Transurethral Thermodilatation vs. Prostatic Urethral Lift for Moderate-to-Severe BPH

Overview

This clinical trial aims to determine whether Prolieve® (microwave with balloon dilation) is as effective as UroLift® (prostate implants) for treating moderate-to-severe lower urinary tract symptoms in men aged 50-80 with enlarged prostates (BPH) who have failed oral medications. The main questions are: 1. Is Prolieve non-inferior to UroLift in improving IPSS symptom scores at 3 months? 2. Does Prolieve cause less pain and avoid the need for injected anaesthesia? Researchers will compare Prolieve (LA urethral gel only, no injections) against UroLift (LA urethral gel with or without local anaesthetic injection) to see if Prolieve offers similar relief with better tolerability. Participants will stop their BPH medications for 2-4 weeks, undergo one of the two same-day office procedures, and attend follow-ups at 1, 3, 6, and 12 months for symptom scores, flow tests, and bladder scans.

Clinical Context and Unmet Need Benign prostatic hyperplasia (BPH) is a common consequence of male ageing. In Hong Kong, over half of men in their 60s experience lower urinary tract symptoms (LUTS) that can significantly impair quality of life-disrupting sleep, limiting social activities, and causing bothersome urgency, frequency, and weak stream. As the local population continues to age, the absolute number of men requiring effective, low-risk procedural relief is set to rise substantially. While traditional surgical options such as transurethral resection of the prostate (TURP) or laser enucleation (HoLEP) offer durable, highly effective outcomes, they mandate general or spinal anaesthesia, carry inherent risks of bleeding and transfusion, and frequently cause permanent retrograde ejaculation. These barriers exclude a significant portion of older men-particularly those on anticoagulants or with significant cardiovascular or respiratory comorbidities-from benefiting from procedural intervention. This trial directly compares two contemporary minimally invasive surgical therapies (MISTs) that operate on fundamentally different biophysical principles: UroLift® (Prostatic Urethral Lift - PUL) acts as a purely mechanical retraction device. Under cystoscopic visualisation, the operator deploys small, permanent nitinol (nickel-titanium) anchors to physically pull the obstructing prostatic lobes apart, widening the urethral channel. It does not ablate, resect, or thermally injure prostate tissue. Its effects are immediate and structural, relying on sustained mechanical traction. Prolieve® (Transurethral Thermodilatation - TUTD) combines two synchronous therapeutic actions: (1) a 46 French (15.3 mm) balloon that mechanically dilates the prostatic urethra, and (2) simultaneous low-power microwave energy (up to 50 W) delivered via an intraurethral antenna, which gently heats the periurethral prostatic tissue to 41-46°C. This thermal dose induces controlled coagulation necrosis and protein denaturation. In the 4 to 12 weeks following the treatment, stromal remodelling results in a patent lumen. The balloon also serves to compress and flatten the obstructing tissue during heating, ensuring uniform energy delivery. Compared to Urolift, a critical practical advantage of the Prolieve system is that its entire procedure can be performed using only topical intraurethral lidocaine gel-no periprostatic nerve blocks, no intravenous sedation, and no operating theatre are required. By contrast, while UroLift is often described as office-based, contemporary real-world practice employs periprostatic local anaesthetic injections (or, in some centres, monitored anaesthesia care or even general anaesthesia) to manage patient discomfort during capsular anchor deployment. This trial is therefore designed not only to test non-inferiority in symptom relief, but also to provide rigorous comparative data on procedural tolerability-specifically, whether avoiding needles and sedation compromises efficacy, or conversely, whether Prolieve offers a more patient-centred, accessible treatment pathway with equivalent clinical outcomes. Trial Operational Framework: This is a prospective, open-label, parallel-group, 1:1 randomised controlled non-inferiority trial, conducted at the Department of Surgery (Division of Urology) at Queen Mary Hospital / The University of Hong Kong. Following a comprehensive screening visit that confirms eligibility (including transrectal ultrasound for prostate volume, uroflowmetry, and post-void residual measurement), participants undergo a mandatory medication washout period-alpha-blockers are stopped for at least 2 weeks, and 5-alpha-reductase inhibitors for at least 4 weeks-to eliminate any confounding drug effects. Randomisation occurs centrally via a validated web-based interactive system immediately prior to the scheduled procedure. Allocation is stratified by two pre-specified factors: prostate volume (\<40 g versus ≥40 g), because the Prolieve pivotal study demonstrated markedly higher responder rates in smaller glands; and baseline IPSS severity (moderate, 13-19, versus severe, ≥20), recognising that minimal important differences may vary with baseline burden. Block randomisation with randomly varied block sizes ensures allocation concealment, and the allocation sequence is held independently of the clinical team. Participant Journey and Procedural Standardisation: On the treatment day, participants in the Prolieve arm receive 10-15 mL of 2% lidocaine gel intraurethrally, left in situ for 10-15 minutes. The Prolieve treatment catheter is then inserted, the anchoring balloon inflated in the bladder, and the 46 Fr compression balloon inflated to 14-15 PSI. Microwave energy is applied for a fixed 45-minute treatment cycle, with a rectal temperature probe providing continuous safety feedback. Immediately after treatment, the balloon is deflated