (84/129 vs 44/90; P = 0.02) and adenomas showing high-grade dysplasia (22/29 vs 104/188; P = 0.04). Deep stromal initial expression of COX-2 predicted recurrence (P = 0.04). Protection by aspirin was mainly observed in patients in whom COX-2 initial expression was low (RR: 0.59; 95% CI = 0.39–0.90; P = 0.02). Aspirin decreased adenoma recurrence significantly at 1 year, marginally at year 1 or 4, and not at year 4, possibly due to attrition but also to a differential effect according to polyp natural history. In a recent patient-level meta-analysis including the four published RCTs, aspirin significantly decreased adenoma risk by 17% and risk of advanced lesions by 28%.