Evidence of Benefit
The Danish trial in Funen, Denmark, entered approximately 31,000 individuals into two arms, in which individuals in the screened arm were offered nonrehydrated gFOBT testing every 2 years for nine rounds over a 17-year period. Sixty-seven percent completed the first screen, and more than 90% of individuals invited to each subsequent screen underwent FOBT testing. This trial demonstrated an 18% reduction in CRC mortality at 10 years of follow-up, 15% at 13 years of follow-up (RR = 0.85; 95% CI, 0.73-1.00), and 11% at 17 years of follow-up (RR = 0.89; 95% CI, 0.78-1.01). CRC incidence and overall mortality were virtually identical in both arms.
The Swedish trial in Goteborg enrolled all 68,308 citizens in the city born between 1918 and 1931 that were aged 60 to 64 years, and randomly assigned them to screening and control groups of nearly equal size. Participants in the control group were not contacted and were unaware they were part of the trial. Screening was offered at different frequencies to three different cohorts according to year of birth. Screening was done using the gFOBT Hemoccult-II test after dietary restriction. Nearly 92% of tests were rehydrated. Individuals with a positive test result were invited to an examination consisting of a case history, FS, and double-contrast barium enema. The range of follow-up times was from 6 years 7 months to 19 years 5 months, depending on the date of enrollment. The primary endpoint was CRC-specific mortality. The overall screening compliance rate was 70%, and 47.2% of participants completed all screenings. Of the 2,180 participants with a positive test, 1,890 (86.7%) underwent a complete diagnostic evaluation with 104 cancers and 305 adenomas of at least 10 mm detected. In total, there were 721 CRCs (152 Dukes D, 184 Dukes C) in the screening group and 754 CRCs (161 Dukes D, 221 Dukes C) in the control group, with an incidence ratio of 0.96 (95% CI, 0.86-1.06). Deaths from CRC were 252 in the screening group and 300 in the control group, with a mortality ratio of 0.84 (95% CI, 0.71-0.99). This CRC mortality difference emerged after 9 years of follow-up. Deaths from all causes were very similar in the two groups, with a mortality ratio of 1.02 (95% CI, 0.99-1.06).
All trials have shown a more favorable stage distribution in the screened population compared with controls (Table 3). Data from the Danish trial indicate that while the cumulative incidence of CRC was similar in the screened and control groups, a higher percentage of CRCs and adenomas were Dukes A and B lesions in the screened group. A meta-analysis of all previously reported randomized trials using biennial FOBT showed no overall mortality reduction by gFOBT screening (RR = 1.002; 95% CI, 0.989-1.085). The RR of CRC death in the gFOBT arm was 0.87 (95% CI, 0.8-0.95), and the RR of non-CRC death in the gFOBT group was 1.02 (95% CI, 1.00-1.04; P = .015).