Testosterone Therapy in Patients with Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes.

PURPOSE: Testosterone deficiency and prostate cancer have an increasing prevalence with age. However, because of the relationship between prostate cancer and androgen receptor activation, testosterone therapy among patients with known prostate cancer has been approached with caution. MATERIALS AND METHODS: We identified a cohort of 82 hypogonadal men with prostate cancer who were treated with testosterone therapy. They included 50 men treated with radiation therapy, 22 treated with radical prostatectomy, 8 on active surveillance, 1 treated with cryotherapy and 1 who underwent high intensity focused ultrasound. We monitored prostate specific antigen, testosterone, hemoglobin, biochemical recurrence and prostate specific antigen velocity. RESULTS: Median patient age was 75.5 years and median followup was 41 months. We found an increase in testosterone (p <0.001) and prostate specific antigen (p = 0.001) in the entire cohort. Prostate specific antigen increased in patients on active surveillance. However, no patients were upgraded to higher Gleason score on subsequent biopsies and none have yet gone on to definitive treatment. We did not note any biochemical recurrence among patients treated with radical prostatectomy but 3 (6%) treated with radiation therapy experienced biochemical recurrence. It is unclear whether these cases were related to testosterone therapy or reflected the natural biology of the disease. We calculated mean prostate specific antigen velocity as 0.001, 0.12 and 1.1 µg/l per year in the radical prostatectomy, radiation therapy and active surveillance groups, respectively. CONCLUSIONS: In the absence of randomized, placebo controlled trials our study supports the hypothesis that testosterone therapy may be oncologically safe in hypogonadal men after definitive treatment or in those on active surveillance for prostate cancer.

Effect of surgical approach on erectile function recovery following bilateral nerve-sparing radical prostatectomy: an evaluation utilising data from a randomised, double-blind, double-dummy multicentre trial of tadalafil vs placebo.

OBJECTIVES: To report pre-specified and exploratory results on the effect of different surgical approaches on erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) obtained from the multicentre, randomised, double-blind, double-dummy REACTT trial of tadalafil (once a day [OaD] or on-demand [pro-re-nata, PRN]) vs placebo. PATIENTS AND METHODS: Patients aged <68 years with normal preoperative EF who underwent nsRP for localised prostate cancer (Gleason ≤7, prostate-specific antigen [PSA] <10 ng/mL) were randomised after nsRP 1:1:1 to 9-month double-blind treatment with tadalafil 5 mg OaD, tadalafil 20 mg PRN, or placebo, followed by 6-week drug-free washout, and 3-month open-label OaD treatment (all patients). Recovery of EF was defined as an International Index of Erectile Function (IIEF)-EF domain score of ≥22 and normal orgasmic function was defined based on IIEF Question 10. Both parameters were analysed at the end of washout using logistic regression including terms for treatment, country, visit, visit-by-treatment interaction, age group, nerve-sparing score (perfect = 2, non-perfect >2), and surgical approach (open surgery, robot-assisted laparoscopy, conventional laparoscopy, other). Time to EF recovery was analysed post hoc with a Cox proportional-hazards model including terms for treatment, age-group, country, surgical approach and surgery-by-treatment interaction. RESULTS: Of 422 patients treated, 189 underwent open surgery, 115 robot-assisted laparoscopy, 88 conventional laparoscopy and 30 surgery classified as 'other'. The odds of achieving EF recovery at the end of drug-free washout were about twice as high for the robot-assisted laparoscopy group compared with the open surgery group (odds ratio 2.42; 95% confidence interval [CI] 1.24, 4.72; P = 0.029). Patients who underwent robot-assisted laparoscopy were significantly more likely to recover during double-blind treatment compared with patients who underwent open surgery (hazard ratio 1.92; 95% CI 1.17, 3.15; P = 0.010). No favourable effect of conventional laparoscopy compared with open surgery could be seen. CONCLUSION: These results may provide further insights into the role of surgery on EF recovery after nsRP. However, the trial was not designed for these analyses and further prospective studies are needed.

Prospective, randomized, double-blind, vehicle controlled, multicenter phase IIb clinical trial of the pore forming protein PRX302 for targeted treatment of symptomatic benign prostatic hyperplasia.

