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

* 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.