Prospective Monitoring of Subjects With Biochemically Recurrent Prostate Cancer Using 18FDCFPyL

Background: * Prostate cancer is the most common malignancy and the second leading cause of cancer-related deaths in American men. * About 25,000 to 50,000 men each year develop a rising prostate-specific antigen (PSA) after definitive radiation or surgery for early-stage disease but have negative findings on computed tomography (CT) and Tc99 bone scan (standard imaging in prostate cancer). * The recent Food and Drug Administration (FDA) approval of 18F-DCFPyL PET imaging provides an opportunity to locate micrometastatic lesions in patients with recurrent disease. * It is unknown how these lesions (or prostate cancer) evolve over time in men with positive findings on 18F-DCFPyL PET imaging. Objective: -To observe participants with biochemically recurrent prostate cancer for 5 years to understand the evolution of 18F-DCFPyL PET lesions in this population. Eligibility: * History of primary treatment for prostate cancer (either surgery or radiation). * PSA \>= 0.50, and testosterone \>100. * Age \>=18 years. * No evidence of metastatic soft tissue disease on CT scan (or MRI), or bone lesions on bone scan. * No androgen deprivation therapy (ADT), no systemic therapy within the 6 months before the study intervention, and no prostatectomy within 1 year before the study intervention. Clinical trial treatments are allowable within the 6 months before study intervention. Design: * Eligible participants will have clinical evaluations and imaging studies. Participants with negative findings on initial/following 18F-DCFPyL scan(s) will be invited approximately every year (+/-12 weeks) for follow-up imaging studies (including 18F-DCFPyL PET scans). Participants with positive findings on initial/following 18F-DCFPyL scan(s) will be invited approximately every 6 months (+/-8 weeks) for repeat scans, not to exceed 2 scans per year. * After the initial evaluation, participants will be invited to NIH approximately every 3 months (+/- 4 weeks) for PSA testing.