The PINNACLE Study: A Double-blind, Randomized, Sham-controlled Study Evaluating the Optilume BPH Catheter System for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: The Optilume BPH Catheter System is a novel drug/device combination minimally invasive surgical therapy for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. The PINNACLE study is a prospective, randomized, double-blind, sham-controlled clinical trial evaluating the safety and efficacy of Optilume BPH against a sham surgical procedure. MATERIALS AND METHODS: Eligible patients were men 50 years or older with symptomatic benign prostatic hyperplasia and a prostate size between 20 and 80 g. Subjects were randomized 2:1 to receive treatment with Optilume BPH or a sham surgical procedure. Blinding was maintained for subjects in both arms and evaluating personnel through 1 year postprocedure. Follow-up assessments included the International Prostate Symptom Score, uroflowmetry, and other quality-of-life and sexual function assessments. RESULTS: A total of 148 men were randomized (100 active, 48 sham) at 18 centers in the U.S. and Canada. Subjects randomized to receive Optilume BPH saw a reduction in International Prostate Symptom Score of 11.5±7.8 points at 1 year posttreatment, as compared to a reduction of 8.0±8.3 points at 3 months in the sham arm. Flow rate was dramatically improved after treatment with Optilume BPH, with an improvement of +10.3 mL/s from baseline to 1 year (+125%). CONCLUSIONS: Treatment with Optilume BPH provides immediate and sustained improvements in obstructive symptoms and flow rate while preserving erectile and ejaculatory function. Treatment is well tolerated and can be done in an office or ambulatory setting.

Durable benefit after treatment of obstructive benign prostatic hyperplasia with a novel drug-device combination product: 2-year outcomes from the EVEREST-I study.

PURPOSE: To evaluate the safety and efficacy of the Optilume BPH Catheter System for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: This open-label, single-arm study enrolled eighty subjects with LUTS secondary to BPH who were treated with the Optilume BPH Catheter System. Symptoms were recorded utilizing the International Prostate Symptom Score (IPSS) and Benign Prostatic Hyperplasia Impact Index (BPH-II). Functional improvement was measured utilizing peak urinary flow rate (Qmax) and post-void residual urine volume (PVR). Adverse events were systematically captured and reported at each follow-up visit. RESULTS: Subjects treated with the Optilume BPH Catheter System experienced a significant improvement in LUTS from baseline through 2 years of follow-up, as measured by IPSS (22.3 vs 8.2, p < 0.001) and BPH-II (6.9 vs 2.3, p < 0.001). Functional improvement was also significant, with Qmax improving from an average of 10.9 mL/s at baseline to 17.2 mL/s at the 2-year follow-up and PVR improving from 63.1 to 45.0 mL. Treatment-related adverse events were typically minor, with none occurring between 1- and 2-year post-treatment. CONCLUSIONS: The Optilume BPH Catheter System is a unique minimally invasive surgical therapy that combines mechanical and pharmaceutical aspects for the treatment of BPH. The functional and symptomatic improvements seen after treatment are significant and have been sustained through 2 years in this early feasibility study. REGISTRATION: NCT03423979, registered February 6, 2018.

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.

How I Do It: Optilume BPH catheter system.

Benign prostatic hyperplasia (BPH) is a common and progressive disease affecting aging men which has a significant impact on quality of life. The Optilume BPH Catheter System (Optilume BPH) is a prostatic dilation system that combines balloon dilation with a localized transfer of paclitaxel to maintain long term patency. Optilume BPH can be deployed using standard rigid cystoscopy without general anesthesia in an office setting. Prospective data indicate that Optilume BPH has favorable functional and sexual patient outcomes. Readers will familiarize themselves with Optilume BPH, significant historical studies and the technique for deploying Optilume BPH.

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.

Male Voiding Behavior: Insight from 19,824 At-Home Uroflow Profiles.

PURPOSE: Benign prostatic hyperplasia is one of the most common conditions seen by a general urologist. Validated questionnaires provide insight into patient symptoms, however office based uroflow devices are limited by the variability of voiding behavior. Using a home uroflow device, we assessed individual voiding variability, temporal distribution of voiding parameters and the impact of age on voiding. MATERIALS AND METHODS: Between April 2019 and June 2020, 19,824 unique voiding profiles were captured using the Stream Dx Uroflowmeter and retrospectively analyzed. Age and number of voids were summarized by mean±standard deviation. We used mixed effects models to compare average values and intrapatient variability of voiding parameters to time of day and age. The coefficient of variation was used to assess intrapatient variability. RESULTS: A total of 637 patients were identified with 625 meeting inclusion criteria, producing 19,824 voids. Mean age was 67 (±10.2) years old, and each patient provided on average 5 (±3.3) voids a day through 7 days. Average intrapatient voiding parameters showed notable variability, where the coefficient of variation for maximum flow was 27.6% (95% CI 26.6-28.6). Early morning voids were associated with higher volume and lower number of voids. As age progressed, voiding profiles worsened in a linear fashion. Afternoon and evening voids were associated with reduced intrapatient variability relative to early morning voids. CONCLUSIONS: Assessment of 19,824 uroflows using an accurate and precise home uroflow device demonstrates that an individual's voiding parameters vary greatly from day to day, throughout the day, and worsen with age. Multiple measurements performed at home provides a more realistic assessment of true voiding behavior by capturing individual voiding variability and can help urologists make better decisions in patient care.

Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART II-Surgical Evaluation and Treatment.

PURPOSE: Surgical therapies for symptomatic bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) are many, and vary from minimally invasive office based to high-cost operative approaches. This Guideline presents effective evidence-based surgical management of male lower urinary tract symptoms secondary/attributed to BPH (LUTS/BPH). See accompanying algorithm for a detailed summary of procedures (figure[Figure: see text]). MATERIALS/METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible studies published between January 2007 and September 2020, which includes the initial publication (2018) and amendments (2019, 2020). The Team also reviewed articles identified by Guideline Panel Members. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). RESULTS: Twenty-four guideline statements pertinent to pre-operative and surgical management were developed. Appropriate levels of evidence and supporting text were created to direct urologic providers towards suitable and safe operative interventions for individual patient characteristics. A re-treatment section was created to direct attention to longevity and outcomes with individual approaches to help guide patient counselling and therapeutic decisions. CONCLUSION: Pre-operative and surgical management of BPH requires attention to individual patient characteristics and procedural risk. Clinicians should adhere to recommendations and familiarize themselves with criteria that yields the highest likelihood of surgical success when choosing a particular approach for a particular patient.

Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART I-Initial Work-up and Medical Management.

PURPOSE: Benign prostatic hyperplasia (BPH) is a histologic diagnosis describing proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and severity of lower urinary tract symptoms (LUTS) in aging men are progressive and impact the health and welfare of society. This revised Guideline provides a useful reference on effective evidence-based management of male LUTS/BPH. See the accompanying algorithm for a summary of the procedures detailed in the Guideline (figures 1 and 2[Figure: see text][Figure: see text]). MATERIALS AND METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible English language studies published between January 2008 and April 2019, then updated through December 2020. Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: Nineteen guideline statements pertinent to evaluation, work-up, and medical management were developed. Appropriate levels of evidence and supporting text were created to direct both primary care and urologic providers towards streamlined and suitable practices. CONCLUSIONS: The work up and medical management of BPH requires attention to individual patient characteristics, while also respecting common principles. Clinicians should adhere to recommendations and familiarize themselves with standards of BPH management.

The state of TURP through a historical lens.

In 1926 Maximilian Stern introduced a new instrument to treat obstructions at the vesical orifice and baptized it resectoscope. With reference to astonishing historical statements about the new instrument and surgical technique made by the pioneers and their critics we will value why transurethral resection of the prostate (TURP) remains the gold standard for most men suffering from lower urinary tract symptoms (LUTS) due to benign prostatic enlargement. TURP is currently challenged by recently introduced new instruments and techniques claiming advantages over TURP. However, TURP offers an excellent balance between high efficacy in symptom relieve and low morbidity along with low costs and favorable long term outcome compared to other treatment options. We will outline these arguments demonstrating that even after a century has elapsed, since its introduction into the urologists armamentarium, TURP continues to stand the passage of time.

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.

Rezum therapy for patients with large prostates (≥ 80 g): initial clinical experience and postoperative outcomes.

PURPOSE: Rezum is a minimally invasive surgery for benign prostatic hyperplasia. Current guidelines recommend Rezum for prostates < 80 cc, but little data exist describing outcomes in patients with prostates ≥ 80 cc. We compare outcomes after Rezum between men with small < 80 cc (SP) and large ≥ 80 cc prostates (LP). METHODS: Patients undergoing Rezum between Jan 2017-Feb 2020 were subdivided by prostate volume (< 80, ≥ 80 cc). Outcomes were documented pre- and postoperatively. Descriptive analyses of urodynamics data (Qmax, PVR), symptom scores (AUA-SS, SHIM), disease management (medications, catheterization, retreatments), and clinical outcomes were conducted. RESULTS: 36 (17.6%) men had prostates ≥ 80 cc (LP mean prostate size 106.8 cc). LP men had improved Qmax and PVR postoperatively; those with longitudinal follow-up exhibited improved Qmax, PVR, and AUA-SS. After one year, alpha-blocker usage decreased significantly (LP 94.44-61.11%, p = 0.001, SP 73.96-46.15%, p = 0.001); other medication usage and self-catheterization rates remained unchanged. Compared to SP patients, differences in passing trial void (LP 94.44%, SP 93.45%), postoperative UTI (LP 19.44%, SP 10.12%), ED visits (LP 22.22%, SP 17.86%), readmissions (LP 8.33%, SP 4.76%), and retreatment (LP 8.33%, SP 4.76%) were insignificant. However, mean days to foley removal (LP 9, SP 5.71, p = 0.003) and urosepsis rates (LP 5.56%, SP 0.00%, p = 0.002) differed. CONCLUSION: In select LP patients, Rezum provided short-term symptomatic relief and improved voiding function comparable to SP patients. Postoperatively, though alpha-blocker usage decreased significantly, use of other medications did not change, and nearly two-thirds of patients still needed alpha-blockade. Further efforts should explore the possibility of expanding Rezum's inclusion criteria.

