Description of the Evidence
In a randomized study of 635 patients with prior CRC (T1-T2 N0 M0) who had undergone curative resection, ASA intake at 325 mg/day was associated with a decrease in the adjusted RR of any recurrent adenoma as compared with the placebo group (0.65; 95% CI, 0.46-0.91) after a median duration of treatment of 31 months. The time to detection of a first adenoma was longer in the ASA group than in the placebo group (hazard ratio [HR] for the detection of a new polyp, 0.54; 95% CI, 0.43-0.94, P = .022). Harms of treatment included upper gastrointestinal hemorrhage and hemorrhagic stroke. In a study of 1,121 patients with a recent history of colorectal adenomas, after a mean duration of treatment of 33 months, the unadjusted RRs of any adenoma (as compared with the placebo group) were 0.81 in the 81-mg ASA group (95% CI, 0.69-0.96) and 0.96 in the 325-mg ASA group (95% CI, 0.81-1.13). For advanced neoplasms (adenomas measuring at least 10.0 mm in diameter or with tubulovillous or villous features, severe dysplasia, or invasive cancer), the RRs were 0.59 (95% CI, 0.38-0.92) in the 81-mg ASA group, and 0.83 (95% CI, 0.55-1.23) in the 325-mg ASA group. Harms of treatment were similar in the two groups and included upper gastrointestinal bleeding and hemorrhagic stroke.
Three reports in 2007, 2010, and 2011 [56,61,62] have analyzed long-term follow-up of RCTs of daily ASA versus the control. The 2007 analysis reported on two RCTs with reliable follow-up of more than 20 years. This report found that the use of 300 mg or more of ASA per day for at least 5 years reduced the incidence of CRC after a latency of 10 years (RR at 10-19 years [0.60; 95% CI, 0.42-0.87]). The 2010 analysis analyzed long-term followup data from four RCTs, finding that allocation to ASA for 5 or more years reduced the 20-year incidence and mortality of proximal colon cancer (adjusted incidence HR = 0.35; 95% CI, 0.20-0.63; adjusted mortality HR = 0.24; 95% CI, 0.11-0.52) and also reduced the 20-year risk of rectal cancer (RR = 0.58; 95% CI, 0.36-0.92) but not distal colon cancer. There was no increase in benefit at doses more than 75 mg/day. The absolute 20-year risk reduction in fatal CRC was 1.76% (95% CI, 0.61-2.91).
The 2011 analysis examined data from eight RCTs, seven of which provided individual patient data and three of which provided 20-year follow-up data. In trials with allocation to ASA of at least 5 years, the 20-year HR for CRC mortality was 0.60 (95% CI, 0.45-0.81).