First, and most importantly, the standard of care for treating
adenomatous polyps is polypectomy and not
therapy with
NSAIDs. The initial clinical observation by Waddell and Loughry in 1983 that
sulindac treatment influenced rectal
polyps in patients with FAP has led to a considerable amount of research, commentary, and discussion during the past decade. These original observations have been validated by controlled clinical trials. Work presented in this issue by Ladenheim et al. indicates that
sulindac may not be effective
therapy for sporadic
polyps that are present before initiation of treatment (
secondary prevention). Even though their study may have failed to show a small effect of
NSAIDs on
polyps, further investigation of the ability of
NSAIDs to cause regression of established
polyps is probably not warranted. A more clinically relevant question, whether or not these agents can be used in a primary prevention strategy to prevent the development of
adenomas in a colon devoid of these lesions, is currently being addressed in a large trial with sufficient statistical power to render firm conclusions (personal communication, January 1995). The multiple reports that
sulindac treatment causes regression of
adenomas in patients with FAP has stimulated research directed at understanding the molecular basis for these effects. If we are able to understand the molecular mechanism by which
NSAIDs decrease the risk of
colorectal cancer, we might be able to design more effective drugs or other approaches that would be clinically useful in humans for
colorectal cancer chemoprevention.