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

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; systematic biopsy pattern 4 that is concordant with MRI target per investigator is permissible
* 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