Optilume drug-coated balloon for anterior urethral stricture: 2-year results of the ROBUST III trial.

Objective: The aim of this study is to report the updated 2-year results of the intervention arm of the ROBUST III randomized trial evaluating the safety and efficacy of the Optilume drug-coated balloon (DCB) versus standard endoscopic management of recurrent male anterior urethral stricture. Materials and Methods: Eligible patients included men with recurrent anterior urethral stricture ≤3 cm in length and ≤12Fr in diameter, International Prostate Symptom Score (IPSS) ≥11 and peak flow rate (Qmax) <15 mL/s. Patients were randomized to treatment with the Optilume DCB or standard-of-care endoscopic management. Primary efficacy endpoints measured at 2 years included freedom from re-intervention and changes in IPSS, Qmax and post-void residual (PVR). Secondary endpoint was impact on sexual function using the International Index of Erectile Function (IIEF). Primary safety endpoint was freedom from serious procedure- or device-related adverse events (AEs). Results: A total of 127 patients enrolled at 22 sites in the United States and Canada (48 randomized to standard-of-care dilation and 79 to DCB dilation). Seventy-five patients in the DCB arm entered the open-label phase after 6 months. Participants averaged 3.2 prior endoscopic interventions (range 2-10); most (89.9%) had bulbar strictures with an average stricture length of 1.63 cm (SD 0.76). Significant improvements in IPSS, average Qmax and PVR were maintained at 2 years. Freedom from repeat intervention was significantly higher in the Optilume DCB arm at 2 years versus the Control arm at 1 year (77.8% vs. 23.6%, p < 0.001). During the follow-up period, there were 15 treatment failures and two non-study-related deaths. Treatment-related AEs were rare and generally self-limited (haematuria, dysuria and urinary tract infection). Conclusion: The Optilume DCB shows sustained improvement in both objective and subjective voiding parameters at 2-year follow-up. Optilume appears to provide a safe and effective endoscopic treatment alternative for short recurrent anterior urethral strictures among men who wish to avoid or delay formal urethroplasty.

Aquablation versus TURP: 5-year outcomes of the WATER randomized clinical trial for prostate volumes 50-80 mL.

INTRODUCTION: To report the 5-year efficacy and safety of Aquablation compared with transurethral resection of the prostate for the management of lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with prostate volumes 50-80 mL. MATERIALS AND METHODS: In a large double-blinded, multicenter, and prospective randomized controlled trial, 96 randomized men with 50-80 mL prostates who underwent Aquablation or transurethral prostate resection were prospectively identified for subgroup analysis. Follow up was performed for up to 5 years. The primary efficacy endpoint was the reduction in International Prostate Symptom Score (IPSS) at 6 months. The primary safety endpoint was the occurrence of Clavien-Dindo (CD) postoperative complications grade 1 persistent and grade 2 or higher at 3 months. RESULTS: Both groups had comparable baseline characteristics. Reduction in IPSS score was significantly higher in the Aquablation group across 5 years of follow up (-14.1 vs. -10.8, p = 0.02). The Aquablation group achieved a significantly lower rate of CD1P and CD2 or higher events at 3 months follow up (risk difference of -23.1%). Among recorded adverse events, de novo postoperative ejaculatory dysfunction was notably lower in Aquablation (risk difference of -21.9%), while the risk of bleeding remained similar after 6 months. The surgical and medical retreatment rate at 6 months was also lower in Aquablation (risk difference of -14.4%). CONCLUSIONS: In the 50-80 mL prostate volume subgroup, Aquablation yields superior long-term symptom relief and lower complication rates than standard transurethral resection, with notably lower rates of ejaculatory dysfunction. This further supports the adoption of Aquablation for men with medium-sized prostates.

Aquablation in Patients on Antithrombotics: Assessment of Safety, Postoperative Bleeding Rates and Clinical Outcomes.

