Surgical Treatment for BPH Refractory to Medication: Robotic Water Jet Ablation vs TURP functional outcomes from two FDA clinical trials

Surgical Treatment for BPH Refractory to Medication: Robotic Water Jet Ablation vs TURP functional outcomes from two FDA clinical trials | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Surgical Treatment for BPH Refractory to Medication: Robotic Water Jet Ablation vs TURP functional outcomes from two FDA clinical trials Alexis Te, Alexis Te, Christina Sze, Steven Kaplan, Bilal Chughtai This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1832879/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose 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. 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 α-blockers (AB) and 5-α-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 150cc) and transurethral resection of the prostate (TURP, prostate sizes up to 80cc) 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. aquablation BPH washout period drug failure Transurethral Prostatectomy Robotic Water Jet Ablation BPH Medical Therapy LUTS Bladder Outlet Obstruction alpha adrenergic blockers 5 alpha reductase inhibitors Figures Figure 1 Figure 2 Introduction Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) is a chronic condition that can have negative impact on the quality of life (QoL) in older men. Treatment therapies range from noninvasive options such as watchful waiting, lifestyle modifications, and pharmacotherapy to surgical interventions. One of the relative indications for any surgical therapy is failure of pharmacotherapy and exhausting other noninvasive options 1 . Minimally invasive surgical therapies (MISTs) have emerged as intermediary options between conservative management including pharmaceutical therapy and the gold standard transurethral resection of the prostate (TURP). Approval of novel MISTs rely on prospective randomized controlled trials (RCTs). Currently, washout periods are prevalent and the standard in pharmaceutical-based clinical trial protocols to reduce user bias and achieve greater internal validity of the research drug. Implementation of the washout period exclusion criteria has been broadened to surgery-based studies 2 . However, these cohorts do not reflect a population that truly failed medical therapy. In fact, most of the Federal Drug Administration (FDA) registered clinical trials on MISTs reflect therapies that are alternative to medical therapy and not truly for medical therapy failure. These trials are typically compared to sham or placebo while off medical therapy at baseline. This can potentially inflate symptoms score improvements with surgical therapy and do not accurately reflect improvement in those who failed medical therapy. In fact, these MIST have not been compared to medical therapy nor been proven superior to medical therapy in randomized clincal trials. There is minimal evidence to explicitly substantiate the use of a washout periods for surgical therapy for BPH since most surgical therapies are utilized in patients with poor symptoms improvement from medical therapy and not as an alternative to surgical therapy. To accurately reflect this practical indication to selecting surgical therapy in a population that truly is medication refractory, we report the efficacy of Robotic Water Jet Ablation Therapy (RWT) and TURP in this cohort. Methods This is a post hoc analysis of subjects from WATER (Waterjet Ablation Therapy for Endoscopic Resection of Prostate Tissue) and WATER II trials. WATER is a prospective, double-blind, multicenter, international clinical trial comparing the safety and efficacy of Robotic Water Jet Ablation Therapy (RWT) and transurethral resection of the prostate (TURP) in the treatment of LUTS/BPH in men aged 45–80 year with a prostate of 30–80 cm 3 3 . WATER II is a prospective, multicenter, single-arm international clinical trial of Aquablation in men with a prostate of 80–150 cm 3 4 . Baseline characteristics for each trial were compared using a student’s t test and Wilcoxon signed-rank test for normally and non-normally distributed continuous variables, respectively. Fisher’s test was used for categorical variables. Repeated-measures analysis of variance was used to compare longitudinal responses at different time points, adjusting for patient clustering. All statistical tests were 2-sided with a p value < 0.05 indicating statistical significance. All statistics were performed using the statistical package JMP® (JMP Pro, Version 16 Software, Microsoft® Windows® for x 64; SAS Institute Inc., Cary, North Carolina, USA, 1989–2019). Results A total of 185 men had alpha blocker (AB) or 5-alpha reductase (5-ARI) prior to undergoing RWT or TURP (Table 1 ) with the majority (79%) undergoing RWT. Median prostate volume was 75 (IQR 52–102). There was significant trend improvement of parameters such as IPSS, QoL, Qmax and PVR from baseline to follow-up at 36-month (Fig. 1A-D). When compared to the men who were not on any AB or 5-ARI prior to surgery (n = 97) in WATER, there was no significant difference in any of the urinary parameters at baseline and at 36-month follow up. Table 1 RWT vs TURP Characteristics On Medical Therapy At Baseline RWT TURP p-value Characteristics N = 146 N = 39 IPSS 24.0 (18.2, 28.0) 21.0 (15.0, 27.5) 0.2 QoL 5.00 (4.00, 5.00) 5.00 (4.00, 5.00) 0.9 Qmax 8.9 (6.4, 11.5) 8.9 (7.2, 11.4) 0.5 PVR 95 (36, 172) 124 (73, 213) 0.2 Prostate Volume (cc) 67.4 (46.03, 93.3) 53.1 (40, 66.2) 0.001 1 Median (IQR) In patients who underwent RWT, erectile (ED) and ejaculation (EjD) dysfunction rate were higher in the patients who were not on BPH medications at baseline however this was not significantly different in both WATER and WATER II trials ( p = 0.14 and p = 0.21, respectively) (Fig. 2A-C). Patients who were on BPH medication at baseline were more likely to return to medication or undergo another BPH intervention at 3 years of follow-up in both aquablation and TURP cohorts however this difference was not significant in both RWT and TURP cohorts (p = 0.81 (WATER ) and p = 0.22, respectively). In men with larger prostates (> 80g) who were medication naïve were more likely to be on BPH medications at 3 years however this did not reach significance (p = 0.22). TURP retreatment rate from the WATER was 1.5%. The patient underwent another TURP. Retreatment rates for aquablation from WATER and WATER II were 4.3% and 3%, respectively. The majority of retreatment procedures was TURP. In the aquablation group, Calvien-Dindo (CD) grade 2 or greater complications were higher in men on BPH medications at baseline compared to men who were not on any BPH medications at 6 months follow-up however this did not reach significance in both WATER and WATER II trials ( p = 0.14, p = 0.52, respectively). Conversely, men on BPH medication at baseline in the TURP arm had lower rates of ≥ CD grade 2 complications compared to those not on BPH medications at baseline however this did not reach significance ( p = 0.2). Discussion TURP continues to be the gold standard for the treatment of LUTs due to BPH with a prostate volume limit of 80cc especially for medical therapy failure since the 1930s 5 . Because of the advent of meds and MISTs, prostate sizes are becoming larger and larger by the time they treated with surgical therapy. With the advent of pharmacotherapy, the landscape of BPH therapy changed from a tradition where surgical prostatectomy was the preferred treatment choice of debulking obstructive tissue. The advent of medical therapy altered the perception for the need for invasive surgical therapy, and eventually the era of MISTs evolved as an alternative option to medical therapy. To emulate it as an alternative option, MISTs in prospective randomized clinical trials were designed to mimic pharmacologic trials with a comparison to sham and included a washout period to report medication free baseline for outcome parameters. The balloon prostatoplasty was the first trial to utilize this design, and it has remained the standard by which clinical trials for minimally invasive therapies are designed as an alternative to medical therapies 6 . Although this study was not designed as a treatment for failed medical therapy, the concept of minimally invasive therapy as a treatment for failed medical therapy was assumed once it was approved for use, and is applied extensively in current clinical practice. Given this need for better information, we present a cohort of patients who truly failed medical therapy and underwent surgical management as a result. WATER and WATER II trials did not have a washout phase prior to enrollment therefore clearly representing a cohort that were symptomatic failure to medical therapy at baseline. As such, indications and inclusion situate these surgical therapies as the clear next step after failure to medical therapy. Both RWT and TURP demonstrated group statistical improvements in IPSS, QoL, Qmax, and PVR at 36-month compared to baseline. Functional outcomes did not statistically differ between RWT and TURP at baseline and at 36-month. TURP has classically been that option and in the WATER studies, RWT has demonstrated non inferiority. In a pre-specified analysis, RWT showed superior results in symptom reduction compared to TURP in prostate sizes 50-80cc. This sub-analysis of medical therapy failure cohort further reinforces the role of these therapies as treatment of choice for medical therapy failures including men who desire to limit their sexual adverse events from surgical therapies. Of note, as an alternative to medical therapy, MISTs do not seem as favorable to medical therapy. When compared to medical therapy, MISTs complications include dysuria, gross hematuria, and urinary frequency. More serious complication though rare include bladder neck contracture and urosepsis were reported in pivotal trials 3 . Additionally, retreatment rate as high as 15.5% for Water Vapor Thermotherapy Treatment (WVTT) (4.4% for surgical reintervention; 11.1% restarting medication) and 33.6% (13.6% for surgical reintervention 7 ; 10.7% restarting medication; 9.3% clip removal) for prostatic urethral lift (PUL) 3 . In a recent meta-analysis looking at surgical reintervention rate after PUL in 2000 patients, reintervention rates were 4.3% per year in studies with < 1 year follow-up and can be as high as 10.7% in studies with longer follow-up up to 3 years 8 . Using a novel composite, symptom-centric metric to measure durability, the rate of medical or surgical retreatment was 10.6% and 31.8% in WVTT and PUL, respectively 9 . In comparisons, the progression to surgical treatment in the Medical Therapy of Prostatic Symptoms (MTOPS) study was only 4% vs placebo and from the Alfuzosin Long-Term Efficacy and Safety Study (ALTESS) study progression to BPH-related surgery was only 