Association between PRO 160/120 prescriptions and incidence of benign prostatic hyperplasia complications in Germany: a retrospective cohort study.

The present study aims to analyze the impact of PRO 160/120 prescriptions on the incidence of urinary incontinence, polyuria (including nocturia), urinary retention, and erectile dysfunction in a real-world setting in Germany and to compare these data with data for the 5-ARIs finasteride and dutasteride, and the α1-adrenoceptor antagonists tamsulosin and tamsulosin/dutasteride fixed-dose combination. This retrospective study was based on the IQVIA Disease Analyzer database and included male patients with an initial prescription of PRO 160/120, finasteride, dutasteride, tamsulosin, or tamsulosin/dutasteride fixed-dose combination between January 2010 and September 2020. Multivariable logistic regression analyses adjusted for age, health insurance, specialty, and relevant co-diagnoses were performed to estimate the association between PRO 160/120 prescriptions and incidence of pre-defined outcomes. A total of 77,923 patients were included in the study, 3,035 of whom received PRO 160/120. PRO 160/120 was significantly associated with reduced incidence of urinary incontinence (OR: 1.48; 95% CI: 1.10-1.98) and urinary retention compared to tamsulosin (OR: 3.39; 95% CI: 1.75-6.57 and tamsulosin/dutasteride (OR: 2.81; 95% CI: 1.35-5.82). Furthermore, PRO 160/120 significantly reduced the incidence of erectile dysfunction compared to dutasteride (OR: 2.79; 95% CI: 1.49-5.25). At the same time, patients receiving PRO 160/120 showed the same incidence of the remaining complications as those taking the reference substances. In conclusion, we observed a significant association between PRO 160/120 prescription and reduced incidence of urinary incontinence and urinary retention compared to tamsulosin and tamsulosin/dutasteride, as well as reduced incidence of erectile dysfunction compared to dutasteride.

Rezum water vapor therapy in multimorbid patients with urinary retention and catheter dependency.

BACKGROUND: Water vapor thermal therapy (Rezum) is a minimally invasive treatment for benign prostatic enlargement (BPE). We report on safety and efficacy of this method for treatment of recurrent urinary retention and relief of catheter dependency owing to BPE in multimorbid patients, considered unfit for surgery. METHODS: We retrospectively evaluated 136 patients with recurrent urinary retention who underwent water vapor therapy in an ambulatory setting with periprostatic block and optional sedation between 11/2017 and 02/2021 in three urological departments. The objective was successful catheter withdrawal and continuing catheter independency after 3- and 12-months following treatment. RESULTS: Mean patient age was 80.3 years (±7.8), mean prostate volume 54 ml (±27.3), and mean catheter dependency before treatment was 4.8 months (±6.0). ASA classification was a followed: II: 10%, III: 71%, and IV: 19%. All procedures were performed successfully in an ambulatory setting. Perioperative complications were infrequent and minor (Clavien-Dindo Grade 1-2) and included haematuria in 4.4% and urinary tract infection in 3.9% of all cases. A total of 103 patients (78.6%) were able to void spontaneously after a median of 31 days. No significant differences in age, prostate volume, duration of catheter dependency, vapor injections, and ASA score were found between patients with successful or unsuccessful outcome. The mean follow-up period was 6.1 months (±5.9, range 1-22 months). A 3-month follow-up was available for 77 patients (75%) and 34 patients (33%) were followed for 12 months. After 3 and 12 months, 93.5 and 91% of patients remained catheter independent. Fifteen patients (11%) died during follow-up, with a mean overall survival of 7.7 months (±4.7). CONCLUSIONS: Water vapor therapy may prove to be a useful, minimally invasive treatment in a multimorbid population with catheter dependency after urinary retention, secondary to BPE, considered at highest risk or unfit for surgery. Future studies are warranted.

[Management of geriatric patients with benign prostatic hyperplasia]. / Das Management geriatrischer Patienten mit benignem Prostatasyndrom.

