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 III. High-risk localized prostate cancer as defined by: * PSA (prostate specific antigen) \>20, any GS or \>8 or * Gleason pattern 4 in 6 or more systematic cores (pattern 4 must be dominant, ≥50% average across 6 or more systematic cores) or * ≥ 50% Gleason pattern 4 in 3 or more systematic or Magnetic Resonance Imaging (MRI)-targeted cores and PSA ≥ 20 (may include G4+3 or G4+4 but pattern 4 must be dominant, ≥50% average across 3 or more systematic cores) or * ≥25% Gleason pattern 5 in 3 or more systematic or MRI-targeted cores (may include G4+5, or G3+5, but pattern 5 must be ≥25% average across 3 or more systematic cores). * Gleason \> 8 or greater on minimum of one core either targeted or systematic biopsy and PSA \>20 * Participants with oligometastatic (\< 3) metastases by PSMA (Prostate-Specific Membrane Antigen) imaging only who are deemed candidates for radical prostatectomy are eligible IV. Participants must consent to genetic testing at registration and prior to assignment by a central reference laboratory V. No prior systemic or localized treatment for prostate cancer. Up to 30 days of LHRHa is allowable prior to treatment. VI. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1 (Appendix II) and a life expectancy of ≥ 3 years VII. Participants must have adequate end-organ function and all laboratory tests must be performed within 4 weeks prior to registration into master protocol. VIII. Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrolment in the trial to document their willingness to participate. Exclusion Criteria: \- I. Received more than 30 days of LHRHa prior to registration and initiation of LHRHa + APA II. Stage T4 prostate cancer by clinical examination or radiologic evaluation III. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone more than 50 ng/dL below the normal range for the institution IV. Participants with serious illnesses or medical conditions which could cause unacceptable safety risks or would not permit the participant to be managed according to the protocol. This includes but is not limited to: * Active infection or chronic liver disease requiring systemic therapy; * Active or known human immunodeficiency virus (HIV) with detectable viral load; * Uncontrolled or recent clinically significant cardiac disease, including: angina pectoris, symptomatic pericarditis, coronary artery bypass grafting, coronary angioplasty, or stenting, or myocardial infarction in the previous 12 months; history of documented congestive heart failure (New York Heart Association functional classification III-IV) or cardiomyopathy; history of any cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months; * Participants with uncontrolled hypertension V. Participants who are unable to swallow oral medication and/or have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) VI. Participants with a history of hypersensitivity to any of the study drugs or any excipient VII. Participants with a history of non-compliance to medical regimen VIII. Severe concurrent disease, infection, or co-morbidity that, in the judgement of the Investigator, would make the participant inappropriate for enrollment or prostatectomy IX. Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer X. Receiving concurrent androgens, estrogens, or pregestational agents, or prior exposure to any of these agents within 6 months prior to randomization XI. M1 by conventional imaging (CT, bone scan)