2.2% 10, 11 . When placed in this context, medical therapy still seems superior to PUL and WVTT. In theory, these randomized prospective MIST RCTs compared to sham are designed to be an alternative to medical therapy. Contrary, in the 3-year trial comparing WVTT to pharmacotherapy show that clinical progression was 5 times more likely in the pharmacotherapy vs a single WVTT therapy suggesting that WVTT may be a reasonable alternative to pharamcotherapy 12 . It should be noted, however, that symptomatic progression on phamacotherapy therapy to surgical therapy was very low, and that progression on MTOPs did not define failure of therapy as a historial comparison. Of note, a combination of pharmacotherapy (AB and 5-ARI) in both the MTOPs trial and Combination of Avodart and Tamsulosin (CombAT) trial has been demonstrated to be superior to monotherapy in controlling of both storage and voiding LUTS 13 – 15 . It maybe that WVTT would benefit with having a 5ARI added ot their post op regimen due to their high retreatment rate. There is currently a need for prospective studies directly comparing MISTs to pharmacotherapy to provide clarity for better identification and management of patients at risk of BPH progression 16 . Finally, the 5 year retreatment rates for surgery as well as back on meds from the WATER study (6% for RWT, 12.3% for TURP) should be noted as well 17 . Since the current clinical practice is to offer MIST to those who fail pharmacotherapy or need surgical intervention who desire a minimally invasive approach, future MIST trials should not have a washout period to demonstrated their role as a alternative to invasive surgical therapy and not pharmacotherapy as represented in current trials against sham. Conclusion We present functional outcomes on patients who truly failed medical therapy and underwent surgical prostatectomy therapies. Washout periods are not necessary in these studies that evaluate efficacy of a BPH surgery therapy. RWT and TURP are effective BPH therapy in patients who truly failed medical therapy, and RWT demonstrated effectiveness in a larger prostate size range. We also suggest that future clinical trials of surgical options including minimally invasive therapy sham should not have a washout period to demonstrate their role in as an option to medical therapy failure. Abbreviations Lower urinary tract symptoms (LUTS) benign prostatic hyperplasia (BPH) αblocker (AB) 5α-reductase inhibitor (5ARI) Declarations Conflict of Interest Alexis E. Te- Procept- PI and Consultant Steven A. Kaplan- Procept- PI Bilal Chughtai-Procept- PI Christina Sze- No conflicts Authors’ Contribution Alexis E.Te 1 , Christina Sze 1 , Steven A. Kaplan 2 , and Bilal Chughtai 1 The above authors all contributed in the development, writing, editing and data analysis of this investigator initiated study and manuscript. Achknowledgement is given to Procept Biorobotics for providing the data for this manuscript. Disclosure of Funding WATER and WATER II were funded by Procept. No funding provided for manuscript development. References Lerner, L. B., McVary, K. T., Barry, M. J. et al.: Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART II-Surgical Evaluation and Treatment. J Urol, 206 : 818, 2021 Campbell, J., Reid, J., Ordon, M. et al.: The Utilization of Benign Prostatic Hyperplasia and Bladder-Related Medications After a Transurethral Prostatectomy. Urology, 130 : 126, 2019 McVary, K. T., Gittelman, M. C., Goldberg, K. A. et al.: Final 5-Year Outcomes of the Multicenter Randomized Sham-Controlled Trial of a Water Vapor Thermal Therapy for Treatment of Moderate to Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia. J Urol, 206 : 715, 2021 Nguyen, D. D., Barber, N., Bidair, M. et al.: WATER versus WATER II 2-Year Update: Comparing Aquablation Therapy for Benign Prostatic Hyperplasia in 30-80-cm(3) and 80-150-cm(3) Prostates. Eur Urol Open Sci, 25 : 21, 2021 Mayer, E. K., Kroeze, S. G., Chopra, S. et al.: Examining the 'gold standard': a comparative critical analysis of three consecutive decades of monopolar transurethral resection of the prostate (TURP) outcomes. BJU Int, 110 : 1595, 2012 Lepor, H., Sypherd, D., Machi, G. et al.: Randomized double-blind study comparing the effectiveness of balloon dilation of the prostate and cystoscopy for the treatment of symptomatic benign prostatic hyperplasia. J Urol, 147 : 639, 1992 Roehrborn, C. G., Barkin, J., Gange, S. N. et al.: Five year results of the prospective randomized controlled prostatic urethral L.I.F.T. study. Can J Urol, 24 : 8802, 2017 Miller, L. E., Chughtai, B., Dornbier, R. A. et al.: Surgical Reintervention Rate after Prostatic Urethral Lift: Systematic Review and Meta-Analysis Involving over 2,000 Patients. J Urol, 204 : 1019, 2020 Miller, L. E., Te, A. E., Bhattacharyya, S. K. et al.: A novel metric for treatment durability in clinical trials of minimally invasive treatments for benign prostatic hyperplasia. Expert Rev Med Devices, 17 : 365, 2020 McConnell, J. D., Roehrborn, C. G., Bautista, O. M. et al.: The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med, 349 : 2387, 2003 Roehrborn, C. G.: Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention: results of a 2-year placebo-controlled study. BJU Int, 97 : 734, 2006 Gupta, N., Rogers, T., Holland, B. et al.: Three-Year Treatment Outcomes of Water Vapor Thermal Therapy Compared to Doxazosin, Finasteride and Combination Drug