Pilot Study to Investigate Magnetic Resonance (MR) Image Guided Focal Therapy in Prostate Cancer

Background: The ability to treat early prostate cancer is still limited. Thermal ablation methods are being tested for focal prostate cancer therapy. Researchers want to improve on these methods. Objective: To understand if Transurethral UltraSound Ablation (TULSA) in combination with MRI guidance is useful to treat localized prostate cancer. Eligibility: English-speaking adults ages 18 and older with localized prostate cancer that can be seen on MRI and can be treated by thermal ablation. Design: Participants will be screened with the following: * Medical history * Physical exam * Digital rectal exam * Blood and urine tests * Electrocardiogram * Tumor biopsy * Questionnaire to assess urinary tract symptoms * MRI of the pelvis. The MRI scanner is a long, narrow tube. Participants will lie on a bed that moves in and out of the scanner. Participants may also be screened with the following: * Echocardiogram * Chest x-ray * Bone scan * Urodynamic studies to see how well the bladder, sphincters, and urethra hold and release urine * MRI of the brain * Transrectal ultrasound * Computer tomography (CT) scan of the chest, abdomen, and pelvis. A CT scan is a series of x-ray images taken of parts of the body. Some screening tests will be repeated during the study. Participants will have the TULSA procedure. They will have an MRI for guidance. A small ultrasound applicator will be placed into their urethra. It uses heat to destroy the cancer areas in the prostate. It is controlled by a robotic arm. A cooling catheter will be placed into their rectum. Participants will use a urethral catheter for 1-7 days. Participants will have follow-up visits at 3, 6, 12, 18, 24, and 36 months.

* INCLUSION CRITERIA: Subjects must have prostate cancer amenable for ultrasound ablation defined as: * diagnosed by transrectal ultrasound-guided prostate biopsy via standard 12 core biopsy and targeted biopsy of any MRI-visible or tracked lesions; pathological diagnosis must be confirmed by Laboratory of Pathology, NCI; * Gleason Score \= 2 prostate cancer must be from an area overlying or within 1cm of an MRI-visible or tracked lesion(s) and reviewed by NCI urologic pathologist. (Left / Right, Base, Mid-Gland, Apex). Systematic and targeted cores of Grade Group 1 prostate cancer outside of proposed ablation zone do not affect inclusion status, as these can be observed by conventional guideline management. * organ confined clinical T1c or clinical T2a prostate cancer that is visualized on MRI. Note: Participants after prostate cancer treatment with local recurrence or residual tumor which is visible on MRI are eligible. * PSA \< 20 ng/ml or PSA \>20 with a PSA density \= 18 years of age) * Participants must have adequate organ and marrow function as defined below: Platelets \>= 50,000/mcL Hemoglobin \>= 8 g/dL Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl)\* \>= 30 mL/min/1.73 m\^2 GFR=glomerular filtration rate; ULN=upper limit of normal. \*Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard. * Subjects must be able to understand and willing to sign a written informed consent document. * Subjects must be co-enrolled to NCI protocol 16-C-0010 "Care of the Prostate Cancer Patient and Prospective Procurement of Prostate Cancer Tissue." EXCLUSION CRITERIA: * Targeted lesion ablation length from apex to base of \>5 cm or lesion extending \>3 cm from the urethra. * Target ablation volume greater than 100 ml. * Presence of calcifications that would impede ultrasound transmission between the urethra and ablative target. * Participants are unable to tolerate MRI (foreign body, i.e., pacemaker or other implanted device; claustrophobia; inability to tolerate rectal coil; etc.) * Acute urinary tract infection * Lower urinary tract symptoms defined by an IPSS \> 20 * Participants with uncontrolled coagulopathies (including liver dysfunction, or untreated hereditary coagulopathies which have a standard of care treatment) per surgeon discretion based on bleeding risk. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation (within time frame) that would limit compliance with study requirements.