Matthias Oelke

EAU Guidelines on the Treatment and Follow-up of Non-neurogenic Male Lower Urinary Tract Symptoms Including Benign Prostatic Obstruction

OBJECTIVE To present a summary of the 2013 version of the European Association of Urology guidelines on the treatment and follow-up of male lower urinary tract symptoms (LUTS). EVIDENCE ACQUISITION We conducted a literature search in computer databases for relevant articles published between 1966 and 31 October 2012. The Oxford classification system (2001) was used to determine the level of evidence for each article and to assign the grade of recommendation for each treatment modality. EVIDENCE SYNTHESIS Men with mild symptoms are suitable for watchful waiting. All men with bothersome LUTS should be offered lifestyle advice prior to or concurrent with any treatment. Men with bothersome moderate-to-severe LUTS quickly benefit from α1-blockers. Men with enlarged prostates, especially those >40ml, profit from 5α-reductase inhibitors (5-ARIs) that slowly reduce LUTS and the probability of urinary retention or the need for surgery. Antimuscarinics might be considered for patients who have predominant bladder storage symptoms. The phosphodiesterase type 5 inhibitor tadalafil can quickly reduce LUTS to a similar extent as α1-blockers, and it also improves erectile dysfunction. Desmopressin can be used in men with nocturia due to nocturnal polyuria. Treatment with an α1-blocker and 5-ARI (in men with enlarged prostates) or antimuscarinics (with persistent storage symptoms) combines the positive effects of either drug class to achieve greater efficacy. Prostate surgery is indicated in men with absolute indications or drug treatment-resistant LUTS due to benign prostatic obstruction. Transurethral resection of the prostate (TURP) is the current standard operation for men with prostates 30-80ml, whereas open surgery or transurethral holmium laser enucleation is appropriate for men with prostates >80ml. Alternatives for monopolar TURP include bipolar TURP and transurethral incision of the prostate (for glands <30ml) and laser treatments. Transurethral microwave therapy and transurethral needle ablation are effective minimally invasive treatments with higher retreatment rates compared with TURP. Prostate stents are an alternative to catheterisation for men unfit for surgery. Ethanol or botulinum toxin injections into the prostate are still experimental. CONCLUSIONS These symptom-oriented guidelines provide practical guidance for the management of men experiencing LUTS. The full version is available online (www.uroweb.org/gls/pdf/12_Male_LUTS.pdf).

EAU Guidelines on the Assessment of Non-neurogenic Male Lower Urinary Tract Symptoms including Benign Prostatic Obstruction

CONTEXT Lower urinary tract symptoms (LUTS) represent one of the most common clinical complaints in adult men and have multifactorial aetiology. OBJECTIVE To develop European Association of Urology (EAU) guidelines on the assessment of men with non-neurogenic LUTS. EVIDENCE ACQUISITION A structured literature search on the assessment of non-neurogenic male LUTS was conducted. Articles with the highest available level of evidence were selected. The Delphi technique consensus approach was used to develop the recommendations. EVIDENCE SYNTHESIS As a routine part of the initial assessment of male LUTS, a medical history must be taken, a validated symptom score questionnaire with quality-of-life question(s) should be completed, a physical examination including digital rectal examination should be performed, urinalysis must be ordered, post-void residual urine (PVR) should be measured, and uroflowmetry may be performed. Micturition frequency-volume charts or bladder diaries should be used to assess male LUTS with a prominent storage component or nocturia. Prostate-specific antigen (PSA) should be measured only if a diagnosis of prostate cancer will change the management or if PSA can assist in decision-making for patients at risk of symptom progression and complications. Renal function must be assessed if renal impairment is suspected from the history and clinical examination, if the patient has hydronephrosis, or when considering surgical treatment for male LUTS. Uroflowmetry should be performed before any treatment. Imaging of the upper urinary tract in men with LUTS should be performed in patients with large PVR, haematuria, or a history of urolithiasis. Imaging of the prostate should be performed if this assists in choosing the appropriate drug and when considering surgical treatment. Urethrocystoscopy should only be performed in men with LUTS to exclude suspected bladder or urethral pathology and/or before minimally invasive/surgical therapies if the findings may change treatment. Pressure-flow studies should be performed only in individual patients for specific indications before surgery or when evaluation of the pathophysiology underlying LUTS is warranted. CONCLUSIONS These guidelines provide evidence-based practical guidance for assessment of non-neurogenic male LUTS. An extended version is available online (www.uroweb.org/guidelines). PATIENT SUMMARY This article presents a short version of European Association of Urology guidelines for non-neurogenic male lower urinary tract symptoms (LUTS). The recommended tests should be able to distinguish between uncomplicated male LUTS and possible differential diagnoses and to evaluate baseline parameters for treatment. The guidelines also define the clinical profile of patients to provide the best evidence-based care. An algorithm was developed to guide physicians in using appropriate diagnostic tests.