PURPOSE: We conducted a safety and efficacy evaluation of intraprostatic injection of PRX302, a modified pore forming protein (proaerolysin) activated by prostate specific antigen, as a highly targeted, localized approach to treat lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 92 patients with I-PSS (International Prostate Symptom Score) 15 or greater, peak urine flow 12 ml or less per second and prostate volume 30 to 100 ml were randomized 2:1 to a single ultrasound guided intraprostatic injection of PRX302 vs vehicle (placebo) in this phase IIb double-blind study. Injection was 20% of prostate volume and 0.6 µg PRX302 per gm prostate. Peak urine flow was determined by a blinded reviewer. Benign prostatic hyperplasia medications were prohibited. The primary data set of efficacy evaluable patients (73) was analyzed using last observation carried forward. RESULTS: PRX302 treatment resulted in an approximate 9-point reduction in I-PSS and 3 ml per second increase in peak urine flow that were statistically significant changes from baseline compared to vehicle. Efficacy was sustained for 12 months. Early withdrawal for other benign prostatic hyperplasia treatment was more common for patients in the vehicle group. Relative to vehicle, PRX302 apparent toxicity was mild, transient, and limited to local discomfort/pain and irritative urinary symptoms occurring in the first few days, with no effect on erectile function. CONCLUSIONS: A single administration of PRX302 as a short, outpatient based procedure was well tolerated in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. PRX302 produced clinically meaningful and statistically significant improvement in patient subjective (I-PSS) and quantitative objective (peak urine flow) measures sustained for 12 months. The side effect profile is favorable with most effects attributed to the injection itself and not related to drug toxicity.

Treatment satisfaction and improvement in health-related quality of life with onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity.

AIMS: OnabotulinumtoxinA significantly reduces urinary incontinence (UI) and improves bladder management in patients with neurogenic detrusor overactivity (NDO). We evaluated the impact of onabotulinumtoxinA on patient-reported outcomes (PROs) in patients with UI due to NDO in a double-blind, placebo-controlled study. METHODS: Patients with UI due to NDO (from multiple sclerosis or spinal cord injury) were randomized to intradetrusor placebo (n = 92) or onabotulinumtoxinA 200 U (n = 92) or 300 U (n = 91). PROs included Incontinence Quality of Life (I-QOL) Questionnaire to assess health-related quality of life (HRQoL), the 16-item modified Overactive Bladder-Patient Satisfaction with Treatment Questionnaire (OAB-PSTQ) to assess treatment satisfaction, and Patient Global Assessment to assess treatment goal achievement. RESULTS: Mean improvement in I-QOL total score at weeks 6 and 12 was significantly greater with both onabotulinumtoxinA 200 U and 300 U versus placebo (Δ12.3 for 200 U and Δ14.9 for 300 U vs. placebo; P < 0.001), and was clinically meaningful. For those patients who completed the OAB-PSTQ, improvement in satisfaction at weeks 6 and 12 was significantly greater for onabotulinumtoxinA versus placebo (P < 0.001, all comparisons). At 6 weeks, greater proportions of onabotulinumtoxinA-treated patients than placebo reported being somewhat or very satisfied (200 U, 77.5% and 300 U, 67.8% vs. placebo, 39.5%), and significant progress toward or complete achievement of primary treatment goal (200 U, 62.9% and 300 U, 61.6% vs. placebo, 16.5%). CONCLUSIONS: NDO patients treated with onabotulinumtoxinA 200 or 300 U had significantly greater improvement in HRQoL and greater treatment satisfaction compared with placebo-treated patients, with no clinically relevant differences between onabotulinumtoxinA doses.

Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a 1-year, open-label extension study.

