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Clinical Trial Results

Summaries of Newsworthy Clinical Trial Results
  • Posted: 05/11/2010

Sigmoidoscopy Markedly Reduces Colorectal Cancer Incidence and Mortality

Adapted from the NCI Cancer Bulletin.

A single sigmoidoscopy procedure between ages 55 and 64 can be an effective screening method for reducing the incidence of and mortality from colon cancer, according to long-term results from a study involving more than 170,000 participants in the United Kingdom, the largest randomized clinical trial of its kind published to date. Published online April 27, 2010, in The Lancet, the trial results are the first to demonstrate that sigmoidoscopy can reduce both the incidence of and mortality from the disease.

In several earlier randomized trials, regular screening with fecal occult blood testing produced a modest improvement in cancer incidence and mortality. But these new trial results, said lead investigator Wendy Atkin, Ph.D., of Imperial College London, show that a single sigmoidoscopy in patients of this age group “gives a very big effect,” reducing overall colorectal cancer incidence and mortality by 31 percent and 43 percent, respectively.

To be part of the study, participants had to return a questionnaire, which was sent to nearly 370,000 people, asking if they would be likely to accept an invitation to undergo a screening procedure. From the group that responded that they would accept an invitation, approximately two-thirds (about 130,000 people) were randomly assigned to the control group, meaning that they did not receive an actual invitation for screening, and the rest (about 57,000 people) were invited to be screened. Of this latter group, 71 percent, or about 41,000 people, underwent a sigmoidoscopy.

Small polyps were removed when found in participants who underwent the procedure. Participants with polyps that met certain high-risk criteria, such as those classified as adenomas, were referred for a colonoscopy. The results cover a median of 11 years of participant follow-up, which was done via a centralized database operated by the United Kingdom’s National Health Service.

When the results were analyzed by area of the colon, incidence of cancer in just the lower part of the colon (or distal colon) was reduced by approximately 50 percent for those who underwent screening compared with those in the control group.

Incidence of cancers in this area of the colon after patients underwent the screening procedure “was very low, and so far there seems to be little attenuation of the protective effect of the screening test,” the study authors wrote. As time passes, Dr. Atkin said, the expectation is that the impact on incidence and mortality will grow.

“The good news is that this size of benefit is large for any cancer screening test, certainly compared with mammography for breast cancer or assay of prostate-specific antigen for prostate cancer,” wrote David Ransohoff, M.D., from the Departments of Medicine and Epidemiology at the University of North Carolina at Chapel Hill, in a commentary that accompanied the study results in The Lancet. But the reductions don’t measure up, he continued, to those “popularly quoted for colonoscopy but on the basis of nonrandomized data.”

The trial did not compare sigmoidoscopy with colonoscopy, which is commonly used in the United States but not in the United Kingdom. Whereas a colonoscopy can be used to view the entire length of the colon, the flexible sigmoidoscope reaches only the lower quarter to half of the colon, explained Theodore R. Levin, M.D., a gastroenterologist and researcher at the Kaiser Permanente Northern California Division of Research.

That fact is not necessarily a downfall of the study, he noted, because the available evidence suggests that 60 to 70 percent of colorectal cancers arise in the area of the colon that can be reached with a sigmoidoscope. The trial design was “novel and innovative,” Dr. Levin continued, because it looked for the “most efficient way to have the maximum impact.”

Is More Better?

There is a question of whether “more frequent endoscopy might lead to still greater reductions in colorectal cancer,” Dr. Ransohoff wrote. The NCI-led Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial may help to answer this question, he said. PLCO involves two sigmoidoscopy procedures, one at study entry and another 5 years later, and has more aggressive requirements than the UK trial for referring patients to colonoscopy.

Whether the magnitude of the benefit is enough to justify more frequent screening is an important issue, Dr. Levin said. “Because the more intensely you screen, the more risk you expose people to.”

In the United States, just getting people over age 50 (the age at which most groups recommend colorectal cancer screening begin) to undergo any screening procedure for colorectal cancer remains a significant clinical challenge. Estimates put the screening rate for this group at about 55 percent. In February, an expert panel participating in a state-of-the-science conference on colorectal cancer identified strategies for improving colorectal cancer screening rates in the United States. Screening rates have improved, due mostly to increased use of colonoscopy. But because of accessibility and staffing issues, the panel acknowledged, there are limits to how much can be achieved with colonoscopy alone.

It is also unclear whether colonoscopy should be the preferred method for screening. Recent studies, Dr. Ransohoff explained, have called into question whether screening with colonoscopy reduces incidence or mortality from cancers in the upper part of the colon. Current guidelines on colorectal cancer screening, meanwhile, are mixed. In its most recent recommendations, for example, the U.S. Preventive Services Task Force did not single out any screening method, which can also include fecal occult blood testing or barium enema, as superior to another. But both the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society’s guidelines favor colonoscopy over the other available methods.

In addition to PLCO, two large randomized trials of colorectal cancer screening with sigmoidoscopy are ongoing, both of them in Europe. However, a trial comparing sigmoidoscopy head-to-head with colonoscopy would be extremely difficult to pull off, Dr. Levin noted. Because of the efficacy of sigmoidoscopy, huge numbers of participants would be required to demonstrate a statistically significant difference between the two screening methods.