Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer

* INCLUSION CRITERIA:
* Patients must have histologically or cytologically confirmed prostate cancer confirmed by the Laboratory of Pathology, National Cancer Institute (NCI) or Pathology Department at Walter Reed Bethesda
* Must have previously untreated (with definitive therapy) prostate cancer with intermediate or high risk features defined as:

  * Intermediate risk:

    * Prostate-specific antigen, (PSA) level is between 10 and 20 ng/ml or
    * Gleason score is 7 or
    * Stage T2b or T2c
  * High Risk:

    * Gleason 8 and higher OR
    * PSA greater than 20 at the time of diagnosis OR
    * Seminal vesicle involvement OR
    * Possible (on magnetic resonance imaging (MRI) Extra-capsular extension (T3 disease)
* Patients must be eligible for and must be planning to undergo radical prostatectomy
* Patients must have testosterone levels greater than or equal to 100 ng/dL
* Men age greater than or equal to 18 years.

  * Children are excluded because prostate cancer is not common in pediatric populations.
  * Women are not eligible because this disease occurs only in men.
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
* Patients must have normal organ and marrow function as defined below:
* Hemoglobin greater than or equal to 9 g/dL
* leukocytes greater than or equal to 3,000/mcL
* absolute neutrophil count greater than or equal to 1,500/mcL
* platelets greater than or equal to 150,000/mcL
* total bilirubin within normal institutional limits
* Aspartate aminotransferase (AST)/Serum glutamic-oxaloacetic transaminase(SGOT)/Alanine aminotransferase (ALT) Serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 X institutional upper limit of normal
* creatinine within normal institutional limits

OR

* creatinine clearance greater than or equal to 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal.
* The effects of enzalutamide on the developing human fetus are unknown. For this reason and because androgen receptor antagonists as well as other therapeutic agents used in this trial are known to be teratogenic, male participants and their female partners of child bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence). Male participants should use a condom if having intercourse with a pregnant woman. Additionally, a condom plus another effective method of birth control is recommended during therapy and for 3 months after treatment for male participants having intercourse with a woman of reproductive potential. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
* Ability of subject to understand and the willingness to sign a written informed consent document.
* Willingness to undergo biopsy.
* Ability to detect lesions within prostate on magnetic resonance imaging (MRI) for biopsy
* Willingness to travel to National Institutes of Health (NIH) for follow-up visits.

EXCLUSION CRITERIA:

* Patients who are receiving any other investigational agents (in the past 28 days) or herbal medications (within 1 day).
* Patients with distant metastatic disease beyond N1(regional) lymph nodes on conventional imaging studies (Computed tomography (CT), MRI or Bone Scan).
* Patients who have received any prior therapy for prostate cancer with surgery, radiation, and/or chemotherapy
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or other agents used in study.
* Clinically significant cardiac disease, e.g. New York Heart Association (NYHA) classes III-IV; uncontrolled angina, uncontrolled arrhythmia or uncontrolled hypertension, myocardial infarction in the previous 6 months as confirmed by an electrocardiogram (ECG).
* Contraindication to biopsy:

  * Bleeding disorders
  * Prothrombin Time (PT)/Partial Thromboplastin Time (PTT) greater than or equal to 1.5 times the upper limit of normal
  * Artificial heart valve
* Contraindication to MRI:

  * Patients weighing more than weight limit for the scanner tables
  * Allergy to MR contrast agent
  * Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic device
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with known human immunodeficiency virus (HIV) are eligible. These patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. In addition, if patients are receiving combination antiretroviral therapy, there is potential for pharmacokinetic interactions with enzalutamide. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
* Patients with known active treatment for Hepatitis B and C infections.
* Patients who are taking medications that are strong inhibitors of Cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (PgP) and need to remain on these medications. For a current table of Substrates, Inhibitors and Inducers please access the following website:

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm

* History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization).
* Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter prostate specific antigen (PSA) (eg phytoestrogens and saw palmetto) cannot be taken while patients are receiving enzalutamide
* Patients with a malignancy within the past 3 years for which study drugs or a prostatectomy is a contraindication.