10523 Background: In 2021, standard-of-care (SoC) screening for breast, cervical, colorectal, lung, and prostate cancers in the United States cost 43. 2 billion to detect 197, 773 cancers, with colonoscopy—used as a primary colorectal screening modality—accounting for 23. 7 billion, the largest share of expenditures (54. 9%). Multi-cancer early detection (MCED) blood tests could complement SoC single-cancer early detection (SCED) screening but may substantially increase overall costs if implemented without concurrent redesign of screening pathways. Methods: A static decision model used 2021 U. S. SoC screening volumes and costs, 2020 Census data, cancer-specific incidence in high- and low-risk groups, and published SCED and MCED performance to simulate 75. 6 million unique screened individuals after adjusting for overlap across programs. We evaluated (1) SoC alone, (2) SoC plus either a low-cost two-step MCED assay (OnceSeek followed by SeekInCare; “OncoSeek Duet”, 143/person) or a higher-priced cfDNA methylation-based MCED test (Galleri, 949/person), and (3) a budget-neutral strategy replacing primary colonoscopy with FIT, designated as SCED 2. 0, with savings reinvested to fund OncoSeek Duet for all screened individuals. Results: SoC alone detected 197, 773 cancers (262 per 100, 000) with a PPV of 0. 7% at a total cost of 43. 2 billion, or 218, 276 per cancer detected. Adding OncoSeek Duet increased detections to 398, 586 (527 per 100, 000; 2. 0-fold), PPV to 43. 3% (61. 9-fold increase) and total cost to 54. 0 billion (25. 0% increase), reducing cost per cancer to 135, 429, while expanding detection to 9 additional cancer types beyond the 5 SoC targets. Adding Galleri yielded 572, 223 cancers (757 per 100, 000; PPV of 60. 7%) at 114. 9 billion total cost (2. 7-fold increase) and 200, 823 per cancer, improving yield but with markedly higher budget impact than OncoSeek Duet. SCED 2. 0 cut costs to 20. 0 billion (2. 2-fold decrease), reduced cost per cancer to 106, 876, saved 23. 1 billion, and yielded 187, 509 detections (5. 2% decrease). Reinvesting these savings to provide OncoSeek Duet for all restored and expanded detection to 391, 022 cancers (2. 1-fold increase), maintained a high PPV of 42. 9%, incurred 78, 899 per cancer and produced a 12. 3 billion surplus without increasing overall screening expenditure. Conclusions: In this U. S. modeling analysis, integrating MCED into SoC screening substantially increased cancers detected and lowered cost per cancer, particularly when using lower-cost OncoSeek Duet. Optimizing high-cost SCED components, such as colonoscopy, can fully finance population-wide MCED while preserving or improving efficiency, supporting a value-based, budget-neutral path for MCED implementation in national screening programs.
Geng et al. (Wed,) studied this question.