Stress-Testing US Colorectal Cancer Screening Guidelines: Decennial Colonoscopy from Age 45 is Robust to Natural History Uncertainty and Colonoscopy Sensitivity Assumptions

Purpose The 2023 American College of Physicians (ACP) guidelines for colorectal cancer (CRC) screening are at odds with the United States Preventive Task Force (USPSTF) guidelines, with the former recommending screening starting at age 50 y and the latter at age 45 y. This article “stress tests†CRC colonoscopy screening strategies to investigate their robustness to uncertainties stemming from the natural history of disease and sensitivity of colonoscopy. Methods This study uses the CRC-SPIN microsimulation model to project the life-years gained (LYG) under several colonoscopy CRC screening strategies. The model was extended to include birth cohort effects on adenoma risk. We estimated natural history parameters under 2 different assumptions about the youngest age of adenoma initiation. For each, we generated 500 parameter sets to reflect uncertainty in the natural history parameters. We simulated 26 colonoscopy screening strategies and examined 4 different colonoscopy sensitivity assumptions, encompassing the range of sensitivities consistent with prior tandem colonoscopy studies. Across this set of scenarios, we identify efficient screening strategies and report posterior credible intervals for benefits of screening (LYG), burden (number of colonoscopies), and incremental burden-effectiveness ratios. Results Projected absolute screening benefits varied widely based on assumptions, but strategies starting at age 45 y were consistently in the efficiency frontier. Strategies in which screening starts at age 50 y with 10-y intervals were never efficient, saving fewer life-years than starting screening at age 45 y and performing colonoscopies every 15 y while requiring more colonoscopies per person. Conclusions Decennial colonoscopy screening initiation at age 45 y remained a robust recommendation. Colonoscopy screening with a 10-y interval starting at age 50 y did not result in an efficient use of colonoscopies in any of the scenarios evaluated. Highlights Colorectal cancer colonoscopy screening strategies initiated at age 45 y were projected to yield more life-years gained while requiring the least number of colonoscopies across different model assumptions about disease natural history and colonoscopy sensitivity. Colonoscopy screening starting at age 50 y with a 10-y interval consistently underperformed strategies that started at age 45 y.