Annual screening for colorectal cancer detection reduced 13-year mortality more than biennial or no screening
ACP J Club. 1993 Sept-Oct;119:37. doi:10.7326/ACPJC-1993-119-2-037
Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. N Engl J Med. 1993 May 13;328:1365-71.
To evaluate the effectiveness of fecal occult blood screening in reducing mortality from colorectal cancer.
Randomized controlled trial with 13 years of follow-up.
Community-based study in Minnesota.
46 551 volunteers (aged 50 to 80 y, 52% women) from the American Cancer Society and fraternal, veterans, and employee groups. Exclusion criteria were history of colorectal cancer, familial polyposis, or chronic ulcerative colitis; or persons bedridden or otherwise disabled. Vital status was determined for 100% of participants.
Participants were randomly assigned to screening once a year (n = 15 570), to screening biennially (n = 15 587), or to a control group with no screening (n = 15 394). Participants in the 2 screening groups submitted 6 guaiac-impregnated paper slides with 2 smears from each of 3 consecutive stools. 83% of the slides were rehydrated. Most participants who tested positive had a diagnostic evaluation that included colonoscopy.
Main outcome measure
Mortality from colorectal cancer determined by a blinded review of death certificates and relevant medical records by 2 pathologists, an oncologist, and a gastroenterologist. The stage of the colorectal cancer was determined by the study pathologist.
Over 13 years of follow-up, 1002 cases of colorectal cancer, 10 097 deaths, and 320 deaths from colorectal cancer occurred. The cumulative annual mortality rate from colorectal cancer was 5.88 per 1000 in the annually screened group compared with 8.33 in the biennially screened group and 8.83 in the control group. The rate ratio for mortality from colorectal cancer was 0.67 (95% CI 0.50 to 0.87) in the annually screened group and 0.94 (CI 0.68 to 1.31) in the biennially screened group relative to the control group. Adjustment for age, sex, and place of residence did not alter these results. Patients with disease detected by screening had higher 13-year survival rates than those with disease not detected by screening. The cumulative 13-year incidence rates of colorectal cancer by stage showed a distribution in the incidences of Dukes stage A and stage D cancers consistent with earlier detection by screening.
Annual fecal occult blood testing with rehydration of the samples decreased the 13-year cumulative mortality from colorectal cancer when compared with biennial screening and with no screening.
Source of funding: National Cancer Institute.
For article reprint: Dr. J.S. Mandel, Division of Environmental and Occupational Health, School of Public Health, University of Minnesota, Box 807 UMHC, 420 Delaware Street S.E., Minneapolis, MN 55455, USA. FAX 612-626-4837.
Despite misgivings about its sensitivity and specificity, colorectal cancer screening with annual fecal occult blood testing has been recommended by the American Cancer Society for years and is widely used. This is the third recent report (1, 2) and the most definitive; it suggests that annual fecal occult blood testing is effective in reducing colorectal cancer mortality by 33%.
Although this large and important study reinforces the recommendation for annual fecal occult blood testing, questions remain. Most important is that the screening in this study used rehydration before developing guaiac slides, increasing the positivity rates from 2.4% to 9.8%. This practice increased the sensitivity from 80.8% to 92.2% and reduced the positive predictive value from 5.6% to 2.2%. Consequently, 38% of the screened group received at least 1 colonoscopy, raising 3 additional issues.
First, was the result of the study related to the planned intervention of fecal occult blood testing or was the true screening test in this population colonoscopy of 38%? Second, in theory, fecal occult blood testing is attractive because of its low cost, but with the high false-positive rate, can we afford to do colonoscopies on 50 persons to find 1 colon cancer and upwards of 175 persons to prevent 1 colon cancer death? Finally, is rehydration necessary?
This study suggests that fecal occult blood testing with rehydration will reduce mortality from colorectal cancer. Although the cost is high, it is not necessarily out of line with other cancer screening tests and needs to be compared with the costs of the alternative strategy of no screening in a formal cost-effectiveness analysis. Further studies have shown that nonrehydrated fecal occult blood testing probably has similar benefits, and also raises questions. Linking biennial screening may indeed be as affordable as annual screening (3, 4). More research is needed to determine whether we should dispense with fecal occult blood testing altogether and pursue other screening modalities such as colonoscopy (5).
Alfred I. Neugut, MD, PhD
Columbia UniversityNew York, New York, USA