OBJECTIVE: To analyze the impact of perioperative antithrombotic use on the bleeding outcomes following Aquablation. METHODS: One hundred sixteen men with who underwent Aquablation as part of the WATER prospective trial (NCT02505919) were assigned to 2 groups based on perioperative antithrombotic status. Antithrombotic cessation and restart timing were based on the surgeon's discretion. Methods of achieving intraoperative hemostasis consisted of no-cautery balloon tamponade or cautery. Primary endpoints included immediate postoperative hematuria rates and changes in hemoglobin. Secondary endpoints included 90-day bleeding complications and nonbleeding postoperative adverse events. RESULTS: Forty-one men took antithrombotic medications in the perioperative period while 75 men had no antithrombotic medication. Preoperative hemoglobin levels were comparable between both groups. Postoperative hemoglobin change from baseline (drop of 1.8 ± 1.5 g/dL among the antithrombotic group vs 1.8 ± 1.7 g/dL among the antithrombotic-naïve group) did not differ between both groups (P = .896). In total, 4 (9.8%) men in the antithrombotic group and 4 (5.3%) patients in the antithrombotic-naïve group experienced a Clavien-Dindo grade 1 complication (P = .451) in the 3-month postoperative period. Eight (19.5%) patients in the antithrombotic group and 11 (14.7%) patients in the antithrombotic-naïve group experienced a Clavien-Dindo grade 2 complication (P = .601), none of which is associated with bleeding in both groups. No men in either group demonstrated de novo erectile dysfunction. One patient (2.4%) in the antithrombotic group and none in the antithrombotic-naïve group required blood products (P = .353). CONCLUSION: Aquablation demonstrates comparable postoperative bleeding outcomes and other adverse effects for men with benign prostatic hypertrophy who are on antithrombotic therapy.

US patterns of care for urodynamic evaluation for BPH.

INTRODUCTION: Practice patterns around the use of urodynamic evaluation (UDS) for benign prostatic hyperplasia (BPH) surgery are largely undefined. As such, we investigated factors associated with the use of UDS for BPH. METHODS: We used American Board of Urology case log data from 2008 to 2020, to compare patient- and surgeon-sided factors associated with UDS utilization and BPH surgeries. We performed logistic regression models to identify factors independently associated with UDS usage for BPH. RESULTS: Among urologists performing UDS, the majority (80%) self-identified as general urologists and practiced in a private practice group (69%). Compared with urologists who performed no UDS, urologists who performed any UDS for BPH were more likely to be from the Mid-Atlantic (20.3% vs. 10.6%, p < 0.01) and practice in regions with populations of >1 000 000 (34.7% vs. 28.5%, p < 0.01). Overall, UDS utilization declined over time (odds ratio [OR]: 0.95 year-to-year, 95% confidence interval [CI]: 0.91-0.99). In adjusted analyses, the odds of performing UDS was higher among male (OR: 2.19, 95% CI: 1.17-4.09), older (OR: 1.05, 95% CI: 1.03-1.06), and female pelvic medicine and reconstructive surgery subspecialty (OR: 3.23, 95% CI: 2.01-5.2) urologists. Additionally, performing UDS for BPH was associated with higher BPH surgical case volume (OR: 1.004, 95% CI: 1.001-1.008). CONCLUSION: There is a significant practice variation in use of UDS for BPH. Although overall BPH surgeries are increasing, urologists are increasingly less likely to perform UDS for BPH. Specifically, urologists who perform UDS have significantly higher BPH case volume than those who do not perform UDS, suggesting that UDS usage may not factor into BPH surgery decision-making.

Surgical treatment for BPH refractory to medication: robotic water jet ablation vs. TURP functional outcomes from two FDA clinical trials.

