Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer.

Background: Cell-free DNA blood tests (cf-bDNA) and next-generation stool tests could change colorectal cancer (CRC) screening.
Objective: To estimate the clinical and economic impacts of novel CRC screening tests.
Design: Cost-effectiveness analysis using MOSAIC (Model of Screening and Surveillance for Colorectal Cancer).
Data Sources: Published data.
Target Population: Average-risk persons.
Time Horizon: Ages 45 to 100 years.
Perspective: Health sector.
Intervention: Novel versus established CRC screening tests.
Outcome Measures: Incidence and mortality of CRC, quality-adjusted life-years (QALYs), costs.
Results of Base-Case Analysis: For colonoscopy every 10 years, annual fecal immunochemical test (FIT), and triennial next-generation multitarget stool DNA, FIT-RNA, cf-bDNA (Guardant Shield), or cf-bDNA (Freenome), the relative rates (RRs) and 95% uncertainty intervals (UIs) versus no screening for CRC incidence were 0.21 (0.19 to 0.22), 0.29 (0.27 to 0.31), 0.33 (0.32 to 0.36), 0.32 (0.30 to 0.34), 0.58 (0.55 to 0.61) and 0.58 (0.55 to 0.60), respectively; the RRs for CRC death were 0.19 (0.17 to 0.20), 0.25 (0.23 to 0.27), 0.28 (0.27 to 0.30), 0.28 (0.26 to 0.30), 0.44 (0.42 to 0.47), and 0.46 (0.44 to 0.49), respectively. The cf-bDNA test (Shield; list price $1495) cost $89 600 ($74 800 to $102 300) per QALY gained versus no screening; alternatives were less costly and more effective.
Results of Sensitivity Analysis: Incremental costs exceeded incremental benefits when novel test intervals were shortened to 2 or 1 years. The cf-bDNA test matched FIT's impact on CRC mortality at 1.35 (1.30 to 1.40)-fold FIT's uptake rate, assuming equal colonoscopy follow-up. If persons who accept colonoscopy or stool tests shifted to cf-bDNA, CRC deaths increased. This adverse effect was overcome if every 3 such substitutions were counterbalanced by cf-bDNA uptake by 2 or more persons refusing alternatives, assuming equal colonoscopy follow-up.
Limitation: Longitudinal test-specific participation patterns are unknown.
Conclusion: First-generation cf-bDNA tests may deliver net benefit or harm, depending on the balance between achieving screening in persons who decline alternatives versus substituting cf-bDNA for more effective alternatives.
Primary Funding Source: The Gorrindo Family Fund.
Competing Interests: Disclosures: Disclosure forms are available with the article online.