Evaluation of the Optilume BPH Catheter System and the Rezum Water Vapor Therapy in Treating Benign Prostatic Hyperplasia

A- Background Lower urinary symptoms (LUTS) affect older men and their frequency and severity increase with age. According to Berry et al., the histological diagnosis of benign prostatic hyperplasia (BPH) increases from 25% in the group age between 40 to 49 years to 80% in the group age between 70 to 79 years. However, this hyperplasia can lead to a bladder outlet obstruction (BOO) secondary to benign prostatic enlargement (BPE), causing storage and voiding symptoms, associated with a considerable impairment of the quality of life.

Surgical therapy of BPH has continuously evolved in recent years. The current gold standard for the endoscopic treatment of BPH is the transurethral resection of the prostate (TURP). Other innovative techniques were developed including Urolift, transurethral laser enucleation (holmium, thulium) and Aquablation therapy. One of the latest technologies for the management of BPH are Optilume BPH Catheter System (Optilume®, Urotronic Inc, Minneapolis, USA) and Rezum Water Vapor Therapy (Rezum System, Bostocn Scientific, Marlborough, MA).

The Optilume BPH Catheter System was approved by the FDA in 2023. The technology is based on a device/drug combination consisting of two catheters: the Optilume BPH Prostatic Pre-dilation Catheter which is a non-drug coated catheter used to start commissurotomy between the lateral lobes of the prostate and the Optilume BPH Prostatic Dilatation DCB Catheter which is a drug coated catheter used to complete the commissurotomy and transfers drug (paclitaxel) to the pre-dilated prostatic urethra and anterior commissure. Hence, the device applies a mechanical dilatation to open prostatic urethral lumen to increase urine flow, followed by the transfer of paclitaxel drug to inhibit cell proliferation and maintain this dilatation.

The Rezum system is minimally invasive therapy for LUTS secondary to BPH. The system injects water vapor at 103°C generated by radiofrequency to create thermal energy via a transurethral approach. The vapor disperses through the tissue interstices within the treatment zone (transition zone). The injection of vapor last for approximatively 9 seconds and the number of injections depends on the prostate volume and length of the prostatic urethra.

The purpose of the present study is to compare between patient experience, symptom relief and functional improvement when using the Optilume BPH Catheter System (Optilume®, Urotronic Inc, Minneapolis, USA) and Rezum Water Vapor Therapy (Rezum System, Boston Scientific, Marlborough, MA).

B-Clinical experience

-Optilume® BPH Catheter System: The PINNACLE study was conducted by Kaplan et al. to evaluate the safety and efficacy of Optilume BPH when compared to a sham surgical procedure. The study was designed as a prospective, randomized, double-blinded, sham-controlled clinical trial. Eighteen participating centers in the United States and Canada recruited 148 patients over 50 years old with symptomatic BPH and a prostate size from 20 cc to 80 cc. Randomization assigned 100 patients to the Optilume BPH group and 48 patients to the sham procedure group. The primary endpoint was the comparison of the improvement in IPSS from baseline to 1 year in the Optilume BPH arm against 3 months in the sham arm. Other measurements included uroflowmetry, quality of life (QoL) and sexual function assessments. A blinded and independent clinical events committee prospectively collected data regarding adverse events (AE).

At one year, IPSS improved by 11.5 +/- 7.8 points in the Optilume BPH arm, which was significantly greater than the sham arm at 3 months (8.0 +/- 8.3). Additionally, QoL, sexual function, peak flow rate (Qmax) and post-void residual (PVR) significantly improved trough 1 year. Five serious adverse events probably related to the study device occurred including four hematuria and 1 urethral false passage. Other non-serious AEs included hematuria, urinary tract infection (UTI), dysuria, incontinence, bladder spasms, elevated PSA and urinary urgency. Ejaculatory dysfunction occurred in four patients in the Optilume arm and in 1 patient in the sham arm and no de novo erectile dysfunction was reported.

\- Rezum Water Vapor Therapy: In recent years, the technology has been evaluated in a prospective, multicenter, double-blinded randomized controlled study conducted by McVary et al. (Clinicaltrials.gov: NCT01912339). Fifteen participating sites in the United States recruited 197 patients with moderate-to-severe LUTS with a prostate size from 30 cc to 80 cc. In this trial, 136 patients were assigned to the water vapor thermal therapy arm and 61 patients to the sham/control procedure. The primary efficacy endpoint was the change in the International Prostate Symptom Score (IPSS) from baseline to 3 months. Additionally, clinical events committees reviewed the safety of the device.

At the 3 months, the water vapor thermal therapy showed an IPSS reduction of 50% whereas the reduction was only 20% in the control group (p\<0.0001). Moreover, other measurements such as Qmax, Qol (p\<0.0001) and BHPII (p=0.0003) significantly improved in the Rezum therapy group when compared to the control group. Three serious adverse events (AE) occurred in two patients. One patient had de novo extended urinary retention and the second patient had nausea and vomiting. Moderate to severe AEs resolved within 3 weeks.

A 4-year outcomes of this trial was reported. Improvement of LUTS remain durable throughout 4 years with a reduction of 47% of the IPSS, 43% of the quality of life (QoL), and 52% of the Benign Prostatic Hyperplasia Impact Index. In addition, the retreatment rate was 4.4% at 4 years with no disturbances of sexual function.