Efficacy and Safety of Mirabegron in Men with Overactive Bladder Symptoms and Benign Prostatic Hyperplasia.

PURPOSE OF REVIEW: To review the efficacy and safety of mirabegron in men with overactive bladder (OAB) and benign prostatic hyperplasia (BPH). RECENT FINDINGS: Numerous studies have shown mirabegron to be efficacious and safe in treating symptoms of OAB. More recent studies evaluating the use of mirabegron in men with OAB and BPH have also shown the medication to be effective with few adverse side effects when used as monotherapy or in combination therapy. Mirabegron is an effective and safe treatment for men with OAB and BPH.

Focal bladder neck cautery associated with low rate of post-Aquablation bleeding.

INTRODUCTION To determine if focal bladder neck cautery is effective in reducing bleeding following prostate tissue resection for benign prostatic hyperplasia using Aquablation. MATERIALS AND METHODS: Consecutive patients at 11 countries in Asia, Europe and North America who underwent Aquablation for symptomatic benign prostatic hyperplasia between late 2019 and January 2021 were included in the analysis. All patients received post-Aquablation non-resective focal cautery at the bladder neck. RESULTS: A total of 2,089 consecutive Aquablation procedures were included. Mean prostate size was 87 cc (range 20 cc to 363 cc). Postoperative bleeding requiring transfusion occurred in 17 cases (0.8%, 95% CI 0.5%-1.3%) and take-back to the operating room for fulguration occurred in 12 cases (0.6%, 95% CI 0.3%-1.0%). This result compares favorably (p < .0001) to the previously published hemostasis transfusion rate of 3.9% (31/801) using methods performed in the years 2014 to 2019. CONCLUSIONS: In prostates sizes averaging 87cc (range 20 cc-363 cc), Aquablation procedures performed with focal bladder neck cautery that required a transfusion postoperatively occurred in a remarkably low number of cases.

Noninvasive Pressure Flow Studies in the Evaluation of Men with Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Review of 50,000 Patients.

PURPOSE: The UroCuff® Test is a noninvasive pressure flow study used to manage men with lower urinary tract symptoms. UroCuff Tests were performed on men with lower urinary tract symptoms to evaluate voiding characteristics and quantify changes in urodynamic parameters with age. MATERIALS AND METHODS: This cross-sectional study included all UroCuff Tests performed at 103 urology practices in the U.S. Tests were de-identified prior to collection and analysis. Inclusion criteria required initial pressure flow study with subsequent tests excluded, voided volume 50 ml or greater, at least 1 cuff inflation and patient age greater than 20 years. Pressure, maximum flow rate, flow rate efficiency (maximum flow rate/Pcuff), voided volume and post-void residual were plotted by age and stratified by Newcastle Noninvasive Nomogram category. RESULTS: A total of 50,680 patients 20 to 100 years old (median age 66.0) met inclusion criteria. Median Pcuff was 144.3 cmH2O and 60.8% of patients were categorized in the obstructed or high pressure/high flow Newcastle Noninvasive Nomogram quadrants. Median maximum flow rate was 10.9 ml per second and 55.8% had maximum flow rate greater than 10 ml per second. Median voided volume and post-void residual were 219.0 and 75.0 ml, respectively. All measures deteriorated with age (p <0.0001). Pcuff reflects the compensated/decompensated bladder function lifecycle. Values initially increased and reached peak pressure at age 62, then decreased by approximately 0.96 cmH2O per year until age 90. CONCLUSIONS: This study demonstrates that symptomatic patients enter urological practices at different urodynamic stages of bladder function and outlet obstruction, that Pcuff, maximum flow rate, voided volume, flow rate efficiency and post-void residual deteriorate with age, and that UroCuff is a sensitive evaluation of bladder performance.

Efficacy and Safety of Mirabegron versus Placebo Add-On Therapy in Men with Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Randomized, Phase 4 Study (PLUS).

