Abstract 4934: Achieving the goal of reducing cancer mortality by 50% through early detection: Insights from simulation modeling of multi-cancer screenings

The Cancer Moonshot aims to reduce cancer mortality by at least 50% (∼4 million cancer deaths) over the next 25 years. While cancer incidence has slightly increased from 2014 to 2018, particularly among young adults aged 15-39, cancer mortality has decreased by 33% from 1991 to 2021. This decline is largely attributed to advances in early detection, improved treatments, and reduced smoking rates, especially for lung cancer. However, the approach and feasibility of meeting the Moonshot goal remain uncertain. This study explores the potential for achieving the Cancer Moonshot goal by focusing on early detection as a primary strategy. We developed a simulation model to evaluate multi-cancer early detection/screening scenarios, using data from the NCI's SEER database. Our model focused on the five leading cancers by mortality—lung, colorectal, pancreatic, breast, and prostate—since these cancers account for the majority of cancer-related deaths in the U.S. and represent the most significant opportunity for mortality reduction through early intervention. Using a discrete event simulation model, we simulated a cohort of U.S. individuals aged 0 to 100 years in 1994 and tracked them over a 25-year period. The model was calibrated to reproduce U.S. population cancer incidence and mortality trends from 1994 to 2019, based on SEER data. To examine the impact of early detection, the model incorporated sojourn time—the period during which preclinical cancer is detectable. Sojourn times for each cancer type were randomly sampled from a triangular distribution based on values derived from a comprehensive literature review. We modeled a “perfect” scenario where cancers were detected at the earliest point in the sojourn period, at localized stages, to estimate the maximum benefit of early detection. We then compared the number of cancer deaths averted in this scenario to a natural history model with no screening. Our preliminary findings suggest that screening for all five cancers could achieve the Cancer Moonshot goal of reducing cancer deaths by 50%. Lung cancer screening provided the greatest benefit, reducing cancer deaths by ∼20%, followed by breast cancer screening (∼5%). Pancreatic cancer screening offered the smallest reduction, at about 2%. While these results underscore the potential of early detection in reducing cancer mortality, the model assumes perfect screening sensitivity and specificity and patient adherence, conditions that do not reflect real-world implementation. To refine these estimates and develop actionable strategies, future research should focus on addressing practical limitations, including variability in screening uptake and accuracy. Improving early detection methods, expanding access to screening, and increasing public awareness are essential to making the Cancer Moonshot goal a realistic and achievable outcome. Citation Format: Jiheum Park, Stephanie Shue, Francesca Lim, Matthew Prest, Jenniffer Ferris, Jeong Yun Yang, Stella Kang, Chin Hur. Achieving the goal of reducing cancer mortality by 50% through early detection: Insights from simulation modeling of multi-cancer screenings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4934.