Colonoscopy and fecal immunochemical testing versus usual care in diagnostic colorectal cancer screening: the SCREESCO randomized controlled trial

There is a need to quantify the benefits and harms of colorectal cancer (CRC) screening using primary colonoscopy or fecal immunochemical testing (FIT) compared with usual care with no screening. Guidelines recommend screening in individuals aged 50-75 years using colonoscopy or FIT, and many screening programs use one-sample biennial FIT. Here we compare incidence of diagnosed CRCs and gastrointestinal and cardiovascular events between screening and usual care during the diagnostic phase of the SCREESCO trial. A randomized block method (no masking) assigned 278,280 individuals aged 60 years to once-only colonoscopy, 2 rounds of two-stool FIT with a low cutoff (10 μg g^-1 feces) or usual care (control group) in a ratio of 1:6 for colonoscopy versus control and 1:2 for FIT versus control. In the analysis, 31,113 individuals were in the primary colonoscopy arm and 60,267 were in the FIT arm, and there were 186,671 primary colonoscopy controls, of whom 120,521 were also controls for comparison with the FIT arm. After a median follow-up of 4.8 years, the incidence rate of CRC was 107.9 in the colonoscopy arm and 99.9 in controls per 100,000 person-years (incidence rate ratio (IRR): 1.08, 95% confidence interval (CI): 0.91-1.28) and 96.0 in the FIT arm and 103.9 in controls (IRR: 0.92, 95% CI: 0.81-1.05). Rates of stage I-II CRC were higher in the colonoscopy arm (IRR: 1.38, 95% CI: 1.09-1.74) and in the FIT arm (IRR: 1.19, 95% CI: 0.99-1.43) versus controls. Rates of cardiovascular and gastrointestinal events were slightly higher in the intervention arms during the first year and were subsequently more similar to controls. Our findings of an increase in CRC detection implies a benefit of screening while the increase in adverse events suggests some initial harm. ClinicalTrials.gov: NCT02078804 .