To systematically review and synthesize the evidence for Prolaris, a combined clinical risk (CCR) score that stratifies individual patient risk and provides a decision-making tool that impacts medical management across key decision points in the localized prostate cancer care continuum.
A systematic literature search was performed, and individual participant data (IPD) were collected where possible to perform a two-step IPD analysis. The primary endpoint was composite distant metastasis (DM) and prostate cancer-specific mortality (PCSM), also analyzed individually. Cox proportional hazards models were fit in individual cohorts. Random-effects meta-analyses with Knapp-Hartung adjustment were used to create combined hazard ratio (HR) estimates across studies.
Fourteen studies (8478 patients, including 7924 with IPD) were identified as eligible. The cohort consisted of 20.0%, 33.9%, 32.5%, and 13.6% NCCN low-, favorable intermediate-, unfavorable intermediate-, and high-risk patients, respectively. Initial management was 43.0% noninterventional (eg, AS), 23.6% surgery, 16.4% radiation therapy, and 13.1% radiation plus androgen deprivation therapy. CCR was prognostic for composite DM-PCSM endpoint after accounting for initial management (HR 2.28 (95% confidence interval 1.98, 2.62), P = 9.1 × 10-9), as well as DM (P = 1.9 × 10⁻⁶) and PCSM (P = 9.7 × 10⁻⁴) individually. Additional meta-analyses demonstrated CCR adds independent prognostic information to Gleason, CAPRA, and NCCN (all P < 10-5), and Prolaris thresholds are prognostic for composite DM-PCSM, as well as the endpoints individually (all P < .005).
CCR is prognostic across NCCN risk groups and management strategies in localized prostate cancer. Prognostic value persists after adjusting for initial management and established clinicopathologic factors, highlighting utility in supplementing conventional risk models.
Clinical genitourinary cancer. 2026 May 20 [Epub ahead of print]
Todd M Morgan, Lauren H Lenz, Ivan Henriquez, Steven M Monda, Raquel García-Pablo, Wyatt Clegg, Robert Finch, Brent Mabey, Cameron Britton, E David Crawford, Patrick Lewicki, Sanoj Punnen, Neal D Shore, Jeffrey J Tosoian, Jeff Jasper, Alexander Gutin, Matthew J Schiewer, Jonathan D Tward
Division of Urologic Oncology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI., Biostatistics, Myriad Genetics, Inc., Salt Lake City, UT., Department of Radiation Oncology, Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan de Reus, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira I Virgili, Reus, Spain., Medical Affairs - Germline Oncology, Myriad Genetics, Inc., Salt Lake City, UT., Department of Urology, Vanderbilit-Ingram Cancer Center, Vanderbilt University, Nashville, TN., Department of Urology, UCSD, San Diego, CA., Department of Urology, Desai Sethi Urology Institute, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL., Genitourinary Oncology Center of Excellence, Carolina Urologic Research Center, Myrtle Beach, SC., Clinical Research, Myriad Genetics, Inc., Salt Lake City, UT., Clinical Research, Myriad Genetics, Inc., Salt Lake City, UT. Electronic address: ., Department of Radiation Oncology, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT.