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

Background: People with prostate cancer usually have their cancer imaged with a CT scan and bone scan. They then have their prostate gland removed. Researchers want to test a scan that might predict if prostate cancer will return after this surgery. Objective: To test if a PET/CT scan before the prostate gland is removed can predict if prostate cancer will return. Also, to test if this approach is better or worse than the usual approach for prostate cancer. Eligibility: Men ages 18 and older with prostate cancer that appears to be contained within the prostate but is at risk of having spread Design: Participants will be screened with: * Medical history * Blood tests * CT and MRI scans: Participants will lie in a machine. The machine will take pictures of the body. * Bone scan Participants will have a radiotracer injected into a vein. They will have a PET/CT scan of their whole body 60-90 minutes later. During the scan, they will lie on their back and stay still. Within 60 days after the scan, participants will have surgery. This will remove the prostate gland and lymph nodes around it. Some tissue will be used for genetic testing. If the PET/CT scan suggests the cancer has spread, participants may need to have another biopsy within 60 days after the scan. After surgery, participants will have follow-up visits for 5 years. They will have 5 visits the first year and 2 the second. Then they will have visits once a year. If participants cancer returns, they will have repeat PET/CT scans.

* INCLUSION CRITERIA: * Patients must have histologically proven prostate adenocarcinoma confirmed by a CLIA certified laboratory. * 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 * Patients must be eligible for and must be planning to undergo radical prostatectomy and lymphadenectomy regardless of findings on 18F-DCFPyL PET/CT * Men age greater than or equal to 18 years. * ECOG performance status \