C- Clinical investigation design

1. Objectives: The primary objective of the present study is to evaluate and compare patient experience, symptom relief and functional improvement when using Optilume® BPH Catheter System and RezumTM Water Vapor Therapy within 100 patients through several timepoints. 2. Sample size: OptiZum is a prospective, single center (Centre hospitalier Universitaire de Montréal), randomized, blinded clinical trial. The investigators expect to recruit 100 participants with a block randomization methodology to either Optilume® BPH Catheter System or RezumTM Water Vapor Therapy (50 participants in each arm). 3. Study duration: Enrollment is expected to take 12 months. Each participant will be followed post-operatively through 1 year with 1 week, 1 month, 3 months, 6 months and 12 months follow-up visits. 4. Number of sites: 1 site (Centre Hospitalier de l'Université de Montréal) 5. Point of enrollment: Each patient will be assigned a study ID after signing the informed consent form.

* Investigators will be responsible for obtaining consent using the current study-specific, REB-approved consent documents prior to any baseline testing for eligibility that goes beyond standard care. * Participants will be consented in a manner understandable by the intended patient population and providing adequate time to address any questions or concerns. * Documentation of the consenting process and the signed/dated consent documents will be filed in the study Trial Master File.

An informed consent form must be signed by each patient prior to study enrollment. Informed consent will be obtained according to the Declaration of Helsinki ("Ethical Principles for Medical Research Involving Human Subjects", The World Medical Association Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013), requirements of the standard ISO 14155:2020 ("Clinical investigation of medical devices for human subjects-Good clinical practice"), and individual institution guidelines.

Re-consent will be required where changes are implemented, new information becomes available, or as required by regulations, and re-consent is needed. 6. Study visits and exams:

6.1. Study visits:

-Screening and baseline : Potential participants will undergo screening at the study center. Any study specific testing for eligibility determination that goes beyond standard care must be performed after REB approved study specific informed consent form is signed by the patients.

Baseline tests and questionnaires will be completed 3 months maximum prior to the procedure. * Preoperative instructions : Patients will be instructed to stop anticoagulants and aspirin 3-5 days prior to the procedure depending on the type of anticoagulation. * Anesthesia : Optilume BPH Catheter System and Rezum water vapor therapy will be performed under general, spinal or local anesthesia . * Follow-ups : Participants will have 5 follow-up visits after the procedure. Patients will be seen in person for evaluation after 1 week, 1 month, 3 months, 6 months and 12 months following the procedure. Uroflowmetry will be performed and questionnaires will be completed by participants (IPSS, IIEF, MSHQ-EjD, Quality of recovery, Satisfaction).

First follow-up visit will be performed 7 days +/- 5 days (1week follow-up visit). Second follow-up visit will be performed 28 days +/- 7 days (1 month follow-up visit). Third, fourth and fifth (3, 6 and 12 months follow-up visit) will be performed 90 days +/- 10 days , 180 days +/- 30 days and 360 days +/- 30 days).

6.2. Study assessments :

Several tests and questionnaires will be completed during this trial: * Uroflowmetry: participants will undergo measurement of urinary flow rate (Qmax), urinary mean flow rate (Qmean), total voided volume (TVV), and post-void residual volume (PVR). For an uroflowmetry test to be valid, the voided volume must be ≥ 125 mL. If the total voided volume is less than 125mL, the voided volume must be equal to or greater than 50% of the bladder capacity (defined as voided volume + PVR). The test can be repeated if necessary. * International Prostate Symptom Score (IPSS): IPSS is a validated measure of urinary symptoms due to BPH. The questionnaire will be completed at baseline and at follow-up visits. * International Index of Erectile Function (IIEF) (10): IIEF is a validated questionnaire used to assess erectile dysfunction. The questionnaire will be completed at baseline and at follow-ups visits. * Male Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD) : MSHQ-EjD is a validated questionnaire used to assess ejaculatory function. The questionnaire will be completed at baseline and at follow-ups visits. * Transrectal ultrasound (TRUS): TRUS is performed to measure patient's prostate size at baseline.

IPSS, QoL, IIEF, MSHQ-EjD, uroflowmetry and TRUS are standard of care tests and questionnaires. * Pain score: A visual Analog Scale (VAS) will be used to assess pain before and after the procedure. * Anxiety Symptoms Questionnaire (ASQ) (12): A questionnaire will be used to assess the intensity and frequency of symptoms related to anxiety. * Satisfaction: A questionnaire will be used to assess patient recovery at 1 month.

D- Risk/benefit analysis

\- Optilume® BPH Catheter System: After treatment with the Optilume BPH Catheter System, the probable benefit is the relief of LUTS maintained at 1 year and the improvement of QoL, as showed by the PINNACLE study.

The FDA summary of safety and effectiveness data (SSED) of the Optilume BPH Catheter System reported possible risks related to the use of the device. According to the report, potential AEs are similar to standard cystoscopic procedures and mechanical dilation. Potential AEs includes and are not limited to the following: * Fever * Bleeding * Pain * Urinary tract infection * False route of the urethra * Dysuria * Difficult urination * Frequency/urgency/irritative urinary symptoms * Urinary retention and related symptoms * Blood in urine (hematuria) * Urinary incontinence * Urethrorrhagia * Blood in semen (hematospermia) * Ejaculatory dysfunction * Bladder