Claus G. Roehrborn

Update on AUA Guideline on the Management of Benign Prostatic Hyperplasia

PURPOSE To revise the 2003 version of the American Urological Associations (AUA) Guideline on the management of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS From MEDLINE® searches of English language publications (January 1999 through February 2008) using relevant MeSH terms, articles concerning the management of the index patient, a male ≥45 years of age who is consulting a healthcare provider for lower urinary tract symptoms (LUTS) were identified. Qualitative analysis of the evidence was performed. Selected studies were stratified by design, comparator, follow-up interval, and intensity of intervention, and meta-analyses (quantitative synthesis) of outcomes of randomized controlled trials were planned. Guideline statements were drafted by an appointed expert Panel based on the evidence. RESULTS The studies varied as to patient selection; randomization; blinding mechanism; run-in periods; patient demographics, comorbidities, prostate characteristics and symptoms; drug doses; other intervention characteristics; comparators; rigor and intervals of follow-up; trial duration and timing; suspected lack of applicability to current US practice; and techniques of outcomes measurement. These variations affected the quality of the evidence reviewed making formal meta-analysis impractical or futile. Instead, the Panel and extractors reviewed the data in a systematic fashion and without statistical rigor. Diagnosis and treatment algorithms were adopted from the 2005 International Consultation of Urologic Diseases. Guideline statements concerning pharmacotherapies, watchful waiting, surgical options and minimally invasive procedures were either updated or newly drafted, peer reviewed and approved by AUA Board of Directors. CONCLUSIONS New pharmacotherapies and technologies have emerged which have impacted treatment algorithms. The management of LUTS/BPH continues to evolve.

Latest Evidence on the Use of Phosphodiesterase Type 5 Inhibitors for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

CONTEXT Several preclinical reports, randomized controlled trials, systematic reviews, and posthoc analyses corroborate the role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of men with lower urinary tract symptoms (LUTS) associated with benign prostatic enlargement (BPE). OBJECTIVE Update of the latest evidence on the mechanisms of action, evaluate the current meta-analyses, and emphasize the results of pooled data analyses of PDE5-Is in LUTS/BPE. EVIDENCE ACQUISITION Literature analysis of basic researches on PDE5-Is, systematic literature search in PubMed and Scopus until May 2015 on reviews of trials on PDE5-Is, and collection of pooled data available on tadalafil 5mg. EVIDENCE SYNTHESIS Latest evidences on the pathophysiology of LUTS/BPE has provided the rationale for use of PDE5-Is: (1) improvement of LUT oxygenation, (2) smooth muscle relaxation, (3) negative regulation of proliferation and transdifferentiation of LUT stroma, (4) reduction of bladder afferent nerve activity, and (5) down-regulation of prostate inflammation are the proven mechanisms of action of PDE5-Is. Data from eight systematic reviews demonstrated that PDE5-Is allow to improve LUTS (International Prostate Symptom Score mean difference vs placebo: 2.35-4.21) and erectile function (International Index of Erectile Function mean difference vs placebo: 2.25-5.66), with negligible change in flow rate (Qmax mean difference vs placebo: 0.01-1.43). Pooled data analyses revealed that tadalafil 5mg once daily allows the clinically-meaningful improvement of LUTS and nocturnal voiding frequency independent of both erectile dysfunction severity and improvement. CONCLUSIONS PDE5-Is are safe and effective in improving both LUTS and erectile function in appropriately selected men with LUTS/BPE. Data on the reduction of disease progression, long-term outcomes, and cost-effectiveness analyses are still lacking. PATIENT SUMMARY We reviewed recent literature on phosphodiesterase type 5 inhibitors in men with lower urinary tract symptoms associated with prostatic enlargement. We found evidence to confirm that phosphodiesterase type 5 inhibitors are a valid treatment option for men affected by bothersome urinary symptoms with or without erectile dysfunction.

Chronic Prostate Inflammation is Associated with Severity and Progression of Benign Prostatic Hyperplasia, Lower Urinary Tract Symptoms and Risk of Acute Urinary Retention

PURPOSE We evaluated associations between histological prostate inflammation, and the development and progression of benign prostatic hyperplasia/lower urinary tract symptoms in men randomized to placebo in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study in a 4-year period. MATERIALS AND METHODS The association of acute and chronic inflammation detected on baseline biopsies and benign prostatic hyperplasia related parameters, including I-PSS (International Prostate Symptom Score) and prostate volume, at multiple time points during 4 years in men randomized to placebo enrolled in the REDUCE prostate cancer prevention study was analyzed with the Student t-test. The association of inflammation with newly developed benign prostatic hyperplasia/lower urinary tract symptoms and benign prostatic hyperplasia progression in patients with existing benign prostatic hyperplasia/lower urinary tract symptoms was analyzed with univariable and multivariable Cox models. RESULTS Acute and chronic inflammation was seen in baseline negative biopsies of 641 (15.6%) and 3,216 (78.3%) of the 4,109 men in the study. Chronic but not acute inflammation was associated with slightly higher baseline I-PSS (0.6 difference, p = 0.001) and larger prostate volume (3.2 cc difference, p <0.001), a difference noted throughout the study interval. The presence of acute and chronic inflammation was not associated with the incidence of benign prostatic hyperplasia/lower urinary tract symptoms in men without those conditions at baseline or the progression of symptomatic benign prostatic hyperplasia in men with benign prostatic hyperplasia/lower urinary tract symptoms at baseline. However, an association was observed with more severe inflammation. Chronic inflammation at baseline was associated with an increased risk of acute urinary retention (HR 1.6-1.8, p = 0.001). CONCLUSIONS Our longitudinal evaluation of REDUCE patients randomized to placebo for 4 years confirmed that chronic inflammation is associated with severity and the progression of benign prostatic hyperplasia and benign prostatic hyperplasia/lower urinary tract symptom outcomes.

