Year: 2026
Type: article
Abstract: Early cancer detection improves survival; however, most cancer types do not have guideline-recommended screening. We previously reported the first PATHFINDER study that established feasibility of cancer screening with a blood-based multi-cancer early detection (MCED) test that predicts cancer signal origin (CSO) to guide diagnostic workup. The prospective, interventional PATHFINDER 2 study expands clinical evidence for the MCED test by evaluating co-primary endpoints of MCED performance metrics and safety in participants aged 50 years or older without clinical suspicion of cancer. Performance measures included cancer detection rate, positive and negative predictive values, episode sensitivity, specificity and CSO prediction accuracy. Safety was evaluated in terms of number and type of invasive procedures performed and adverse events due to diagnostic testing, after 12 months of follow-up. Endpoints were analyzed descriptively; no hypothesis testing was performed. Between December 2021 and July 2024, 35,878 participants were enrolled. Among 32,007 performance-analyzable participants, cancer detection rate was 0.54% (95% confidence interval (CI): 0.47-0.63%), positive predictive value was 60.3% (95% CI: 54.5-65.8%), negative predictive value was 99.2% (95% CI: 99.1-99.3%) and specificity was 99.64% (95% CI: 99.57-99.70%). Episode sensitivity was 39.3% (95% CI: 34.9-44.0%; all cancers) and 69.8% (95% CI: 62.8-76.0%; prespecified 12-cancer subgroup). Positive and negative likelihood ratios were 108.9 (95% CI: 87.6-135.2) and 0.61 (95% CI: 0.56-0.66), respectively, and the number needed to screen to detect one cancer was 185 (95% CI: 159-215). CSO prediction accuracy was 91.3%. Among 35,335 safety-analyzable participants, 213 (0.6%) had invasive procedure(s) after a positive MCED test; 90.5% were nonsurgical. No serious study-related adverse events were reported by the time of this analysis. These results provide insights into performance and safety of the MCED test in an intended-use population. Randomized trials and longer follow-up are needed to assess the clinical utility of MCED tests. ClinicalTrials.gov identifier: NCT05155605 .
Source: Nature Medicine
Authors: Nima Nabavizadeh, Charles McDonnell, Dax Kurbegov, Marc Matrana, Shirish Gadgeel, Raymond H. Kim, Gretchen Stipec, Kevin C. Oeffinger, Michael J. Demeure, James W. Lillard, Rebecca Kaltman, Jennifer Tran, Alan Roth, Sami Tahhan, Andrew Poklepovic, Donald Richards, Margarita Lopatin, Celine Marquez, Margaret McCusker, Karthik V. Giridhar
Institutions: Oregon Health & Science University, OHSU Knight Cancer Institute, Sutter Health, Sutter Institute for Medical Research, HCA Healthcare, Sarah Cannon, Ochsner Medical Center, Emory University, Henry Ford Health, Winship Cancer Institute, University Health Network, Princess Margaret Cancer Centre, MemorialCare Long Beach Medical Center, Long Beach Medical Center, Duke University Health System, Hoag Memorial Hospital Presbyterian, Morehouse School of Medicine, Inova Fairfax Hospital, MedStar Washington Hospital Center, Georgetown University, Jamaica Hospital, Eastern Virginia Medical School, Old Dominion University, Virginia Commonwealth University, Texas Oncology, Grail (United States), Mayo Clinic
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7214028868