ABSTRACT
BACKGROUND: This is 1 of 3 randomized trials undertaken to demonstrate a reduction in mortality from CRC by annual or biennial screening with an FOBT. In this study, the authors report on their 13-year experience of biennial screening with FOBT and its effect on mortality from CRC. They also evaluated the possible influence of compliance with screening on mortality from CRC.
POPULATION STUDIED: In August 1985, 140,000 people aged 45 to 75 years were living in Funen, Denmark. On the basis of information obtained from public registers, inhabitants with a known history of CRC, colorectal adenomas, or any type of malignancy with distant spread were not included by the authors for randomization. A balanced randomization was carried out in groups of 14 (3 to the screening group, 3 to the control group, and 8 not enrolled). Married couples were allocated to the same group. Subjects in the screening group were mailed invitations requesting participation. Only those attending previous screening rounds were invited back for repeat screening. Subjects in the control group were not informed of their participation in the study. In total, 61,933 men and women were studied; 30,967 subjects were assigned to biennial screening with Hemoccult II and 30,966 in the control group received usual care. Subjects were followed up until death or August 1, 1998.
STUDY DESIGN AND VALIDITY: This was a population-based, randomized controlled trial. Randomization of subjects in this trial was performed in a single-blinded fashion. Hemoccult II was used without rehydration but with dietary restrictions (no red meat, fresh fruit, iron preparations, vitamin C, aspirin, or other nonsteroidal anti-inflammatory drugs). Subjects were asked to provide 2 fecal samples from each of 3 consecutive stools. Subjects with a positive FOBT result (1 or more blue slides) were offered colonoscopy. It is not known how many in this group may have received screening for CRC as part of their usual care. Events (CRC, adenoma, death) in both groups were tracked using public databases and registers. The authors were unaware of the subjects’ screening status during assessment of death certificates.
OUTCOMES MEASURED: The primary outcome measured was death from CRC.
RESULTS: The risk of death from CRC was significantly reduced in the screening group compared with the control group (relative risk [RR] = 0.82; 95% confidence interval [CI], 0.69-0.97), even after adjusting for age, sex, and complications from treatment (RR = 0.86; 95% CI, 0.73–1.0). There was no difference in the rate of all-cause mortality between groups. In the screening group, the cumulative risk of having a positive test result was 5% over 13 years and 7 rounds of screening. Of those who tested positively, 94% went on to have at least 1 colonoscopy. There were 55 fewer deaths due to CRC in the screening group over 13 years in a population of 30,762 patients invited for screening. That is, screening saved 1 life for every 559 patients screened every other year for 13 years. Subjects who refused any screening had a significantly increased risk of death from CRC compared with those who participated in all screening rounds (RR = 1.65; 95% CI, 1.30-2.08).
Use of the fecal occult blood test (FOBT) every other year for 13 years to screen patients aged 45 years to 75 years will save 1 life for every 559 patients screened. Screening with FOBT does not alter the risk of death from all causes, which is felt by some physicians to be a more unbiased end point than cancer-specific mortality.1 This study, and others, suggests that individuals who refuse screening with FOBT may be at increased risk of dying from colorectal cancer (CRC). Special efforts should be made to ensure their participation in screening programs.2