Long-Term Follow-up of the Italian Flexible Sigmoidoscopy Screening Trial.

Background Recent reports showed that the protective effect of flexible sigmoidoscopy (FS) screening was maintained up to17 years, although differences were reported by sex. Objective To assess long-term reduction of colorectal cancer (CRC) incidence and mortality after a single FS screening. Design Parallel randomized controlled trial. (ISRCTN registry number: 27814061). Setting 6 centers in Italy. Participants Persons aged 55 to 64 years expressing interest in having FS screening if invited, recruited from 1995 to 1999 and followed until 2012 (incidence) and 2014 to 2016 (mortality). Intervention Eligible persons were randomly assigned (1:1 ratio) to either the once-only FS screening group or control (usual care) group. Measurements Incidence and mortality rate ratios (RRs) and rate differences. Results A total of 34 272 persons (17 136 in each group) were included in the analysis; 9911 participants had screening in the intervention group. Median follow-up was 15.4 years for incidence and 18.8 years for mortality. Incidence of CRC was reduced by 19% (RR, 0.81 [95% CI, 0.71 to 0.93]) in the intention-to-treat (ITT) analysis, comparing the intervention with the control group, and by 33% (RR, 0.67 [CI, 0.56 to 0.81]) in the per protocol (PP) analysis, comparing participants screened in the intervention group with the control persons. Colorectal cancer mortality was reduced by 22% (RR, 0.78 [CI, 0.61 to 0.98]) in the ITT analysis and by 39% (RR, 0.61 [CI, 0.44 to 0.84]) in the PP analysis. Incidence of CRC was statistically significantly reduced among both men and women. Colorectal cancer mortality was statistically significantly reduced among men (ITT RR, 0.73 [CI, 0.54 to 0.97]) but not among women (ITT RR, 0.90 [CI, 0.59 to 1.37]). Limitation Self-selection of volunteers from the general population sample targeted for recruitment may limit generalizability. Conclusion The strong protective effect of a single FS screening for CRC incidence and mortality was maintained up to 15 and 19 years, respectively. Primary funding source Italian Association for Cancer Research, Italian National Research Council, Istituto Oncologico Romagnolo, Fondo "E. Tempia," University of Milan, and Local Health Unit ASL-Torino.