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Sigmoidoscopy Proves to Be Effective Screening Tool for Colorectal Cancer

In a large randomized trial involving healthy men and women aged 55 to 74, sigmoidoscopy substantially reduced the incidence of and mortality from colorectal cancer. Newly diagnosed cases of the disease fell by 21 percent and colorectal cancer deaths fell by 26 percent after a median of 12 years of follow-up. The findings, from the NCI-funded Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial appeared online May 21, 2012, in the New England Journal of Medicine.

The results add to a growing body of evidence that endoscopic screening with sigmoidoscopy or colonoscopy can prevent deaths from colorectal cancer. In 2010, a large trial in the United Kingdom found that a single sigmoidoscopy exam between the ages of 55 and 64 substantially reduced colorectal cancer incidence and mortality.

In the PLCO trial, Robert Schoen, M.D., of the University of Pittsburgh Cancer Institute and his colleagues did not remove polyps during sigmoidoscopy; instead, participants who were found to have a polyp or suspected cancer during the screening examination were referred for colonoscopy. Polyps could then be removed during colonoscopy. (Smaller polyps in the distal colon—on the left side; closer to the rectum—can be removed by sigmoidoscopy, but this wasn't done in the PLCO trial.)

"In large measure, the efficacy [seen in the PLCO trial] was due to the colonoscopies that were triggered by sigmoidoscopy," explained Barry Kramer, M.D., director of NCI's Division of Cancer Prevention and a PLCO investigator.

From 1993 to 2001, PLCO investigators randomly assigned nearly 155,000 people at average risk of colorectal cancer to receive either screening with sigmoidoscopy at study entry, followed by a repeat exam 3 or 5 years later, or usual care.

Of the 77,445 people assigned to the sigmoidoscopy group, 84 percent underwent a first sigmoidoscopy and 54 percent returned for a second exam. About 80 percent of participants with an abnormal sigmoidoscopy result had a diagnostic procedure—in most cases, a colonoscopy—within 1 year of the abnormal screening exam.

Overall, 22 percent of patients assigned to the screening group had a colonoscopy as a direct consequence of an abnormal result on their sigmoidoscopy.

Because acceptance of colorectal cancer screening in the United States rose as the PLCO trial was being conducted, almost half of the participants in the usual care group also received an endoscopic colorectal cancer screening exam outside the trial. This "contamination" likely lessened the magnitude of the screening effect, explained Christine Berg, M.D., chief of NCI's Early Detection Research Group and project officer for the PLCO trial. Nevertheless, incidence of and mortality from colorectal cancer were substantially lower in the screening group.

Interestingly, although sigmoidoscopy and subsequent colonoscopy reduced colorectal cancer incidence in both the distal and proximal colon (right side; closer to the small intestine), sigmoidoscopy screening reduced mortality only for cancers in the distal colon.

Colonoscopy may be "more effective for reducing deaths from cancer in the left side of the colon—the portion of the colon that sigmoidoscopy reaches—than in the right side of the colon," explained Dr. Kramer.

One possible reason for this is a higher frequency of flat polyps—which are harder to detect with endoscopy—in the proximal colon. Genetic changes driving the polyps in the proximal colon could also lead to more aggressive cancers, noted John Inadomi, M.D., of the University of Washington in an accompanying editorial.

Currently, the U.S. Preventive Services Task Force recommends three colorectal cancer screening tests: sigmoidoscopy, colonoscopy, and high-sensitivity fecal occult blood testing (FOBT)—a noninvasive test that can detect colorectal cancer but not smaller precancerous polyps—for adults aged 50 to 75.

Having more than one effective screening option is important, said Dr. Kramer, because "patient preferences for screening tests should be identified and respected. Some patients may be more willing to undergo FOBT or sigmoidoscopy than colonoscopy. But whichever commonly available screening test they choose to get, the mounting evidence is that it's going to be effective."

"[People] shouldn't neglect colorectal cancer screening altogether just because they don't want colonoscopy," urged Dr. Berg.

Further research is needed to determine optimal screening practices and intervals, she added. For example, could some patients at low risk of colorectal cancer be safely screened with colonoscopy only once in their life? And can noninvasive, less-sensitive tests like FOBT or fecal immunochemical testing find more cancers in a population, since they may be performed more frequently and be accepted by more patients?

In the last decade, use of sigmoidoscopy has decreased in the United States. In a recent study, 53 percent of primary care physicians surveyed reported that their sigmoidoscopy volume had fallen either substantially or somewhat since 2003.

This abandonment of the technique may be premature: "High-quality evidence must show the superiority of colonoscopy over other screening tests before we dismiss the use of flexible sigmoidoscopy and fecal occult-blood testing, both of which have randomized, controlled trials supporting their benefit," concluded Dr. Inadomi.

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