The American Urological Association Symptom Index for Benign Prostatic Hyperplasia.

A symptom index for benign prostatic hyperplasia (BPH) was developed and validated by a multidisciplinary measurement committee of the American Urological Association (AUA). Validation studies were conducted involving a total of 210 BPH patients and 108 control subjects. The final AUA symptom index includes 7 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency. On revalidation, the index was internally consistent (Cronbach's α = 0.86) and the score generated had excellent test-retest reliability (r = 0.92). Scores were highly correlated with subjects' global ratings of the magnitude of their urinary problem (r = 0.65 to 0.72) and powerfully discriminated between BPH and control subjects (receiver operating characteristic area 0.85). Finally, the index was sensitive to change, with preoperative scores decreasing from a mean of 17.6 to 7.1 by 4 weeks after prostatectomy (p <0.001). The AUA symptom index is clinically sensible, reliable, valid and responsive. It is practical for use in practice and for inclusion in research protocols.

Finasteride treatment alters tissue specific androgen receptor expression in prostate tissues.

BACKGROUND: Normal and pathologic growth of the prostate is dependent on the synthesis of dihydrotestosterone (DHT) from testosterone by 5α-reductase. Finasteride is a selective inhibitor of 5α-reductase 2, one isozyme of 5α-reductase found in abundance in the human prostate. The objective of this study was to investigate the effects of finasteride on androgen receptor expression and tissue morphology in human benign prostatic hyperplasia specimens. METHODS: Patients undergoing transurethral resection of the prostate and either treated or not treated with finasteride between 2004 and 2010 at the University of Wisconsin-Hospital were retrospectively identified using an institutional database. Prostate specimens from each patient were triple-stained for androgen receptor, prostate-specific antigen, and basal marker cytokeratin 5. Morphometric analysis was performed using the multispectral imaging, and results were compared between groups of finasteride treated and non-treated patients. RESULTS: Epithelial androgen receptor but not stromal androgen receptor expression was significantly lower in patients treated with finasteride than in non-treated patients. Androgen receptor-regulated prostate-specific antigen was not significantly decreased in finasteride-treated patients. Significant luminal epithelial atrophy and basal cell hyperplasia were prevalent in finasteride treated patients. Epithelial androgen receptor expression was highly correlated to the level of luminal epithelial atrophy. CONCLUSIONS: In this study, finasteride decreased the expression of epithelial androgen receptor in a tissue specific manner. The correlation between epithelial androgen receptor and the extent of luminal epithelial atrophy suggests that epithelial androgen receptor may be directly regulating the atrophic effects observed with finasteride treatment.

Effects of 100 and 300 units of onabotulinum toxin A on lower urinary tract symptoms of benign prostatic hyperplasia: a phase II randomized clinical trial.

PURPOSE: We conducted a 2-stage, multicenter, double-blind, randomized phase II clinical trial of 100 and 300 unit doses of onabotulinum toxin A to treat the lower urinary tract symptoms of benign prostatic hyperplasia. MATERIALS AND METHODS: Men 50 years old or older with clinically diagnosed benign prostatic hyperplasia, American Urological Association symptom index 8 or greater, maximum urinary flow rate less than 15 ml per second, voided volume 125 ml or greater, and post-void residual 350 ml or less were randomized to prostatic transrectal injection of 100 or 300 units of onabotulinum toxin A. The primary outcome was at least 30% improvement from baseline to 3 months in American Urological Association symptom index and/or maximum urinary flow rate and safety. The men were followed for 12 months. RESULTS: A total of 134 men were randomized and treated (68 with 100 units, 66 with 300 units), with 131 assessed at 3 months and 108 assessed at 12 months. Each dose met the 3-month primary outcome criteria. In the 100 unit arm the mean baseline American Urological Association symptom index of 18.8 decreased by 7.1 and 6.9 at 3 and 12 months, respectively. In the 300 unit arm the baseline of 19.5 decreased by 8.9 and 7.1, respectively. In the 100 unit arm the mean baseline maximum urinary flow rate of 10.0 ml per second increased by 2.5 and 2.2, respectively, and in the 300 unit arm the baseline of 9.6 increased by 2.6 and 2.3, respectively. CONCLUSIONS: The intraprostatic injection of 100 or 300 units of onabotulinum toxin A passed predetermined criteria for treatment efficacy and safety, and a randomized trial with either dose is warranted. The 100 unit dose may be preferable due to similar efficacy with reduced costs and adverse effects.