Therapy in Men with Benign Prostatic Hyperplasia: Cohort Data from the MTOPS Trial. J Urol, 200 : 405, 2018 Kaplan, S. A., Lee, J. Y., Meehan, A. G. et al.: Time Course of Incident Adverse Experiences Associated with Doxazosin, Finasteride and Combination Therapy in Men with Benign Prostatic Hyperplasia: The MTOPS Trial. J Urol, 195 : 1825, 2016 Kaplan, S. A., McConnell, J. D., Roehrborn, C. G. et al.: Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 ml or greater. J Urol, 175 : 217, 2006 Montorsi, F., Roehrborn, C., Garcia-Penit, J. et al.: The effects of dutasteride or tamsulosin alone and in combination on storage and voiding symptoms in men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH): 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study. BJU Int, 107 : 1426, 2011 Roehrborn, C. G.: BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU Int, 101 Suppl 3 : 17, 2008 Gilling, P. J., Barber, N., Bidair, M. et al.: Five-year outcomes for Aquablation therapy compared to TURP: results from a double-blind, randomized trial in men with LUTS due to BPH. Can J Urol, 29 : 10960, 2022 Additional Declarations Yes there is potential conflict of interest. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1832879","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":121608205,"identity":"95362e70-5738-436e-91c0-4b48512d4288","order_by":0,"name":"Alexis Te","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYHACxgcJBv/kgAwDCJ+duYGBgQ2fDmZmgw8VB4wRWpgZCWphk5xx5kBiA9Fa+Nv7D0jztt1JX9vevIHhR8W9PH6Qlg9lh3FqkThzmMGYt+1Z7rYzxwoYe84UF0s2MzYwzjiHWwvDjWSGZN425txtN3IMmBnbEhI3HGZsYOZtw61F/v5jhsNALelm999AtOwHafmLR4vBDWbGxhlnDieY3eCB2gL0C5CBW4vhmWRjhg8VaYbbzqQVHOw5k5A4A2jLwZ5z6Ti1yB0/+PxHgoGNvNnxwxsf/KhISOxvbz744EeZNW7vI4MDGIxRMApGwSgYBeQBAMi4XZp2ozBcAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-5815-7196","institution":"Weill Medical College of Cornell University/ New York Presbyterian","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Alexis","middleName":"","lastName":"Te","suffix":""},{"id":121608206,"identity":"098dc03f-e7a3-44e8-b461-455c8d557f12","order_by":1,"name":"Alexis Te","email":"","orcid":"","institution":"Weill Medical College of Cornell University/ New York Presbyterian","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alexis","middleName":"","lastName":"Te","suffix":""},{"id":121608207,"identity":"15d65fb7-54da-427a-a07b-ac35a955a269","order_by":2,"name":"Christina Sze","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Christina","middleName":"","lastName":"Sze","suffix":""},{"id":121608208,"identity":"c78140bc-d950-479f-b2ad-3247889b4cbb","order_by":3,"name":"Steven Kaplan","email":"","orcid":"https://orcid.org/0000-0003-2558-7306","institution":"Icahn School of Medicine at Mount Sinai","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Steven","middleName":"","lastName":"Kaplan","suffix":""},{"id":121608209,"identity":"5808037e-a726-47ec-9aa8-980d80b657a2","order_by":4,"name":"Bilal Chughtai","email":"","orcid":"","institution":"Weill Cornell Medical College/New York Presbyterian","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bilal","middleName":"","lastName":"Chughtai","suffix":""}],"badges":[],"createdAt":"2022-07-06 22:10:51","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1832879/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1832879/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":24287247,"identity":"bb808790-83be-422f-abee-0a8e1db4d0c6","added_by":"auto","created_at":"2022-07-25 13:54:36","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":547084,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e - Friedman test demonstrating trend in IPSS with follow-up (up to 36 months) comparing Aquablation and TURP \u003cstrong\u003e(B)\u003c/strong\u003e - Friedman test demonstrating trend in QoL with follow-up (up to 36 months) comparing Aquablation and TURP \u003cstrong\u003e(C)\u003c/strong\u003e – Total IPSS at 36 months of followup comparing Aquablation and TURP . Krushkal-Wallis Tests p = 0.25. \u003cstrong\u003e(D)\u003c/strong\u003e – Total QoL at 36 months of followup comparing Aquablation and TURP . Krushkal-Wallis Tests p = 0.10\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1832879/v1/df9e6791337442a9b6ba727c.jpg"},{"id":24288421,"identity":"3064ac26-1218-4b54-869b-9edc9577b3e7","added_by":"auto","created_at":"2022-07-25 13:59:36","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":190279,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A) \u003c/strong\u003ePercentage of men who experienced erectile dysfunction (ED) or ejaculation dysfunction (EjD) at 6 months of follow-up\u003cstrong\u003e (B) \u003c/strong\u003ePercentage of men who are on BPH medications or underwent a BPH intervention after TURP/Aquablation at 3 years of follow-up\u003cstrong\u003e (C) \u003c/strong\u003ePercentage of men with Calvien-Dindo (CD) grade 2 or greater complications at 6 months of follow-up\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1832879/v1/af0fefe90279b7aea721b35c.jpg"},{"id":26203438,"identity":"4d19ee68-dc3d-47a9-a055-c660474c12a7","added_by":"auto","created_at":"2022-09-08 08:31:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":404398,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1832879/v1/2b4d3e28-63bb-42f0-badf-ba2fa3a14d40.