Abiraterone, Enzalutamide, or Apalutamide in Castrate-sensitive Prostate Cancer.

Inclusion Criteria: * Veterans must meet the following to be eligible to participate: * Be willing and able to provide written informed consent for the trial. * Age ≥18 years of age on day of signing informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (on a scale from 0 to 5, with higher scores indicating greater disability and a score of 5 indicating death). * Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet-cell features, or small-cell features in either a recently obtained sample or in the archival sample at the time of diagnosis. * Have been receiving or will receive androgen-deprivation therapy with a gonadotropin releasing hormone agonist or antagonist or have undergone bilateral orchiectomy (i.e., medical, or surgical castration). * High risk for the development of progression of disease/metastasis, defined as (i) a minimum of three rising PSA values (PSA1 \< PSA2 \< PSA3) at an interval of at least 1 week apart; (ii) a PSA level of 2 ng per milliliter (2 μg/L) or greater; and (iii) a PSA doubling time of 9 months or less during continuous androgen-deprivation therapy (bilateral orchiectomy or treatment with gonadotropin-releasing hormone analogue agonists or antagonists) as calculated with the use of the method of Pound et al. * Has not received abiraterone acetate, enzalutamide, or apalutamide at the time of enrollment. * Have a predicted life expectancy of \>12 months. * For patients receiving bisphosphonates or denosumab, dose must be stable for at least 4 weeks before randomization. * Able to swallow the study drug and comply with study requirements. * Laboratory tests meet minimum safety requirements: * Hepatic: AST ≤2.5 X institutional ULN, ALT ≤2.5 X institutional ULN * Renal: Creatinine clearance ≥30 ml/min or serum creatinine ≤1.8 mg/dl * Hematological: Absolute neutrophil count ≥1000/mm3, Platelet count ≥100,000/mm3; Hemoglobin \>9 g/dL Note: The presence of metastatic disease as assessed by any modality is not a contraindication for enrollment. Exclusion Criteria: Subjects with any of the following will not be enrolled: * Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, apalutamide or enzalutamide for the treatment of prostate cancer or participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (unless treatment was placebo). * Treatment with hormonal therapy (e.g., androgen receptor inhibitors, estrogens, 5-alpha reductase inhibitors) or biologic therapy for prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist therapy) within 4 weeks of randomization * Other malignancy except: (a) Subjects who have been successfully treated and are disease free for 3 years; (b) a history of completely resected non-melanoma skin cancer; or (c) successfully treated in situ carcinoma. * History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma). * Deep vein thrombosis or pulmonary embolism in the past 3 months that in the opinion of the physician makes the patient medically unstable. * Patients who are receiving any other investigational agents concurrently.