INTRODUCTION: A common indication for benign prostate hyperplasia (BPH) therapies is failure to improve with medical therapy. However, pivotal Federal Drug Administration (FDA) registered randomized clinical trials (RCTs) for minimally invasive surgical therapies (MISTs) are designed to be compared to either sham or placebo while off medical therapy at baseline, and as an alternative to medical therapy. There are few if any RCTs reporting the MISTS efficacy in patients with true medical therapy failure. We report on the efficacy of robotic water jet ablation therapy (RWT) and TURP in patients who have failed to improve with medical therapy. MATERIALS AND METHODS: Data was obtained from the WATER and WATER II clinical trials. Both clinical trials did not implement a drug washout period. Only patients with reported BPH medical therapy such as alpha-blockers (AB) and 5-alpha-reductase inhibitors (5-ARIs) usage were included. Functional outcomes as post-void residual volume (PVR), peak urinary flow rate (Qmax), internal prostate symptom score (IPSS), and quality of life score (QoL) were analyzed. RESULTS: AB and/or 5-ARIs usage at baseline were reported in 146 and 39 patients who underwent RWT (prostate sizes up to 150 cc) and transurethral resection of the prostate (TURP, prostate sizes up to 80 cc) respectively. Baseline median (IQR) IPSS, QoL, Qmax and PVR were 24 (18,28), 5 (4,5), 8.9 (6.4,11.5), and 95 (36,172), respectively. Functional outcomes did not statistically differ between Aquablation and TURP at baseline and at 36-month. In cohort of true medical failure, both RWT and TURP demonstrated group statistical improvements in PVR, Qmax, IPSS, and QoL at 36-month compared to baseline. CONCLUSIONS: RWT and TURP are effective BPH therapy in patients who truly failed medical therapy, and RWT demonstrated this in a much broader prostate size range.

Development of a North American coordinated registry network for surgical treatment of benign prostatic hyperplasia.

PURPOSE: To create a prospective, multicenter coordinated registry network (CRN) of robust "real world" data for benign prostatic hyperplasia (BPH) that links surgical practices to objective and subjective outcomes of patients who undergo surgery for the improvement in lower urinary tract symptoms (LUTS) secondary to BPH. METHODS: We gathered a group of BPH experts from various institutions to identify the minimum core data elements needed to assess BPH procedures. To achieve consensus on the data elements, we used a Delphi method adaptation, in which a series of surveys were answered by the expert panel individually and anonymously. Survey results were collected and analyzed. Questions for the following round were based on response analysis from the prior survey. This process was repeated until consensus was achieved. RESULTS: Participation rates in the first and second rounds were 100% and 90%, respectively. The expert panel reached consensus on 148 data elements out of the 182 proposed, capturing patient medical and surgical history, procedure, discharge, short- and long-term follow-up, device factors, surgery, and surgeon factors. CONCLUSION: We have successfully developed a set of core data elements to support the study of BPH surgical therapies by gathering an expert panel on BPH and using the Delphi method. These data elements influence provider decisions about treatment and include important outcomes related to efficacy and safety.

Five-year outcomes for Aquablation therapy compared to TURP: results from a double-blind, randomized trial in men with LUTS due to BPH.

INTRODUCTION: To determine if Aquablation therapy can maintain long term effectiveness in treating men with moderate to severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) with a baseline prostate volume between 30 and 80 mL at 5 years compared to TURP. MATERIALS AND METHODS: In a double-blinded, multicenter prospective randomized controlled trial, 181 patients with moderate to severe LUTS secondary to BPH underwent TURP or Aquablation. The primary efficacy endpoint was reduction in International Prostate Symptom Score (IPSS) at 6 months. The primary safety endpoint was the occurrence of Clavien-Dindo persistent Grade 1 or Grade 2 or higher operative complications at 3 months. The assessments included IPSS, Male Sexual Health Questionnaire (MSHQ), International Index of Erectile Function (IIEF) and uroflow (Qmax). The patients were followed for 5 years. RESULTS: The primary safety endpoint was successfully achieved at 3 months where the Aquablation group had a lower event rate than TURP (26% vs. 42%, p = .0149 for superiority). Procedure-related ejaculatory dysfunction was lower for Aquablation (7% vs. 25%, p = .0004). The primary efficacy endpoint was successfully achieved at 6 months, where the mean IPSS decreased from baseline by 16.9 points for Aquablation and 15.1 points for TURP; the mean difference in change score at 6 months was 1.8 points larger for Aquablation (p < .0001 for non-inferiority, p = .1346 for superiority). At 5 years, IPSS scores improved by 15.1 points in the Aquablation group and 13.2 points in TURP (p = .2764). However, for men with larger prostates (≥ 50 mL), IPSS reduction was 3.5 points greater across all follow up visits in the Aquablation group compared to the TURP group (p = .0123). Improvement in peak urinary flow rate was 125% and 89% compared to baseline for Aquablation and TURP, respectively. The risk of patients needing a secondary BPH therapy, defined as needing BPH medication or surgical intervention, up to 5 years due to recurrent LUTS was 51% less in the Aquablation arm compared to the TURP arm. CONCLUSIONS: The improvement in net health outcomes from Aquablation therapy outweigh those offered by a TURP when considering the efficacy benefit along with the lower risk of needing a secondary BPH therapy and avoiding retrograde ejaculation. Following Aquablation therapy, symptom reduction and uroflow improvement at 5 years have shown to be durable and consistent across all years of follow up compared to TURP. Larger prostates (≥ 50 mL) demonstrated a larger safety and efficacy benefit for Aquablation over TURP.