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential conflict of interest.","formattedTitle":"Surgical Treatment for BPH Refractory to Medication: Robotic Water Jet Ablation vs TURP functional outcomes from two FDA clinical trials","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) is a chronic condition that can have negative impact on the quality of life (QoL) in older men. Treatment therapies range from noninvasive options such as watchful waiting, lifestyle modifications, and pharmacotherapy to surgical interventions. One of the relative indications for any surgical therapy is failure of pharmacotherapy and exhausting other noninvasive options\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Minimally invasive surgical therapies (MISTs) have emerged as intermediary options between conservative management including pharmaceutical therapy and the gold standard transurethral resection of the prostate (TURP).\u003c/p\u003e \u003cp\u003eApproval of novel MISTs rely on prospective randomized controlled trials (RCTs). Currently, washout periods are prevalent and the standard in pharmaceutical-based clinical trial protocols to reduce user bias and achieve greater internal validity of the research drug. Implementation of the washout period exclusion criteria has been broadened to surgery-based studies\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. However, these cohorts do not reflect a population that truly failed medical therapy. In fact, most of the Federal Drug Administration (FDA) registered clinical trials on MISTs reflect therapies that are alternative to medical therapy and not truly for medical therapy failure. These trials are typically compared to sham or placebo while off medical therapy at baseline. This can potentially inflate symptoms score improvements with surgical therapy and do not accurately reflect improvement in those who failed medical therapy. In fact, these MIST have not been compared to medical therapy nor been proven superior to medical therapy in randomized clincal trials.\u003c/p\u003e \u003cp\u003eThere is minimal evidence to explicitly substantiate the use of a washout periods for surgical therapy for BPH since most surgical therapies are utilized in patients with poor symptoms improvement from medical therapy and not as an alternative to surgical therapy. To accurately reflect this practical indication to selecting surgical therapy in a population that truly is medication refractory, we report the efficacy of Robotic Water Jet Ablation Therapy (RWT) and TURP in this cohort.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis is a post hoc analysis of subjects from WATER (Waterjet Ablation Therapy for Endoscopic Resection of Prostate Tissue) and WATER II trials. WATER is a prospective, double-blind, multicenter, international clinical trial comparing the safety and efficacy of Robotic Water Jet Ablation Therapy (RWT) and transurethral resection of the prostate (TURP) in the treatment of LUTS/BPH in men aged 45\u0026ndash;80\u0026nbsp;year with a prostate of 30\u0026ndash;80 cm\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. WATER II is a prospective, multicenter, single-arm international clinical trial of Aquablation in men with a prostate of 80\u0026ndash;150 cm\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBaseline characteristics for each trial were compared using a student\u0026rsquo;s t test and Wilcoxon signed-rank test for normally and non-normally distributed continuous variables, respectively. Fisher\u0026rsquo;s test was used for categorical variables. Repeated-measures analysis of variance was used to compare longitudinal responses at different time points, adjusting for patient clustering.\u003c/p\u003e \u003cp\u003eAll statistical tests were 2-sided with a p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicating statistical significance. All statistics were performed using the statistical package JMP\u0026reg; (JMP Pro, Version 16 Software, Microsoft\u0026reg; Windows\u0026reg; for x 64; SAS Institute Inc., Cary, North Carolina, USA, 1989\u0026ndash;2019).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 185 men had alpha blocker (AB) or 5-alpha reductase (5-ARI) prior to undergoing RWT or TURP (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) with the majority (79%) undergoing RWT. Median prostate volume was 75 (IQR 52\u0026ndash;102). There was significant trend improvement of parameters such as IPSS, QoL, Qmax and PVR from baseline to follow-up at 36-month (Fig.\u0026nbsp;1A-D). When compared to the men who were not on any AB or 5-ARI prior to surgery (n\u0026thinsp;=\u0026thinsp;97) in WATER, there was no significant difference in any of the urinary parameters at baseline and at 36-month follow up.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRWT vs TURP Characteristics On Medical Therapy At Baseline\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRWT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTURP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIPSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.0 (18.2, 28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.0 (15.0, 27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQoL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.00 (4.00, 5.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.00 (4.00, 5.