OBJECTIVE: • To evaluate the 1-year safety of 5 mg of tadalafil once daily in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS); efficacy measures were included to evaluate the maintenance of efficacy after an additional year of treatment. PATIENTS AND METHODS: • In total, 427 men who completed a 12-week, placebo-controlled, dose- finding study assessing once-daily tadalafil (2.5, 5, 10 or 20 mg) or placebo elected to continue into the open-label extension period. Safety and efficacy parameters were assessed after 1 month and every 3 months. RESULTS: • In total, 299 patients (69.9%) completed the 1-year, open-label extension period. Treatment-emergent adverse events (TEAEs) were reported by 57.6% of patients, with most TEAEs being mild (44%) or moderate (45%) in severity; the most common TEAEs (≥ 2%) were dyspepsia, gastro-oesophageal reflux disease, back pain, headache, sinusitis, hypertension and cough. Twenty-two patients (5.2%) discontinued as a result of AEs. During the open-label extension period, mean prostate-specific antigen increased from 1.6 ± 1.3 ng/mL to 1.8 ± 1.4 ng/mL. • Mean post-void residual volume was 61.1 ± 60.4 mL at study entry and 42.2 ± 64.1 mL after the open-label extension period. Changes in the total International Prostate Symptom Score (IPSS), IPSS irritative and obstructive subscores, IPSS health-related quality of life and BPH Impact Index were maintained after 1 year. In sexually-active patients with erectile dysfunction, improvements in the International Index of Erectile Function-Erectile Function domain were maintained after 1 year. CONCLUSION: • In men with BPH-LUTS, 5 mg of tadalafil once daily during 1 year of treatment was well tolerated and efficacy changes were maintained.

Treatment of moderate to severe female stress urinary incontinence with the adjustable continence therapy (ACT) device after failed surgical repair.

INTRODUCTION: Treatment of recurrent stress incontinence after a failed surgical procedure is more complicated, and repeat surgeries have higher rates of complications and limited efficacy. We determined the technical feasibility, efficacy, adjustability, and safety of adjustable continence therapy device for treatment of moderate to severe recurrent urinary incontinence after failed surgical procedure. MATERIALS AND METHODS: Female patients with moderate to severe recurrent stress urinary incontinence who had at least one prior surgical procedure for incontinence were enrolled. All patients underwent percutaneous placement of adjustable continence therapy (ACT) device (Uromedica, Plymouth, Minnesota). Baseline and regular follow-up tests to determine subjective and objective improvement were performed. RESULTS: A total of 89 patients have undergone implantation with 1-3 years of follow-up. Data are available on 77 patients at 1 year. Of the patients, 47% were dry at 1 year and 92% improved after 1-year follow-up. Stamey score improved from 2.25 to 0.94 at 1 year (P < 0.001). IQOL questionnaire scores improved from 33.9 to 71.6 at 1 year (P < 0.001). UDI scores reduced from 60.7 to 33.3 (P < 0.001) at 1 year. IIQ scores reduced from 57.0 to 21.6 (P < 0.001) at 1 year. Diary incontinence episodes per day improved from 8.1 to 3.9 (P < 0.001) at 1 year. Diary pads used per day improved from 4.3 to 1.9 (P < 0.001). Explantation was required in 21.7% of patients. CONCLUSION: The ACT device is an effective, simple, safe, and minimally invasive treatment for moderate to severe recurrent female stress urinary incontinence after failed surgical treatment.

Tolerability of 5 mg solifenacin once daily versus 5 mg oxybutynin immediate release 3 times daily: results of the VECTOR trial.

PURPOSE: Although antimuscarinic treatment is indicated for overactive bladder, many patients discontinue it because of dry mouth. Of available antimuscarinics oxybutynin is associated with the highest dry mouth rate. We compared the safety and tolerability of 5 mg solifenacin vs 15 mg oxybutynin immediate release. MATERIALS AND METHODS: At 12 Canadian centers a total of 132 patients with overactive bladder symptoms (greater than 1 urgency episode per 24 hours, and 8 or greater micturitions per 24 hours) were randomized to 5 mg solifenacin once daily or 5 mg oxybutynin 3 times daily for 8 weeks. The primary end point was the incidence and severity of dry mouth reported after direct questioning. Efficacy end points (3-day diary documented changes in urgency, frequency, incontinence, nocturia and voided volume), and changes on the Patient Perception of Bladder Condition scale and the Overactive Bladder Questionnaire were evaluated secondarily. RESULTS: Of patients on solifenacin vs oxybutynin immediate release 35% vs 83% reported dry mouth (p <0.0001). Of patients reporting dry mouth severity was graded moderate by 13% and 42% of those on solifenacin and oxybutynin immediate release, and severe by 13% and 28%, respectively (p = 0.001). Patients in each group showed improvements in efficacy end points, and Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire scores from baseline to treatment end. CONCLUSIONS: Significantly fewer patients on 5 mg solifenacin once daily reported dry mouth vs those receiving 5 mg oxybutynin immediate release 3 times daily. Significantly fewer patients on solifenacin reported moderate/severe dry mouth. Significantly fewer patients on solifenacin withdrew from study due to dry mouth and there were significantly fewer overall adverse events. Solifenacin and oxybutynin immediate release were efficacious in decreasing efficacy end points, and improved Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire results from baseline to treatment end.

