The incorporation of a risk-stratification biomarker to complement standard clinicopathologic tools (Gleason grade, NCCN risk groups) may help improve disease management in patients with localized PCa. In what is the largest individual-patient-data (IPD) meta-analysis of the Prolaris Prostate Cancer Prognostic Test conducted to date, Morgan et al demonstrated that Prolaris Test was consistently prognostic for distant metastasis (DM) and PCSM across risk groups and intervention strategies.
Prolaris Test results are based on the quantification of cell cycle progression (CCP) genes combined with clinicopathologic features (CAPRA Score, The UCSF Cancer of the Prostate Risk Assessment Score) to provide individualized patient risk assessments. Prolaris Test threshold-informed decision making allows for intensification/de-intensification based on molecular profiling and individualized risk assessments with independent, additive prognostic information beyond standard clinicopathologic features.
The authors performed a systematic review of the literature (published 2005-2024), identifying 14 eligible cohorts (n = 8,478 patients) with IPD available for 7924 patients. The NCCN risk categorization for the combined cohort was 20.0% low-risk, 33.9% favorable-intermediate, 32.5% unfavorable-intermediate, and 13.6% high-risk. Initial disease management among the combined cohort was 43% noninterventional (e.g., active surveillance), 23.6% surgical, 16.4% radiotherapy, and 14.6% multimodal. The IPD meta-analysis was performed with composite DM + PCSM as a primary endpoint and secondary endpoints of either DM or PCSM alone.
The Prolaris Test was highly prognostic for the composite endpoint (DM + PCSM) after adjusting for initial management strategy with a Hazard Ratio (HR) of 2.28 (95% Confidence Interval [CI] 1.98–2.62), p=9.1×10⁻⁹, as well as DM and PCSM individually (all p<.001) and remained significantly prognostic after adjusting for Gleason grade (p=1.2×10⁻⁷), CAPRA score (p=1.9×10⁻⁶) and NCCN risk group (p=2.1×10⁻⁸), thus demonstrating the prognostic ability of the Prolaris Test above standard risk categorization with clinical variables alone.
|
Hazard Ratio (95% CI) |
p-value |
|
|
Composite Distant Metastasis & Prostate Cancer Specific Mortality (DM + PCSM) |
2.28 (1.98, 2.62) |
9.14x10-9 |
|
Distant Metastasis (DM) |
2.8 (2.22, 3.53) |
1.87x10-6 |
|
Prostate Cancer Specific Mortality (PCSM) |
2.09 (1.98, 2.21) |
3.14x10-4 |
Additionally, the Prolaris Test meaningfully altered treatment candidacy with nearly 30% of Gleason 3+3 patients reclassified upward and 17.3% of Gleason ≥8 patients reclassified downward, suggesting that the Prolaris Test has the capacity to provide personalized risk stratification to inform treatment decisions that result in reductions in both under-treatment and over-treatment. What is more, patients with PCa who are below the AS threshold per NCCN’s favorable intermediate risk designation may be spared the toxicity associated with definitive treatment, whereas those patients with PCa who are above the threshold for combined therapy may putatively benefit from intensifying treatment.
The findings from Morgan and associates reveal that the Prolaris Test is a robust, prognostic tool with broad applicability for patients with localized PCa. The implementation of this adjunctive tool can assist health care professionals by providing accurate and actionable risk stratification of patients with localized PCa to refine treatment decisions, particularly around AS, definitive therapy, and multimodal escalation.
Written by: Todd M. Morgan,1 Lauren H. Lenz,2 Ivan Henriquez,3 Steven M. Monda,1 Raquel García-Pablo,3 Wyatt Clegg,2 Robert Finch,4 Brent Mabey,2 Cameron Britton,5 E. David Crawford,6 Patrick Lewicki,1 Sanoj Punnen,7 Neal D. Shore,8 Jeffrey J. Tosoian,5 Jeff Jasper,9 Alexander Gutin,2 Matthew J. Schiewer,9 Jonathan D. Tward,10
- 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, Vanderbilt-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.
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