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQmax\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.9 (6.4, 11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.9 (7.2, 11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (36, 172)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124 (73, 213)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate Volume (cc)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.4 (46.03, 93.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.1 (40, 66.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003csup\u003e1\u003c/sup\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn patients who underwent RWT, erectile (ED) and ejaculation (EjD) dysfunction rate were higher in the patients who were not on BPH medications at baseline however this was not significantly different in both WATER and WATER II trials ( p\u0026thinsp;=\u0026thinsp;0.14 and p\u0026thinsp;=\u0026thinsp;0.21, respectively) (Fig.\u0026nbsp;2A-C). Patients who were on BPH medication at baseline were more likely to return to medication or undergo another BPH intervention at 3 years of follow-up in both aquablation and TURP cohorts however this difference was not significant in both RWT and TURP cohorts (p\u0026thinsp;=\u0026thinsp;0.81 (WATER ) and p\u0026thinsp;=\u0026thinsp;0.22, respectively). In men with larger prostates (\u0026gt;\u0026thinsp;80g) who were medication na\u0026iuml;ve were more likely to be on BPH medications at 3 years however this did not reach significance (p\u0026thinsp;=\u0026thinsp;0.22).\u003c/p\u003e \u003cp\u003eTURP retreatment rate from the WATER was 1.5%. The patient underwent another TURP. Retreatment rates for aquablation from WATER and WATER II were 4.3% and 3%, respectively. The majority of retreatment procedures was TURP.\u003c/p\u003e \u003cp\u003eIn the aquablation group, Calvien-Dindo (CD) grade 2 or greater complications were higher in men on BPH medications at baseline compared to men who were not on any BPH medications at 6 months follow-up however this did not reach significance in both WATER and WATER II trials ( p\u0026thinsp;=\u0026thinsp;0.14, p\u0026thinsp;=\u0026thinsp;0.52, respectively). Conversely, men on BPH medication at baseline in the TURP arm had lower rates of \u0026ge;\u0026thinsp;CD grade 2 complications compared to those not on BPH medications at baseline however this did not reach significance ( p\u0026thinsp;=\u0026thinsp;0.2).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTURP continues to be the gold standard for the treatment of LUTs due to BPH with a prostate volume limit of 80cc especially for medical therapy failure since the 1930s\u003csup\u003e5\u003c/sup\u003e. Because of the advent of meds and MISTs, prostate sizes are becoming larger and larger by the time they treated with surgical therapy. With the advent of pharmacotherapy, the landscape of BPH therapy changed from a tradition where surgical prostatectomy was the preferred treatment choice of debulking obstructive tissue. The advent of medical therapy altered the perception for the need for invasive surgical therapy, and eventually the era of MISTs evolved as an alternative option to medical therapy. To emulate it as an alternative option, MISTs in prospective randomized clinical trials were designed to mimic pharmacologic trials with a comparison to sham and included a washout period to report medication free baseline for outcome parameters. The balloon prostatoplasty was the first trial to utilize this design, and it has remained the standard by which clinical trials for minimally invasive therapies are designed as an alternative to medical therapies\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Although this study was not designed as a treatment for failed medical therapy, the concept of minimally invasive therapy as a treatment for failed medical therapy was assumed once it was approved for use, and is applied extensively in current clinical practice.\u003c/p\u003e \u003cp\u003eGiven this need for better information, we present a cohort of patients who truly failed medical therapy and underwent surgical management as a result. WATER and WATER II trials did not have a washout phase prior to enrollment therefore clearly representing a cohort that were symptomatic failure to medical therapy at baseline. As such, indications and inclusion situate these surgical therapies as the clear next step after failure to medical therapy. Both RWT and TURP demonstrated group statistical improvements in IPSS, QoL, Qmax, and PVR at 36-month compared to baseline. Functional outcomes did not statistically differ between RWT and TURP at baseline and at 36-month. TURP has classically been that option and in the WATER studies, RWT has demonstrated non inferiority. In a pre-specified analysis, RWT showed superior results in symptom reduction compared to TURP in prostate sizes 50-80cc. This sub-analysis of medical therapy failure cohort further reinforces the role of these therapies as treatment of choice for medical therapy failures including men who desire to limit their sexual adverse events from surgical therapies.