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

Inclusion Criteria

• - INCLUSION CRITERIA: - Participants must have histologically confirmed, low or intermediate risk prostatic adenocarcinoma verified by biopsy (NIH Laboratory of Pathology confirmation is required). - Unifocal prostate cancer defined as a single focus of prostate cancer on MRI and PSMA PET/CT imaging which is correlated with a positive targeted biopsy. - Age >=18 years. - ECOG performance status <=2 (Karnofsky >60%). - Men must agree to use highly effective contraception with their partner (barrier method of birth control; abstinence) for the duration of study participation and up to 120 days after the last radiation treatment. - Ability of individual to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: - Participants with NCCN high-risk prostate cancer features (Gleason score >=8, >cT2c, or PSA >= 20 ng/mL). - Participants with prostate biopsies which show >= grade group 2 adenocarcinoma determined to be outside of the radiographically visible lesion (systematic biopsies which map to a radiographically detected lesion are not an exclusion criterion). - Participants in whom concurrent systemic Androgen Deprivation Therapy (ADT) or chemotherapy is planned. - Participants who are receiving any other investigational agents. - Participants found to have pelvic or distant metastases on pre-treatment staging studies. - Participants with an AUA-SI/IPSS score > 18. - Participants who have previously received curative treatment for a prior or the current diagnosis of prostate cancer. - Active urinary tract infection assessed by urinalysis. - Human immunodeficiency virus (HIV)-infected individuals who are not on effective anti-retroviral therapy. Participants on anti-retroviral therapy with undetectable viral load within the 6 months prior to registration are eligible for this trial. - Participants with hepatitis B virus (HBV) infection who have not been treated and cured. - Participants with chronic HBV at screening must have an undetectable HBV viral load on suppressive therapy. - Participants with hepatitis C virus (HCV) infection who have not been treated and cured. - Participants with HCV infection who are currently on treatment, are eligible if they have an undetectable HCV viral load at screening. - Anatomic relationship between the tumor and adjacent normal tissues judged to be unfeasible for the planned treatment by the PI. - Participants with connective tissue diseases. - Participants with radiation hypersensitivity syndromes. - Ongoing active inflammatory bowel disease within the radiation field. - Participants with prior medical comorbidity or surgical history involving the low pelvis which is expected to confer a high risk of toxicity to the experimental radiation regimen. - Ineligibility or unwillingness to undergo a contrast-enhanced MRI due to inadequate renal function (eGFR < 30), severe claustrophobia, a weight above tolerance of the scanner (> 350 lbs.), a body size unable to fit into the scanner, or implanted devices incompatible with an MRI (implanted cardiac devices, surgical hardware, retained shrapnel, cerebral aneurysm clips, or other incompatible objects. - Unwillingness to undergo an 18F-DCFPyL PET/CT or known allergy to the 18F-DCFPyL tracer. - Contraindication or inability to undergo fiducial marker implantation. - History of prior radiotherapy overlapping with the intended radiation field. - Uncontrolled intercurrent illness, factors, or social situations that would limit compliance with study requirements.