Consider COX-2s to prevent colon cancer

Cyclooxgenase-2 inhibitors are appropriate as a supplemental strategy for prevention of colorectal cancer in patients at highest risk for the disease. The current standard for preventing colon cancer, colonoscopy and polypectomy, virtually eliminates the chances of polyps progressing to cancer. But colonoscopy is not perfect. About 5 percent of polyps are missed. As the scope moves through the colon, there are blind spots. In 1 out of 20 colonoscopies, a polyp will be left behind. That’s typically not a major clinical problem because not all polyps progress to cancer.

Not all patients with polyps have the same risk of colon cancer. Clearly, some patients have a greater propensity to develop cancerous polyps. These include patients with a history of adenomatous polyps greater than 1 cm in diameter, patients with many polyps, or patients with polyps that show a villous type of architecture on histology. Such polyps are more likely to be aggressive and to proceed to colon cancer.

High-risk patients typically undergo colonoscopy every three years, but that may not be adequate if polyps grow rapidly. These high-risk patients should get adjunctive therapy in addition to colonoscopy to reduce the risk of progression from polyps to colon cancer. Options include nonsteroidal anti-inflammatory drugs such as aspirin or a cyclooxygenase-2 (COX-2) inhibitor.

Three studies have shown that administration of a COX-2 inhibitor is associated with a reduction in polyps in high-risk patients. In two prospective, randomized, placebo-controlled trials published in 2005, preventive therapy with celecoxib or rofecoxib reduced the number of polyps in patients at high risk for colon cancer. A third study that has not yet been published – the Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) trial – found similar results in high-risk patient randomized to celecoxib, compared with placebo.

In all three trials, there was a reduction in polyps compared with baseline – about a 25%-30% reduction in the number of polyps. That is the good news. COX-2 inhibitors are effective for the reduction of adenomatous polyps. A reduction in adenomatous polyps does not eliminate the risk of colon cancer; it only mitigates the risk. Clearly it doesn’t eliminate the need for a colonoscopy.

The only therapy that is going to be effective ultimately for preventing cancer is one in which all polyps are removed. COX-2 inhibitors would be a reasonable therapy for patiens who are at high risk for colon cancer, because the medication might reduce the likelihood of progression to colon cancer. We always balance risks and benefits. The risk of giving a COX-2 inhibitor that has been most widely discussed in recent years is the cardiovascular risk. A patient who had, for example, several large polyps on previous colonoscopy might be considered a candidate for a COX-2 inhibitor, but this must be balanced against other aspects of the patient’s medical profile. What is his or her cardiovascular status? Does the patient have a history of coronary artery disease, myrocardial infunction, or other cardiothrombotic events? We have to balance the medication’s potential risk versus the potential benefits when considering COX-2 inhibitors as adjunctive therapy for prevention of colon cancer.

That said, for patients with an average risk for developing colon cancer those with a few polyps, none of which is larger than 1 cm – the current approach of colonoscopy every 3-5 years without a COX-2 inhibitor is probably the most prudent course.