The potential of multi-cancer early detection screening in reducing cancer incidence and mortality in high-risk groups: A modeling study.

10542 Background: Emerging liquid biopsy multi-cancer early detection (MCED) tests have the potential to revolutionize early cancer detection. Using a simulation model, we estimated their impact on cancer incidence and mortality in high-risk groups. Methods: We developed Simulation Model for MCED(SiMCED), a microsimulation model of 14 solid tumor cancer types. MCED test sensitivities were derived from the ASCEND-2 case-control study. Using a 10-year horizon, we simulated the life course of 100,000 adults aged 50-84 years, representing the US general population. In addition, we simulated screening in three high-risk groups: smokers (former and current), heavy alcohol users, and individuals with a family history of cancer in ≥1 first-degree relatives (FDRs). Cancer diagnosis could arise from usual care or annual MCED screening. After a cancer diagnosis, individuals followed SEER survival curves to determine the time and cause of death (cancer- or non-cancer-related). Results: The table presents overall 10-year reductions in stage IV cancer incidence and mortality per 100,000. Among smokers, MCED screening had the greatest impact (in absolute reduction terms) on lung cancer, which accounted for more than 50% of late-stage incidence. Compared to usual care only, MCED screening reduced stage IV lung cancer incidence by 43% (2,028 vs 1,146) and cancer mortality by 16% (2,589 vs 2,247). Among heavy alcohol users, MCED screening had the greatest impact on lung, colorectal, and head and neck cancer. The stage IV incidence reduction in these three cancer types were, respectively, 44% (805 vs 454), 57% (286 vs 122), and 33% (398 vs 265). The cancer mortality reduction in these three cancer types were, respectively, 14% (1,014 vs 876), 33% (371 vs 248), and 16% (265 vs 223). In the familial cancer cohort, MCED screening had the greatest impact on lung, colorectal, and pancreatic cancer. The stage IV incidence reduction in these three cancer types were, respectively, 44% (821 vs 461), 57% (257 vs 111), and 58% (233 vs 98). The cancer mortality reduction in these three cancer types were, respectively, 14% (1,030 vs 888), 33% (328 vs 220), and 14% (326 vs 279). Conclusions: MCED screening demonstrates potential to reduce late-stage cancer incidence and mortality in both the general population and high-risk groups. These findings highlight the value of MCED tests in advancing early detection and improving cancer outcomes. Cohort Usual care: Stage IV cancer incidence Usual care + MCED: Stage IV cancer incidence Reduction: Stage IV cancer incidence Usual care: Cancer mortality Usual care + MCED: Cancer mortality Reduction: Cancer mortality General population 2,117 1,229 888 (42%) 2,612 2,149 463 (18%) Smokers 3,523 2,034 1,489 (42%) 4,392 3,691 701 (16%) Heavy alcohol users 2,619 1,548 1,071 (41%) 3,099 2,552 547 (18%) Family history of cancer in ≥1 FDRs 2,365 1,360 1,005 (42%) 2,899 2,374 525 (18%)