ArticleJNCI cancer spectrum2025
Tumor localization strategies of multicancer early detection tests: a quantitative assessment.
Article in JNCI cancer spectrum, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Molecular Cancer Signal Origin Minimizes Diagnostic Burden: Letter.Cancer prevention research (Philadelphia, Pa.) · 2026Article
- Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study.Nature medicine · 2026Article
- Molecular Cancer Signal Localization in MCED Testing Minimizes Radiation and Imaging Burden Compared with Whole-body Imaging Approaches.Cancer prevention research (Philadelphia, Pa.) · 2026Article
- Enhanced multicancer screening assay through whole-genome methylation sequencing-based multimodal cell-free DNA analysis.Experimental & molecular medicine · 2026Article
- Multi-cancer early detection tests: Attributes for clinical implementation.Cancer biomarkers : section A of Disease markers · 2025Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMulticancer early detection tests may expand cancer screening. Characterizing diagnostic resolution approaches following positive multicancer early detection tests is critical. Two trials employed distinct resolution approaches: a molecular signal to predict tissue of origin and an imaging-based diagnostic strategy. This modeling study characterizes diagnostic journeys and impact in a hypothetical population of average-risk multicancer early detection-eligible patients.
methodsA mathematical expression for diagnostic burden was derived using positive predictive value (PPV), molecular tissue of origin localization accuracy, and numbers of procedures associated with each diagnostic outcome. Imaging-based and molecular tissue of origin-informed strategies were compared. Excess lifetime cancer risk due to futile radiation exposure was estimated using organ-specific diagnostic imaging radiation doses.
resultsAcross all PPVs and localization performances, a molecular tissue of origin strategy resulted in a higher diagnostic burden (mean = 3.6 [0.445] procedures vs mean = 2.6 [0.100] procedures) for the imaging strategy. Estimated diagnostic burden was higher for molecular tissue of origin in 95.5% of all PPV and tissue of origin accuracy combinations; at least 79% PPV and 90% accuracy would be required for a molecular tissue of origin-informed strategy to be less burdensome than imaging. The maximum rate of excess cancer incidence from radiation exposure for multicancer early detection false-positive results (individuals aged 50-84 years) was 64.6 of 100 000 (annual testing, 99% specificity), 48.5 of 100 000 (biennial testing, 98.5% specificity), and 64.6 of 100 000 (biennial testing, 98% specificity).
conclusionsAn imaging-based diagnostic strategy is more efficient than a molecular tissue of origin-informed approach across almost all PPV and tissue of origin accuracy combinations. The use of an imaging-based approach for cancer localization can be efficient and low-risk compared with a molecular-informed approach.
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