Update on AUA guideline on the management of benign prostatic hyperplasia.

PURPOSE: To revise the 2003 version of the American Urological Association's (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.

Safety and feasibility of the prostatic urethral lift: a novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).

OBJECTIVES: • To investigate the Prostatic Urethral Lift (PUL) procedure, a novel, minimally invasive treatment for symptomatic benign prostatic hyperplasia (BPH), which aims to mechanically open the prostatic urethra without ablation or resection. • To demonstrate the safety and feasibility of this procedure and to make an initial assessment of effectiveness. PATIENTS AND METHODS: • The PULprocedure was performed on 19 men in Australia. • Small suture-based implants were implanted transurethrally under cystoscopic visualisation to separate encroaching lateral prostatic lobes. • Patients were evaluated at 2 weeks and 3, 6, and 12 months after PUL. RESULTS: • All cases were successfully completed with no serious or unexpected adverse events (AEs). • Between two and five sutures were delivered in each patient and the prostatic urethral lumen was visually increased in all patients. • Reported postoperative AEs were typically mild and transient and included dysuria and haematuria. • Follow-up cystoscopy at 6 months in a subset of patients showed no calcification. Histological findings from two of three patients who progressed to transurethral resection of the prostate for return of symptoms showed no evidence of inflammation related to the implanted materials. • The mean International Prostate Symptom Score was reduced by 37% at 2 weeks and 39% at 1 year after PUL as compared with baseline. CONCLUSIONS: • We demonstrated in this initial experience that the PUL procedure is safe and feasible. • The safety profile of the PUL procedure appears favourable; most patients reported sustained symptom relief to 12 months with minimal morbidity • PUL therefore warrants further study as a new option for the many patients who seek an alternative to current therapies.

Variation in institutional review board responses to a standard protocol for a multicenter randomized, controlled surgical trial.

PURPOSE: The primary responsibility of institutional review boards is to protect human research subjects and, therefore, ensure that studies are performed in accordance with a standard set of ethical principles. A number of groups have compared the responses of institutional review boards in multicenter clinical trials involving medical therapies. To our knowledge no such studies have been performed to date of trials investigating surgical intervention. We investigated the consistency of the recommendations issued by various institutional review boards in the Minimally Invasive Surgical Therapies study for benign prostatic hyperplasia, a multicenter trial with a uniform consent and study protocol. MATERIALS AND METHODS: We obtained the institutional review board response from 6 of the 7 participating institutions after initial submission of the Minimally Invasive Surgical Therapies study protocol and classified the responses. We then redistributed the approved protocols to an institutional review board at another participating institution and analyzed that review of these protocols. RESULTS: We found that the number and type of responses required for institutional review board approval of an identical study protocol varied significantly among participating institutions. We also found that institutional review board responses were inconsistent in the second review, although all protocols were ultimately approved. CONCLUSIONS: The current system of local institutional review board review in the context of a multicenter surgical trial is inefficient in the review process and may not provide expertise for overseeing surgical trials. Based on these results a central surgical institutional review board may be needed to improve the ethical review process in multicenter trials.

Reduced bladder cancer recurrence rate with cardioprotective aspirin after intravesical bacille Calmette-Guérin.

