Description of the Evidence
The NSAID piroxicam, at a dose of 20 mg/day, reduced mean rectal prostaglandin concentration by 50% in individuals with a history of adenomas. Several studies assessing the effect of ASA or other nonsteroidals on polyp recurrence following polypectomy are in progress. In several of these studies, mucosal prostaglandin concentration is being measured.
The potential for the use of NSAIDs as a primary prevention measure is being studied. There are, however, several unresolved issues that mitigate against making general recommendations for their use. These include a paucity of knowledge about the proper dose and duration for these agents, and concern about whether the potential preventive benefits such as a reduction in the frequency or intensity of screening or surveillance could counterbalance long-term risks such as gastrointestinal ulceration and hemorrhagic stroke for the average-risk individual.
The preponderance of evidence from both observational studies and long-term follow-up of RCTs indicates that daily ASA for at least 5 years reduces the incidence of CRC. Among a group of more than 600,000 adults enrolled in an American Cancer Society study, mortality in regular users of ASA was about 40% lower for cancers of the colon and rectum.[52,53] In a report from the Health Professionals Follow-up Study of 47,000 males, regular use of ASA (at least 2 times per week) was associated with a 30% overall reduction in CRC, including a 50% reduction in advanced cases. In a Women's Health Study of a randomized 2 x 2 factorial trial of 100 mg of ASA every other day for an average of 10 years, similar rates of breast, colorectal, or other site-specific cancers were observed in both the ASA and placebo arms. In a report from the Nurses' Health Study involving 82,911 women followed for 20 years, the multivariate RR for colon cancer was 0.77 (95% CI, 0.67-0.88) among women who regularly used ASA (?2 standard 325-mg tablets per week) compared with nonregular use. Significant RR was not observed, however, until more than 10 years of use. The benefit appeared to be dose-related (e.g., women who used more than 14 ASA per week for longer than 10 years had a multivariate RR for cancer of 0.47 [95% CI, 0.31-0.71]).
A systematic review of 46 observational studies of ASA and CRC in 2007 found a reduction in CRC (OR for any use 0.80 [0.73-0.87]).
In the Physicians' Health Study, 22,000 men aged 40 to 84 years were randomly assigned to receive placebo or ASA (325 mg every other day) for 5 years. There was no reduction in invasive cancers or adenomas at a median follow-up of 4.5 years. In a subsequent analysis of more than 12 years, both randomized and observational analyses indicated that there was no association between the use of ASA and the incidence of CRC. The low dose of ASA and the short treatment period may account for the null findings.