Zenflow Spring System for Benign Prostatic Hyperplasia - 24 Month Outcomes of the ZEST Pilot Studies - Beyond the Abstract
The emergence of minimally invasive surgical therapies (MISTs) over the past decade promised a middle ground — but even among established MISTs such as prostatic urethral lift (PUL) and water vapor thermal therapy (WVTT), procedures require a rigid cystoscope, moderate anesthesia, and involve some degree of irreversible tissue alteration. Importantly, none of these therapies can be reversed or removed.
The Zenflow Spring System was developed to address these gaps. It represents a new conceptual category — what some have called a First-line Interventional Therapy (FIT) — delivered entirely through a flexible cystoscope, often under light sedation or local anesthesia, and crucially, retrievable at any time. Our goal with the ZEST studies was to rigorously evaluate whether this device could deliver clinically meaningful, durable outcomes in a real-world, geographically diverse patient population.
A key methodological decision in this work was the pooling of data from three contemporaneous but separately conducted pilot studies, carried out across four countries (Mexico, Australia, New Zealand, and Canada) between 2018 and 2021. While each study enrolled modest numbers individually, their identical designs, enrollment criteria, and follow-up schedules made the combination both scientifically appropriate and statistically sound.
Rather than simply merging all 72 subjects into a single analysis — which would have allowed the largest study to disproportionately influence results — we employed a mixed model for repeated measures (MMRM) framework with study included as a fixed effect. This design produces marginal means weighted equally across studies, not by subject count. The result is a more conservative and methodologically rigorous estimate of treatment effect. Readers should appreciate that the outcomes reported are not inflated by a single large-enrollment site; they reflect the consistency of the device's performance across diverse clinical settings and patient populations. One of the more striking findings was the speed of improvement. At the 2-week visit — the earliest post-procedure follow-up — patients were already demonstrating clinically meaningful reductions in their International Prostate Symptom Score (IPSS). This is consistent with the mechanism of the device: the nitinol spring mechanically dilates the prostatic urethra upon deployment, providing lumenal opening without ablating or altering surrounding tissue.
There is no obligate inflammatory phase, no tissue sloughing, and no requirement for a catheter upon discharge in the vast majority of patients. By 3 months — the primary endpoint — the mean IPSS improvement was -10.71 points (49%), the IPSS-Quality of Life improvement was -2.09 points (47%), and peak urinary flow rate (Qmax) improved by 2.86 mL/s (27%). These magnitudes are essentially comparable to published pivotal data for PUL (LIFT study: -11.1 points IPSS, 50%) and WVTT (Rezūm II study: -11.2 points IPSS, 51%) — a notable observation given that the Spring System is less invasive than either comparator by most practical measures. Critically, these improvements held through 24 months. The 48% IPSS improvement, 55% QoL improvement, and 32% Qmax improvement at 2 years suggest that the mechanical dilation achieved by the spring implant is stable over time. This durability was not guaranteed — urethral stents from earlier eras were plagued by encrustation, migration, and loss of effect — and represents an important advance in device design.A concern frequently voiced by patients considering BPH treatment is the preservation of sexual function. Both erectile and ejaculatory dysfunction are recognized complications of surgical therapies, and even some MISTs carry non-trivial rates of ejaculatory disturbance. In the ZEST pooled analysis, there was no evidence of de novo erectile or ejaculatory dysfunction as assessed by the Sexual Health Inventory for Men (SHIM) and the Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ) at any time point through 24 months. No procedure-related or device-related adverse events involving sexual function were reported. For many patients — particularly younger men or those for whom preserving sexual function is paramount — this profile will be clinically important when counseling about treatment options.Perhaps the most conceptually important feature of the Zenflow Spring System is that it is removable. In this study, 12 of 72 subjects (17%) had their device explanted during the 24-month follow-up period.
Of those removed in the first year (n=8), reasons were evenly split between adverse events and lack of efficacy. All second-year removals (n=4) were for lack of efficacy — though it is notable that all four patients in this group had met at least one validated responder threshold at their prior visit, suggesting these decisions reflected patient preference and shared decision-making rather than frank treatment failure.
Critically, no removal procedure resulted in an adverse event. Patients undergoing explant who chose to pursue further therapy immediately transitioned to TURP, laser vaporization, or bladder neck incision without complication, and none required an indwelling catheter upon discharge after explant. This has profound clinical implications: the Spring System can serve as a "bridge" or "trial" therapy. A patient uncertain about committing to an irreversible MIST, or a patient who is a poor surgical candidate at the time of presentation, can experience the benefit of the device without permanently foreclosing other options. The ZEST studies were conducted across diverse healthcare environments, including operating rooms, ambulatory surgery centers, and hospital endoscopy suites. Anesthesia ranged from general to spinal to conscious sedation to local/topical alone.
Despite this heterogeneity, procedural outcomes were consistent: 100% implant success rate, minimal procedural pain (mean VAS change from baseline of 0.9 at discharge, returning to pre-implant levels by 1 month), and same-day discharge in the majority of subjects. This adaptability in a procedural setting is a practical advantage that will resonate with busy clinicians working in varied institutional contexts.
We are transparent about the limitations of this work. Without a randomized control group, causality cannot be established with the same rigor as a pivotal randomized controlled trial, and comparisons to other MIST therapies remain contextual rather than definitive. The pilot study design, while sufficient to demonstrate proof-of-concept and support regulatory pathways, means the sample size is modest, and longer-term data beyond 24 months remain forthcoming. Furthermore, the COVID-19 pandemic necessitated relaxation of uroflow enrollment criteria in certain study periods, which introduces some heterogeneity in baseline characteristics.
The ZEST data serve their intended purpose: to establish that the Zenflow Spring System is safe, feasible, and produces clinically meaningful improvements across a geographically and institutionally diverse patient population. The ZEST pilot studies demonstrate that the Zenflow Spring System offers something genuinely new in the BPH treatment landscape: a reversible, tissue-preserving, flexible cystoscope-delivered implant that achieves symptomatic and functional improvements comparable to established MISTs, while preserving sexual function and allowing uncomplicated removal if needed. The durability of benefit through 24 months, combined with the safety record and procedural flexibility observed in this diverse multinational cohort, makes this a compelling addition to the armamentarium available to urologists managing men with lower urinary tract symptoms due to BPH.
For patients who are seeking meaningful relief from BPH symptoms but are hesitant to commit to tissue-altering or irreversible procedures, the Spring System offers a new option that does not require them to choose between efficacy and optionality.
Written by: Dean Elterman, MD, MSc, FRCSC, Lang Family Endowed Chair in Urologic Innovation, Associate Professor, Department of Surgery, University of Toronto, Urologic Surgeon, Division of Urology, University Health Network, Fellowship Director, Functional Urology, Toronto Western Hospital, Clinician Investigator, Krembil Research Institute, University Health Network, Toronto, Canada
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