BACKGROUNDColorectal cancer (CRC) risk varies by race and sex. This study, 1 of 2 microsimulation analyses to inform the 2018 American Cancer Society CRC screening guideline, explored the influence of race and sex on optimal CRC screening strategies.METHODSTwo Cancer Intervention and Surveillance Modeling Network microsimulation models, informed by US incidence data, were used to evaluate a variety of screening methods, ages to start and stop, and intervals for 4 demographic subgroups (black and white males and females) under 2 scenarios for the projected lifetime CRC risk for 40‐year‐olds: 1) assuming that risk had remained stable since the early screening era and 2) assuming that risk had increased proportionally to observed incidence trends under the age of 40 years. Model‐based screening recommendations were based on the predicted level of benefit (life‐years gained) and burden (required number of colonoscopies), the incremental burden‐to‐benefit ratio, and the relative efficiency in comparison with strategies with similar burdens.RESULTSWhen lifetime CRC risk was assumed to be stable over time, the models differed in the recommended age to start screening for whites (45 vs 50 years) but consistently recommended screening from the age of 45 years for blacks. When CRC risk was assumed to be increased, the models recommended starting at the age of 45 years, regardless of race and sex. Strategies recommended under both scenarios included colonoscopy every 10 or 15 years, annual fecal immunochemical testing, and computed tomographic colonography every 5 years through the age of 75 years.CONCLUSIONSMicrosimulation modeling suggests that CRC screening should be considered from the age of 45 years for blacks and for whites if the lifetime risk has increased proportionally to the incidence for younger adults. Cancer 2018;124:2974‐85. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Background: There is growing evidence for personalising colorectal cancer (CRC) screening based on risk factors. We compared the cost-effectiveness of personalised CRC screening based on polygenic risk and family history to uniform screening.Methods: Using the MISCAN-Colon model, we simulated a cohort of 100 million 40-year-olds, offering them uniform or personalised screening. Individuals were categorised based on polygenic risk and family history of CRC. We varied screening strategies by start age, interval and test and estimated costs and quality-adjusted life years (QALYs). In our analysis we: 1) assessed the costeffectiveness of uniform screening; 2) developed personalised screening scenarios based on optimal screening strategies by risk group; 3) compared the cost-effectiveness of both.Results: At a willingness-to-pay threshold of $50,000/QALY, the optimal uniform screening scenario was annual faecal immunochemical testing (FIT) from 50-74 years, whereas for personalised screening the optimal screening scenario consisted of annual and biennial FIT screening except for those at highest risk who were offered 5-yearly colonoscopy from age 50. Although these scenarios gained the same number of QALYs (17,887), personalised screening was not cost effective, costing an additional $428,953 due to costs associated with determining risk