Optimizing colonoscopy-based colorectal cancer screening by low-barrier, low-threshold pretesting.

'Gateopener' colonoscopy-based screening is an innovative concept to better target colonoscopy to those who are most likely to benefit from it. It combines invitations to screening colonoscopy with the offer of pretesting with a single 'gateopener' fecal immunochemical test (FIT) which is applied with a lower positivity threshold than in conventional FIT-based screening. We explored optimized use of this approach for reducing CRC incidence and mortality. Using COSIMO, a previously validated simulation tool, we compared outcomes of gateopener screening to those of conventional FIT- or colonoscopy-based screening strategies. Gateopener screening was modelled using SENTiFIT-FOB Gold as exemplary 'gateopener' FIT at various low hemoglobin cut-offs (10, 8, 6, 4, and 3 μg/g feces). We found that Gateopener screening at cut-offs of 6, 4, or 3 μg/g outperformed conventional screening colonoscopy in terms of CRC incidence reduction, with 16%-25%, 50%-57%, and 66%-72% more prevented cases, respectively, after 10 years. All gateopener scenarios significantly increased prevented deaths, at low cut-offs more than doubling the numbers achieved by conventional screening colonoscopy. Compared to biennial FIT, gateopener screening prevented 7%-163% more cases, with lower cut-offs associated with higher gains, and prevented approximately equal to significantly more (12%-21%) CRC deaths. Cut-offs of 10 and 8 μg/g required fewer colonoscopies per prevented case and death. Gateopener screening outperforms conventional CRC screening by offering considerably stronger reduction of CRC incidence and mortality rates as well as considerably increased screening effectiveness. The feasibility of the concept should be assessed by a pilot study in real-life practice.