Screening for colon cancer and evaluation of chemoprevention with coxibs

Although colorectal cancer is one of the most preventable forms of visceral cancer, it remains the second leading cause of cancer death in the United States. Most colorectal cancers are believed to arise from adenomatous polyps, premalignant mucosal masses that account for up to two thirds of colorectal polyps. Early identification and removal of adenomas prevent the development of colorectal cancer. Colonoscopy has emerged as the dominant method for evaluating symptomatic patients with colorectal cancer and for surveillance of patients with previous colon polyps or cancer. In the United States, fecal occult blood testing and flexible sigmoidoscopy are the most commonly used screening methods in average-risk persons, although there is an emerging trend toward the use of colonoscopy. For both screening and surveillance, the type of screening test used and the intervals at which it is performed are based on risk stratification, which also serves as the basis for selecting potential candidates for chemoprevention. Because colonoscopy, like most screening procedures, has several disadvantages, including risk of perforation and bleeding and an inherent "miss rate," alternative methods of prevention are being explored. A variety of agents with potential chemopreventive benefits have been identified, including cyclooxygenase (COX)-2-specific inhibitors (coxibs) even though these agents have not been approved for this use in the United States. COX-2 is overexpressed in colonic adenomas and cancers, and its inhibition has been shown to produce regression of polyps in familial adenomatous polyposis. Nonselective COX inhibition with nonsteroidal anti-inflammatory drugs (NSAIDs) has been consistently associated with reductions in the risk of mortality and the incidence of colorectal adenomas and cancers in case-control studies. Thus, selective COX-2 inhibition is a potential method of risk reduction in high-risk screening and surveillance groups, and large-scale trials of coxibs for the prevention of recurrence of adenomas after polypectomy are currently underway.