One-Year Results for the ROBUST III Randomized Controlled Trial Evaluating the Optilume® Drug-Coated Balloon for Anterior Urethral Strictures.

PURPOSE: The Optilume® drug-coated balloon (DCB) is a urethral dilation balloon with a paclitaxel coating that combines mechanical dilation for immediate symptomatic relief with local drug delivery to maintain urethral patency. The ROBUST III study is a randomized, single-blind trial evaluating the safety and efficacy of the Optilume DCB against endoscopic management of recurrent anterior urethral strictures. MATERIALS AND METHODS: Eligible patients were adult males with anterior strictures ≤12Fr in diameter and ≤3 cm in length, at least 2 prior endoscopic treatments, International Prostate Symptom Score ≥11 and maximum flow rate <15 ml per second. A total of 127 subjects were enrolled at 22 sites. The primary study end point was anatomical success (≥14Fr by cystoscopy or calibration) at 6 months. Key secondary end points included freedom from repeat treatment, International Prostatic Symptom Score and peak flow rate. The primary safety end point included freedom from serious device- or procedure-related complications. RESULTS: Baseline characteristics were similar between groups, with subjects having an average of 3.6 prior treatments and average length of 1.7 cm. Anatomical success for Optilume DCB was significantly higher than control at 6 months (75% vs 27%, p <0.001). Freedom from repeat intervention was significantly higher in the Optilume DCB arm. Immediate symptom and urinary flow rate improvement was significant in both groups, with the benefit being more durable in the Optilume DCB group. The most frequent adverse events included urinary tract infection, post-procedural hematuria and dysuria. CONCLUSIONS: The results of this randomized controlled trial support that Optilume is safe and superior to standard direct vision internal urethrotomy/dilation for the treatment of recurrent anterior urethral strictures <3 cm in length. The Optilume DCB may serve as an important alternative for men who have had an unsuccessful direct vision internal urethrotomy/dilation but want to avoid or delay urethroplasty.

Safety and efficacy of TURP vs. laser prostatectomy for the treatment of benign prostatic hyperplasia in multi-morbid and elderly individuals aged ≥ 75.

PURPOSE: To compare the safety and durability of transurethral resection of the prostate (TURP) and Laser prostatectomy (LP) among multi-morbid and elderly patients. METHODS: Using data retrieved from the New York State Department of Health Statewide Planning and Research Cooperative System and the California Office of Statewide Health Planning and Development, we selected cohorts of 1) multi-morbid (Charlson comorbidity index ≥ 3) and 2) elderly (aged ≥ 75) patients with benign prostatic hyperplasia who underwent laser coagulation, vaporization, enucleation, or TURP between January 2005 and December 2016. We assessed the post-operative incidence of hospital readmission and ER visit at 30 days and 90 days, complications at 90 days, and reoperation and the development of urethral stricture at 6 months or longer. RESULTS: We found 12,815 and 29,806 patients in the multi-morbid and elderly cohort, respectively. Compared to LP, TURP was associated with lower odds of 90-day hospital readmission and ER visit in the multi-morbid cohort (OR 0.92, 95% CI 0.85-1.00) and higher odds in the elderly cohort (OR 1.07, 95% CI 1.01-1.14). The multi-morbid cohort showed lower odds of urinary tract infections (Ref: LP, OR 0.83, 95% CI 0.73-0.93). The elderly cohort showed higher odds of experiencing hematuria (OR 1.28, 95% CI 1.03-1.59) post TURP. TURP was associated with a 19% (95% CI 0.66-1.00) and 20% (95% CI 0.71-0.91) reduced hazard of reoperation at 6 months or longer for multi-morbid and elderly cohorts, respectively. CONCLUSION: Compared to LP, TURP was associated with higher complication rates for the multi-morbid and elderly cohorts overall but a lower hazard of reoperation, supporting its durability.

