Prostate Specific Membrane Antigen (PMSA)-Based PET Imaging of High Risk Prostate Cancer

Background: * About 30,000 men will die from prostate cancer in the US in 2018. The majority of these men originally presented with localized cancer. * Treatment options for patients with high risk, localized disease typically involve radical prostatectomy (RP) or radiation therapy (RT) in combination with androgen deprivation therapy (ADT). Following RP, 70% of patients with high-risk disease will experience a biochemical recurrence at 5 years, and approximately 20% will die of their disease in 10-15 years, likely due to metastatic disease that was not detectable using conventional imaging (99mTc-methylene diphosphonate bone scan and X-ray computed tomography) at the time of prostatectomy. * Prostate-specific membrane antigen (PSMA) is commonly expressed in prostate cancers and is associated with biologic aggressiveness. * The second generation, PET tracer 18F-DCFPyl binds to the enzymatic portion of PSMA. It exhibits high uptake in tumor and rapid washout in normal tissues leading to high tumor to background ratios and the possibility of detecting metastases when conventional imaging is negative. Objective: -To determine if patients with a preoperative 18F-DCFPyL PET/CT that is negative for metastases experience 5 year progression free survival (PFS) which is improved (40%) over that of historical data (30%) based on a general population of similar patients who have not undergone imaging with 18F-DCFPyL PET/CT Eligibility: * 18 years of age at the time of providing informed consent. * Patients must have histologically proven prostate adenocarcinoma confirmed by a CLIA certified laboratory * Eastern Cooperative Oncology Group (ECOG) performance status: \<=2. * Must have prostate cancer with high risk features defined as: * Gleason 8 and higher OR * PSA \> 20 ng/mL OR * Clinical stage T3a (i.e. likely extraprostatic extension on MRI) or T3b * Laboratory parameters: * Hemoglobin \>= 9 g/dL * Leukocytes \>=3,000/mcL * Platelets \>=100,000/mcL * Total bilirubin \<2 X normal institutional limits * AST(SGOT)/ALT(SGPT) \<=3 X normal institutional limits * Creatinine \<2 X normal institutional limits OR * eGFR \>=50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated via the MDRD equation) * Patients must be planning to undergo radical prostatectomy and lymphadenectomy regardless of findings on 18F-DCFPyL PET/CT. * Willingness and ability to undergo multiparametric prostate MRI and 18F-DCFPyL PET/CT Design: * This is an open-label, non-randomized, multi-center trial designed to evaluate the impact of 18F-DCFPyL PET/CT imaging on Progression-Free Survival at 5 years in patient with high risk localized prostate cancer. * All subjects meeting eligibility criteria will undergo baseline assessments to include multiparametric MRI of the prostate, 99mTc-methylene diphosphonate bone scan and contrast-enhanced CT of the abdomen and pelvis. * All subjects meeting eligibility criteria will undergo 18F-DCFPyL PET/CT. * The study will enroll up to 200 patients from 7 centers. Up to 40 patients will be enrolled at NCI. * All subjects will undergo radical prostatectomy and lymphadenectomy within 60 days following PET/CT imaging. * Subjects will be evaluated at 6 weeks, at 3, 6, 9, 12, and 18 months, at 2, 3, 4, and 5 years post-prostatectomy to determine if there has been progression and to record details of subsequent treatment and response. * 18F-DCFPyL PET/CT imaging will be repeated at the time of progression.