Multimorbid older men are increasingly more common in daily practice and present a challenge because they are often affected by lower urinary tract symptoms (LUTS) and age-associated benign prostatic hyperplasia (BPH). In order to identify possible risks in diagnostics, therapy and counselling at an early stage, screening for functional deficits or risk factors with standardized procedures is helpful. An initial screening with subsequent assessment of everyday skills using the Barthel Index, Timed up & Go Test, and a cognitive test are recommended. If frailty syndrome is detected, it should be taken into account during the pre-, peri-, and postoperative management, as it may indicate increased morbidity and mortality. Noninvasive methods for reducing the prostate volume without anesthesia can be a therapy option in older multimorbid patients, and with individual planning and consideration of risk factors, up to 70% of individuals become symptom-free. However, there is currently no gold standard for this vulnerable patient group. Number of medications and concomitant diseases and higher need for help are per se risk factors for unsatisfactory results after transurethral resection of the prostate (TURP) or laser vaporization. With drug therapy, concomitant medications and their interactions, especially in the cytochrome system, an existing multimorbidity and adherence to therapy must be taken into account. Combination therapies may complement each other and may bridge the time until surgery. Minimally invasive methods that can be performed without general anesthesia are suitable for geriatric patients, especially those with recurrent retention. Studies with the Rezüm® system (NxThera Inc., Maple Grove, MN, USA) and UroLift® (NeoTract Inc., Pleasanton, CA, USA) show that about 70% of patients can be relieved from the permanent catheter.

[Sophisticated surgical management of distinctive patients with benign prostatic hyperplasia (BPH)]. / Differenziertes operatives Management unterschiedlicher Patienten mit benignem Prostatasyndrom (BPS).

Herein we describe four clinical scenarios. For the standard patient (prostate volume 30-80 ml, life expectancy >10 years) transurethral resection of the prostate (TURP) remains the standard of care, while endoscopic enucleation is a valuable alternative. Patients with a relevant middle lobe profit most from TURP, endourological enucleation procedures, or laser vaporization. In the case of the absence or a moderate-sized middle lobe and the absence of severe bladder outlet obstruction (BOO), minimally invasive procedures such as Rezum®, UroLift® or prostate artery embolization (PAE) can be offered. Patients have to be informed that long-term data on this specific indication are lacking. Particularly younger men requiring BPH surgery are interested in preserving ejaculatory function. In the presence of severe BOO, ejaculatory-protective TURP or endoscopic enucleation by preserving the pericollicular region or aquablation are the methods of choice providing an antegrade ejaculation in 60-90% of cases. Rezum®, AquaBeam®, and UroLift® enable preservation of ejaculation in almost 100%; data on PAE with this respect are more controversial. For patients with a small prostate and significant post void residual, a thorough preoperative work-up, including urodynamics and bladder/detrusor wall thickness measurement, is of great importance. Desobstructive surgery provides satisfactory short- and midterm outcome, yet the long-term outcome is disappointing and remains to be determined in greater detail. The broad spectrum of therapeutic options enables today an individualized minimally invasive or surgical management of BPH considering patient wishes, anatomical factors or urodynamic factors. The time of a "one therapy fits all" strategy is definitely history.

[Do benign prostatic hyperplasia drugs affect mood or cognition?] / Beeinflussen Medikamente gegen das benigne Prostatasyndrom Stimmung oder Kognition?

Based on new evidence, we discuss the risk of central nervous side effects, mainly reduced cognition/dementia and depressive symptoms during the use of drugs for the treatment of lower urinary symptoms suggestive of benign prostatic hyperplasia. Cognitive impairments during use of muscarinic antagonists are well documented and mechanistically well understood, but their occurrence differs quantitatively between members of this drug class. The occurrence of depressive symptoms while using 5α-reductase inhibitors only became known recently but has now been observed consistently in several studies and is mechanistically plausible; it appears to occur with similar incidence when using dutasteride and finasteride. A moderate increase in new diagnoses of dementia has recently been reported from a single study upon use of tamsulosin but not other α1-adrenoceptor antagonists. The plausibility of a mechanistic cause-effect relationship is only moderate, and the association could be explained based on selection bias. Overall, physicians should be alert for the occurrence of central nervous side effects during the treatment of lower urinary tract symptoms.

