Enzalutamide Versus Standard Androgen Deprivation Therapy for the Treatment Hormone Sensitive Prostate Cancer

Inclusion Criteria:

* Histologically or cytologically proven adenocarcinoma of the prostate; if pathology is unavailable, the principal investigator (PI) may also make a determination of prostate cancer based on unequivocal clinic data
* Patients with advanced prostate cancer suitable for systemic treatment defined as: having metastatic disease, a biochemical relapse after primary therapy, or patients in whom primary therapy is not appropriate or feasible; patients without metastatic disease will need evaluation for local therapy and deemed inappropriate or have refused this treatment option
* Eastern Cooperative Oncology Group (ECOG) 0-2
* Age \> 18 years
* Must use a condom if having sex with a pregnant woman
* A male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration
* Life expectancy estimated at \> 12 months
* Ability to understand and willingness to provide written informed consent document

Exclusion Criteria:

* A history of androgen deprivation therapy; patients receiving hormonal therapy in the adjuvant and/or neoadjuvant setting must have discontinued therapy at least 6 months prior to day 1 of treatment AND have a serum testosterone level \>= 50 ng/dL AND cannot have received more than 18 months of previous ADT
* A history of orchiectomy
* Previous androgen blockade (e.g. antiandrogens) in the last 3 months
* Patients already meeting the criteria for metabolic syndrome as defined by the Adult Treatment Panel III Criteria which requires 3/5 parameters encompassing glucose control, blood pressure, lipids and waist circumference; patients with 2 of the parameters at baseline will be allowed enrollment provided that one of those risk factors is hypertension (\>= 130/\>= 85 mm Hg)
* Baseline hypogonadism as defined as a testosterone \< 50 ng/dL
* PSA \< 0.5 ng/dL
* Serum vitamin D 25, hydroxy (OH) \< 12 ng/mL
* Active hepatitis C virus
* Use of corticosteroids as defined by a daily dose of prednisone (or equivalent) of 5 mg or greater for more than 1 month continuously within 3 months of screening
* Corrected calcium \> 10.6 mg/dL
* Absolute neutrophil count \< 1500/uL
* Platelet count \< 100,000/uL
* Hemoglobin \< 9 g/dL
* Total bilirubin \>= 1.5 x upper limit of normal (ULN) (unless documented Gilbert's)
* Alanine aminotransferase or aspartate aminotransferase \>= 2.5 x ULN
* Creatinine \> 2 mg/dL
* Clinically significant cardiovascular disease as evidenced by: myocardial infarction within 6 months of screening; uncontrolled angina within 3 months of screening; New York Heart Association (NYHA) class 3 or 4 congestive heart failure; clinically significant ventricular arrhythmia; Mobitz II/2nd degree/or 3rd degree heart block without a pacemaker in place; uncontrolled hypertension (HTN) (systolic \> 180 mmHg or diastolic \> 105 mmHg at screening)
* Previous exposure to enzalutamide
* Use of an investigational therapeutic within 30 days
* History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agent
* Known or suspected brain metastasis or active leptomeningeal disease
* History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visit
* Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements