Randomized trial of percutaneous tibial nerve stimulation versus Sham efficacy in the treatment of overactive bladder syndrome: results from the SUmiT trial.

PURPOSE: The Study of Urgent PC vs Sham Effectiveness in Treatment of Overactive Bladder Symptoms (SUmiT) was a multicenter, double-blind, randomized, controlled trial comparing the efficacy of percutaneous tibial nerve stimulation to sham through 12 weeks of therapy. The improvement in global response assessment, voiding diary parameters, and overactive bladder and quality of life questionnaires was evaluated. MATERIALS AND METHODS: A total of 220 adults with overactive bladder symptoms were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or sham therapy. Overactive bladder and quality of life questionnaires as well as 3-day voiding diaries were completed at baseline and at 13 weeks. Subject global response assessments were completed at week 13. RESULTS: The 13-week subject global response assessment for overall bladder symptoms demonstrated that percutaneous tibial nerve stimulation subjects achieved statistically significant improvement in bladder symptoms with 54.5% reporting moderately or markedly improved responses compared to 20.9% of sham subjects from baseline (p <0.001). All individual global response assessment subset symptom components demonstrated statistically significant improvement from baseline to 13 weeks for percutaneous tibial nerve stimulation compared to sham. Voiding diary parameters after 12 weeks of therapy showed percutaneous tibial nerve stimulation subjects had statistically significant improvements in frequency, nighttime voids, voids with moderate to severe urgency and urinary urge incontinence episodes compared to sham. No serious device related adverse events or malfunctions were reported. CONCLUSIONS: This pivotal multicenter, double-blind, randomized, sham controlled trial provides level I evidence that percutaneous tibial nerve stimulation therapy is safe and effective in treating overactive bladder symptoms. The compelling efficacy of percutaneous tibial nerve stimulation demonstrated in this trial is consistent with other recently published reports and supports the use of peripheral neuromodulation therapy for overactive bladder.

Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial.

PURPOSE: Interstitial cystitis is a painful bladder condition of unknown etiology and poorly understood pathophysiology. Current therapies have met with limited success. Vanilloid receptor agonists such as resiniferatoxin (RTX) desensitize C-fibers that transmit pain; it is hypothesized that such drugs will be effective in the treatment of interstitial cystitis and painful bladder syndrome by decreasing the pain that leads to urinary frequency and urgency. MATERIALS AND METHODS: A randomized, double-blind, placebo controlled study was conducted in 163 patients with interstitial cystitis. Participants were randomly assigned to receive a single intravesical dose of 50 ml of either RTX 0.01 microM, 0.05 microM, 0.10 microM, or placebo. Safety and efficacy was evaluated over 12 weeks. The primary efficacy endpoint was the Global Response Assessment, a 7-point scale rating overall change in symptoms of interstitial cystitis after 4 weeks. Secondary efficacy endpoints included reduction in pain, urgency, frequency, nocturia, average void volume, and the O'Leary-Sant Symptom and Problem Indexes. RESULTS: RTX did not improve overall symptoms, pain, urgency, frequency, nocturia, or average void volume during 12 weeks followup. RTX resulted in a dose-dependent increase in the incidence of instillation pain, but was otherwise generally well tolerated. CONCLUSIONS: In the largest prospective, randomized clinical trial reported to date with intravesical vanilloid therapy, single administration of RTX at doses of 0.01 microM to 0.10 microM was not effective in patients with interstitial cystitis.

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.

A subcutaneous delivery system for the extended release of leuprolide acetate for the treatment of prostate cancer.

Following Huggins' original observation of the dependence of the prostate on androgens, testosterone suppression by either orchiectomy or oestrogen compounds (e.g., diethylstilbesterol [DES]) became the standard palliative treatment for advanced prostate cancer. Early studies showed testosterone suppression improved symptoms and patient survival by several months but was not curative. In addition, DES treatment resulted in significant cardiovascular morbidity and mortality from increased thrombotic events. Thus, both orchiectomy and DES were indicated for palliation in late stage disease, but were considered too extreme for earlier stage disease. The discovery of the hypothalamic peptide, luteinising hormone releasing hormone (LHRH), and its stimulatory release of luteinising hormone (LH) from the pituitary gland led to the synthesis of LHRH analogues (i.e., hormone therapy). LHRH analogues (e.g., leuprolide acetate) desensitise and downregulate pituitary LHRH receptors, thus reducing LH synthesis and release. The reduced release, in turn, decreases testosterone levels to those observed in DES-treated and orchiectomised patients. In contrast, LHRH analogues do not increase cardiovascular events. Therefore, leuprolide acetate therapy has been adopted as a safer alternative to DES and is considered to be generally reversible. This increased safety has allowed LHRH therapy to be applied in earlier stage prostate cancer. Recent studies have shown decreased rates of biochemical failure and a potential for increased patient survival with hormone therapy in conjunction with radical prostatectomy or radiation therapy. This article will focus on the literature supporting early, adjuvant LHRH therapy and Eligard 7.5 mg, a new depot formulation of leuprolide acetate that uses the Atrigel drug delivery system, causing an increase in bioavailability and optimising testosterone suppression - two key features of depot hormone suppression.