Evaluating the Safety and Efficacy of the "HIFU" High-intensity Focused Ultrasound Treatment of Benign Prostatic Hyperplasia;

Phase 1-2 Dose-escalation Study, Evaluating the Safety and Efficacy of the "HIFU" High-intensity Focused Ultrasound Treatment of Benign Prostatic Hyperplasia After 3 Months, 6 Months, 12 Months, 18 Months and 36 Months.

Prostate adenoma, also known as benign prostatic hypertrophy or hyperplasia (BPH), involves an increase in the size of the prostate, forming a benign tumor. It is the most common benign tumor in men, generally affecting those over 40 years old. The risk of BPH is more than 50% in men aged 50 to 60 and rises to 90% in men by age 80.

This hyperplasia leads to altered urinary flow and bladder outlet obstruction, referred to as "lower urinary tract symptoms" or LUTS, which become more frequent with age. These symptoms are categorized as obstructive or irritative. In the early stages, men with BPH may have difficulty starting urination and may feel as if their bladder is not completely empty. As a result, they need to urinate more often, especially at night, a condition known as nocturia. Additionally, the volume and velocity of the urinary flow may decrease significantly, as evidenced by flow measurements, and residual urine discharge may occur at the end of urination.

High-intensity focused ultrasound (HIFU) is a medical technique that uses high-intensity ultrasonic waves to treat various medical conditions, including malignant and benign tumors, without the need for invasive surgery or ionizing radiation. HIFU generates heat between 80° to 95°C at the focal point, causing necrosis of the targeted area with pinpoint accuracy. In urology, HIFU is used to treat prostate cancer in a minimally invasive manner, with focused ultrasounds delivered endorectally using a transducer that targets the treatment area with real-time monitoring.

Exclusively targeted HIFU treatment has been suggested for BPH, where localized necrosis of the side lobes reduces the volume of the prostatic transition zone, alleviating compression of the prostatic urethra and improving urinary symptoms.

This new study was initiated to evaluate the safety and efficacy of HIFU for BPH treatment.

Inclusion Criteria:

Men aged ≥ 50 to ≤ 85

Patient diagnosed with benign prostatic hyperplasia evaluated by:

• Prostate volume ranging from 30 cc to 80 cc evaluated by MRI
• Qmax < 15ml/s
• IPSS ≥ 8
• IPSS-QoL ≥ 3
• IIEF-5 > 17

Patient for whom medical treatment failed (having been taken regularly for more than 12 weeks) OR patient with a contraindication to the initiation of medical treatment OR patient refusing medical treatment Patient whose prostate show no sign of cancerous lesion confirmed by MRI Patient capable of reading and understanding French or with a carer who speaks French and could help the patient understand the leaflet and the questionnaires Patient registered with a social security scheme Patient having given their free and informed consent to participate in the study

Exclusion Criteria:

Presence of a median lobe preventing the HIFU treatment to be delivered according to the investigator's judgment Prostate cancer confirmed or suspected History of surgical treatment of the prostate History of radiotherapy of the prostate History of bladder cancer History of urethral stricture Presence of a urinary tract fistula Urethral stricture or untreated bladder neck stenosis Untreated urinary lithiasis Neurological bladder or neurological bladder disease or any other neurological disease likely to affect the functioning of the bladder-sphincter system History of pelvic radiotherapy Patient with renal failure with GFR < 35ml/min Patient currently undergoing anticoagulant therapy (antivitamins K (AVK) and new oral anticoagulants (NOACs) for which the stop window cannot exceed 48H at the time of the HIFU procedure Contraindication to the surgical procedure, in particular anesthesia Contraindication to the pelvic MRI Patient with a rectal wall > 10mm

Contraindication to the HIFU treatment procedure:

• Active urogenital infection (the infection must be treated before HIFU treatment)
• Anal or rectal fibrosis, anal or rectal stenosis or any other abnormalities making it difficult to insert the Focal One® probe
• Urinary tract or rectal fistula
• Anatomic abnormalities of the rectum or rectal mucosa
• Presence of permanent radioactive implants in the rectal wall
• Presence of prostatic calcification the location of which interferes with the HIFU treatment
• Patient with an artificial sphincter, a penile prosthesis or intra-prostatic implant; for example, an endoprosthesis
• Presence of an implant (stent, catheter) within 1cm of the treatment area
• History of inflammatory bowel disease
• Presence of metal stents or implants in the urethra Patient refusing to participate in the study Person under guardianship considered legally incapable of giving their informed consentPatient unable or refusing to complete the questionnaires Persons placed under judicial protection Subject participating in another study including an exclusion period that is still running at the time of pre-inclusion