OBJECTIVE: To evaluate the recurrence-free survival (RFS) rate of patients taking cardioprotective aspirin after intravesical bacille Calmette-Guérin (BCG) for high-grade noninvasive urothelial carcinoma of the bladder, as preventing the recurrence of superficial bladder cancer might decrease patient morbidity and mortality from this disease, and nonsteroidal anti-inflammatory agents (NSAIDs) have shown promise in preclinical prevention through inhibition of the prostaglandin pathway and other mechanisms. PATIENTS AND METHODS: In all, 43 patients with carcinoma in situ (CIS) and/or high-grade papillary bladder cancer were treated with intravesical BCG. Patients were stratified according to whether they took cardioprotective aspirin after treatment, and Kaplan-Meier curves of RFS were compared by log-rank analysis. Multivariable analysis was used for potentially confounding factors, including maintenance BCG, the presence of CIS, and smoking status. RESULTS: Of patients taking cardioprotective aspirin, the 5-year RFS rate was 64.3%, compared with 26.9% for patients not taking aspirin, with a significantly higher RFS by univariable log rank analysis (P = 0.03). Even after adjusting for the other factors by multivariable analysis, aspirin seems to affect recurrence (hazard ratio 0.179, P = 0.001). Maintenance BCG (hazard ratio 0.233, P = 0.02) and smoking history (hazard ratio 3.199, P = 0.05) also significantly affected recurrence. CONCLUSION: There was a significantly higher RFS rate in patients taking cardioprotective aspirin after intravesical BCG therapy for bladder cancer. The results of this study support the further investigation of aspirin and other NSAIDs as preventive agents in patients being treated for superficial bladder cancer.

Flexible and rigid cystoscopy in women.

PURPOSE: Previous studies have evaluated the tolerability of rigid versus flexible cystoscopy in men. Similar studies, however, have not been performed in women. We sought to determine whether office-based flexible cystoscopy was better tolerated than rigid cystoscopy in women. MATERIALS AND METHODS: Following full IRB approval, women were prospectively randomized in a single-blind manner. Patients were randomized to flexible or rigid cystoscopy and draped in the lithotomy position to maintain blinding of the study. Questionnaires evaluated discomfort before, during, and after cystoscopy. RESULTS: Thirty-six women were randomized to flexible (18) or rigid (18) cystoscopy. Indications were surveillance (16), hematuria (15), recurrent UTIs (2), voiding dysfunction (1), and other (2). All questionnaires were returned by 31/36 women. Using a 10-point visual analog scale (VAS), median discomfort during the procedure for flexible and rigid cystoscopy were 1.4 and 1.8, respectively, in patients perceiving pain. Median recalled pain 1 week later was similar at 0.8 and 1.15, respectively. None of these differences were statistically significant. CONCLUSIONS: Flexible and rigid cystoscopy are well tolerated in women. Discomfort during and after the procedure is minimal in both groups. Urologists should perform either procedure in women based on their preference and skill level.

Long-term complications associated with the Indiana pouch urinary diversion in patients with recurrent gynecologic cancers after high-dose radiation.

Few studies have assessed the long-term risks associated with the Indiana pouch continent urinary diversion after high-dose radiation therapy. A retrospective review of consecutive female patients who underwent cystectomy and Indiana pouch urinary diversion identified 12 with a history of high-dose pelvic irradiation (mean total 78.1 Gy). Long-term complications and outcomes in this group were compared to a synchronous group of patients (n = 14) with no history of radiation. Mean follow-up in the radiation therapy (RT) and nonirradiated comparison group (CG) were 48.5 and 40.8 months, respectively, with all patients having over 12 months of outcomes assessed. In the RT group, 83% of patients experienced a one or more complications (n = 29) while 57% of the CG did (n = 15; P = 0.2). Complications seen more commonly in the RT group included ureteral stricture/obstruction (5 vs. 2), renal insufficiency (3 vs. 1) and severe incontinence (3 vs. 0). Notably, 23 secondary operative procedures were required in the RT group versus CG (n = 11, P = 0.2). Percutaneous nephrostomy (6 vs. 1; P = 0.03) and ureteral reimplantation (4 vs. 0; P = 0.03) were seen significantly more commonly in the RT group than the CG. Long-term follow-up is critical to assess the complications associated with urinary diversions. We conclude that frequent complications and a significant increase in specific operative procedures are observed in heavily irradiated patients with recurrent gynecologic cancers receiving an Indiana Pouch urinary diversion. Given the risk of renal insufficiency, close monitoring of renal drainage and function is recommended. These considerable long-term complications should be considered when counseling patients contemplating Indiana Pouch urinary diversion after radiation therapy.

