Comparing Two Different Boost Approaches in Radiation Therapy for People With Prostate Cancer

In this study we will find out whether the use of a new type of boost approach called irreversible electroporation (IRE) is as effective as the standard boost approach of radiation therapy for people with intermediate-risk prostate cancer receiving standard stereotactic body radiotherapy (SBRT).

Inclusion Criteria: * Biopsy proven grade group 2 or 3 (GS 3+4 or GS 4+3) cancer with all pattern 4 found only in the MRI target * Gland size ≤ 80 cc * Prostate MRI \< rT3b disease * IPSS \< 20 * No contraindication to IRE, RT, anesthesia, or transperineal procedure Exclusion Criteria: * Any Grade Group ≥4 disease, or any cribriform and/or intraductal carcinoma * Evidence of nodal or /metastatic disease on MRI and/or PSMA PET/CT * Unfit for general anesthesia, or contraindication/hypersensitivity to required neuromuscular blocking agents * Active urinary tract infection (UTI) at the time of IRE or biopsy; must be treated and resolved prior to proceeding * Actively bleeding, known bleeding disorder, or inability to interrupt anticoagulants/antiplatelet therapy as clinically indicated for biopsy/IRE safety * Any history of cardiac arrhythmia or epilepsy, or recent myocardial infarction, consistent with NanoKnife contraindication statements * Presence of an implanted pacemaker/defibrillator or other active implanted electronic device, or other device-related contraindications per current NanoKnife labeling/user manual * Inability to undergo pelvic MRI * Prior treatment of prostate cancer including androgen deprivation therapy, focal therapy, radiation therapy, or prostatectomy * Current or intended use of androgen deprivation therapy