PURPOSE: PLUS investigated the efficacy and safety of mirabegron add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying lower urinary tract symptoms attributable to benign prostatic hyperplasia. MATERIALS AND METHODS: In this phase 4 study a 4-week 0.4 mg tamsulosin run-in period was followed by a 12-week, randomized, double-blind, treatment period in which patients initially received 25 mg mirabegron or placebo add-on therapy. At 4 weeks doses were titrated to 50 mg mirabegron or placebo equivalent. Efficacy end points were changes from baseline to end of treatment in mean number of micturitions per day (primary), mean volume voided per micturition, number of urgency episodes per day, total urgency and frequency score, and total International Prostate Symptom Score (secondary). Safety assessments included treatment emergent adverse events, and post-void residual volume, and maximum urinary flow measurements. RESULTS: Of the 676 men most were 65 years old or older (380, 56.2%). Tamsulosin plus mirabegron was statistically superior to tamsulosin plus placebo in reducing the mean number of micturitions per day (-2.00 vs -1.62; adjusted difference -0.39; 95% CI -0.76, -0.02). Statistically superior results were noted for tamsulosin plus mirabegron in mean volume voided per micturition, urgency episodes per day, and total urgency and frequency score (not International Prostate Symptom Score). Higher overall treatment emergent adverse event rates were observed with tamsulosin plus placebo, although higher rates of drug related treatment emergent adverse events were noted with tamsulosin plus mirabegron. Urinary retention rates were higher in the tamsulosin plus mirabegron group. Post-void residual volume and maximum urinary flow results were not clinically meaningful. CONCLUSIONS: The results of PLUS underscore the utility of mirabegron add-on therapy to treat men with overactive bladder symptoms receiving tamsulosin for benign prostatic hyperplasia.

Prospective evaluation of fexapotide triflutate injection treatment of Grade Group 1 prostate cancer: 4-year results.

PURPOSE: This study was undertaken to determine the safety and efficacy of fexapotide triflutate (FT) 2.5 mg and 15 mg for the treatment of Grade Group 1 prostate cancer. METHODS: Prospective randomized transrectal intraprostatic single injection FT 2.5 mg (n = 49), FT 15 mg (n = 48) and control active surveillance (AS) (n = 49) groups were compared in 146 patients at 28 U.S. sites, with elective AS crossover (n = 18) to FT after first follow-up biopsy at 45 days. Patients were followed for 5 years including biopsies (baseline, 45 days, and 18, 36, and 54 months thereafter), and urological evaluations with PSA every 6 months. Patients with Gleason grade increase or who elected surgical or radiotherapeutic intervention exited the study and were cumulatively included in the data analysis. Percentage of normal biopsies in baseline focus quadrant, tumor grades, and volumes; and outcomes including Gleason grade in entire prostate as well as treated prostate lobe, interventions associated with Gleason grade increase and total incidence of interventions were assessed. RESULTS: Significantly improved long-term clinical outcomes were found after 4-year follow-up, with percentages of patients progressing to interventions with and without Gleason grade increase significantly reduced by FT single treatment. Results in the FT 15-mg group were superior to the FT 2.5-mg dose group. There were no drug-related serious adverse events (SAEs). CONCLUSIONS: FT showed statistically significant long-term efficacy in the treatment of Grade Group 1 patients regarding clinical and pathological progression. FT 15 mg showed superior results to FT 2.5 mg. There were no drug-related SAEs; FT injection was well tolerated.

Diagnostic and methodological evaluation of studies on the urinary shedding of SARS-CoV-2, compared to stool and serum: A systematic review and meta-analysis.

Investigating the infectivity of body fluid can be useful for preventative measures in the community and ensuring safety in the operating rooms and on the laboratory practices. We performed a literature search of clinical trials, cohorts, and case series using PubMed/MEDLINE, Google Scholar, and Cochrane library, and downloadable database of CDC. We excluded case reports and searched all-language articles for review and repeated until the final drafting. The search protocol was registered in the PROSPERO database. Thirty studies with urinary sampling for viral shedding were included. A total number of 1,271 patients were enrolled initially, among which 569 patients had undergone urinary testing. Nine studies observed urinary viral shedding in urine from 41 patients. The total incidence of urinary SARS-CoV-2 shedding was 8%, compared to 21.3% and 39.5 % for blood and stool, respectively. The summarized risk ratio (RR) estimates for urine positive rates compared to the pharyngeal rate was 0.08. The pertaining RR urine compared to blood and stool positive rates were 0.20 and 0.33, respectively. Our review concludes that not only the SARS-CoV-2 can be excreted in the urine in eight percent of patients but also its incidence may have associations with the severity of the systemic disease, ICU admission, and fatality rates. Moreover, the findings in our review suggest that a larger population size may reveal more positive urinary cases possibly by minimizing biases.