Abstract Background Real-world data for patients with positive colorectal cancer (CRC) screening stool-tests demonstrates that adenoma detection rates are lower when endoscopists are blinded to the stool-test results. This suggests adenoma sensitivity may be lower for screening colonoscopy than for follow-up to a known positive stool-based test. Previous CRC microsimulation models assume identical sensitivities between screening and follow-up colonoscopies after positive stool-tests. The Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM) was used to explore the impact on screening outcomes when assuming different adenoma sensitivity between screening and combined follow-up/surveillance colonoscopies. Methods Modeled screening strategies included colonoscopy every 10 years, triennial multitarget stool DNA (mt-sDNA), or annual fecal immunochemical test (FIT) from 50-75 years. Outcomes were reported per 1,000 individuals without diagnosed CRC at age 40. Base-case adenoma sensitivity values were identical for screening and follow-up/surveillance colonoscopies. Ranges of adenoma sensitivity values for colonoscopy performance were developed using different slopes of odds ratio adjustments and were designated as small, medium, or large impact scenarios. Results As the differences in adenoma sensitivity for screening versus follow-up/surveillance colonoscopies became greater, life-years gained (LYG) and reductions in CRC-related incidence and mortality versus no screening increased for mt-sDNA and FIT and decreased for screening colonoscopy. The LYG relative to screening colonoscopy reached &gt;90% with FIT in the base-case scenario and with mt-sDNA in a “medium impact” scenario. Conclusions Assuming identical adenoma sensitivities for screening and follow-up/surveillance colonoscopies underestimates the potential benefits of stool-based screening strategies.

Impact of Screening and Follow-up Colonoscopy Adenoma Sensitivity on Colorectal Cancer Screening Outcomes in the CRC-AIM Microsimulation Model