Phase I trial of 1alpha-hydroxyvitamin d(2) in patients with hormone refractory prostate cancer.

This Phase I study of 1alpha-hydroxyvitamin D(2), an p.o. administered vitamin D analogue, in patients with advanced hormone-refractory prostate cancer was designed to assess the toxicity, pharmacokinetic and biological markers of drug activity, and lastly tumor response data to recommend a dose for Phase II studies. 1alpha-Hydroxyvitamin D(2) was administered daily at doses ranging from 5 to 15 microg/day. Patients were monitored for toxicity and tumor response, and blood and urine samples were collected for pharmacokinetics (1alpha,25-dihydroxyvitamin D(2) levels) and other parameters of biological activity (bone markers, parathyroid hormone, urine calcium, and serum phosphorus levels). Twenty-five patients were enrolled. Main toxicities were hypercalcemia with associated renal insufficiency. No other significant toxicity was seen. Pharmacokinetics showed an increase in the active metabolite 1alpha,25-dihydroxyvitamin D(2) that reached a plateau by week 4 despite continuous drug dosing. Elevation in daily urinary calcium excretion and serum phosphorus levels was seen, whereas a decrease in serum parathyroid hormone was evident. Two patients showed evidence of a partial response, whereas 5 others achieved disease stabilization for > or =6 months. 1alpha-Hydroxyvitamin D(2) was well tolerated with main toxicities being hypercalcemia and renal insufficiency. All of the toxicity was reversible with drug discontinuation. Evidence for drug activity was seen in surrogate markers, and pharmacokinetic analysis showed substantial increases in vitamin D metabolite levels among the various cohorts. Whereas the defined maximum tolerated dose was not reached, the recommended Phase II dose was 12.5 microg/day given continuously.

Meta-analysis of the complications of laparoscopic renal surgery: comparison of procedures and techniques.

PURPOSE: We performed a meta-analysis of the literature to define the current expectations of complications during laparoscopic renal surgery. MATERIALS AND METHODS: References were searched in the MEDLINE database from 1995 to 2004 using the terms complications and laparoscopic nephrectomy. Inclusion criteria were any series with greater than 20 cases, patient age older than 16 years and any complications listed for certain procedures, including laparoscopic radical nephrectomy, HA laparoscopic radical nephrectomy, LPN, HALPN, laparoscopic donor nephrectomy, HA laparoscopic donor nephrectomy, laparoscopic simple nephrectomy, laparoscopic nephroureterectomy and retroperitoneal laparoscopic nephrectomy. A data extraction form was created to categorize major or minor complications. A 5 member panel adhered to the strict criteria and extracted data from articles that met inclusion criteria. Data were entered into a spreadsheet and a meta-analysis was performed. RESULTS: Initial review identified 73 of 405 references that were acceptable for retrieval and data extraction, of which 56 met inclusion criteria. The overall major and minor complication rates of laparoscopic renal surgery were 9.5% and 1.9%, respectively. There was a significant difference between the major complication rates of LPN and HALPN (21.0% vs 3.3%, p <0.05). CONCLUSIONS: Our results show that patients who undergo laparoscopic renal surgery may have an overall major complication rate of 9.5%. The highest major complication rate is associated with technically challenging LPN (21%). There appears to be a significantly higher wound complication rate associated with HA surgery in comparison to that of standard laparoscopy (1.9% vs 0.2%, p <0.05).

Quality of life and sexual function in patients with benign prostatic hyperplasia.

Incidence of benign prostatic hyperplasia (BPH), one of the most common conditions affecting adult men, increases dramatically after the age of 50. The various symptoms of BPH, which include lower urinary tract symptoms (LUTS), can adversely affect quality of life (QOL). Many men with BPH and LUTS wait until symptoms become significantly bothersome before seeking medical attention. Evaluating the exact severity and significance of symptoms has been difficult with previous methodology. Over the last decade, assessment tools have become available to quantify the symptoms of BPH and LUTS. This article addresses the impact of BPH, its management, and the overall effects it has on QOL.

