Medical Treatment of Nocturia in Men with Lower Urinary Tract Symptoms : Systematic Review by the European Association of Urology Guidelines Panel for Male Lower Urinary Tract Symptoms

Context: The treatment of nocturia is a key challenge due to the multi-factorial pathophysiology of the symptom and the disparate outcome measures used in research. Objective: To assess and compare available therapy options for nocturia, in terms of symptom severity and quality of life. Evidence acquisition: Medical databases (Embase, Medline, Cochrane Systematic Reviews, Cochrane Central) were searched with no date restriction. Comparative studies were included which studied adult men with nocturia as the primary presentation and lower urinary tract symptoms including nocturia or nocturnal polyuria. Outcomes were symptom severity, quality of life, and harms. Evidence synthesis: We identified 44 articles. Antidiuretic therapy using dose titration was more effective than placebo in relation to nocturnal voiding frequency and duration of undisturbed sleep; baseline serum sodium is a key selection criterion. Screening for hyponatremia (<130 mmol/l) must be undertaken at baseline, after initiation or dose titration, and during treatment. Medications to treat lower urinary tract dysfunction (alpha-1 adrenergic antagonists, 5-alpha reductase inhibitors, phosphodiesterase type 5inhibitor, antimuscarinics, beta-3 agonist, and phytotherapy) were generally not significantly better than placebo in short-term use. Benefits with combination therapies were not consistently observed. Other medications (diuretics, agents to promote sleep, nonsteroidal anti-inflammatories) were sometimes associated with response or quality of life improvement. The recommendations of the Guideline Panel are presented. Conclusions: Issues of trial designmake therapy of nocturia a challenging topic. The range of contributory factors relevant in nocturia makes it desirable to identify predictors of response to guide therapy. Consistent responses were reported for titrated antidiuretic therapy. For other therapies, responses were less certain, and potentially of limited clinical benefit. Patient summary: This review provides an overview of the current drug treatments of nocturia, which is the need to wake at night to pass urine. The symptom can be caused by several different medical conditions, and measuring its severity and impact varies in separate research studies. No single treatment deals with the symptom in all contexts, and careful assessment is essential to make suitable treatment selection. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewe

Management of Urinary Retention in Patients with Benign Prostatic Obstruction : A Systematic Review and Meta-analysis

Context: Practice patterns for the management of urinary retention (UR) secondary to benign prostatic obstruction (BPO; UR/BPO) vary widely and remain unstandardized. Objective: To review the evidence for managing patients with UR/BPO with pharmacological and nonpharmacological treatments included in the European Association of Urology guidelines on non-neurogenic male lower urinary tract symptoms. Evidence acquisition: Search was conducted up to April 22, 2018, using CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. This systematic review included randomized controlled trials (RCTs) and prospective comparative studies. Methods as detailed in the Cochrane handbook were followed. Certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Evidence synthesis: Literature search identified 2074 citations. Twenty-one studies were included (qualitative synthesis). The evidence for managing patients with UR/BPO with pharmacological or nonpharmacological treatments is limited. CoE for most outcomes was low/very low. Only alpha 1-blockers (alfuzosin and tamsulosin) have been evaluated in more than one RCT. Pooled results indicated that a1-blockers provided significantly higher rates of successful trial without catheter compared with placebo [alfuzosin: 322/540 (60%) vs 156/400 (39%) (odds ratio {OR} 2.28, 95% confidence interval {CI} 1.55 to 3.36; participants = 940; studies = 7; I-2 = 41%; low CoE); tamsulosin: 75/158 (47%) vs 40/139 (29%) (OR 2.40, 95% CI 1.29 to 4.45; participants = 297; studies = 3; I-2 = 30%; low CoE)] with rare adverse events. Similar rates were achieved with tamsulosin or alfuzosin [51/87 (59%) vs 45/84 (54%) (OR 1.28, 95% CI 0.68 to 2.41;participants = 171; studies = 2; I-2 = 0%; very low CoE)]. Nonpharmacological treatments have been evaluated in RCTs/prospective comparative studies only sporadically. Conclusions: There is some evidence that usage of alpha 1-blockers (alfuzosin and tamsulosin) may improve resolution of UR/BPO. As most nonpharmacological treatments have not been evaluated in patients with UR/BPO, the evidence is inconclusive about their benefits and harms. Patient summary: There is some evidence that alfuzosin and tamsulosin may increase the rates of successful trial without catheter, but little or no evidence on various nonpharmacological treatment options for managing patients with urinary retention secondary to benign prostatic obstruction. (c) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewe

What are the short-term benefits and potential harms of therapeutic modalities for the management of overactive bladder syndrome in women? : A review of evidence under the auspices of the European Association of Urology, Female Non-Neurogenic LUTS Guidelines Panel

Peer reviewe

Diagnostic Tests for Female Bladder Outlet Obstruction : A Systematic Review from the European Association of Urology Non-neurogenic Female LUTS Guidelines Panel

