OBJECTIVES: Blood-based MCED tests utilizing circulating cell-free DNA (cfDNA) methylation patterns have been shown to detect a shared cancer signal from more than 50 cancer types. Recent research suggests that DNA shedding may be a marker of tumor aggressiveness and cancers missed by MCED are relatively indolent, concentrating death in those detected. A model evaluated the economic impact of the differential survival of cfDNA-detectable (cfDNA+; i.e., shedding) cancers versus cfDNA-non-detectable (cfDNA–) cancers.

METHODS: A hybrid model compared annual MCED plus standard of care (SoC) screening between ages 50-79 years with SoC alone in a US commercial population. A two-population model for survival accounted for differential survival depending on cfDNA detectability status. The incidences of detectable and undetectable cancers were assigned proportionally to each group based on published test sensitivity by stage. Scenarios with survival hazard ratio (HR) of 1 (i.e., no differential survival) vs. 1.5 and 3 (i.e., extreme scenario) for cfDNA+ relative to cfDNA– cancers were tested, with the mortality rates set such that the total mortality in the overall population was preserved and the cost of cancer treatments assumed to be the same regardless of prognosis. The stage shift was updated to reflect the detectability of cancers.

RESULTS: At an MCED cost of $949, the incremental cost-effectiveness ratio (ICER) of MCED plus SoC screening vs SoC alone increased from $66,044 to $77,781 and $106,962 per quality-adjusted life-year (QALY) gained for HR = 1, 1.5, and 3, respectively. The increase in relative hazard of death resulted in lower impact of earlier detection on QALY gains and treatment cost savings for MCED detectable cancers leading to higher ICERs.

CONCLUSIONS: MCED testing stays cost-effective at commonly accepted willingness-to-pay thresholds and remains near or below $100k/QALY even for an extreme scenario of differential survival by cfDNA detectability.