How I Handle Retreatment of LUTS Following a Failed MIST.

PURPOSE OF REVIEW: The goal of this paper is to review retreatment management after failed minimally invasive treatment (MIST) of various technologies. RECENT FINDINGS: A failed MIST can be defined by the return, persistence, or worsening of LUTS, as documented by symptom scores. Persistence, development, or recurrence of comorbidities such as recurrent urinary tract infection (UTI), retention, stones, hematuria, and incontinence can also signal a failed MIST. The common etiology for MIST failure is the preoperative consequence of long-term bladder outlet obstruction (BOO) on the bladder function. Close monitoring of therapies with antimuscarinics or beta-agonists can be empirically utilized if post-void bladder residual (PVR) is low. If there is a high PVR, urodynamic studies and cystoscopy can be used to determine overactive bladder (OAB), BOO, or necrosis. Depending on the timing of the observed BOO/OAB, subsequent retreatments involving transurethral debridement, medical and behavioral therapies, or repeat surgical debulking can be employed.

An evaluation of the federal adverse events reporting system data on adverse effects of 5-alpha reductase inhibitors.

OBJECTIVE: To investigate the sexual, physical, and mental adverse effects associated with exposure to 5-alpha reductase inhibitors (5ARIs). METHODS: FAERS data containing finasteride and dutasteride reports were analyzed from January 2000 to April 2019. Reports identified one or more adverse effects, along with all concurrent medications. Cases of monotherapy of finasteride or dutasteride were identified. We conducted a chi-square test of independence to assess the relationship between the three drug groups and adverse event (AE) occurrence across 19 sexual, physical, and mental AE categories. The frequency procedure in SAS was utilized to summarize rates of AEs between various dosages of each drug. RESULTS: A total of 16,014 case reports were obtained. After excluding females, 7436 case reports of 5ARI monotherapy were identified: 2628 of dutasteride 0.5 mg, 3266 of finasteride 1 mg, and 744 of finasteride 5 mg. Differences in rates of AEs occurrence were statistically significant across all 19 variables (p < 0.001) with a significantly higher proportion of AEs attributed to finasteride 1 mg, with gynecomastia being the only exception. Case report submissions rose dramatically following FDA-mandated finasteride label change. CONCLUSIONS: Analysis of FAERS data suggests AEs of 5ARIs are dose-independent with greater likelihood of occurrence in younger patients, particularly in sexual and mental domains. The causality and the rate of AEs are not certain based on the FAERS data and future prospective studies are necessary to determine the true rates.

A Systematic Review on the Timing of Surgical Intervention for Benign Prostatic Enlargement (BPE).

PURPOSE OF REVIEW: Surgical intervention for benign prostatic enlargement (BPE) is typically reserved for those who fail medical therapy (i.e., α-blocker or 5-α reductase inhibitor treatment). We conducted a systematic review to determine whether timing of surgical intervention for BPE affects patient outcomes. RECENT FINDINGS: The studies we reviewed suggested that patients who undergo surgical intervention for BPE after failing medical therapy may have worse outcomes. Increased age, worsened bladder function, and worse overall health may contribute to worsened outcomes. To date, there are few high-quality studies on the timing of surgical intervention for BPE in the literature. Further prospective trials are needed to determine ideal timing for intervention.

A novel metric for treatment durability in clinical trials of minimally invasive treatments for benign prostatic hyperplasia.

Introduction: Clinical trial manuscripts commonly report results of individual endpoints. However, durability of a medical treatment may be difficult to determine when evaluating endpoint outcomes individually. We reviewed pivotal trial manuscripts of two minimally invasive benign prostatic hyperplasia (BPH) treatments and estimated the rate of treatment durability using a composite, symptom-centric metric.Methods: Data were derived from published pivotal trial reports of two minimally invasive BPH treatments - water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL). We estimated the risk of medical or surgical retreatment using life-table methods, and the number of patients achieving the minimal clinically important difference (MCID) for the International Prostate Symptom Score (IPSS) using z-score methods. Treatment durability was defined as a MCID on the IPSS at the 4-year follow-up visit while free from medical or surgical retreatment.Results: Comparing WVTT to PUL, the rate of medical or surgical retreatment was 10.6% vs. 31.8%, the IPSS MCID was achieved in 82.2% vs. 79.5%, and treatment durability rates were 71.8% vs. 51.7%.Conclusions: Utilization of a composite treatment durability metric derived from endpoints commonly reported in the BPH literature may allow patients and their providers to make better informed treatment decisions.