Acknowledgements Jae Hung Jung, Murat Gul, Ege Can Serefoglu (translation of foreign language articles) and Karin Plass for administrative support.Peer reviewedPostprin

Pattern of somatostatin receptor, Kiss-1 and GPR54 receptor expression in the bladder cancer

Bladder cancer is the 4th most common cancer in men and the 9th most common cancer in female in developed countries. The prognosis of bladder cancer become worse with advancing stage. Five year survival rate drops from 80-90% in superficial cancer to only 10-15% in metastatic cancer. Risks factors for tumor progression and recurrence include previous tumor recurrence rate, number of tumors, tumor diameter, tumor stage, tumor grade and the presence of carcinoma in situ. Unfortunately, these clinicopathological parameters are limited in their prognostic ability. Therefore identification of molecular determinant of disease progression could provide more specific prognostic information and could be translated into new approaches for drug and biomarker development. In the present study we evalutated for the first time the expression pattern of Kiss1, GPR54 and of the somatostatin receptors 1-5 (SSTRs) in bladder cancer. We initially collected 73 samples from 64 patients, 59 pathological with bladder cancer and 14 with normal urothelium. There were no expression neither of Kiss 1 nor of GPR54. With regard to the SSTRs, SSTR1 was expressed in 24 samples, SSTR2 in 15 samples, SSTR3 in 23 samples, SSTR4 in 16 samples and SSTR5 in all but one. Patients were stratified according to disease status ie normal and pathological, according to stage ie superficial and muscle invasive and according to the presentation ie first presentation or recurrence. Bladder cancer tissue samples expressed lower levels of SSTR3 (p=0.03). We also studied the co-expression patterns of SSTRs in the bladder cancer tissue samples. In 8 cases SSTR5 was the only SSTR expressed, in 8 cases there was coexpression between SSTR5 with another SSTR, in 17 cases there were coexpression of more than 2 SSTRs while in one case there were no expression of SSTR. It is worthy to note that between the 8 cases with coexpression between 2 SSTRs, there were only 3 recurrence and there was no a case with muscle invasive disease. In contrast, there were 4 cases with muscle invasive disease in the samples with expression of only SSTR5 (p=0.05). Our results demonstrate for the first time that there is expression of SSTRin bladder cancer and normal bladder urothelium. Further studies are required to evaluate the significance of our findings.Ο καρκίνος της ουροδόχου κύστης είναι ο 4ος πιο συχνός καρκίνος στους άνδρες και ο 9ος πιο συχνός καρκίνος στις γυναίκες. Η πρόγνωση του καρκίνου της ουροδόχου κύστης χειροτερεύει στα προχωρημένα στάδια, με την 5ετής επιβίωση να μειώνεται από 80-90% στους επιφανειακούς καρκίνους σε μόλις 10-15% στους μεταστατικούς καρκίνους. Δυστυχώς οι μέχρι σήμερα παράγοντες κινδύνου για την εξέλιξη και την υποτροπή της νόσου όπως στάδιο, μέγεθος όγκου, βαθμός διαφοροποίησης και παρουσία in situ έχουν περιορισμένη προγνωστική αξία. Ο προσδιορισμός και ταυτοποίηση μοριακών μηχανισμών που σχετίζονται με την ανάπτυξη και εξέλιξη του καρκίνου της ουροδόχου κύστης θα μπορούσε να συμβάλει στην ακριβέστερη κατανόηση της κλινικής πορείας και πρόγνωσης των όγκων της κύστης καθώς και στην ανακάλυψη διαγνωστικών μεθόδων και θεραπειών που θα έχουν ως στόχο την αντιμετώπιση τόσο του πρωτοπαθούς όγκου όσο και της μετάστασης. Στην παρούσα μελέτη προσπαθήσαμε για πρώτη φορά να διευκρινίσουμε τα μοντέλα έκφρασης της KISS-1, του GPR54 και των υποδοχέων της σωματοστατίνης 1-5 (SSTR 1-5) στον καρκίνο της ουροδόχου κύστης. Αρχικώς συλλέξαμε 73 δείγματα από 64 ασθενείς, 59 παθολογικά με καρκίνο και 14 δείγματα φυσιολογικού ουροθηλίου. Τελικώς, ικανά προς ανάλυση ήταν 46 δείγματα. Δεν προέκυψε έκφραση τόσο της Kiss 1 όσο και του υποδοχέα της GPR54. Σχετικά με τους SSTRs, οι SSTR1 ανιχνεύθηκαν σε 24 δείγματα, οι SSTR2 σε 15 δείγματα, οι SSTR3 σε 23 δείγματα, οι SSTR4 σε 16 δείγματα και οι SSTR5 σε όλα πλην ενός. Πραγματοποιήθηκε διαστρωμάτωση των ασθενών σε φυσιολογικούς και παθολογικούς, επιφανειακούς και μυοδιηθητικούς, και πρωτοεμφανιζόμενους και υποτροπιάζων. Η μόνη στατιστικώς σημαντική συσχέτιση παρουσιάστηκε στους SSTR3 όπου τα ποσοστά έκφρασης ήταν μειωμένα στους παθολογικούς ιστούς (p=0.03). Μελετήσαμε επίσης και μοντέλα συνέκφρασης των υποδοχέων SSTRs στα 34 παθολογικά δείγματα όπου και διαπιστώσαμε αποκλειστική έκφραση των SSTR5 σε 8 περιπτώσεις, συνέκφραση SSTR5 με ένα άλλο SSTR σε 8 περιπτώσεις, συνέκφραση πέραν των 2 SSTRs σε 17 περιπτώσεις, ενώ σε μια περίπτωση δεν παρουσιάστηκε καθόλου έκφραση των SSTRs. Είναι χαρακτηριστικό ότι μεταξύ των 8 περιπτώσεων όπου παρουσιάστηκε συνέκφραση μεταξύ SSTR5 και ενός άλλου SSTR μόνο 3 αφορούσαν υποτροπές ενώ δεν διαπιστώθηκε μυοδιηθητική νόσο σε αντίθεση με τις 8 περιπτώσεις με αποκλειστική έκφραση των SSTR5 όπου στις 4 εξ αυτών υπήρχε μυοδιηθητική νόσο (p=0.05). Τα αποτελέσματα αυτά αναδεικνύουν για πρώτη φορά στην διεθνή βιβλιογραφία την έκφραση των SSTRs στην ουροδόχο κύστη και θέτουν το βιολογικό πλαίσιο για την περαιτέρω μελέτη των μοντέλων έκφρασης τους καθώς και της σημασία τους στον καρκίνο της ουροδόχου κύστης

