Abstract PR006: The potential of multi-cancer early detection screening for reducing cancer mortality
Authors: Chhatwal Jagpreet , Xiao Jade , ElHabr Andrew , Tyson Christopher , Cao Xiting , Raoof Sana , Fendrick A. Mark , Ozbay A. Burak , Limburg Paul , Beer Tomasz M. , Deshmukh Ashish , Briggs Andrew 
Published: November 2024

Abstract
Background: Currently, routine screening is recommended for only four cancer types (i.e., breast, cervical, colorectal, and lung) by the United States Preventive Services Task Force (USPSTF), and two-thirds of incident cancers have no screening guidelines. Emerging liquid biopsy multi-cancer early detection (MCED) tests have the potential to revolutionize early cancer detection. Their impact on cancer mortality remains uncertain. Computer models are needed to forecast long-term outcomes. Methods: We developed Simulation Model for MCED (SiMCED), a continuous-time, discrete-event microsimulation model of 14 solid tumor cancers: breast, cervical, colorectal, endometrial, esophageal, gastric, head and neck, kidney, liver, lung, ovarian, pancreatic, prostate, and urinary bladder. Cancer type- and stage-specific dwell times informed the transitions between cancer stages I-IV. Cancer type- and stage-specific MCED test sensitivities were derived from a large, multi-center, prospective, case-control study: Ascertaining Serial Cancer patients to Enable New Diagnostic 2 (ASCEND-2). The model was calibrated to reproduce annual incidence rates of cancer diagnosis as captured in the Surveillance, Epidemiology, and End Results (SEER) database, while accounting for the unobserved cancer burden. Using a 10-year time horizon, we simulated the life course of 5 million US adults aged 50-84 years, representative of the US population age distribution. Cancer diagnosis could arise from usual care or annual MCED screening. The MCED test was administered at the beginning of each year to individuals aged 50-84 years. After a cancer diagnosis, individuals followed SEER survival curves to determine the time and cause of death (cancer- or non-cancer-related). Results: Over the 10-year time horizon, the supplemental use of MCED screening reduced stage IV incidence by 876 (42%) per 100,000, relative to usual care. The 10-year reduction in cancer mortality was 439 (17%) per 100,000, which translates to 505,600 cancer-related deaths averted among US adults aged 50-84 years. Lung cancer had the highest absolute 10-year cancer mortality reduction at 126 (13%) per 100,000. Among the cancer types for which there is no routine screening, the 10-year cancer mortality reduction was 175 (15%) per 100,000, equating to 201,500 cancer-related deaths averted among US adults aged 50-84 years. Within the 10-year time window, earlier diagnosis by MCED led to an aggregated life-year gain of 1,165 per 100,000, which translates to a gain of 1,340,000 life-years among US adults aged 50-84 years. Conclusion: Our study suggests that MCED screening could be effective for reducing both stage IV incidence and cancer mortality. The real-world impact of MCED tests and their cost-effectiveness require further investigation.
Citation Format: Jagpreet Chhatwal, Jade Xiao, Andrew ElHabr, Christopher Tyson, Xiting Cao, Sana Raoof, A. Mark Fendrick, A. Burak Ozbay, Paul Limburg, Tomasz M. Beer, Ashish Deshmukh, Andrew Briggs. The potential of multi-cancer early detection screening for reducing cancer mortality [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR006.