The procedural position of multi-cancer early detection (MCED) in cancer screening paradigm: A simulation modelling study.

Abstract

e23138 Background: While multi-cancer early detection (MCED)—a promising approach using one blood sample to detect multiple cancers—could supplement or replace standard-of-care (SOC) screening, its optimal position in population-based screening paradigm remains uncertain. This study aimed to evaluate the effectiveness and cost-effectiveness of integrating MCED at various phases of the screening process. Methods: We recalibrated the National Cancer Center (NCC) modeling framework to align with the latest population-based empirical data. The calibrated model was then used to simulate the natural history of the five highest-mortality cancers in China (lung, liver, colorectal, esophageal, and stomach) over a lifetime horizon for the entire Chinese population, with screening targeted at ages 50–74.The evaluated screening scenarios included no screening, risk-based SOC screening, and four screening strategies incorporating MCED: MCED used as a risk-assessment method (S1), MCED used as a clinical screening method (S2), MCED interception followed by SOC triage for MCED-negative individuals (S3), and MCED used as a supplemental screening for questionnaire non-high-risk individuals and SOC non-compliers (S4). The primary outcome was the 5% discounted incremental cost-effectiveness ratio (ICER), with a willingness-to-pay (WTP) threshold of three times per-capita GDP ($42,857 per quality-adjusted life-year [QALY] gained). Secondary outcomes included stage III-IV cancer diagnoses, cancer deaths, number needed to screen (NNS) to prevent one death. Sensitivity analyses were performed to assess the probability of cost-effective. Results: Compared with no screening, discounted ICERs for risk-based SOC and MCED strategies S1 to S4 were $1,808, $52,195, $26,726, $26,876, and $16,595 per QALY, respectively. Versus risk-based SOC, the ICERs for S4 and S3 were $33,809/QALY and $39,761/QALY. When using risk-based SOC as reference, S3 reduced stage III–IV cancer diagnoses by 6.9% and cancer mortality by 4.3%, while also improving screening efficiency by reducing the NNS from 240 to 81. S4 provided intermediate benefits with a 1.8% reduction in mortality, whereas S1 and S2 yielded smaller mortality reductions (<1.2%). Probabilistic sensitivity analysis indicated that S3 had the highest probability of being cost-effective at the WTP threshold (43.9%). Conclusions: Using MCED interception followed by SOC triage for MCED-negative individuals (S3) likely represents the most appropriate position for MCED in the cancer screening paradigm. In contrast, using MCED as a supplemental screening for questionnaire non-high-risk individuals and SOC non-compliers (S4) offers a lower-cost but suboptimal alternative.