Convective Thermal Therapy: Durable 2-Year Results of Randomized Controlled and Prospective Crossover Studies for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia

Purpose: We report 2‐year outcomes of a multicenter randomized controlled trial plus 1‐year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia. Materials and Methods: A total of 197 men at least 50 years old with I‐PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezūm® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. Results: Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8‐point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. Conclusions: Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe.

Magnetic resonance/transrectal ultrasound fusion biopsy of the prostate compared to systematic 12-core biopsy for the diagnosis and characterization of prostate cancer: Multi-institutional retrospective analysis of 389 patients

OBJECTIVE To determine the incremental diagnostic value of targeted biopsies added to an extended sextant biopsy scheme on a per-patient, risk-stratified basis in 2 academic centers using different multiparametric magnetic resonance imaging (MRI) protocols, a large group of radiologists, multiple biopsy systems, and different biopsy operators. MATERIALS AND METHODS All patients with suspected prostate cancer (PCa) who underwent multiparametric MRI of the prostate in 2 academic centers between February 2013 and January 2015 followed by systematic and targeted MRI-transrectal ultrasound fusion biopsy were reviewed. Risk-stratified detection rate using systematic biopsies was compared with targeted biopsies on a per-patient basis. The McNemar test was used to compare diagnostic performance of the 2 approaches. RESULTS A total of 389 men met eligibility criteria. PCa was diagnosed in 47% (182/389), 52%(202/389), and 60%(235/389) of patients using the targeted, systematic, and combined (targeted plus systematic) approach, respectively. Compared with systematic biopsy, targeted biopsy diagnosed 11% (37 vs. 26) more intermediate-to-high risk (P<0.0001) and 16% (10 vs. 16) fewer low-risk tumors (P<0.0001). These results were replicated when data from each center, biopsy-naïve patients, and men with previous negative biopsies were analyzed separately. CONCLUSION Targeted MRI-transrectal ultrasound fusion biopsy consistently improved the detection of clinically significant PCa in a large patient cohort with diverse equipment, protocols, radiologists, and biopsy operators as can be encountered in clinical practice.

Low Serum Testosterone Level Predisposes to Artificial Urinary Sphincter Cuff Erosion

OBJECTIVE To examine the association between decreased serum testosterone levels and artificial urinary sphincter (AUS) cuff erosion. MATERIALS AND METHODS We evaluated serum testosterone levels in 53 consecutive patients. Low testosterone was defined as <280 ng/dL and found in 30/53 patients (56.6%). Chi-square and Student t tests, Kaplan-Meier analysis, binary logistic regression, and Cox regression analysis were used to determine statistical significance. RESULTS Nearly all men with AUS cuff erosions had low serum testosterone (18/20, 90.0%) compared to those without erosions (12/33, 36.4%, P < .001). Mean time to erosion was 1.70 years (0.83-6.86); mean follow-up was 2.76 years (0.34-7.92). Low testosterone had a hazard ratio of 7.15 for erosion in a Cox regression analysis (95% confidence interval 1.64-31.17, P = .009) and Kaplan-Meier analysis demonstrated decreased erosion-free follow-up (log-rank P = .002). Low testosterone was the sole independent risk factor for erosion in a multivariable model including coronary artery disease and radiation (odds ratio 15.78; 95% confidence interval 2.77-89.92, P = .002). Notably, history of prior AUS, radiation, androgen ablation therapy, or concomitant penile implant did not confound risk of cuff erosion in men with low testosterone levels. CONCLUSION Men with low testosterone levels are at a significantly higher risk to experience AUS cuff erosion. Appropriate counseling before AUS implantation is warranted and it is unclear whether testosterone resupplementation will mitigate this risk.