Anatomically biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy

Objectives: Since tumor focality in prostate cancer continues to be considered a major limitation for focal prostate therapy, in this study we attempted to compare the pathological features and the proportion of patients with anatomically unifocal versus biologically unifocal tumors (i.e. multifocal prostate cancer in which the secondary nonindex elements are small, low grade and clinically insignificant) who were suitable for focal therapy. Methods: Ninety-five consecutive whole mount laparoscopic radical prostatectomy samples underwent pathological assessment (from January 2007 to November 2009). Tumor focality, laterality, Gleason score and volume of individual foci, total tumor volume, pathological stage and surgical margin status were assessed. The index lesion was defined as the largest by volume. Patients suitable for focal ablation were defined as having tumors that were unifocal, organ confined, with a Gleason score (GS) up to 7 prostate cancer, or multifocal, organ confined, GS up to 7 prostate cancer, with one large index lesion and the remaining foci demonstrating features of clinically insignificant disease (total tumor volume of all secondary foci ≤0.5 cm 3 with GS ≤ 6). Results: Patients with biologically unifocal cancer had significantly lower total tumor volume (3.26 versus 7.28 cm 3 ; p < 0.001), index lesion volume (2.9 versus 7.16 cm 3 ; p < 0.001), rates of seminal vesicle invasion (4% versus 34%; p < 0.001), rates of positive surgical margins (22.4% versus 52.1%; p < 0.001) and rates of 4+3 GS tumors (10.2% versus 29.1%; p = 0.018). The proportion of patients suitable for focal therapy was higher in the biologically unifocal versus anatomically unifocal cancer group, although without reaching statistical significance (65.3% versus 45.8%; p = 0.11). Conclusions: Patients with biologically unifocal tumors have better pathological outcome than those with anatomically unifocal disease. At present the assumption that multifocality should a priori exclude patients from any organ-preserving prostate cancer treatment is only theoretical and needs to be validated by future clinical trials since there are a large proportion of patients with multifocal disease apparently suitable for focal prostate therapy

Summary Paper on the 2023 European Association of Urology Guidelines on the Management of Non-neurogenic Male Lower Urinary Tract Symptoms

International audienc

Nondetectable Prostate Carcinoma (pT0) after Radical Prostatectomy: A Narrative Review

(1) Background: Following radical prostatectomy (RP), the absence of a demonstrable tumor on the specimen of a previously histologically proven malignancy is known as the pT0 stage. The aim of our present study is to perform a narrative review of current literature in order to determine the frequency and oncological outcomes in patients with pT0 disease. (2) Methods: A narrative review of all available literature was performed. (3) Results: The incidence of pT0 ranges between 0.07% and 1.3%. Predictors of the pT0 stage are only a single biopsy core with low-grade cancer, a cancer length not exceeding 2 mm and a high prostate volume. Biochemical recurrence ranges between 0 and 11%. (4) Conclusions: The absence of malignancy in the RP specimen despite a previous positive biopsy is a rare and unpredictable finding. Although the prognosis is considered to be excellent in most of the cases, a continued close follow-up is warranted