Prostate Transition Zone Fibrosis is Associated with Clinical Progression in the MTOPS Study

No AccessJournal of UrologyAdult Urology1 Dec 2019Prostate Transition Zone Fibrosis is Associated with Clinical Progression in the MTOPS StudyThis article is commented on by the following:Editorial Comment Jill A. Macoska, Kristen S. Uchtmann, Glen E. Leverson, Kevin T. McVary, and William A. Ricke Jill A. MacoskaJill A. Macoska Center for Personalized Cancer Therapy, University of Massachusetts, Boston, Massachusetts George M. O'Brien Center for Benign Urologic Research, University of Wisconsin, Madison, Wisconsin , Kristen S. UchtmannKristen S. Uchtmann George M. O'Brien Center for Benign Urologic Research, University of Wisconsin, Madison, Wisconsin Department of Urology, University of Wisconsin, Madison, Wisconsin , Glen E. LeversonGlen E. Leverson Department of Urology, University of Wisconsin, Madison, Wisconsin , Kevin T. McVaryKevin T. McVary Department of Urology, Loyola University Medical Center, Maywood, Illinois , and William A. RickeWilliam A. Ricke †Correspondence: Department of Urology, 7107 Wisconsin Institute of Medical Research, University of Wisconsin-Madison, Madison, Wisconsin 53705 telephone: 608-265-3202; FAX: 608-265-0614; E-mail Address: [email protected] George M. O'Brien Center for Benign Urologic Research, University of Wisconsin, Madison, Wisconsin Department of Urology, University of Wisconsin, Madison, Wisconsin View All Author Informationhttps://doi.org/10.1097/JU.0000000000000385AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Medications targeting androgen receptor activity (eg finasteride) or smooth muscle contractility (eg doxazosin) do not resolve lower urinary tract symptoms indicative of lower urinary tract dysfunction in an important subgroup of men. Recently fibrosis has been implicated as another pathobiology contributing to male lower urinary tract symptoms but to our knowledge no systematic studies have been done to assess fibrosis in the context of medical treatment. We determine whether fibrotic changes in the prostate transition zone are associated with an increased risk of clinical progression in participants treated with doxazosin, finasteride or finasteride plus doxazosin in the MTOPS (Medical Therapy of Prostatic Symptoms) study. Materials and Methods: Transition zone biopsy tissues from men who did or did not experience clinical progression on placebo, doxazosin, finasteride or combination therapy were assessed for collagen content and architectural changes using picrosirius red birefringence and CT-FIRE (Curvelet Transform-Fiber Extraction) analysis. Correlations were made with annotated demographic and clinical data. Statistical analyses were done with the Pearson correlation coefficient, ANOVA and the t-test. Results: High levels of wavy, aligned prostate transition zone collagen significantly correlated with an increased risk of clinical progression among MTOPS trial participants treated with doxazosin plus finasteride, particularly those with a high body mass index. Conclusions: Fibrotic changes in the prostate transition zone are associated with an increased risk of clinical progression in men treated with doxazosin plus finasteride. Antifibrotic therapeutics might provide a new treatment approach in men with lower urinary tract dysfunction who do not respond to current medical treatment approaches. References 1. : The epidemiology of benign prostatic hyperplasia associated with lower urinary tract symptoms: prevalence and incident rates. Urol Clin North Am 2016; 43: 289. Google Scholar 2. : A review of combination therapy in patients with benign prostatic hyperplasia. Clin Ther 2007; 9: 387. Google Scholar 3. : Medical management of lower urinary tract symptoms. 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Google Scholar The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. Supported by NIH (National Institutes of Health)/NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) Awards U54 DK104310 (WAR, JAM) and ES001332 (WAR). No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. Editor's Note: This article is the fifth of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1277 and 1278. © 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited bySmith J (2019) This Month in Adult UrologyJournal of Urology, VOL. 202, NO. 6, (1069-1070), Online publication date: 1-Dec-2019.Related articlesJournal of Urology11 Sep 2019Editorial Comment Volume 202Issue 6December 2019Page: 1240-1247 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.Keywordsfinasteridefibrosisdoxazosinprostatelower urinary tract symptomsAcknowledgmentMike Guill, NIDDK Central Repository, assisted with acquiring and understanding data annotated to biopsy specimens. Dr. Reginald Bruskewitz provided clinical insight and reviewed the manuscript.MetricsAuthor Information Jill A. Macoska Center for Personalized Cancer Therapy, University of Massachusetts, Boston, Massachusetts George M. O'Brien Center for Benign Urologic Research, University of Wisconsin, Madison, Wisconsin Equal study contribution. More articles by this author Kristen S. Uchtmann George M. O'Brien Center for Benign Urologic Research, University of Wisconsin, Madison, Wisconsin Department of Urology, University of Wisconsin, Madison, Wisconsin Equal study contribution. More articles by this author Glen E. Leverson Department of Urology, University of Wisconsin, Madison, Wisconsin More articles by this author Kevin T. McVary Department of Urology, Loyola University Medical Center, Maywood, Illinois More articles by this author William A. Ricke George M. O'Brien Center for Benign Urologic Research, University of Wisconsin, Madison, Wisconsin Department of Urology, University of Wisconsin, Madison, Wisconsin †Correspondence: Department of Urology, 7107 Wisconsin Institute of Medical Research, University of Wisconsin-Madison, Madison, Wisconsin 53705 telephone: 608-265-3202; FAX: 608-265-0614; E-mail Address: [email protected] More articles by this author Expand All The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. Supported by NIH (National Institutes of Health)/NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) Awards U54 DK104310 (WAR, JAM) and ES001332 (WAR). No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. Editor's Note: This article is the fifth of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1277 and 1278. Advertisement PDF downloadLoading ...