Transurethral needle ablation versus transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia: 5-year results of a prospective, randomized, multicenter clinical trial.

PURPOSE: We report the 5-year efficacy and safety of transurethral needle ablation of the prostate (TUNA) compared to transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 121 men 50 years or older with LUTS secondary to BPH a minimum of 3 months in duration were enrolled in this prospective, randomized clinical trial at 7 medical centers across the United States. Of the participants 65 (54%) were randomly selected to receive TUNA and 56 (46%) were selected to receive TURP. International Prostate Symptom Score, quality of life, peak urinary flow rate, post-void residual urinary volume, and prostate size and configuration were evaluated before the procedure and then annually for 5 years after the procedure. Adverse events were also recorded throughout the study. RESULTS: Improvement from baseline for TUNA and TURP retained statistical significance at each interval for International Prostate Symptom Score, quality of life and peak flow rate. Post-void residual volume was statistically significant at all time points for TURP and at year 5 for TUNA. The TURP group reported 41% retrograde ejaculation, while the TUNA group reported none. The incident of erectile dysfunction, incontinence and stricture formation was also greater in TURP than in TUNA cases with significantly fewer adverse events for TUNA than for TURP. CONCLUSIONS: The results of this study demonstrate stable treatment outcomes after 5 years of followup and suggest that TUNA is an attractive treatment option for men with LUTS due to BPH.

Sustained decrease in incidence of acute urinary retention and surgery with finasteride for 6 years in men with benign prostatic hyperplasia.

PURPOSE: We determined the effect of long-term treatment with finasteride on the incidence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH) related surgery in men with BPH. MATERIALS AND METHODS: The Proscar (Merck and Co., Inc., Whitehouse Station, New Jersey) Long-Term Efficacy and Safety Study (PLESS) was comprised of 3040 men with enlarged prostates, moderate to severe symptomatic BPH and no clinical evidence of prostate cancer. Patients were randomized to placebo or 5 mg finasteride daily for 4 years. Of the 3016 randomized patients with available efficacy data 62% completed the original 4-year study (1006 on finasteride and 891 on placebo) and 89% of these (908 from the original finasteride arm and 785 from the placebo arm) continued in a 2-year open extension on finasteride. Followup was attempted in discontinued patients. Complete 6-year outcomes data, including 6-year followup in 770 men who had discontinued treatment during years 1 to 6, were available for 2463 (82%) of the 3016 originally randomized patients. RESULTS: For patients on continuous finasteride treatment the decrease in incidence of AUR and/or BPH related surgery in the 4-year base study was sustained during the open extension. In patients who were switched from placebo to finasteride in the extension, the incidence of AUR and/or BPH related surgery was similar to that in the continuous finasteride arm. CONCLUSIONS: The 6-year data from PLESS confirmed and further extended the findings from the original 4-year trial, demonstrating that finasteride treatment led to a sustained decrease in the incidence of AUR and/or BPH related surgery in men with BPH and enlarged prostates.

Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia.

OBJECTIVES: To summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important. METHODS: The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate glands. The initial 1-year placebo-controlled study was followed by a 5-year open-label extension. In total, 6-year finasteride data were available in 487 patients originally randomized to finasteride, and 5-year data were available on 238 patients originally randomized to placebo. RESULTS: After 6 years of treatment with finasteride 5 mg, the mean quasi-American Urological Association Symptom Score improved by 4.0 points, the median prostate volume decreased by 24%, and the mean maximal urinary flow rate increased by 2.9 mL/s (P <0.001 for all parameters). Long-term finasteride treatment was well tolerated, with a low incidence of drug-related sexual adverse events occurring during the first year and even fewer occurrences during the 5-year open extension. CONCLUSIONS: Treatment with finasteride leads to durable improvement in urinary tract symptoms, flow rate, and prostate volume, with no increase in the prevalence of drug-related adverse events over time.