Focal Therapy With Stereotactic Body Radiation Therapy (SBRT) for Patients With a Single Prostate Tumor

Background: * Prostate cancer is the most common cancer among American men. * The best current validated treatment options include whole gland radiotherapy and radical prostatectomy. * Based on recent advances in imaging, focal ablative therapies are under investigation in attempts to deliver comparable rates of tumor control with less side effects. * Thus far, focal therapies such as cryotherapy, high-intensity focused ultrasound, or focal laser ablation have resulted in poor local control with the exception of implanted radiation sources which have shown in-field control rates \> 90%. * As such, the proposed trial is designed to investigate the efficacy of a novel form of focal stereotactic body radiation therapy (SBRT) for the treatment of localized, unifocal prostate cancer. * Prostate specific membrane antigen (PSMA) targeted PET imaging was recently FDA approved for imaging men with suspected prostate cancer metastases who are potentially curable by radiation or surgery. 18F-DCFPyL, a second generation PSMA PET agent that binds with high affinity to PSMA yet clears rapidly from the blood pool will be used in this study. Objective: -To determine whether localized, tumor-directed SBRT can produce biopsy-confirmed tumor response at 24 months in participants with unifocal prostatic adenocarcinoma. Eligibility: * Histologically confirmed, low or intermediate risk prostatic adenocarcinoma verified by biopsy. * Unifocal prostate cancer defined as a single focus of prostate cancer on imaging which is correlated with a positive targeted biopsy. * Age \>= 18. * No concurrent systemic Androgen Deprivation Therapy (ADT) is planned. Design: * This is a single-arm phase II trial designed to measure the efficacy of a novel application of SBRT guided with advanced prostate-specific imaging techniques. * Participants will initially undergo a treatment planning CT, multiparametric MRI (mpMRI), 18F-DCFPyL PET/CT imaging, a biopsy, quality of life (QoL) questionnaires and laboratory evaluations. SBRT will be administered at 26Gy in two fractions on two separate days. * Following completion of treatment, participants will be followed for up to 2 years through clinical evaluation, laboratory evaluations (including a complete blood count (CBC), prostate specific antigen (PSA) and testosterone measurements), QoL assessments, mpMRI, 18FDCFPyL PET/CT imaging, and a biopsy. * The accrual ceiling is set to 42 participants with the goal of recruiting 30 evaluable participants.