GnRH antagonists in the treatment of advanced prostate cancer.

Analogues of the gonadotropin releasing hormone (GnRH) inhibit the hypothalamic-pituitary-gonadal axis. This has provided treatment modalities for advanced and metastatic prostate cancer. The latest group of analogues, the GnRH antagonists, make promising treatments available that avoid the transient surge in testosterone that occurs with the use of GnRH agonists. Such surges may stimulate tumor growth, causing patients to experience new or worsening cancer symptoms and potential serious adverse effects, including increased bone pain, urinary retention, and spinal cord compression and consequently delay the therapeutic benefits of agonist therapy. Degarelix, an antagonist, recently approved in the United States and Europe, achieves faster, more profound and sustained testosterone suppression and with fewer adverse effects when compared with agonists and other antagonists. This review discusses and compares the compounds degarelix, abarelix, and cetrorelix.

The adjustable continence therapy system for recurrent female stress urinary incontinence: 1-year results of the North America Clinical Study Group.

PURPOSE: We determined the efficacy, safety, adjustability and technical feasibility of the adjustable continence therapy device (Uromedica, Plymouth, Minnesota) for the treatment of recurrent female stress urinary incontinence. MATERIALS AND METHODS: Female patients with recurrent stress urinary incontinence were enrolled in the study and a defined set of exclusionary criteria were followed. Baseline and regular followup tests to determine eligibility, and to measure subjective and objective improvement were performed. A trocar was passed fluoroscopically and with digital vaginal guidance to the urethrovesical junction through small incisions between the labia majora and minora. The adjustable continence therapy device was delivered and the balloons were filled with isotonic contrast. The injection ports for balloon inflation were placed in a subcutaneous pocket in each labia majora. Device adjustments were performed percutaneously in the clinic postoperatively. An approved investigational device exemption Food and Drug Administration protocol was followed to record all adverse events. RESULTS: A total of 162 subjects underwent implantation with 1 year of data available on 140. Mean Stamey score improved by 1 grade or more in 76.4% (107 of 140) of subjects. Improvement in the mean incontinence quality of life questionnaire score was noted at 36.5 to 70.7 (p <0.001). Reductions in mean Urogenital Distress Inventory (60.3 to 33.4) and Incontinence Impact Questionnaire (54.4 to 23.4) scores also occurred (p <0.001). Mean provocative pad weight decreased from 49.6 to 11.2 gm (p <0.001). Of the patients 52% (67 of 130) were dry at 1 year (less than 2 gm on provocative pad weight testing) and 80% (102 of 126) were improved (greater than 50% reduction on provocative pad weight testing). Complications occurred in 24.4% (38 of 156) of patients. Explantation was required in 18.3% (28 of 153) of the patients during 1 year. In terms of the complications 96.0% were considered to be mild or moderate. CONCLUSIONS: The Uromedica adjustable continence therapy device is an effective, simple, safe and minimally invasive treatment for recurrent female stress urinary incontinence. It can be easily adjusted percutaneously to enhance efficacy and complications are usually easily manageable. Explantation does not preclude later repeat implantation.

Tuberculous epididymitis following intravesical Bacillus Calmette-Guérin immunotherapy.

Intravesical Bacillus Calmette-Guérin (BCG) is widely used as an adjuvant therapy in the treatment of superficial bladder cancer. BCG is administered as a live, attenuated form of Mycobacterium bovis, and acts as an immunomodulary agent to delay tumor progression. BCG is generally well tolerated, though localized and systemic infectious complications may occur. A literature search revealed that tuberculous epididymitis is a rarely reported complication of intravesical BCG therapy. We report the case of an 82-year-old male who developed tuberculous epididymitis while undergoing intravesical BCG treatment for transitional cell carcinoma of the bladder. Right orchiectomy was performed, followed by rifampin and isoniazid therapy once M. bovis was identified as the infectious agent. The patient responded well to these treatments, and made a full recovery. Tuberculous epididymitis is an uncommon complication resulting from intravesical BCG therapy, which is likely explained by retrograde migration from the prostatic urethra in this case.

A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America.

