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 Findings Using 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 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 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 µg/g required fewer colonoscopies per prevented case and death. Conclusions 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding: Financial support for this study was provided in part by grants from the German Federal Ministry of Education and Research (grant numbers 01GL1712 and 01KD2104A) and from the German Cancer Aid (70114735). The funding agreements ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval: The BLITZ study was approved by the ethics committees of Heidelberg University (178/2005) and the state medical chambers of Baden-Württemberg (M118-05-f), Saarland (217/13), Rhineland Palatinate (837.047.06(5145)) and Hesse (MC 254/2007). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable All analyses relevant to the study are included in the article or uploaded as supplementary information. The model source code is freely available from the DKFZ website (https://www.dkfz.de/de/klinepi/download/index.html).