The Best Screening Test for Colorectal Cancer -- A Personal Choice

It is well established that screening for colorectal cancer with the fecal occult-blood test significantly lowers the rate of death from the disease. The report by Mandel   suggests that it also prevents cancer, reaffirming prior research about the benefits of detecting adenomatous polyps.  The mounting evidence that early detection saves lives has sharpened the consensus among professional groups that screening for colorectal cancer should begin routinely at the age of 50.

Fecal occult-blood screening, the only test shown in randomized trials to lower mortality from colorectal cancer, ranks highest in this regard. Trials of screening with sigmoidoscopy are under way,  but case-control studies currently provide the only evidence that sigmoidoscopy lowers mortality. Some observers find retrospective evidence unconvincing; patients who undergo sigmoidoscopy may have fewer complications from colorectal cancer for other reasons (e.g., a healthier lifestyle). Others are persuaded by these studies, because mortality was lower exclusively for cancers that could be reached by the sigmoidoscope.

No direct evidence proves that whole-bowel screening (colonoscopy or barium enema) reduces mortality, though studies of this topic are in process. Those who require such evidence consider the endorsement of whole-bowel screening to be premature. If one selects tests on the basis of their accuracy, colonoscopy wins. It enables inspection of the entire colon, detection of almost all important neoplasms, and immediate polypectomy. Barium enema also enables whole-bowel examination but is less accurate. Flexible sigmoidoscopy is as accurate as colonoscopy, but only for the distal bowel.  Fecal occult-blood screening, a test for peroxidase, has limited sensitivity for neoplasms (37 percent to 69 percent) and must be repeated every one to two years. Approximately 85 percent to 90 percent of positive screening tests are false positives. Performing fecal occult-blood screening together with sigmoidoscopy improves sensitivity for lesions that elude sigmoidoscopy alone but not for nonbleeding lesions, particularly polyps.

Concern about harms might seem unwarranted, given the safety of colonoscopy and sigmoidoscopy. Bleeding or perforation occurs in only 10 to 30 persons per 10,000 examinations, and death occurs in 1 per 10,000 colonoscopies. But if the probability of benefit is also small (e.g., the rate of death from colorectal cancer among persons 50 to 54 years of age is 1.8 per 10,000 , the number of persons harmed by screening could offset the number who benefit.

Those who advocate a specific screening test for colorectal cancer have taken a position -- reflecting their priorities with regard to scientific certainty, accuracy, the magnitude of benefit, safety, costs, and feasibility -- that they presume is universal. This approach is justified only when it can be safely assumed that most people, given the same facts, would make the same choice. This is a safe bet when the trade-offs are clear but not, as in this case, when subjective and situational factors determine how the scales tip. Although the average patient has the most to gain from certain screening protocols (e.g., fecal occult-blood screening every 1 to 2 years plus sigmoidoscopy every 5 years or colonoscopy alone every 10 years), the best choices are made when patients, physicians, and insurers weigh the trade-offs from their own perspectives.

Sixty percent of eligible people in the United States have never been screened for colorectal cancer. Allowing patients to select the tests they prefer may do more good -- as long as they choose something -- than whatever is gained with a "preferred" test. The difficulties of shared decision making notwithstanding, patients have the right to make their own choices. Someday, noninvasive forms of screening technology may render today's choices obsolete. Until then, redefining the best test as the one the patient wants may save the most lives.

Steven H. Woolf, M.D., M.P.H.
Virginia Commonwealth University

Going the Distance -- The Case for True Colorectal-Cancer Screening

Available screening methods should make it possible to prevent most deaths from colorectal cancer. Almost all colorectal cancers arise from adenomatous polyps that develop over a period of years. During this time, polyps can be detected and then removed by colonoscopic polypectomy.

Standard recommendations include annual testing for fecal occult blood and periodic sigmoidoscopy after the age of 50 years for persons at average risk for colorectal cancer. The Balanced Budget Act of 1997 provided an important, if imperfect, endorsement of these screening methods by establishing coverage of fecal occult-blood testing and sigmoidoscopy for all Medicare beneficiaries. Screening with the use of colonoscopy was approved only for beneficiaries considered to be at high risk for colorectal cancer. Barium-enema evaluation was covered as an alternative to colonoscopy or sigmoidoscopy, at the discretion of the physician.

Together, these studies reinforce the intuitive assumption that flexible sigmoidoscopy frequently fails to detect important colorectal neoplasms. Furthermore, the studies probably underestimate the limitations of sigmoidoscopy, because in practice, the splenic flexure is not usually reached. The findings are not surprising in the context of temporal trends in the distribution of polyps and cancer. Whereas earlier surveys showed that the preponderance of lesions were in the distal colon, supporting the reliance on sigmoidoscopy for screening, a more recent survey has shown that advanced neoplasia is now more uniformly distributed throughout the colon.

The net benefit of colonoscopy depends on the costs of the procedure (both direct and indirect) and the rate of complications, as well as on the technical factors that may prevent a thorough examination. The most serious complications of diagnostic colonoscopy -- perforation and problems associated with the use of conscious sedation -- have been estimated to occur in less than 0.2 percent of examinations performed by experienced gastroenterologists. Bleeding after polypectomy occurs in 1 percent of persons. Lieberman et al. report an overall complication rate of 0.3 percent.

