EvaluatioN of HIFU Hemiablation and Short Term AndrogeN Deprivation Therapy Combination to Enhance Prostate Cancer Control.

Prior treatment

• Metal implants/stents in the urethra.
• Men who have previously received any form of PCa treatment (e.g. external beam radiation therapy (EBRT), brachytherapy, HIFU, cryosurgery, thermal or microwave therapy and/or hormonal therapy).
• Patient treated with 5 α-reductase inhibitors in the previous 3 months and during the study.
• Men who have undergone surgery for benign prostatic hyperplasia in the previous 6 months; i.e. a transurethral resection of the prostate (TURP), holmium laser enucleation (HOLEP), greenlight laser vaporization, others.
• Men with an inability to tolerate a transrectal ultrasound probe or have undergone prior significant rectal surgery preventing insertion of transrectal HIFU probe.
• WHO performance status of grade 3-4 / men unfit for surgery.
• Patients who previously underwent orchidectomy.
• Men with relative and/or absolute contraindications to androgen deprivation therapy.

Other illness

• Active urinary tract infection.
• Men unable to have MRI scanning (e.g. men with severe claustrophobia, permanent cardiac pacemaker or metallic implant which may likely contribute to significant image artefacts).
• Hypersensitivity to leuprorelin acetate, to other GnRH agonists or to any of the excipients.

Lab values

• Men with renal impairment and a glomerular filtration rate (GFR) of \<35 ml/min (unable to tolerate Gadolinium dynamic contrast enhanced MRI).
• Men with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, or taking drugs known to prolong the QT interval.

Age

• Men under the age of 40.

Other

• Life expectancy less than 10 years.
• Any Gleason score ≤6 (3 + 3) (ISUP1).
• Any Gleason score≥ 7 (4+3) (ISUP3).
• PI-RADS \< 3 lesions in MRI (PI-RADS v2.1).
• Apex lesions may ≥ 10 mm away from the urethral sphincter.
• PSA \>15 ng/ml.
• Clinical stage \> cT2b (based on MRI and rectal examination).
• Evidence of extra-prostatic extension or seminal vesicle invasion.
• Evidence of lymph node or distant metastases.
• Prostate volume \> 40 ml when lesion is located in the anterior zone of the prostate.
• Prostatic calcifications or cysts whose location may interfere with effective delivery of HIFU energy.
• Language barriers that might hinder the communications, understanding of written and verbal information about the trial, consenting process, or completing the questionnaires.
• Men refusing to sign an informed consent to participate in the trial.

• Men aged 40 and over.
• Life expectancy ≥ 10 years.
• Localized, intermediate-risk PCa (according to the most recent version of the European Association of Urology Prostate Cancer Guidelines).
• PI-RADS ≥ 3 lesions in MRI (PI-RADS v2.1).
• Unilateral (unifocal or multifocal) PCa or bilateral disease allowing unilateral GS 3+3 up to 1mm in the non-treated side.
• Histopathologically verified PCa by any mpMRI-targeted prostate biopsy (3 cores per each target lesion + 12 random cores performed).
• Any Gleason score 7 (3 + 4) (ISUP2).
• Prostate specific antigen (PSA) ≤15 ng/ml.
• Clinical stage T1c-T2b (based on MRI and/or rectal examination).
• Absence of lymph node and distant metastases.
• Prostate volume ≤ 60 ml. Patient with prostate volume between 40 ml and 60 ml could be included only if lesion is located in posterior zone of the prostate.
• Treatment-naive patients (received no previous treatments for PCa, apart from active surveillance).
• World Health Organization (WHO) performance status of grade 0-2.
• Men who are sexually active with women of chidbearing potential must use a highly effective method of contraception prior the first administration of hormonal therapy and must agree to continue using such precautions for 130 days after the final administration of the treatment.
• Having signed a written informed consent form.