[Interdisciplinary position paper "Perioperative pain management"]. / Interdisziplinäres Positionspapier "Perioperatives Schmerzmanagement".

Despite many positive developments, postoperative pain and its treatment is still not always given the necessary attention. Severe pain after surgical procedures affects a significant proportion of patients. This very fact is not only detrimental to the immediate recovery process, but can also form the basis for the development of chronic pain conditions.An adequate and effective management of perioperative pain requires appropriate organizational structures. This multidisciplinary paper which was initiated by the Austrian Society for Anaesthesiology and Intensive Care and the Austrian Pain Society and developed together with numerous specialist and professional societies dealing with the subject aims at supporting the organization of perioperative pain management structures and to make best use of proven concepts. Additional recommendations describe specific interventions for selected types of intervention.

[Bladder storage and voiding dysfunctions : Side effects of drug therapy]. / Blasenspeicher- und Entleerungsstörungen : Nebenwirkungen der medikamentösen Therapie.

Bladder storage and voiding dysfunctions primarily affect patients aged 60 and upwards. Demographic changes and an age-related rise in prevalence underline the clinical relevance of these disorders. Besides behavior modification, the primary therapeutic approach is drug therapy. Therefore, a profound knowledge of the potential side effects is essential, particularly regarding the ever rising multidrug administration in the elderly. In this article, we provide a review concerning the potential adverse effects of the most popular therapeutic agents for bladder storage and voiding symptoms.

[S2e guideline of the German urologists: Conservative and pharmacologic treatment of benign prostatic hyperplasia]. / S2e-Leitlinie der Deutschen Urologen : Konservative und medikamentöse Therapie des benignen Prostatasyndroms.

This report summarizes the relevant aspects of the S2e guideline of the German Urologists for the conservative and pharmacological treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Recommendations are given regarding watchful waiting, behavioral therapy, phytotherapy and pharmacological mono- and combination therapy. The influence of the different therapeutic options on bladder outlet obstruction (BOO) is described in detail.

[S2e guideline of the German urologists: Instrumental treatment of benign prostatic hyperplasia]. / S2e-Leitlinie der Deutschen Urologen : Instrumentelle Therapie des benignen Prostatasyndroms.

This report summarizes the relevant aspects of the S2e guideline of the German Urologists for the instrumental treatment of the lower urinary tract symptoms due to benign prostatic hyperplasia. Recommendations are given regarding open and transurethral procedures (TUR-P, bipolar TUR-P, TUI-P, HE-TUMT, TUNA, and the different Laser techniques). Recommendations are also given concerning intraprostatic stents and injection therapies. The influence of the different therapeutic options on bladder outlet obstruction (BOO) is described in detail.

Have rates of erectile dysfunction improved within the past 17 years after radical prostatectomy? A systematic analysis of the control arms of prospective randomized trials on penile rehabilitation.

Based on case series, potency rates after radical prostatectomy (RPE) differ substantially and - furthermore - it remains unclear whether they have improved in more recent surgical series. The purpose of this study was to investigate whether potency rates after RPE have improved over the years. A systematic analysis of the control arms of all randomized controlled trials (RCT; n = 11) on penile rehabilitation after RPE was carried out. In total, 2009 patients were included in these RCTs, 685 thereof in the respective control arms, who were either observed or received placebo. Assessment of erectile function in these studies was carried out by the Sexual Encounter Profile (SEP) or the International Index of Erectile Function (IIEF). Eight trials used SEP3 as study endpoint. The rate of positive response to SEP3 (=erectile function sufficient for successful intercourse) in the control arms was 20% in 1997 (year of publication), 10% in 2003, 19% in 2004, 25% in 2008, 21% in 2010, 67% in 2011, 10% in 2013, and 22% in 2014. Eight RCTs assessed the IIEF-EF, yet results were not reported uniformly. In the control arms the IIEF-EF was 9.2 (year of publication 2003), 13.3 (2004), 8.8 (2008), 25% ≥22.0 (2008), 17.4 (2010), 58% ≥26.0 (2011), 9.3 (2013), and 11.6 (2014). Limitations of this analysis are a positive selection bias regarding patient recruitment, surgical approach, and the non-uniform inclusion and outcome criteria. This systematic analysis of the control arms of all RCTs on penile rehabilitation after nerve-sparing RPE shows (i) that the rate of undisturbed erectile function is in the range 20-25% in most studies and (ii) that these rates have not substantially improved or changed over the past 17 years.