These two new reports reinforce the growing suspicion among physicians that in recommending flexible sigmoidoscopy to screen persons for colorectal cancer, we are promoting a suboptimal approach. The failure of insurance companies to cover the costs of colonoscopic screening is no longer tenable.

The barrier to reducing the number of deaths from colorectal cancer is not a lack of scientific data but a lack of organizational, financial, and societal commitment. All persons 50 years of age or older who are at average risk for colorectal cancer should undergo comprehensive evaluation of the entire large bowel. In my judgment, such screening is currently best accomplished by colonoscopy rather than by barium-enema evaluation, especially given the results of recent comparative studies.However, ensuring that all persons undergo some form of comprehensive screening is even more important than deciding whether colonoscopy or barium enema is used for the screening evaluation. If a patient has no abnormalities, colonoscopy need not be repeated for at least 5 years and perhaps up to 10 years. I believe it is time for both government and private insurers to provide coverage for colonoscopic screening for all persons 50 years of age or older who are at average risk for colorectal cancer. As many people have pointed out, relying on flexible sigmoidoscopy is as clinically logical as performing mammography of one breast to screen women for breast cancer. It is time to go the distance.

Daniel K. Podolsky, M.D.
Massachusetts General Hospital


The Effect of Fecal Occult-Blood Screening on the Incidence of Colorectal Cancer

Background. Both annual testing for fecal occult blood and biennial testing significantly reduce mortality from colorectal cancer. However, the effect of screening on the incidence of colorectal cancer remains uncertain, despite the diagnosis and removal of precancerous lesions in many persons who undergo screening.

Methods. We have followed the participants in the Minnesota Colon Cancer Control Study for 18 years. A total of 46,551 people, most of whom were 50 to 80 years old, were enrolled between 1975 and 1978 and randomly assigned to annual screening, biennial screening, or usual care (the control group). Those assigned to the screening groups were asked to prepare and submit two samples from each of three consecutive stools for guaiac-based testing. Those with at least one positive slide in the set of six were offered a diagnostic examination that included colonoscopy. Screening was conducted between 1976 and 1982 and again between 1986 and 1992. Study participants have been followed with respect to newly diagnosed cases of colorectal cancer and deaths. Follow-up has been more than 90 percent complete.

Results. During the 18-year follow-up period, we identified 1359 new cases of colorectal cancer: 417 in the annual-screening group, 435 in the biennial-screening group, and 507 in the control group. The cumulative incidence ratios for colorectal cancer in the screening groups as compared with the control group were 0.80 (95 percent confidence interval, 0.70 to 0.90) and 0.83 (95 percent confidence interval, 0.73 to 0.94) for the annual-screening and biennial-screening groups, respectively. For both screening groups, the number of positive slides was associated with the positive predictive value both for colorectal cancer and for adenomatous polyps at least 1 cm in diameter.

Conclusions. The use of either annual or biennial fecal occult-blood testing significantly reduces the incidence of colorectal cancer. (N Engl J Med 2000;343:1603-7.)

Use of Colonoscopy to Screen Asymptomatic Adults for Colorectal Cancer

Background and Methods. The role of colonoscopy in screening for colorectal cancer is uncertain. At 13 Veterans Affairs medical centers, we performed colonoscopy to determine the prevalence and location of advanced colonic neoplasms and the risk of advanced proximal neoplasia in asymptomatic patients (age range, 50 to 75 years) with or without distal neoplasia. Advanced colonic neoplasia was defined as an adenoma that was 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. In patients with more than one neoplastic lesion, classification was based on the most advanced lesion.

Results. Of 17,732 patients screened for enrollment, 3196 were enrolled; 3121 of the enrolled patients (97.7 percent) underwent complete examination of the colon. The mean age of the patients was 62.9 years, and 96.8 percent were men. Colonoscopic examination showed one or more neoplastic lesions in 37.5 percent of the patients, an adenoma with a diameter of at least 10 mm or a villous adenoma in 7.9 percent, an adenoma with high-grade dysplasia in 1.6 percent, and invasive cancer in 1.0 percent. Of the 1765 patients with no polyps in the portion of the colon that was distal to the splenic flexure, 48 (2.7 percent) had advanced proximal neoplasms. Patients with large adenomas (greater than or equal to 10 mm) or small adenomas (<10 mm) in the distal colon were more likely to have advanced proximal neoplasia than were patients with no distal adenomas (odds ratios, 3.4 [95 percent confidence interval, 1.8 to 6.5] and 2.6 [95 percent confidence interval, 1.7 to 4.1], respectively). However, 52 percent of the 128 patients with advanced proximal neoplasia had no distal adenomas.

Conclusions. Colonoscopic screening can detect advanced colonic neoplasms in asymptomatic adults. Many of these neoplasms would not be detected with sigmoidoscopy. (N Engl J Med 2000;343:162-8.)