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

Background: * There are several ways to treat prostate cancer. Researchers want to see how well a certain kind of imaging helps detect prostate cancer. They also want to see if a particular drug combination used before surgery will benefit people with prostate cancer that hasn't spread in the body (non-metastatic). The combination will be androgen deprivation therapy and enzalutamide. * The combination of androgen deprivation therapy and enzalutamide has been shown to make patients with advanced (metastatic disease) live longer. The investigators want to see if using it earlier can increase cure rate of surgery and identify genetic or molecular characteristics that are associated with better outcomes. Objectives: \- To develop better ways of detecting prostate cancer before and after pre-operative treatment. Eligibility: \- Men at least 18 years old with non-metastatic prostate cancer. They must be candidates for a radical prostatectomy. Design: * Participants will be screened with medical history, physical exam, and blood tests. They will have scans and X-rays. * Before starting the study drugs, participants will have: * Vital signs taken, medical history, and blood tests. * Electrocardiogram (ECG) heart test, with patches stuck on the skin. * Small piece of tumor removed (biopsy) using image guidance from magnetic resonance imaging (MRI) and ultrasound. * 3T multi-parametric magnetic resonance imaging (mpMRI). Participants will lie on a table that slides into a metal cylinder. A probe will be inserted in the rectum. They will be in the scanner for about 60 minutes, lying still. The scanner makes loud knocking sounds. Participants will get earplugs. * Participants will take the 2 study drugs for 6 months. * Enzalutamide is taken as 4 pills once a day. * Androgen deprivation therapy is given by injection 2 times over 6 months. * During these 6 months, participants will visit the clinic monthly. They will have physical exam, vital signs, and blood drawn. * After finishing the study drugs, participants will have another 3T mpMRI. Then they will have prostate removal surgery.

Background: * Most men diagnosed with prostate cancer will present with intermediate or high-risk disease * Many develop castrate resistant prostate cancer (CRPC) as curative strategies are often unsuccessful * Treatment options typically involve radical prostatectomy (RP) or radiation therapy (RT) in combination with androgen deprivation therapy (ADT) * Even when cancers are initially sensitive to ADT, resistance ultimately emerges either through clonal selection or through a variety of adaptive mechanisms (secondary resistance). * The recent introduction of novel androgen pathway inhibitors offers an opportunity to potentially improve the cure rate of men with intermediate and high risk localized prostate cancer * There remains a great need for improved techniques to determine mechanisms of treatment response and resistance. Objectives: -To test the feasibility of multi parametric magnetic resonance imaging (mpMRI) for the localization and detection of focal prostate cancer both before and after pre-operative treatment with ADT and enzalutamide. Eligibility: * Patients with nonmetastatic castration sensitive prostate cancer with intermediate or high-risk features * Patients with testosterone levels greater than or equal to 100 ng/dL. * Eastern Cooperative Oncology Group (ECOG) 0-1. Design: * Patients will be treated with ADT and enzalutamide for 6 months * Two 3T mpMRI endorectal examinations (One at screening and after 6 month of treatment) * Screening biopsy (magnetic resonance (MR)/ultrasound (US) guided) samples * Standard of care prostatectomy (RP) following post treatment mpMRI * All tumor specimens will undergo genomic analysis