Emerging Minimally Invasive Treatment Options for Male Lower Urinary Tract Symptoms

CONTEXT Lower urinary tract symptoms (LUTS) are one of the most common and troublesome nonmalignant conditions affecting quality of life in aging men. A spectrum of established medical and surgical options is available to provide relief of bothersome LUTS. Both the adverse events of medication and the morbidity with surgical treatment modalities have to be counterbalanced against efficacy. Novel minimally invasive treatment options aim to be effective, ideally to be performed in an ambulatory setting under local anaesthesia and to offer a more favourable safety profile than existing reference techniques. OBJECTIVE A comprehensive, narrative review of novel minimally invasive treatment modalities for the management of male LUTS due to benign prostatic enlargement is presented. EVIDENCE ACQUISITION Medline, PubMed, Cochrane database, and Embase were screened for randomised controlled trials (RCTs), clinical trials, and reviews on novel minimally invasive treatment options for male LUTS due to benign prostatic enlargement. EVIDENCE SYNTHESIS With regard to newly devised intraprostatic injectables (botulinum neurotoxin A, NX1207, PRX302), PRX302 is currently the only substance that was superior to placebo in a phase 3 RCT providing proof of efficacy and safety. The prostatic urethral lift technique has been evaluated in several phase 3 trials showing rapid and durable relief of LUTS without compromising sexual function in carefully selected patients without a prominent median lobe. The first clinical experience of the temporary implantable nitinol device demonstrated that implantation of this novel device is a safe procedure, easy, and fast to perform. Further studies are required to evaluate efficacy, durability, and to define appropriate patient selection. New ablative approaches like the image guided robotic waterjet ablation (AquaBeam) or procedures based on convective water vapour energy (Rezūm) are in the early stages of development. Prostatic artery embolization performed by interventional radiologists at specialised centres shows a high technical success rate in the treatment of bothersome LUTS. However, a substantial clinical failure rate and a particular spectrum of complications not commonly seen after urologic interventions do occur and need to be critically evaluated. CONCLUSIONS Initial promising clinical results on novel minimally invasive treatment options indicate efficacy comparable to standard techniques, often associated with a more favourable safety profile, in particular with preservation of sexual function. Many of these techniques are in their infancy and based on experience of new developments in the past. Further RCTs are required to evaluate efficacy, safety, and durability of novel techniques with long-term follow-up and careful evaluation of the selection criteria, which have been applied in clinical trials. The prostatic urethral lift is the only procedure with Level 1 evidence data and that can therefore be recommended for treatment of male LUTS in clinical practice for selected patients. PATIENT SUMMARY Minimally invasive treatment options have been developed to provide relief of lower urinary tract symptoms comparable to standard surgical techniques with a more favourable safety profile. However, long-term clinical evaluation is still needed for most of these innovations before they can be recommended to be an effective replacement for standard surgical treatment.

A prospective randomised placebo-controlled study of the impact of dutasteride/tamsulosin combination therapy on sexual function domains in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH)

To prospectively assess the impact of the fixed‐dose combination (FDC) of the 5α‐reductase inhibitor (5ARI), dutasteride 0.5 mg and the α1‐adrenoceptor antagonist, tamsulosin 0.4 mg (DUT‐TAM FDC) therapy on sexual function domain scores in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), using the Mens Sexual Health Questionnaire (MSHQ).

Quantitative diffusion‐weighted imaging and dynamic contrast‐enhanced characterization of the index lesion with multiparametric MRI in prostate cancer patients

To compare a simplified intravoxel incoherent motion (sIVIM) model to commonly used monoexponential and biexponential models in the characterization of prostate cancer (PCa) and noncancerous prostate tissues, and to investigate combinations of diffusion‐weighted imaging (DWI) measures with dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI)‐derived parameters in MRI‐visible index lesions, to facilitate PCa risk stratification.

Robot-Assisted Versus Open Simple Prostatectomy for Benign Prostatic Hyperplasia in Large Glands: A Propensity Score–Matched Comparison of Perioperative and Short-Term Outcomes

OBJECTIVE To report the largest comparative analysis of robotic vs open simple prostatectomy (OSP) for large-volume prostate glands. MATERIALS AND METHODS We retrospectively reviewed 103 patients that underwent open and 64 patients that underwent robotic simple prostatectomy from 2012 to 2016 at a single institution. A propensity score-matched analysis was performed with five covariates, including age, body mass index, race, Charlson comorbidity index, and prostate volume. Perioperative, postoperative, and functional outcomes were compared between groups. RESULTS After propensity score matching there were 59 patients in each group available for comparison. There was no statistically significant difference between groups for all preoperative demographic variables. Robotic compared with OSP demonstrated a significant shorter average length of stay (LOS) (1.5 vs 2.6 days, p < 0.001), but longer mean operative time (161 vs 93 minutes, p < 0.001). The robotic approach was also associated with a lower estimated blood loss (339 vs 587 mL, p < 0.001) and lower percentage hematocrit drop (12.3% vs 19.5%, p = 0.001). Two patients required blood transfusions in the robot group compared with four in the open group, but this was not significant (p = 0.271). Improvements in maximal flow rate, International Prostate Symptom Score, quality of life, postvoid residual, and postoperative prostate-specific antigen levels were similar before and after surgery for both groups, but there was no difference between groups. There was no difference in complications between groups. CONCLUSION Robotic simple prostatectomy is a safe and effective treatment for the surgical management of benign prostatic hyperplasia. It provides similar function outcomes to the open approach; however, offers the advantage of reduced LOS and reduced blood loss.