Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer

Inclusion Criteria: i. Males ≥ 18 years of age. ii. Histologically confirmed adenocarcinoma of the prostate without pathologic evidence of small cell differentiation at the time of initial diagnosis. Screening biopsy must be performed within 4 months of the screening visit. iii. High-risk localized prostate cancer as defined by at least one of the following: * Any combination of Gleason Score 4+3=7 and Gleason Score 8 (4+4 or 5+3) in ≥6 systematic cores (with ≥1 core Gleason Score 8 \[4+4 or 5+3\] included); * Any combination of Gleason Score 4+3 and Gleason Score 8 (4+4 or 5+3) in ≥3 systematic cores and PSA ≥20 ng/mL (with at least 1 core Gleason Score 8 \[4+4 or 5+3\] included); * Gleason Score ≥9 in at least 1 systematic or targeted core; * At least 2 systematic or targeted cores with Gleason Score ≥8, each with at least 80% involvement"; or * Gleason Score 4+3=7 in at least 6 systematic or targeted cores and PSA ≥20 ng/mL iv. Participants must provide consent blood collection and evaluation of diagnostic prostate tissue for genetic testing at registration and prior to assignment by a central reference laboratory. v. No prior systemic or localized treatment for prostate cancer (exception: up to 12 weeks of luteinizing hormone-releasing hormone agonist or antagonist (LHRHa) and bicalutamide is allowable prior to registration). vi. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix II) and a life expectancy of ≥ 3 years in the opinion of th…