\u003c/p\u003e \u003cp\u003eOf note, as an alternative to medical therapy, MISTs do not seem as favorable to medical therapy. When compared to medical therapy, MISTs complications include dysuria, gross hematuria, and urinary frequency. More serious complication though rare include bladder neck contracture and urosepsis were reported in pivotal trials\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Additionally, retreatment rate as high as 15.5% for Water Vapor Thermotherapy Treatment (WVTT) (4.4% for surgical reintervention; 11.1% restarting medication) and 33.6% (13.6% for surgical reintervention\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e; 10.7% restarting medication; 9.3% clip removal) for prostatic urethral lift (PUL) \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. In a recent meta-analysis looking at surgical reintervention rate after PUL in 2000 patients, reintervention rates were 4.3% per year in studies with \u0026lt;\u0026thinsp;1 year follow-up and can be as high as 10.7% in studies with longer follow-up up to 3 years \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Using a novel composite, symptom-centric metric to measure durability, the rate of medical or surgical retreatment was 10.6% and 31.8% in WVTT and PUL, respectively\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. In comparisons, the progression to surgical treatment in the Medical Therapy of Prostatic Symptoms (MTOPS) study was only 4% vs placebo and from the Alfuzosin Long-Term Efficacy and Safety Study (ALTESS) study progression to BPH-related surgery was only 2.2%\u003csup\u003e10, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. When placed in this context, medical therapy still seems superior to PUL and WVTT. In theory, these randomized prospective MIST RCTs compared to sham are designed to be an alternative to medical therapy.\u003c/p\u003e \u003cp\u003eContrary, in the 3-year trial comparing WVTT to pharmacotherapy show that clinical progression was 5 times more likely in the pharmacotherapy vs a single WVTT therapy suggesting that WVTT may be a reasonable alternative to pharamcotherapy\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. It should be noted, however, that symptomatic progression on phamacotherapy therapy to surgical therapy was very low, and that progression on MTOPs did not define failure of therapy as a historial comparison. Of note, a combination of pharmacotherapy (AB and 5-ARI) in both the MTOPs trial and Combination of Avodart and Tamsulosin (CombAT) trial has been demonstrated to be superior to monotherapy in controlling of both storage and voiding LUTS \u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. It maybe that WVTT would benefit with having a 5ARI added ot their post op regimen due to their high retreatment rate. There is currently a need for prospective studies directly comparing MISTs to pharmacotherapy to provide clarity for better identification and management of patients at risk of BPH progression\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Finally, the 5 year retreatment rates for surgery as well as back on meds from the WATER study (6% for RWT, 12.3% for TURP) should be noted as well\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSince the current clinical practice is to offer MIST to those who fail pharmacotherapy or need surgical intervention who desire a minimally invasive approach, future MIST trials should not have a washout period to demonstrated their role as a alternative to invasive surgical therapy and not pharmacotherapy as represented in current trials against sham.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe present functional outcomes on patients who truly failed medical therapy and underwent surgical prostatectomy therapies. Washout periods are not necessary in these studies that evaluate efficacy of a BPH surgery therapy. RWT and TURP are effective BPH therapy in patients who truly failed medical therapy, and RWT demonstrated effectiveness in a larger prostate size range. We also suggest that future clinical trials of surgical options including minimally invasive therapy sham should not have a washout period to demonstrate their role in as an option to medical therapy failure.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eLower urinary tract symptoms (LUTS)\u003c/p\u003e\n\u003cp\u003ebenign prostatic hyperplasia (BPH)\u003c/p\u003e\n\u003cp\u003e\u0026alpha;blocker (AB)\u003c/p\u003e\n\u003cp\u003e5\u0026alpha;-reductase inhibitor (5ARI)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlexis E. Te- Procept- PI and Consultant\u003c/p\u003e\n\u003cp\u003eSteven A. Kaplan- Procept- PI\u003c/p\u003e\n\u003cp\u003eBilal Chughtai-Procept- PI\u003c/p\u003e\n\u003cp\u003eChristina Sze- No conflicts\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlexis E.Te\u003csup\u003e\u0026nbsp;1\u003c/sup\u003e, Christina Sze\u003csup\u003e\u0026nbsp;1\u003c/sup\u003e, Steven A. Kaplan\u003csup\u003e2\u003c/sup\u003e, and Bilal Chughtai\u003csup\u003e\u0026nbsp;1\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThe above authors all contributed in the development, writing, editing and data analysis of this investigator initiated study and manuscript.\u003c/p\u003e\n\u003cp\u003eAchknowledgement is given to Procept Biorobotics for providing the data for this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure of Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWATER and WATER II were funded by Procept. No funding provided for manuscript development.