Cost-effectiveness analysis of integrating multi-cancer early detection into current cancer screenings in the United States

Background: Cancer remains a major global health challenge. While standard-of-care (SoC) screenings (e.g., colonoscopy, mammography) improve early detection and survival, limitations persist: many cancer types lack screening guidelines, existing methods are single-cancer early detection (SCED) tests, and invasive protocols with low adherence lead to inefficiencies. Multi-cancer early detection (MCED) tests using liquid biopsy technologies provide a potential solution by screening for multiple cancers, including those not targeted by current SoC, within a single test. From a health economic perspective, supplementing SoC with MCED could enhance cost-effectiveness by broadening detection and reducing missed diagnoses. Methods: This modeling study evaluated two strategies: 1) integrating MCED testing into SoC screenings, and 2) optimizing colorectal cancer screening with a two-step process (FIT followed by colonoscopy), further enhanced by MCED. U.S. SoC screening data from 2021 for five common cancers (breast, cervical, colorectal, lung, prostate), U.S. Census 2020 statistics, and real-world screening cohort parameters informed screening population overlap, cancer incidence, and detection rates for both SoC screenings and MCED. Results: Among 75.6 million individuals screened in 2021, SoC alone detected 193,554 cancer cases at a total cost of $43.2 billion ($223,034 per detected case). Integrating SeekIn's two-step MCED test (OnceSeek followed by SeekInCare, $190 per person) raised total cost to $57.5 billion but increased detected cases to 539,909, nearly three times SoC alone, while halving the cost per case to $106,556. In contrast, using GRAIL's Galleri MCED ($949 per person) increased detected cases further, with an additional 297,141 cases, but escalated total costs to $114.9 billion. Notably, optimizing the colorectal screening protocol (FIT followed by colonoscopy) reduced SoC spending by $22.1 billion, covering all participants' TwoStep MCED costs and achieving a surplus of $7.7 billion. This strategy yielded 531,556 detected cases (2.7x SoC) and reduced per-case cost to $66,637 (29.9% of SoC). Conclusion: Integrating cost-effective MCED tests, such as TwoStep test, into current SoC screenings can substantially improve cancer detection, lower per-case identification costs, and keep overall expenditures manageable. Targeted optimization, exemplified by a FIT-first colorectal approach, maximizes cost savings and amplifies the benefits of adding MCED tests to established national screening programs, all without requiring an increase in the overall budget. Collectively, these findings highlight a unique opportunity: with thoughtful integration, MCED can reshape population health by delivering timely, accessible, and affordable screening that saves more lives.