PURPOSE: Degarelix is a gonadotropin-releasing hormone receptor antagonist (blocker) with rapid onset of action suppressing gonadotropins, testosterone and prostate specific antigen in prostate cancer. In the present open label, randomized study in North America we evaluated the efficacy and safety of a starting dose of 200 mg degarelix followed by monthly injections of 60 or 80 mg during 1 year of prostate cancer treatment. MATERIALS AND METHODS: A total of 127 patients (median age 76 years, range 47 to 93) with histologically confirmed prostate cancer were enrolled in the study. Efficacy was assessed by measuring serum testosterone and prostate specific antigen. RESULTS: Median baseline testosterone and prostate specific antigen levels were 4.13 ng/ml (P25-P75 3.03-5.11) and 13.4 ng/ml (P25-P75 6.80-25.7), respectively. The starting dose induced a rapid suppression of testosterone in that 88% of the patients had testosterone levels of 0.5 ng/ml or less 1 month after the injection. For patients who had testosterone levels of 0.5 ng/ml or less after 1 month, 93% and 98% of those receiving maintenance doses of 60 and 80 mg, respectively, had testosterone levels that were consistently 0.5 ng/ml or less at all monthly measurements from 1 month to 1 year. No evidence of testosterone surge was detected. In both groups prostate specific antigen decreased by 96% after 1 year and median time to 90% reduction in prostate specific antigen was 56 days. Six patients (5%) withdrew from the study due to adverse events. CONCLUSIONS: Degarelix treatment for 1 year resulted in a fast, profound and sustained suppression of testosterone and prostate specific antigen with no evidence of testosterone surge. Degarelix was well tolerated.

The effect of physician and patient education when combined with vardenafil treatment in Canadian males with erectile dysfunction: an open-label, factorial-designed, cluster-randomized clinical trial.

INTRODUCTION: Studies evaluating the effect of education on treatment success with phosphodiesterase type 5 (PDE5) inhibitor therapy in men with erectile dysfunction (ED) are limited. Additional education of the primary care physician (PCP) and the patient are thought to optimize the treatment of ED. AIM: To assess the impact of education of the PCP or of the patient in the treatment of ED with vardenafil relative to usual care. METHODS: In this 12-week, open-label, multicenter, factorial-designed, cluster-randomized Canadian study, 1,029 patients with ED were enrolled into four different education groups: usual care, patient education, PCP education, and both PCP and patient education. All groups started on vardenafil 10 mg, with the option to titrate at weeks 4 and 8. MAIN OUTCOME MEASURES: The primary efficacy measure was the difference at week 4 last observation carried forward (LOCF) in the overall improvement in erectile function (EF) as measured by the Global Assessment Question (GAQ), while on background vardenafil, between those receiving education vs. those who did not. Other secondary assessments included responses to diary questions regarding penetration (sexual encounter profile, SEP2) and erection maintenance (SEP3), and to questionnaires regarding treatment satisfaction (Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS]). RESULTS: A total of 956 patients were included in the intent-to-treat population. Mean baseline International Index of Erectile Function-EF domain score was 13. GAQ response rates at week 4 LOCF were high (>80%) for all groups, regardless of the education given. Mean per patient SEP2 and SEP3 rates at week 12 LOCF were 86-89% and 79-83%, respectively. In an exploratory analysis, a positive relationship between GAQ responses and EDITS scores was observed (P < or = 0.0007). Vardenafil was generally well tolerated. CONCLUSIONS: In men with moderate ED, vardenafil led to high success rates and satisfaction regardless of the education given. The benefits of education for PCP and patients in Canada were possibly masked by a ceiling effect in this study population.

Tuberculosis of the bladder without previous renal infection.

Tuberculous (TB) infections are usually limited to the pulmonary system but the hematogenous spread of TB can result in secondary infections in any part of the body. Genitourinary TB is uncommon and follows hematogenous spread from a primary pulmonary infection to the kidneys. A rare case of a TB infection of the bladder without renal involvement is described.

Anticholinergics for overactive bladder: Temporal trends in prescription and treatment persistence.