Monotherapy with Tadalafil or Tamsulosin Similarly Improved Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia in an International, Randomised, Parallel, Placebo-Controlled Clinical Trial

BACKGROUND Tadalafil improved lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH; LUTS/BPH) in clinical studies but has not been evaluated together with an active control in an international clinical study. OBJECTIVE Assess tadalafil or tamsulosin versus placebo for LUTS/BPH. DESIGN, SETTING, AND PARTICIPANTS A randomised, double-blind, international, placebo-controlled, parallel-group study assessed men ≥45 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥13, and maximum urinary flow rate (Q(max)) ≥4 to ≤15ml/s. Following screening and washout, if needed, subjects completed a 4-wk placebo run-in before randomisation to placebo (n=172), tadalafil 5mg (n=171), or tamsulosin 0.4mg (n=168) once daily for 12 wk. MEASUREMENTS Outcomes were assessed using analysis of covariance (ANCOVA) or ranked analysis of variance (ANOVA) (continuous variables) and Cochran-Mantel-Haenszel test or Fisher exact test (categorical variables). RESULTS AND LIMITATIONS IPSS significantly improved versus placebo through 12 wk with tadalafil (-2.1; p=0.001; primary efficacy outcome) and tamsulosin (-1.5; p=0.023) and as early as 1 wk (tadalafil and tamsulosin both -1.5; p<0.01). BPH Impact Index significantly improved versus placebo at first assessment (week 4) with tadalafil (-0.8; p<0.001) and tamsulosin (-0.9; p<0.001) and through 12 wk (tadalafil -0.8, p=0.003; tamsulosin -0.6, p=0.026). The IPSS Quality-of-Life Index and the Treatment Satisfaction Scale-BPH improved significantly versus placebo with tadalafil (both p<0.05) but not with tamsulosin (both p>0.1). The International Index of Erectile Function-Erectile Function domain improved versus placebo with tadalafil (4.0; p<0.001) but not tamsulosin (-0.4; p=0.699). Q(max) increased significantly versus placebo with both tadalafil (2.4ml/s; p=0.009) and tamsulosin (2.2ml/s; p=0.014). Adverse event profiles were consistent with previous reports. This study was limited in not being powered to directly compare tadalafil versus tamsulosin. CONCLUSIONS Monotherapy with tadalafil or tamsulosin resulted in significant and numerically similar improvements versus placebo in LUTS/BPH and Q(max). However, only tadalafil improved erectile dysfunction. TRIAL REGISTRATION Clinicaltrials.gov ID NCT00970632.

Age and Bladder Outlet Obstruction Are Independently Associated with Detrusor Overactivity in Patients with Benign Prostatic Hyperplasia

BACKGROUND Detrusor overactivity is one known cause of lower urinary tract symptoms and has been linked to bladder storage symptoms (urgency, frequency, or urge incontinence). OBJECTIVE To determine clinical and urodynamic parameters associated with detrusor overactivity in patients with suspected benign prostatic hyperplasia. DESIGN, SETTING, AND PARTICIPANTS During 1993-2003, urodynamic investigations were performed in patients aged 40 yr or older and with lower urinary tract symptoms, benign prostatic enlargement, and/or suspicion of bladder outlet obstruction (maximum flow rate < 15 ml/s or postvoid residual urine > 50 ml). MEASUREMENTS Detrusor overactivity was defined according to the new International Continence Society classification (2002) as involuntary detrusor contractions during cystometry, which may be spontaneous or provoked, regardless of amplitude. The Schäfer algorithm was used to determine bladder outlet obstruction. RESULTS In total, 1418 men were investigated (median age: 63 yr) of whom 864 men (60.9%) had detrusor overactivity. In univariate analysis, men with detrusor overactivity were significantly older, more obstructed, had larger prostates, higher irritative International Prostate Symptoms Score subscores, a lower voiding volume at free uroflowmetry, and a lower bladder capacity at cystometry. The prevalence of detrusor overactivity rose continuously with increasing bladder outlet obstruction grade. Multivariate analysis showed that only age and bladder outlet obstruction grade were independently associated with detrusor overactivity. After age adjustment, the odds ratios of detrusor overactivity compared to Schäfer class 0 were 1.2 for class I, 1.4 for class II, 1.9 for class III, 2.5 for class IV, 3.4 for class V, and 4.7 for class VI. CONCLUSIONS In patients with clinical benign prostatic hyperplasia, detrusor overactivity is independently associated with age and bladder outlet obstruction. The probability of detrusor overactivity rises with increasing age and bladder outlet obstruction grade.

Detrusor Underactivity: A Plea for New Approaches to a Common Bladder Dysfunction

Detrusor underactivity (DU) is defined by the International Continence Society as a contraction of reduced strength and/or duration resulting in prolonged or incomplete emptying of the bladder but has yet received only little attention. The purpose of this report is to summarize the ICI‐RS meeting in Bristol in 2010 exploring current knowledge on DU and outline directions for future research.