[Importance of adrenoceptor blockers and alpha reductase inhibitors : Monotherapy for treatment of benign prostate syndrome]. / Stellenwert der α1-Adrenozeptorblocker und 5α-Reduktaseinhibitoren : Monotherapie bei der Behandlung des benignen Prostatasyndroms.

Medicinal treatment is the primary conservative treatment option for patients with moderate to severe lower urinary tract symptoms (LUTS). Monotherapy with alpha-blockers may be a suitable option for patients with a low risk of progression and with moderate to severe LUTS due to the rapid onset of action. However, alpha-blockers do not have any impact on disease progression and 5-alpha-reductase inhibitors (5-ARIs) are not recommended as initial monotherapy due to a slow onset of action. In the medium and long term 5-ARIs have been shown to have a positive effect on symptoms and the maximum flow rate and are also the only substance group to have a positive effect on disease progression. The positive effects of 5-ARIs on prevention of benign prostate syndrome are based on scientific findings but the use is not yet recommended in any guidelines.

[Intraprostatic injection therapy in patients with benign prostatic syndrome]. / Intraprostatische Injektionstherapien beim benignen Prostatasyndrom.

Intraprostatic injection therapy is a minimally invasive treatment of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and could be a therapeutic alternative in increasingly older and co-morbid patients. Nowadays only botulinum neurotoxin A (BoNT/A), absolute ethanol, NX-1207 and PRX302 are of relevance but none of these substances has yet been authorized for treatment use (off-label use). There have been only three randomized, placebo-controlled trials (RCTs) for BoNT/A, whereas none exist for ethanol and the results of existing studies are inconsistent and without convincing proof of efficacy. NX-1207 is a protein with selective pro-apoptotic properties and non-inferiority compared to finasteride has been demonstrated. PRX302 is a modified proaerolysin that can be activated by prostate-specific antigen and is therefore (prostate) cell-specific. Safety and efficacy are well documented; however, intraprostatic injection therapy should presently only be performed in clinical trials, irrespective of the substance used.

[Combination therapy of benign prostate syndrome/lower urinary tract symptoms]. / Kombinationstherapie bei benignem Prostatasyndrom/unterer Harntraktsymptomatik.

The pathophysiology of lower urinary tract symptoms (LUTS) is multifactorial. The fact that none of the available drugs impacts on more than one of these pathomechanisms, provides the rationale for combined medical treatment strategies. The combination of α-blocker and a 5-reductase inhibitor is recommended by all major benign prostate hyperplasia (BPH/LUTS) guidelines as a first line approach for men with moderate to severe LUTS and a higher risk for disease progression. The efficacy of this approach has been proven in prospective randomized trials for up to 4 years. The combination of α-blocker and antimuscarinics has been tested in several randomized trials as a primary approach or as add on therapy but the maximum study duration was only 3 months. The add on approach is suitable in particular for men with persisting storage symptoms under α-blockade. The risk for acute retention in appropriately selected men is low. The scientific basis for all other combinations is not solid enough to recommend the use outside clinical trials.

[Phytotherapy of benign prostate syndrome and prostate cancer: better than placebo]. / Phytotherapie bei benignem Prostatasyndrom und Prostatakarzinom : Besser als Placebo?