and the catheter withdrawn; the bladder is filled with 200 mL sterile water to provoke an immediate trial of voiding. Participants are observed for 1-2 hours and discharged if they can void a sufficient volume with an acceptable residual. Participants in the UroLift arm undergo cystoscopic deployment of 4-6 permanent implants to retract the lateral lobes, per the manufacturer's standard technique. Anaesthetic modality is not mandated but is captured prospectively in the electronic case report form; it may be topical gel alone or topical gel supplemented with a periprostatic nerve block, reflecting real-world variation. No routine post-procedural catheter is placed unless the patient fails the immediate voiding trial. To ensure fair comparison, both arms receive identical post-procedural supportive care: a short course of oral NSAIDs for discomfort (up to 5 days, unless contraindicated) and a standardised, time-limited course of tamsulosin 0.4 mg once daily from the day of procedure, tapered and discontinued at the 1-month visit. This standardisation eliminates post-procedural medication as a source of differential bias. From month 1 onward, BPH medical therapy is not routinely prescribed unless pre-defined rescue criteria are met (persistent severe symptoms with bother), ensuring that the 3-, 6-, and 12-month outcomes reflect the intrinsic durability of the device effect rather than pharmacological rescue. Non-Inferiority Margin and Sample Size: The non-inferiority margin is set at 3 absolute IPSS points, derived from the classic distribution-based minimal important difference (MID) of approximately 3.1 points. Importantly, more recent anchor-based estimates suggest the MID may be as large as 5.2-5.3 points; therefore, the chosen 3-point margin is conservative and stringent, requiring Prolieve to fall well within the modern anchor-based clinically meaningful threshold. The primary analysis uses an ANCOVA model adjusted for baseline IPSS and the two stratification factors, with the between-arm difference in 3-month IPSS change calculated as Prolieve minus UroLift. Non-inferiority is declared only if the upper bound of the one-sided 97.5% confidence interval is strictly less than +3.0 points. As per ICH E9 guidelines, non-inferiority must be demonstrated consistently in both the intention-to-treat (ITT) and per-protocol (PP) populations for the conclusion to be robust. The sample size of 75 participants per arm (150 total) provides 80% power under the assumptions of a pooled standard deviation of 6 points and an expected mean improvement of -9 points in both arms, with a 15% allowance for dropout and protocol deviations. A formal interim analysis, conducted by an independent Data Safety Monitoring Board (DSMB) after 50% of participants have completed the 3-month primary endpoint, will focus on safety surveillance and sample size re-estimation based on observed variance. Early stopping for efficacy is not planned, consistent with the conservative principles governing non-inferiority designs. The DSMB will, however, recommend early termination if the rate of serious adverse events (Clavien-Dindo Grade ≥3) in either arm exceeds 10%, or if a statistically significant and clinically meaningful imbalance in serious harms is detected. Blinding and Bias Mitigation: While it is not feasible to blind participants or treating operators to the distinct procedural experiences (one involves cystoscopic implant deployment, the other a 45-minute microwave session with a balloon catheter), stringent measures are in place to minimise assessment and analytical bias. All outcome assessors conducting IPSS interviews, uroflowmetry, and bladder ultrasound at follow-up visits are kept unaware of the treatment allocation. The IPSS questionnaire is self-administered by participants without interviewer interference, further reducing interviewer-driven bias. Finally, the primary statistician remains blinded to group labels until the database is locked and the analysis plan is fully executed. Safety Monitoring and Ethical Oversight: The study is conducted under the ethical oversight of the Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster (HKU/HA HKW IRB), and all participants provide written informed consent in either English or Traditional Chinese. Personal data are handled in strict compliance with the Hong Kong Personal Data (Privacy) Ordinance (Cap. 486), captured and stored on the secure, encrypted REDCap platform hosted on HKU servers, with access rigorously restricted to delegated study personnel. Data are retained for 10 years following study conclusion, after which they are securely destroyed per Hospital Authority standards. Broader Implications and Health Economic Exploration: If this trial establishes non-inferiority of Prolieve relative to UroLift, it will provide the first high-level, head-to-head randomised evidence supporting a truly needle-free, sedation-free, and injection-free office MIST as a viable alternative to implant-based mechanical retraction. Such evidence could expand procedural access to patients with prohibitive anaesthetic risk, or those with a strong preference to avoid periprostatic injections. Additionally, the trial incorporates an exploratory health economic analysis-calculating the direct procedural cost plus downstream resource utilisation (general practitioner visits, retreatments, hospitalisations) per responder (IPSS reduction ≥5 points at 3 months)-to inform local healthcare policymakers and ensure that any clinical advantage is interpreted alongside its financial sustainability within the Hong Kong public healthcare system. The trial is investigator-initiated; Prolieve procedure kits are provided as an in-kind contribution by Medifocus Inc., but the funding body has no role in study design, data collection, analysis, interpretation, or publication decisions, ensuring full academic independence.