OBJECTIVES: An MCED test has been projected to be cost-effective in the population aged ≥50 years. Prognostic factors such as family history, comorbidities, and lifestyle can define a range of subpopulations with varying cancer incidence, which each cover a subset of cancer burden. This study evaluates how cost-effectiveness relates to cancer risk in representative subpopulations of varying prevalence.

METHODS: A Markov model compared the outcomes of annual MCED testing plus standard of care (SoC) versus SoC alone in US adults aged 50 to 79 years, tailored for various high-risk groups. Analyses were conducted in the overall population aged ≥50 years and several subpopulations: first degree family history (1.38 incidence rate ratio vs general population, 55% prevalence), obesity (1.14, 38.7%), diabetes (1.12, 24%), current smoking (1.57, 16.9%), cancer survivor (1.69, 11%), heavy alcohol use (1.26, 9.4%), solid organ transplant recipients (SOT) (2.9, 2%), hereditary cancer syndromes (HCS) (1.86, 2.2%). Subpopulations were defined by cancer incidence and excess competing mortality. Survival, costs, and quality of life were calculated over a lifetime horizon.

RESULTS: MCED testing demonstrated lower incremental cost-effectiveness ratios (ICERs) for subpopulations with elevated cancer risk versus the overall population aged ≥50 years ($66,043/QALY). ICERs were: diabetes ($66,010), obesity ($60,245), family history ($40,155), cancer survivor ($36,774), heavy alcohol use ($35,515), current smokers ($26,850), SOT ($18,013), HCS ($544). Several high-prevalence subpopulations had ICERs <$50,000/QALY, while the lowest ICERs were predicted in smaller subpopulations.

CONCLUSIONS: While MCED testing has been projected to be cost-effective for the general population aged ≥50 years, prioritizing higher cancer risk groups allows targeting more favorable ICERs at the cost of addressing a smaller fraction of the total population burden.