INTRODUCTION: We sought to understand the contemporary pharmacologic management of overactive bladder (OAB) in a single-payer system. We examined temporal trends in the use of anticholinergic medications and assessed whether the likelihood of patients changing their anticholinergic therapy was predicted by their current therapy. METHODS: We conducted a retrospective, population-based analysis of prescription records from the PharmaNet database in BC, Canada. We identified patients treated with one or more anticholinergic prescriptions between 2001 and 2009. We characterized temporal trends in the use of anticholinergic medications. We used generalized estimating equations with a logit wing to assess the relationship between the type of anticholinergic medication and the change in prescription. RESULTS: The 114 325 included patients filled 1 140 296 anti-cholinergic prescriptions. The number of prescriptions each year increased over the study, both in aggregate and for each individual medication. While oxybutynin was the most commonly prescribed medication (68% of all prescriptions), the proportion of newer anticholinergics (solifenacin, darifenacin, and trospium) prescribed increased over time (p<0.0001). Patients taking tolterodine (odds ratio [OR] 1.03; p=0.01) and darifenacin (OR 1.12; p=0.0006) were significantly more likely to change their prescription than those taking oxybutynin. There was no association seen for patients taking solifenacin (p=0.6) and trospium (p=0.9). CONCLUSIONS: There are an increasing number of anticholinergic prescriptions being filled annually. Patients taking newer anticholinergics are at least as likely to change therapy as those taking oxybutynin. The reimbursement environment in BC likely affects these results. Restrictions in the available data limit assessment of other relevant predictors.

Erectile dysfunction: an overview.

Sexual function is a central part of a man's identity, helping to define who he is, and how he feels about himself. It is also a key determinant of relationship health. Erectile dysfunction (ED) threatens all of this, and is thus an important topic in male health. Erectile dysfunction is common around the world, especially in older men. Risk factors for ED overlap significantly with those for cardiovascular disease and endothelial dysfunction, especially diabetes.

Canadian experience with high intensity focused ultrasound for the treatment of BPH.

INTRODUCTION: High Intensity Focused Ultrasound (HIFU) ablates benign prostatic tissue in a minimally invasive manner with low morbidity. The safety and effectiveness of treating of benign prostatic hypertrophy (BPH) with HIFU using 3 different protocols are reported. METHODS: Forty six male patients with a mean age of 65 (range 47-84) were treated using the Sonablate HIFU device (Focus Surgery, Indianapolis IN) with 3 different protocols at 3 centres (LDS n=20, PJP n=12, RWC n=14). Baseline and outcome measures included AUA symptom score, peak urinary flow rate (Qmax) and quality of life (QOL) score. Early and long term complications were recorded. RESULTS: At 12 months post-HIFU, patients showed improvements in AUA symptom scores of 35% (LDS), 43% (PJP) and 59% (RWC). Qmax improved by 30% (LDS), 37% (PJP) and 63% (RWC). QOL scores improved by 63% (LDS) and 58% (RWC). Minor complications included hematospermia (13%), mild to moderate hematuria (9%), acute retention (4%), perineal pain (11%) and epididymitis (9%). Recatheterization occurred in up to 16% of patients. Eleven patients in the LDS and PJP series required a transurethral resection of the prostate (TURP) for symptoms of urinary obstruction after HIFU treatment. There were no TURP's following HIFU in the RWC series. CONCLUSIONS: HIFU is safe, produces acceptable complications and effectively relieves BPH symptoms.

A survey of urological manpower, technology, and resources in Canada.

INTRODUCTION: Knowledge of the current status of manpower and resources is important in understanding the state of any medical specialty, and critical in planning for future recruitment, funding and infrastructure development. METHODS: In 2003, the Canadian Urological Association (CUA) conducted two nationwide surveys examining manpower, resources, and the technology available. One survey went only to academic and hospital leaders across the country (the resources survey), while the other was sent to the entire general membership of the CUA. RESULTS: The response rate for the resources survey was 67%, while that for the membership survey was 50.4%. The respondents' ages were evenly distributed, with the modal 5-year range being 51 to 55 years of age. Eighty-eight percent of respondents were Canadian-trained. Two-thirds of respondents spent over 80% of their practice time in direct patient care, and most practiced general urology. The majority of respondents practiced in smaller hospitals: 57.6% in centres with 300 or fewer inpatient beds, and 47.2% of centres reported < 500 procedures/year. Community hospitals (62% of responses to the resources survey) generally had fewer advanced technologies than academic centres. A quarter of the cystoscopy equipment used by respondents was over 15 years old. CONCLUSIONS: The results of these surveys present a snapshot of the current state of urology resources and manpower across Canada, potentially allowing better planning and negotiations with hospitals and governments.