Three-year outcomes after Aquablation therapy compared to TURP: results from a blinded randomized trial.

INTRODUCTION: To compare 3-year efficacy and safety after prostate resection with Aquablation therapy or transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms related to benign prostate hyperplasia (BPH). MATERIALS AND METHODS: One hundred and eighty-one patients assigned to either Aquablation therapy or TURP were followed for 3 years postoperatively. Patients and follow up assessors were blinded to treatment. Assessments included International Prostate Symptom Score (IPSS), Male Sexual Health Questionnaire (MSHQ-EjD), International Index of Erectile Function (IIEF) and uroflow. RESULTS: Over 3 years of treatment, improvements in IPSS scores were statistically similar across groups. Mean 3-year improvements were 14.4 and 13.9 points in the Aquablation and TURP groups, respectively (difference of 0.6 points, 95% CI -3.3-2.2, p = .6848). Similarly, 3-year improvements in Qmax were 11.6 and 8.2 cc/sec (difference of 3.3 [95% CI -0.5-7.1] cc/sec, p = .0848). At 3 years, PSA was reduced significantly in both groups by 0.9 and 1.1 ng/mL, respectively; the reduction was similar across groups (p = .5983). There were no surgical retreatments for BPH beyond 20 months for either Aquablation or TURP. CONCLUSIONS: Three-year BPH symptom reduction and urinary flow rate improvement were similar after TURP and Aquablation therapy. No subjects required surgical retreatment beyond 20 months postoperatively. (ClinicalTrials.gov number, NCT02505919).

Ejaculatory Hood-Sparing Photoselective Vaporization of the Prostate vs Bipolar Button Plasma Vaporization of the Prostate in the Surgical Management of Benign Prostatic Hyperplasia.

Introduction and Objectives: After transurethral prostatectomy, erectile dysfunction and ejaculatory dysfunction are significant concerns for patients. We compared ejaculatory hood-sparing technique in patients who underwent photoselective vaporization of the prostate using the GreenLight Laser (EjS-PVP) with the ejaculatory hood-sparing technique in patients who underwent bipolar button plasma vaporization of the prostate (EjS-BPVP) in the surgical management of benign prostatic hyperplasia (BPH). Materials and Methods: Twenty-seven patients were randomized to either undergo EjS-PVP or EjS-BPVP from August 2016 to March 2018. All of the patients were sexually active with antegrade ejaculation before prostatectomy. We evaluated International Prostate Symptom Score (IPSS), quality of life (QoL), peak flow rate (Qmax), postvoid residual volume (PVR), International Index of Erectile Function and ejaculatory function by the Male Sexual Health Questionnaire (MSHQ). Men were evaluated preoperatively and at 1, 3, and 6 months postoperatively. The primary outcome was ejaculation preservation measured as no change or preservation in antegrade ejaculate at the last follow-up visit by MSHQ (6 months). Results: Twenty-seven patients with a mean age of 65.6 ± 8.4 years underwent either EjS-BPVP or EjS-PVP (Table 1). There were no differences in baseline characteristics between the two groups. Improvements in IPSS, QoL, Qmax, and PVR were durable throughout the study period in both groups. There was no difference in outcomes between groups. Postoperatively, there was no change in ejaculatory function with EjS-BPVP utilizing either 180 W EjS-PVP or bipolar energy. The change in MSHQ Ejaculation Scale was -2.1 and -5.4 at 6 months in both arms. The 6-month ejaculatory preservation rate was 85% in the EjS-PVP group and 78% in the EjS-BPVP group. Conclusions: EjS GreenLight photoselective vaporization and bipolar plasma button vaporization is a safe and effective method for treating men with lower urinary tract symptoms secondary to BPH with maintenance of antegrade ejaculation.