Metabolic syndrome and benign prostatic enlargement: a systematic review and meta-analysis.

To summarise and meta‐analyse current literature on metabolic syndrome (MetS) and benign prostatic enlargement (BPE), focusing on all the components of MetS and their relationship with prostate volume, transitional zone volume, prostate‐specific antigen and urinary symptoms, as evidence suggests an association between MetS and lower urinary tract symptoms (LUTS) due to BPE.

Is the use of parasympathomimetics for treating an underactive urinary bladder evidence-based?

An underactive urinary bladder (UUB), often occurring after surgery, can lead to urinary retention even in otherwise healthy people. We systematically reviewed published reports to determine whether the use of parasympathomimetic agents is warranted in patients with a UUB. Agents allegedly useful in treating UUB were identified from urology and pharmacology textbooks. A systematic search for randomized clinical trials in patients with UUB using these agents revealed 10 such studies. Controls typically received placebo or no treatment. While three studies reported statistically significant improvements relative to the control group, six did not and one even reported a significant worsening of symptoms. There was no evidence for differences between individual drugs, specific uses of such drugs, or in outcome measures. We conclude that the available studies do not support the use of parasympathomimetics for treating UUB, specifically when frequent and/or serious possible side‐effects are taken into account.

Systematic Review of Combination Drug Therapy for Non-neurogenic Male Lower Urinary Tract Symptoms

BACKGROUND Several drugs are approved for the treatment of lower urinary tract symptoms (LUTS) in men, but these are mostly used by clinicians as monotherapies. The combination of different compounds, each of which targets a different aspect of LUTS, seems appealing. However, only few clinical trials have evaluated the effects of combination therapies. OBJECTIVE This systematic review analyzes the efficacy and adverse events of combination therapies for male LUTS. EVIDENCE ACQUISITION PubMed and Cochrane databases were used to identify clinical trials and meta-analyses on male LUTS combination therapy. The search was restricted to studies of level of evidence ≥ 1b. A total of 49 papers published between January 1988 and March 2012 were identified. EVIDENCE SYNTHESIS The α1-adrenoceptor antagonist (α1-blocker)/5α-reductase inhibitor (5-ARI) combination provides the most data. This combination seems to be more efficacious in terms of several outcome variables in patients whose prostate volume is between 30 ml and 40 ml when treatment is maintained for >1 yr; when given for <1 yr, α1-blockers alone are just as effective. The combination of α1-blocker/5-ARI shows a slightly increased rate of adverse events. It remains unknown whether its safety and superiority over either drug as monotherapy are sustained after >6 yr. The α1-blocker/muscarinic receptor antagonist (antimuscarinic) combination was most frequently assessed as an add-on therapy to already existing α1-blocker therapy. Inconsistent data derive from heterogeneous study populations and different study designs. Currently, the α1-blocker/antimuscarinic combination appears to be a second-line add-on for patients with insufficient symptom relief after monotherapy. The combination seems to be safe in men with postvoid residual <200 ml. However, there are no trials >4 mo concerning safety and efficacy of this combination. The α1-blocker/phosphodiesterase type 5 inhibitor combination is a new treatment option with only preliminary reports. More studies are needed before definitive conclusions can be drawn. CONCLUSIONS An α1-blocker/5-ARI combination is beneficial for patients whose prostate volume is between 30 ml and 40 ml when medical treatment is intended for >1 yr. Based on short-term follow-up studies, add-on of antimuscarinics to α1-blockers is an option when postvoid residual is <200 ml.

Clinical relevance of urodynamic investigation tests prior to surgical correction of genital prolapse: a literature review

Urodynamic investigations have been advocated to be incorporated in the standard diagnostic workup of patients undergoing surgical correction of genital prolapse. Stress incontinence is reported by 40% of patients with genital prolapse. Urodynamic stress incontinence (USI) is diagnosed in 70–75% of these patients. Occult urodynamic stress incontinence (OUSI) is diagnosed in about 50% of the patients with genital prolapse not reporting stress incontinence before surgery. Performing urodynamic investigation in patients undergoing prolapse surgery may be valuable if diagnosing USI or OUSI results in the selection of the optimal treatment strategy. This treatment strategy is either a combination of prolapse and stress incontinence surgery or prolapse surgery at the beginning and re-evaluation of possible stress incontinence afterwards. The combination of prolapse and stress incontinence surgery has the advantage of attempting to solve two problems at the same moment, but carries an increased risk on unwanted side-effects, of which, voiding dysfunction and detrusor overactivity are the most important. This review presents a literature overview of what has been proven about the diagnostic and therapeutic value of urodynamic investigations in patients undergoing prolapse surgery.

Flexible-dose fesoterodine in elderly adults with overactive bladder: results of the randomized, double-blind, placebo-controlled study of fesoterodine in an aging population trial.

To assess the efficacy and safety of flexible‐dose fesoterodine in elderly adults with overactive bladder (OAB).