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLerner, L. B., McVary, K. T., Barry, M. J. et al.: Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART II-Surgical Evaluation and Treatment. J Urol, \u003cb\u003e206\u003c/b\u003e: 818, 2021\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCampbell, J., Reid, J., Ordon, M. et al.: The Utilization of Benign Prostatic Hyperplasia and Bladder-Related Medications After a Transurethral Prostatectomy. Urology, \u003cb\u003e130\u003c/b\u003e: 126, 2019\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcVary, K. T., Gittelman, M. C., Goldberg, K. A. et al.: Final 5-Year Outcomes of the Multicenter Randomized Sham-Controlled Trial of a Water Vapor Thermal Therapy for Treatment of Moderate to Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia. J Urol, \u003cb\u003e206\u003c/b\u003e: 715, 2021\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNguyen, D. D., Barber, N., Bidair, M. et al.: WATER versus WATER II 2-Year Update: Comparing Aquablation Therapy for Benign Prostatic Hyperplasia in 30-80-cm(3) and 80-150-cm(3) Prostates. Eur Urol Open Sci, \u003cb\u003e25\u003c/b\u003e: 21, 2021\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMayer, E. K., Kroeze, S. G., Chopra, S. et al.: Examining the 'gold standard': a comparative critical analysis of three consecutive decades of monopolar transurethral resection of the prostate (TURP) outcomes. BJU Int, \u003cb\u003e110\u003c/b\u003e: 1595, 2012\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLepor, H., Sypherd, D., Machi, G. et al.: Randomized double-blind study comparing the effectiveness of balloon dilation of the prostate and cystoscopy for the treatment of symptomatic benign prostatic hyperplasia. 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D., Roehrborn, C. G., Bautista, O. M. et al.: The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med, \u003cb\u003e349\u003c/b\u003e: 2387, 2003\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoehrborn, C. G.: Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention: results of a 2-year placebo-controlled study. BJU Int, \u003cb\u003e97\u003c/b\u003e: 734, 2006\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGupta, N., Rogers, T., Holland, B. et al.: Three-Year Treatment Outcomes of Water Vapor Thermal Therapy Compared to Doxazosin, Finasteride and Combination Drug Therapy in Men with Benign Prostatic Hyperplasia: Cohort Data from the MTOPS Trial. J Urol, \u003cb\u003e200\u003c/b\u003e: 405, 2018\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaplan, S. A., Lee, J. Y., Meehan, A. G. et al.: Time Course of Incident Adverse Experiences Associated with Doxazosin, Finasteride and Combination Therapy in Men with Benign Prostatic Hyperplasia: The MTOPS Trial. J Urol, \u003cb\u003e195\u003c/b\u003e: 1825, 2016\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaplan, S. A., McConnell, J. D., Roehrborn, C. G. et al.: Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 ml or greater. J Urol, \u003cb\u003e175\u003c/b\u003e: 217, 2006\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMontorsi, F., Roehrborn, C., Garcia-Penit, J. et al.: The effects of dutasteride or tamsulosin alone and in combination on storage and voiding symptoms in men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH): 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study. BJU Int, \u003cb\u003e107\u003c/b\u003e: 1426, 2011\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoehrborn, C. G.: BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU Int, \u003cb\u003e101 Suppl 3\u003c/b\u003e: 17, 2008\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGilling, P. J., Barber, N., Bidair, M. et al.: Five-year outcomes for Aquablation therapy compared to TURP: results from a double-blind, randomized trial in men with LUTS due to BPH. Can J Urol, \u003cb\u003e29\u003c/b\u003e: 10960, 2022\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"aquablation, BPH, washout period, drug failure, Transurethral Prostatectomy, Robotic Water Jet Ablation, BPH Medical Therapy, LUTS, Bladder Outlet Obstruction, alpha adrenergic blockers, 5 alpha reductase inhibitors","lastPublishedDoi":"10.21203/rs.3.rs-1832879/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1832879/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eA 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.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eData 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 α-blockers (AB) and 5-α-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.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAB and/or 5-ARIs usage at baseline were reported in 146 and 39 patients who underwent RWT (prostate sizes up to 150cc) and transurethral resection of the prostate (TURP, prostate sizes up to 80cc) 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.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eRWT and TURP are effective BPH therapy in patients who truly failed medical therapy, and RWT demonstrated this in a much broader prostate size range.\u003c/p\u003e","manuscriptTitle":"Surgical Treatment for BPH Refractory to Medication: Robotic Water Jet Ablation vs TURP functional outcomes from two FDA clinical trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-25 13:54:34","doi":"10.21203/rs.3.rs-1832879/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7126559a-f10b-4766-b12c-de7de9d75d74","owner":[],"postedDate":"July 25th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-09-08T08:31:04+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-25 13:54:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1832879","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1832879","identity":"rs-1832879","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}