Colorectal Cancer Screening Working, But Challenges Remain Remain

HOUSTON—Colorectal cancer mortality has declined slightly in the last 10 years, and the decrease appears to be accelerating. This decline is due in large part to screening and early detection, said Patrick M. Lynch, MD, associate professor of medicine, University of Texas M.D. Anderson Cancer Center.

Dr. Lynch addressed current colorectal screening recommendations and controversies at a week-long medical oncology review sponsored by M.D. Anderson Cancer Center.

In the general population, the lifetime risk of developing colorectal cancer is 5%. The percentages rise to 15% to 20% for individuals with a personal history of colorectal cancer or adenomas, 15% to 40% for those with inflammatory bowel disease, 70% to 80% in families with hereditary nonpolyposis colorectal cancer (HNPCC), and more than 95% for those with familial adenomatous polyposis (FAP).

Screening recommendations are based on assignment of patients into average-risk, moderate-risk, and high-risk groups (see Table), Dr. Lynch said.

Dilemmas in Average-Risk Persons

Average-risk individuals continue to pose surveillance dilemmas, and the optimal protocol remains to be determined. Among average-risk patients, age is probably the single most important factor that determines the need for screening.

In this group, age 50 remains the “magic number,” Dr. Lynch said, “only because that is where the risk for colorectal cancer really takes off.” He noted, however, that the disease does seem to be occurring more often in younger patients.

Fecal occult blood testing (FOBT) remains a mainstay of average-risk screening despite limitations in sensitivity and specificity. False-positive tests are common and are often attributable to other

sources of colorectal bleeding or to dietary interference, such as peroxidase activity in red meats, vegetables, and some fish. False-negative tests can be caused by such things as ingestion of vitamin C or a delay in sample processing.

Moreover, Dr. Lynch said, FOBT’s low cost must be weighed against the cost of performing follow-up tests, typically colonoscopy, after a positive result. Studies suggest that colonoscopy after a positive FOBT has a cancer-detection rate of about 10% to 15% and an adenoma detection rate of 40% to 50%.

The degree of mortality reduction associated with FOBT screening varies widely among the various controlled trials, ranging from 19% to 57%. Despite the “considerable scatter” in the reductions, Dr. Lynch said, “we now have hard data that FOBT reduces mortality.”

Underuse of the test, however, continues to be a concern. “A multistate assessment of colorectal cancer surveillance found that only one fourth to one third of the people who should be having FOBT were actually having it done,” Dr. Lynch noted. “So there continues to be a disconnect between what we recommend and what really happens.”

Sigmoidoscopy is associated with even greater mortality reductions—59% in a Kaiser-Permanente study reported in the early 1990s and similar benefits in more recent trials. The caveat—and the technique’s greatest limitation—is that these mortality reductions apply only to lesions within the reach of the scope.

Questions to Be Answered

Among the questions that need to be answered are the following: Which lesions found by sigmoidoscopy predict proximal neoplasia? and Can mortality reductions be improved by combining sigmoidoscopy with FOBT or air-contrast barium enema?

“If you detect an adenoma on sigmoidoscopy, does the size of the adenoma, the degree of dysplasia, or the number of adenomas predict proximal neoplasia? Standard of care is to always perform co-lonoscopy,” Dr. Lynch said.

But, he added, adenomas of less than 1 cm are not strong predictors of proximal risk and may not warrant colon-oscopy. Hyperplastic polyps, which were once thought to be a predictor of proximal neoplasia, have now been shown not to predict proximal risk.

“Concerning the question of whether mortality reductions with sigmoidoscopy could be improved with combined FOBT or air-contrast barium enema, the answer is yes—but the extent of the mortality reductions is not known,” he said.

Sigmoidoscopy, like FOBT, is underutilized. “Less than half of individuals in the target age range have ever had sigmoidoscopy,” Dr. Lynch said. “So, again, we have a mortality reduction test out there, but people really aren’t availing themselves of it.”

Colonoscopy

Because of the limitations of current screening methods—such as false-negatives with FOBT and the limited reach of sigmoidoscopy—colonoscopy is being looked at as a potential surveillance method in the general population.

“More and more data are starting to be compiled on the use of what’s being called ‘primary colonoscopy’ to screen average-risk individuals,” Dr. Lynch said. “With increasing patient age, the likelihood of identifying a colorectal neoplasm on colonoscopy increases.”

Among individuals undergoing colonoscopy for the first time at age 60 or 65, he said, about 30% of women and about 40% of men will have a polyp or cancer identified. “I think the emphasis more and more is that it simply isn’t enough to be screening for cancer,” he said. “We want to detect adenomas so that we can remove them and actually prevent colorectal cancer.”

Dr. Lynch added that as the cost of colonoscopy is coming down, cost-benefit models suggest that the yield from colonoscopy may be significantly greater than the difference in cost among the various surveillance methods. He predicted that primary colonoscopy increasingly will be recommended more strongly as a screening alternative.

“I wouldn’t be surprised if in the next 10 to 15 years colonoscopy comes to be the preferred method of surveillance,” he said, “simply because of the greater mortality reductions that can be achieved with relatively modest increments in cost.”

Multiple Choice Proposition

For now, however, Dr. Lynch said, colorectal cancer screening for average-risk individuals remains a multiple choice proposition, with recommendations varying by organization.

• The American Cancer Society (ACS) currently maintains that FOBT in conjunction with flexible sigmoidoscopy is preferable to FOBT alone. As an alternative, ACS recommends “total colon examination”: air-contrast barium enema at 5 to 10-year intervals or colonoscopy at 10-year intervals.

• Recommendations from a multidis-ciplinary consensus development panel convened by the Agency for Healthcare Research and Quality (AHRQ) (formerly known as the Agency for Health Care Policy and Research) suggest an annual FOBT and flexible sigmoidoscopy at 5-year intervals.

Other options offered in the AHRQ-sponsored guidelines, which were published in the February 1997 issue of Gastroenterology, include FOBT combined with flexible sigmoidoscopy; air-contrast barium enema at intervals of 5 to 10 years; or colonoscopy at intervals of 5 to 10 years.

• The US Preventive Services Task Force supports annual FOBT, flexible sigmoidoscopy (no recommended interval), and combined FOBT and sigmoidoscopy as screening options. The task force cites insufficient data, pro or con, to support air-contrast barium enema or colonoscopy as primary screening tests for average-risk patients.

No One Right Answer

“I don’t think there is one right answer,” Dr. Lynch said. “Right now, all the approaches are considered to be appropriate for screening the average-risk patient.”