Clinical evaluation of cancer signal origin prediction and diagnostic resolution following multicancer early detection testing in the PATHFINDER study Journal Article


Authors: Marinac, C. R.; McDonnell, C. H. 3rd; Nadauld, L. D.; Dilaveri, C. A.; Reid, R.; Chung, K. C.; Lopatin, M.; Fung, E. T.; Schrag, D.; Shaknovich, R.; Klein, E. A.
Article Title: Clinical evaluation of cancer signal origin prediction and diagnostic resolution following multicancer early detection testing in the PATHFINDER study
Abstract: Blood-based multicancer early detection (MCED) tests represent a new approach for cancer detection. To gain insights into the utility of various approaches of evaluating a cancer signal detected (CSD) test result, we evaluated diagnostic journeys of a subset of 6,662 participants in PATHFINDER who had a CSD on both an initial and refined version of an MCED test that also provided a prediction of cancer signal origin (CSO). We sought to determine whether CSO prediction-guided diagnostic evaluations led to diagnostic resolution; whether participants with known risk factors for cancer beyond age alone and a negative initial diagnostic evaluation had a cancer diagnosis during study follow-up; the utility of whole-body imaging in reaching diagnostic resolution; and differences in the diagnostic journeys needed to reach diagnostic resolution for both true- and false-positive results. Of the 39 participants in this analysis, 82% (32/39) achieved diagnostic resolution after the initial evaluation, including 78% (25/32) who reached resolution specifically with a CSO prediction-directed workup. Eighteen percent (7/39) required additional evaluation for persistent clinical suspicion of cancer, all of whom achieved resolution (3 with and 4 without cancer). Whole-body imaging contributed to diagnostic resolution in only 49% of CSD cases. Approximately 90% of true- and false-positive cases had imaging tests; more true positives versus false positives (81.0% vs. 38.9%) had nonsurgical and/or surgical procedures. In conclusion, CSO prediction-directed evaluations enabled diagnostic resolution for most participants, although some with negative initial evaluations but persistent suspicion of cancer required additional testing. PREVENTION RELEVANCE: MCED testing has the potential to increase detection of cancer at earlier stages. As MCED testing is a new technology, there are few data on the diagnostic journeys patients undergo following testing. We observed that for most patients, CSO prediction-directed workups were efficient, leading to diagnostic resolution after initial evaluation. This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
Keywords: adult; aged; middle aged; follow up; follow-up studies; neoplasm; neoplasms; risk factors; tumor marker; risk factor; blood; diagnosis; early detection of cancer; procedures; humans; human; male; female; biomarkers, tumor; early cancer diagnosis
Journal Title: Cancer Prevention Research
Volume: 18
Issue: 8
ISSN: 1940-6207
Publisher: American Association for Cancer Research  
Date Published: 2025-08-01
Start Page: 475
End Page: 483
Language: English
DOI: 10.1158/1940-6207.Capr-24-0468
PUBMED: 40265568
PROVIDER: scopus
PMCID: PMC12314506
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Deborah Schrag
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