Effectiveness of Colorectal Cancer (CRC) Screening on All-Cause and CRC-Specific Mortality Reduction: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Colorectal cancer (CRC) screening is one of the most effective measures to prevent CRC resulting in a decrease in CRC mortality. Mortality reduction (MR) from CRC screening was estimated based on large-scale randomized control trials (RCTs) as well as in model studies, as there is a wide range on CRC-specific MR and a lack of estimates of all-cause MR. We found that biennial FIT, gFOBT, single/5-yearly FS, and 10-yearly colonoscopy screenings reduced CRC-specific mortality significantly, and 10-yearly colonoscopy is the most effective with a mortality reduction of 73%. The effectiveness of screening increases at younger screening initiation ages and higher adherences. Our findings also suggest that adherence is an important factor in CRC-specific mortality and is an explanation for discrepancy in thus far published pooled estimates. ABSTRACT: (1) Background: The aim of this study was to pool and compare all-cause and colorectal cancer (CRC) specific mortality reduction of CRC screening in randomized control trials (RCTs) and simulation models, and to determine factors that influence screening effectiveness. (2) Methods: PubMed, Embase, Web of Science and Cochrane library were searched for eligible studies. Multi-use simulation models or RCTs that compared the mortality of CRC screening with no screening in general population were included. CRC-specific and all-cause mortality rate ratios and 95% confidence intervals were calculated by a bivariate random model. (3) Results: 10 RCTs and 47 model studies were retrieved. The pooled CRC-specific mortality rate ratios in RCTs were 0.88 (0.80, 0.96) and 0.76 (0.68, 0.84) for guaiac-based fecal occult blood tests (gFOBT) and single flexible sigmoidoscopy (FS) screening, respectively. For the model studies, the rate ratios were 0.45 (0.39, 0.51) for biennial fecal immunochemical tests (FIT), 0.31 (0.28, 0.34) for biennial gFOBT, 0.61 (0.53, 0.72) for single FS, 0.27 (0.21, 0.35) for 10-yearly colonoscopy, and 0.35 (0.29, 0.42) for 5-yearly FS. The CRC-specific mortality reduction of gFOBT increased with higher adherence in both studies (RCT: 0.78 (0.68, 0.89) vs. 0.92 (0.87, 0.98), model: 0.30 (0.28, 0.33) vs. 0.92 (0.51, 1.63)). Model studies showed a 0.62–1.1% all-cause mortality reduction with single FS screening. (4) Conclusions: Based on RCTs and model studies, biennial FIT/gFOBT, single and 5-yearly FS, and 10-yearly colonoscopy screening significantly reduces CRC-specific mortality. The model estimates are much higher than in RCTs, because the simulated biennial gFOBT assumes higher adherence. The effectiveness of screening increases at younger screening initiation ages and higher adherences.