Testosterone deficiency syndrome and cardiovascular health: An assessment of beliefs, knowledge and practice patterns of general practitioners and cardiologists in Victoria, BC.

INTRODUCTION: Testosterone deficiency syndrome (TDS) has been shown to be an independent cardiovascular risk factor and a predisposing factor for metabolic syndrome. As general practitioners and cardiologists primarily care for these patients, we sought to assess their knowledge, beliefs and practice patterns with respect to TDS and cardiac health. METHODS: We distributed a questionnaire to all 20 cardiologists and a cohort of 128 family practitioners in Victoria, British Columbia. Of the 13 questions, 10 assessed knowledge and beliefs on TDS and 3 assessed current practice patterns. RESULTS: Most respondents believed that TDS is a medical condition (66.7%) and could negatively affect body composition (62%), but a similar majority was unsure whether it was a cardiac risk factor (66.7%). While most believed that testosterone replacement therapy (TRT) could improve exercise tolerance (62%), most were unsure if it was beneficial in cardiac patients. Cardiologists were significantly less likely to believe that TRT was beneficial in preventing recurrent myocardial infarction and improving myocardial perfusion (p = 0.0133, 0.00186, respectively). The vast majority (88%) did not screen cardiac patients for TDS. If a patient was identified as having TDS, only10% of those surveyed would refer these patients to a urologist. CONCLUSION: Despite its prevalence in cardiac patients, TDS is not well-understood by general practitioners and cardiologists; they lack knowledge on its deleterious cardiovascular effects. In their role as men's health advocates, urologists should educate our colleagues regarding the correlation between TDS and cardiovascular mortality and risk factors. Limitations of this study include small sample size and restricted geographic scope.

A surgical challenge: Idiopathic scrotal elephantiasis.

Scrotal elephantiasis is a condition rarely encountered in developed nations. It is endemic in tropical regions due to the presence of filariasis (Wucheria bancrofti). We report 2 cases of idiopathic scrotal elephantiasis in Canadian citizens with no history of travel to endemic filariasis regions, malignancy, surgery or radiation. Both patients underwent complete excision of the involved tissue with reconstruction. We found that for advanced cases of scrotal lymphedema, surgery is currently the only solution. In our cases of advanced idiopathic disease, surgical treatment combining the expertise of a plastic surgeon and a urologist provided a successful functional and cosmetic result.

Phase 1 and 2 studies demonstrate the safety and efficacy of intraprostatic injection of PRX302 for the targeted treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

BACKGROUND: PRX302 is a prostate specific antigen (PSA)-activated pore-forming protein toxin under development as a targeted approach for improving lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) without affecting sexual function. OBJECTIVE: To evaluate the safety and efficacy of PRX302 in men with moderate to severe BPH. DESIGN, SETTING, AND PARTICIPANTS: Eligible subjects were refractory, intolerant, or unwilling to undergo medical therapies for BPH and had International Prostate Symptom Score (IPSS) ≥12, a quality of life (QoL) score ≥3, and prostate volumes between 30 and 80 g. Fifteen patients were enrolled in phase 1 studies, and 18 patients entered phase 2 studies. INTERVENTIONS: Subjects received intraprostatic injection of PRX302 into the right and left transition zone via a transperineal approach in an office-based setting. Phase 1 subjects received increasing concentrations of PRX302 at a fixed volume; phase 2 subjects received increasing volumes per deposit at a fixed concentration. MEASUREMENTS: IPSS, QoL, prostate volume, maximum flow rate (Q(max)), International Index of Erectile Function, serum PSA levels, pharmacokinetics, and adverse events were recorded at 30, 60, 90, 180, 270, and 360 d after treatment with PRX302. RESULTS AND LIMITATIONS: Sixty percent of men in the phase 1 study and 64% of men in the phase 2 study treated with PRX302 had ≥30% improvement compared to baseline in IPSS out to day 360. Patients also experienced improvement in QoL and reduction in prostate volume out to day 360. Patients receiving ≥1 ml of PRX302 per deposit had the best response overall. PRX302 had no deleterious effect on erectile function. Adverse events were mild to moderate and transient in nature. The major study limitation was the small sample size. CONCLUSIONS: The promising safety profile and evidence of efficacy in the majority of treated subjects in these phase 1 and 2 studies supports further development of PRX302 as a minimally invasive, targeted treatment for BPH.