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.

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.

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.

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.

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.

Recurrent idiopathic high-flow priapism treated with selective arterial embolization after repeated initial treatments for low-flow priapism.

High-flow priapism is most often seen following perineal and penile trauma. We report the case of a 32-year-old man who presented with recurrent idiopathic priapism initially treated as low-flow priapism on 8 previous emergency department visits. Pelvic angiography revealed an abnormal communication between the left cavernosal artery and the left corpus cavernosum and led to the diagnosis of high-flow priapism. Treatment involved embolization of the left common penile artery, which resulted in successful resolution of the recurrent priapism. Our patient's case highlights the importance of an appropriate work-up, including imaging, to distinguish high- and low-flow priapism and to provide appropriate care.

Vardenafil improves ejaculation success rates and self-confidence in men with erectile dysfunction due to spinal cord injury.

STUDY DESIGN: Multicenter, double-blind, placebo-controlled, parallel-group study. OBJECTIVE: To assess the effect of the oral phosphodiesterase type-5 inhibitor, vardenafil, on ejaculation rates and self-confidence in men with spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: Spinal command of male sexual functions is often seriously impaired by traumatic spinal cord injury (SCI). A high proportion of men with SCI cannot ejaculate during sexual intercourse. SCI-related ejaculatory disorders are often responsible for male infertility. Sexual dysfunction associated with SCI can also affect men's self-confidence. METHODS: In this 12-week study, 418 men aged >or=18 years with erectile dysfunction >6 months resulting from a traumatic SCI were randomized to vardenafil (n = 207) or placebo (n = 211) 10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8. Assessments included questions of the International Index of Erectile Function (IIEF) about ejaculation success and orgasmic perception; the Global Confidence Question; and quality-of-life scales to measure psychological well-being, self-esteem, depression, and mental health status. RESULTS: Overall per patient ejaculation success rates were significantly greater with vardenafil than placebo over 12 weeks of treatment (19% vs. 10%; P < 0.001). At last observation carried forward, the IIEF "orgasmic function" score increased from 2.9 at baseline to 4.0 for vardenafil and from 3.0 at baseline to 3.4 for placebo. Sixteen percent of men receiving vardenafil and 8% receiving placebo felt orgasm "almost always" or "always" at weeks 8-12, compared with 4% and 6%, respectively, at baseline. Significant improvements in confidence scores were observed with vardenafil compared with placebo (P < 0.0001). There were no clinically significant differences between vardenafil and placebo in the quality-of-life measures at the study endpoint, but these had been in the normal range at baseline. CONCLUSION: Vardenafil significantly improved ejaculation and self-confidence in men with erectile dysfunction due to SCI.

Andropause: knowledge and awareness among primary care physicians in Victoria, BC, Canada.

UNLABELLED: The causes, symptoms and treatment options for andropause have been well documented; however, not enough is known about the primary care physicians' (PCPs) knowledge in this therapeutic area. This study assesses the PCPs' awareness and knowledge of andropause in Victoria, British Columbia, Canada. METHODS: Self-administered questionnaires were developed for family physicians and general practitioners. Each questionnaire included questions in three domains: 1) General knowledge, beliefs and exposure; 2) Knowledge of diagnostic and treatment options and; 3) General demographics. RESULTS: A very high percentage of PCPs had heard of andropause (96.3%). Of the physicians who completed the survey, 92.6% agreed that men experience something similar to women's menopause when they age and 98.0% agreed that andropause is associated with an increased risk of osteoporosis. Almost all PCPs (91.5%) agreed that prostate cancer is a contraindication to treatment while around one-third (33.9%) agreed that breast cancer was a contraindication. Slightly more than half of physicians (57.4%) felt that they encountered obstacles to their investigation of andropause with the most prevalent complaint being a lack of access to education resources. There is a need for improved continuing medical education (CME) programmes in the Greater Victoria region to give PCPs the skills to diagnose and manage andropause with confidence.

Efficacy and safety of oral tadalafil in the treatment of men in Canada with erectile dysfunction: a randomized, double-blind, parallel, placebo-controlled clinical trial.

INTRODUCTION: Erectile dysfunction (ED) is a highly prevalent, often undertreated condition. AIM: This 12-week, double-blind, parallel, placebo-controlled study was conducted at 25 sites in Canada to evaluate the efficacy and safety of oral tadalafil, a phosphodiesterase type 5 inhibitor, for the treatment of ED. METHODS: Men with ED of organic, psychogenic, or mixed etiology were stratified by baseline ED severity then randomly assigned to placebo (N = 50), tadalafil 10 mg (N = 103), or tadalafil 20 mg (N = 100), taken as needed (maximum, once daily). MAIN OUTCOME MEASURES: Efficacy was assessed by the International Index of Erectile Function (IIEF), a Sexual Encounter Profile diary, and a global assessment question (GAQ). RESULTS: Tadalafil 10 mg and tadalafil 20 mg significantly improved erectile function compared with placebo (P < 0.001, all measures). At end point, the mean IIEF erectile function (EF) domain scores were 14.5, 21.2, and 23.3 of a possible score of 30 for placebo, tadalafil 10 mg, and tadalafil 20 mg, respectively. Patients treated with tadalafil reported greater change from baseline on the IIEF EF domain score compared with placebo, regardless of baseline ED severity. During treatment, the mean per-patient proportion of successful intercourse attempts was higher for tadalafil 10 mg and 20 mg than for placebo (placebo, 31.9%; tadalafil 10 mg, 56.7%; and tadalafil 20 mg, 61.5%), and a greater proportion of patients reported improved erections with tadalafil (GAQ; placebo, 22.0%; tadalafil 10 mg, 67.0%; tadalafil 20 mg, 79.0%). Fifty percent and 62% of patients treated with tadalafil 10 mg and 20 mg, respectively, achieved successful sexual intercourse after their first dose, compared with 31% with placebo. Treatment-emergent adverse events were generally mild or moderate. CONCLUSION: Tadalafil was an effective, well-tolerated therapy for ED of broad-spectrum etiology and severity.

Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial.

OBJECTIVES: To perform a Canadian multicenter randomized placebo-controlled trial to evaluate the safety and efficacy of 6 weeks of levofloxacin therapy compared with placebo in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Uncontrolled studies have supported the use of antibiotics in CP/CPPS. METHODS: Men with a National Institutes of Health (NIH) diagnosis of CP/CPPS (specifically, no infection localized to the prostate) were randomized to levofloxacin (500 mg/day) or placebo for 6 weeks in 11 Canadian centers. Patients were assessed at baseline and at 3, 6, and 12 weeks with the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and global patient assessments (subjective global assessment and patient assessment questionnaire). RESULTS: Eighty men (average age 56.0 years, range 36 to 78; duration of symptoms 6.5 years, range 0.6 to 32) were randomized to receive levofloxacin (n = 45) or placebo (n = 35). All were evaluated in an intent-to-treat analysis. Both groups experienced progressive improvement in symptoms as measured by the NIH-CPSI. However, the difference in response was not statistically or clinically significant at end of treatment (6 weeks) or at the end of the follow-up visits (12 weeks). No patients withdrew because of adverse events. One patient withdrew before the 6-week assessment. Adverse events (all mild) were reported in 20% of the levofloxacin group and 17% of the placebo group. CONCLUSIONS: This pilot placebo-controlled study showed that 6 weeks of levofloxacin therapy in men diagnosed with CP/CPPS resulted in symptom improvement that was not significantly different from that with placebo at end of treatment or follow-up. The clinical ramifications of these findings need to be addressed.