Modeling Population-Level Impacts of Cell-Free DNA Screening for Colorectal Cancer in Canada

Importance: Cell-free DNA (cfDNA) testing is an emerging approach for colorectal cancer screening that has been approved in the US. The impact of cfDNA testing in the Canadian setting, assuming adherence mirroring prior real-world cfDNA work and assay performance from a Guardant Health study, is unknown. Objective: To estimate how cfDNA screening impacts clinical and economic outcomes in Canada compared with existing screening approaches (fecal immunochemical testing [FIT] or colonoscopies). Design, Setting, and Participants: The OncoSim-Colorectal model (version 3.6.5.7) was used to simulate participation, relative effectiveness, and cost of introduction of cfDNA tests every 3 years. A population of 32 million Canadians were simulated and examined for outcomes and costs between 2024 and 2092. Exposures: Screening with colonoscopy, FIT, or cfDNA. Main Outcomes and Measures: Screen-detected colorectal cancer cases, deaths, health-adjusted person-years, potential years of life lost, and cost of cancer screening and management were examined. Results: Under higher participation, cfDNA detected 393 087 cases of colorectal cancer between 2024 and 2092 compared with 156 009 cases in the FIT scenario, and cfDNA reduced overall mortality by 121 383 deaths compared with current predictions with FIT. Linear regression models indicated that approximately 78% participation with 80% adherence or 69% participation with 100% adherence to cfDNA screening would be required to reduce deaths below the levels achieved by colonoscopy testing. Higher costs were associated with cfDNA testing, where each health-adjusted person-year had a cost of CAD $234.80 (US $164.06), and 0.025 deaths were averted per CAD $100 000 (US $69 874) additional dollars spent compared with FIT testing. When cfDNA testing was modeled with the same participation as FIT testing (43%), there was worse overall population impact (eg, greater number of deaths), emphasizing the importance of high participation for cfDNA testing to improve outcomes. Conclusions and Relevance: This study suggests that cfDNA testing could result in increased detection of colorectal cancer and reduced mortality if higher participation than reported in previous studies is achieved at the population level. Patient input on acceptance of blood-based vs stool-based screening may help inform real-world implementation.