In some countries plant extracts have belonged to the most popular drugs for the treatment of the benign prostatic syndrome (BPS) for decades; however, only few of the large number of published studies meet the criteria of the WHO benign prostatic hyperplasia (BPH) consensus conference. The few placebo-controlled long-term (study period >6 months) studies suggest a positive effect of some extracts (saw palmetto fruit, ß-sitosterol, urtica, rye grass and a saw palmetto/urtica combination) on lower urinary tract symptoms (LUTS), urinary flow rate, post-void residual volume but effects on prostate volume or prostate-specific antigen (PSA) were only inconsistently demonstrable. To date no study has proven an effect on disease progression, such as acute urinary retention or need for surgical interventions. Due to the controversial data various extraction techniques and compositions of various products, neither American, European, British nor German BPH guidelines recommend plant extracts for the indication BPS although some placebo-controlled trials provided encouraging data. Further prospective studies according to WHO standards are required to determine the role of plant extracts for the management of BPS. For the indication of prostate cancer (PCa) plant extracts have been evaluated for disease prevention and management of several tumor stages but none of these studies have provided convincing evidence that plant extracts are superior to placebo and none of the Pica guidelines have recommended their use.Based on current knowledge plant extracts can never supplement evidence-based PCa management and should be used only in addition to the standard treatment. There is no scientific evidence for the use of dietary supplementation with high doses of vitamins or selenium-containing products.

[Medical therapy of lower urinary tract symptoms [corrected]]. / Medikamentöse Therapie des benignen Prostatasyndroms.

Male lower urinary tract symptoms (LUTS) include storage and voiding disorders and should be carefully evaluated before the start of any treatment. Medical therapy is directed at improving symptoms and reducing the risk of progression in order to improve quality of life and prevent complications, such as acute urinary retention, or the need for surgical intervention. Careful assessment of the individual complaints helps to identify the best drug which should be adapted to each individual patient's risk profile. At present, α(1)-adrenoreceptor inhibitors and 5-alpha reductase inhibitors and their combination form the gold standard for pharmacological treatment. In addition, anticholinergic agents are increasingly being used as monotherapy or in combination with α1-adrenocepetor inhibitors for patients with predominant storage disorders while phosphodiesterase 5 (PDE5) inhibitors may be suitable for patients suffering from LUTS and concomitant erectile dysfunction.

Is penile atherosclerosis the link between erectile dysfunction and cardiovascular risk? An autopsy study.

Erectile dysfunction (ED) is increasingly linked to coronary heart disease risk. Aim of this study was to test the hypothesis whether this association is due to penile atherosclerosis. We evaluated the prevalence and severity of penile atherosclerosis in relation to coronary and peripheral atherosclerosis. Between January and June 2010, a consecutive series of 31 men underwent an autopsy at the Department of Pathology at the Medical University Vienna. Atherosclerosis at the following localizations were histologically classified: right coronary artery, left coronary artery, left circumflex artery, internal iliac artery, dorsal penile artery and deep penile artery (bilateral). Coronary and peripheral atherosclerosis was present in 87.1 and 77.4% of cases. Atherosclerosis of penile arteries was detectable in only 4 men (12.9%). The only factor linked to penile atherosclerosis was diabetes (P=0.03). All other parameters as assessed according to medical history, general finding from autopsy or histological results regarding arterial lesions in general were not correlated to penile arterial lesions. In contrast to the high prevalence of atherosclerosis in general, penile arterial lesions are rarely present.

[Primary and secondary prevention of benign prostatic hyperplasia: current knowledge and implications for clinical management]. / Primär- und Sekundärprävention des benignen Prostatasyndroms: Aktueller Wissenstand und Auswirkungen auf die klinische Routine.

