Abstract IA022: Assessing implementation of a multi-cancer early detection blood test for population screening in a clinical practice setting: prospective PATHFINDER cohort study

Abstract

Abstract Background: A validated blood-based multi-cancer early detection (MCED) test uses cfDNA and machine learning to detect a shared cancer signal across >50 cancer types and predict cancer signal origin. PATHFINDER is a prospective study in a screening population to evaluate the clinical feasibility of MCED testing. Methods: Between December 2019 and 2020, 6662 adults aged ≥50 years with or without additional cancer risk factors (smoking history, genetic predisposition, prior cancer diagnosis) were enrolled from 7 US health systems’ outpatient practices. Blood samples were collected, cfDNA was analyzed, and MCED test results were returned. Diagnostic evaluation was conducted at the discretion of the physician. Cancer status was ascertained after one year. Primary outcomes were extent of diagnostic testing and time to diagnostic resolution. Performance measures included signal detection rate, accuracy of predicted cancer signal origin, specificity, and positive and negative predictive values. Findings: Of the 6621 (99.4%) with analyzable samples, cancer signal was detected in 92 (1.4%), 91 reached diagnostic resolution, 90 were evaluable for the primary outcome, and 35 were true positives (TP). Median time to diagnostic resolution was 79 days overall and 57 days in TPs; 73% of TPs achieved resolution in <3 months. Among TPs, signal origin was predicted accurately for 33/34 (97.1%). Specificity was 99.1% (6235/6290), positive predictive value was 38.0% (35/92), and negative predictive value was 98.6% (6235/6321). Adverse events were rare (0.06%); none due to confirmatory diagnostic procedures. Interpretation: A blood-based assay to screen for multiple cancers was safely implemented in adults ≥50 years with and without additional cancer risk. It is feasible to use MCED testing for early detection of cancer in routine outpatient practice. Citation Format: Eric Klein, Tomasz Beer. Assessing implementation of a multi-cancer early detection blood test for population screening in a clinical practice setting: prospective PATHFINDER cohort study. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA022.