More efficient use of colonoscopy-based colorectal cancer screening by low-barrier, low-threshold pretesting

Background Gateopener colonoscopy-based screening is an innovative concept to better target colonoscopy to those most likely to benefit. 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 screening. We explored optimized use of this approach for reducing CRC incidence and mortality. Methods and FindingsUsing COSIMO, a validated Markov-based 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 (Sentinel Diagnostics) as exemplary gateopener FIT. We assessed various low hemoglobin cut-offs (10,8,6,4, and 3 {micro}g/g feces). We found that gateopener screening at cut-offs of 6, 4 or 3 {micro}g/g outperformed conventional screening colonoscopy in terms of CRC incidence reduction, with 16-25%, 50-57% and 66-72% more prevented cases, respectively, after ten 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 CRC cases, with lower cut-offs associated with higher gains, and prevented approximately equal to significantly higher (12-21%) numbers of CRC deaths. Cut-offs of 10 and 8 {micro}g/g required fewer colonoscopies per prevented case and death. ConclusionsGateopener 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. Author SummaryO_ST_ABSWhy was this study done?C_ST_ABS{checkmark} Screening colonoscopy is used inefficiently as most individuals have no benefit from this invasive procedure. {checkmark}Efficiency could be enhanced by pre-selecting those most likely to benefit, e.g., by use of a single low-threshold fecal immunochemical test ( gateopener FIT). {checkmark}Such pre-test may lower the barrier against using screening colonoscopy and may better target use of colonoscopy. What Did the Researchers Do and Find?{checkmark} A simulation study comparing application of the gateopener approach to conventional colonoscopy or FIT-based screening approaches demonstrated higher proportions of prevented colorectal cancer cases or deaths and/or a more effective use of colonoscopies as compared to conventional screening. What Do These Findings Mean?{checkmark} Inviting subjects to undergo pre-testing with low-threshold FITs could markedly improve outcomes and efficiency of colonoscopy-based colorectal cancer screening. Lay summaryThis simulation study demonstrates that introducing a simple, highly sensitive pre-test (e.g., an adjusted modern stool test) to identify individuals most likely to benefit from screening colonoscopy could markedly improve the benefits of colorectal cancer screening.