Histological benign prostatic hyperplasia (BPH) and the BPH disease are frequent, lead to a reduction of quality of life, are both progressive and potentially associated with complications in the lower and upper urinary tract. A PubMed/MEDLINE search was conducted for the years 1990 to 2011. This article summarizes known selective measures of primary and secondary disease prevention.Measures of primary disease prevention aim to inhibit histological BPH and the development of clinically relevant BPH. Weight loss, regular physical activity, vegetable consumption, alcohol intake, 5α-reductase inhibitors, avoidance of overweight and reduction of fatty food can reduce the probability of histological and clinical BPH. Selective measures of secondary prevention aim to inhibit disease progression and BPH-associated complications. The regular and long-term use of α1-blockers reduces lower urinary tract symptoms (LUTS) and inhibits symptomatic disease progression but cannot prevent BPH-associated complications (e.g. urinary retention or need for prostate surgery). 5α-Reductase inhibitors can reduce the probability of symptomatic disease progression, urinary retention or need for surgery but the combination of α1-blocker and 5α-reductase inhibitor is more efficacious than either monotherapy. Especially older men with enlarged prostates (>40 cm(3)) and elevated serum PSA concentration (>1.6 µg/l) profit from measures of secondary disease prevention.For primary disease prevention, data quality is low and early treatment with 5α-reductase inhibitors is not been approved. For secondary disease prevention, men with risk factors of disease progression should use a treatment containing 5α-reductase inhibitors. Despite several epidemiological and clinical investigations on BPH disease progression no official programme exists in Germany for disease prevention.

Prostate cancer at the peripheral end of a prostate biopsy specimen as assessed by a novel marking technique may indicate increased risk of locally advanced disease.

The objective of this study was to test a novel technique of processing a prostate biopsy (PB) specimen by marking its peripheral end (PE) as a predictive tool for locally advanced prostate cancer (PC) or margin-positive resection (R1) after radical prostatectomy (RP). Prospective evaluation of a consecutive cohort of men who underwent PB and subsequent RP was carried out. Transrectal ultrasound-guided 10-20 core PB was performed according to a standardized protocol. Each biopsy core was inked at the PE and classified as PE positive or negative. The study cohort comprised 100 men with a mean age of 62.3 years (41-75 years). Overall, PE-positive cores were found in 71 men, postoperative tumour (pT)3/pT4 stages were diagnosed in 33 men and R1 status in 45 men after RP. In univariate analysis, the presence of at least one PE-positive core was correlated to an increased risk for pT3/pT4 stage (relative risk (RR): 3.15; 95% confidence interval (95% CI): 1.1-9.9; P = 0.03) and R1 status (RR: 2.9; 95% CI: 1.1-7.5; P = 0.03). In multivariate analysis including Gleason score, total number of positive cores, PE positivity and PSA, PE positivity was correlated to pT3/pT4 stage (P = 0.04). In conclusion, PC at the PE of a PB specimen predicts non-organ-confined tumour stage in subsequent prostatectomy. This simple, new technique may contribute to increasing the accuracy of risk stratification for curative treatment of PC.

Is erectile dysfunction a predictor of cardiovascular events or stroke? A prospective study using a validated questionnaire.

Erectile dysfunction (ED) is linked to various cardiovascular risk factors and may therefore serve as a predictor of cardiovascular events. To gain further insight into this relationship, we reviewed all data regarding hospital admission for cardial or cerebral vascular disease that occurred until 2008 in a cohort of men who underwent a health investigation in 2001. Erectile function was assessed using the International Index of Erectile Function (IIEF-5) questionnaire. In total, 2506 men with a negative history of cardial or cerebral vascular disease were analysed. During the 6.5-year follow-up, 58 cardiovascular events (2.3%) occurred. Men without ED (IIEF-5 >22; n=1636) at baseline developed a cardiovascular event in 1.9% (n=32) as compared with 2.9% (+52%; n=26) in those with ED (IIEF-5 < or =22; n=670). In contrast to age (hazard ratio (HR): 1.6; 1.2-1.8 for every decade), hypertension (HR: 1.88; 1.1-3.1) and diabetes (HR: 2.6; 1.2-5.8), ED was not an independent risk factor for a cardiovascular event. Although men with ED were at increased risk for future cardiovascular events, ED was not an age-independent predictor of cardiovascular events in our cohort.