Indolent prostate cancer (PCa) is prevalent in the intended use population (adults age 50-79 years) for blood-based multicancer early detection (MCED) tests. We examined the detectability of PCa by a clinically validated, targeted methylation-based MCED test.
Detectability by Gleason grade group (GG), clinical stage, association of detection status with tumor methylated fraction (TMeF), and overall survival (OS) were assessed in substudy 3 of Circulating Cell-Free Genome Atlas (CCGA; ClinicalTrials.gov identifier: NCT02889978) and PATHFINDER (ClinicalTrials.gov identifier: NCT04241796) studies.
Test sensitivity for PCa in substudy 3 of CCGA was 11.2% (47/420). The test detected 0 (0%) of 58 low-grade (GG1), 3 (1.9%) of 157 favorable intermediate-grade (GG2), 4 (5.1%) of 78 unfavorable intermediate-grade (GG3), and 36 (31.9%) of 113 high-grade (GG4 and 5) cancers and 3 (3.2%) of 95 stage I, 11 (4.7%) of 235 stage II, 7 (14.9%) of 47 stage III, and 22 (81.5%) of 27 stage IV cases. The median TMeF was higher for detected than nondetected cases (2,106.0 parts per million [PPM]; IQR, 349.8-24,376.3 v 24.4 PPM; IQR, 17.8-38.5; P < .05). Nondetected cases had better OS (P < .05; hazard ratio [HR], 0.263 [95% CI, 0.104 to 0.533]) and detected cases had similar survival (P = .2; HR, 0.672 [95% CI, 0.323 to 1.21]) compared with SEER adjusted for age, GG, and stage. Performance was similar in PATHFINDER, with no detected GG1/2 (0/13) or stage I/II (0/16) cases.
This MCED test preferentially detects high-grade, clinically significant PCa. Use in population-based screening programs in addition to standard-of-care screening is unlikely to exacerbate overdiagnosis of indolent PCa.
JCO precision oncology. 2024 Aug [Epub]
Brandon A Mahal, Matthew Margolis, Earl Hubbell, Cheng Chen, Jeffrey M Venstrom, John Abran, Jordan J Kartlitz, Alexander W Wyatt, Eric A Klein
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL., GRAIL, Inc, Menlo Park, CA., Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.