Impact of Population Cancer Risk on the Cost-effectiveness of Multi-cancer Early Detection Testing in the US

Cancer remains a significant global health challenge, particularly for subpopulations with risk factors including genetic predisposition, comorbidities, and lifestyle, along with age. The Galleri® multi-cancer early detection (MCED) test is projected to be cost-effective for individuals aged ≥50 years. However, its potential value in subpopulations with elevated cancer risk remains underexplored. This study evaluates the cost-effectiveness of the Galleri® test combined with usual care screening in subpopulations with varying cancer risk, including impact on overall cancer burden. A hybrid cohort-level model evaluated US subpopulations aged 50-79 years with additional risk factors, incorporating updated cancer incidence rates and excess competing mortality. The model estimated lifetime economic and clinical outcomes of annual MCED testing. Analyses focused on individuals with obesity, diabetes, smoking history, heavy alcohol use, genetic predispositions, immunocompromising conditions, family history, and cancer survivors. The Galleri® test was cost-effective across all specified subpopulations, with incremental cost-effectiveness ratios (ICERs) below the general population benchmark of $66,043 per quality-adjusted life-year. Subpopulations with higher cancer incidence, such as those with hereditary cancer syndromes, showed lower ICERs, underscoring the cost-effectiveness (CE) in targeted screening. However, targeted approaches address a smaller fraction of the population burden. These findings depend on translating overall MCED test performance to higher-risk groups. Sensitivity analyses confirmed the robustness of these findings, emphasizing MCED's potential to reduce late-stage cancer burden. Prioritizing higher-risk groups yields more favorable CE but impacts a smaller overall population burden. This study compares how MCED testing strategies affect CE and population health benefits.