Genitourinary Cancer

SS 28 - GU 3 - New Insights Into Treatment Intensification Strategies for Prostate Cancer

202 - Genomic Validation of Three-Tiered Sub-Classification of High-Risk Prostate Cancer

Tuesday, October 23
3:15 PM - 3:25 PM
Location: Room 007 A/B

Genomic Validation of Three-Tiered Sub-Classification of High-Risk Prostate Cancer
V. Muralidhar1, D. E. Spratt2, F. Y. Feng3, E. Davicioni4, K. Yousefi4, J. Zhang5, Q. Wang6, V. Choeurng7, and P. L. Nguyen8; 1Harvard Radiation Oncology Program, Boston, MA, 2Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 3Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 4GenomeDx Biosciences, Vancouver, BC, Canada, 5GenomeDx, Vancouver, BC, Canada, 6GenomeDx Biosciences, Inc., Vancouver, BC, Canada, 7GenomeDx Biosciences Inc., Vancouver, BC, Canada, 8Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Purpose/Objective(s): Recent data and National Comprehensive Cancer Network (NCCN) guidelines suggest that high-risk prostate cancer (cT3-4, Gleason score >= 8, or prostate-specific antigen [PSA] > 20 ng/mL) is a heterogenous group in terms of long-term patient outcomes. We sought to determine whether sub-classification of high-risk prostate cancer based on clinical factors correlates with genomic markers of risk. Materials/Methods: We identified 2,983 patients with NCCN unfavorable intermediate-risk (n=1,778) or high-risk (n=1,205) prostate cancer. We defined the following sub-classification of high-risk prostate cancer based on previously published data: favorable high-risk (cT1c, Gleason 6, and PSA > 20 ng/mL or cT1c, Gleason 4+4=8, PSA < 10 ng/mL); very high-risk (cT3b-T4 or primary Gleason pattern 5); and standard high-risk (all others with cT3a, Gleason score >=8, or PSA > 20 ng/mL). We used a set of 39 previously published genomic classifiers, including the 22-gene Decipher assay, to determine whether high-risk genomic features correlated with the clinical sub-classification of high-risk prostate cancer. Results: Among those with favorable high-risk, standard high-risk, and very high-risk prostate cancer, 51.1%, 64.7%, and 81.5% had a high-risk Decipher score, respectively (p < 0.001). Among 38 other high-risk genomic signatures, 34 had a similar increasing trend across the three sub-classes of high-risk (p < 0.05 after Benjamini-Hochberg correction for multiple hypothesis testing). Patients in the three sub-classes of high-risk disease were positive for a median number of 6, 8, and 15 high-risk signatures. Under a novel clinical-genomic risk group classification (Spratt et al., 2017), 27.0%, 19.1%, and 7.0% of patients with favorable, standard, or very high-risk disease would be re-classified as intermediate-risk, respectively. In comparison, among those with unfavorable intermediate-risk prostate cancer, 38.9% had a high-risk Decipher score (and would be re-classified as Spratt high-risk) and the median number of high-risk signatures was 4. Conclusion: Genomic markers of risk correlate with the clinical sub-classification of high-risk prostate cancer into favorable high-risk, standard high-risk, and very high-risk disease, validating the prognostic utility of this stratification.
Author Disclosure: V. Muralidhar: None. D.E. Spratt: None. F.Y. Feng: Research Grant; GenomeDx. Advisory Board; GenomeDx, Dendreon, Sanofi. Travel Expenses; GenomeDx. Liaison, GU Translational Research Program; Radiation Therapy Oncology Group. President and Founder; PFS Genomics. K. Yousefi: None. J. Zhang: None. Q. Wang: None. P.L. Nguyen: Honoraria; Bayer. Consultant; Nanobiotix, Infinity Pharmaceuticals, GI Windows, Astellas, Augmenix. Advisory Board; Ferring, Medivation, Genome DX, Dendreon. Stock Options; Augmenix. Program Committee; Genitourinary Cancers Symposium.

Paul Nguyen, MD

Brigham and Women's Hospital

Disclosure:
Employment
Dana-Farber/Brigham and Women's Cancer Center: Director of Prostate Brachytherapy/Associate Professor of Radiation Oncology: Employee

Compensation
Astellas: Research Grants; Augmenix: Consultant; Ferring: Consultant; Genome DX: Advisory Board; Janssen: Research Grants; Nanobiotix: Consultant

Ownership
Augmenix: Stock Options

Leadership
Genitourinary Cancers Symposium: Program Committee Chair

Presentation(s):

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