First Report®: American Urological Association Annual Meeting Chicago, IL; April 25-30, 2009

Silodosin Rapidly Reduces BPH Symptoms in Two Studies

Chicago, IL—In two clinical studies recently conducted in the United States, treatment of benign prostatic hyperplasia (BPH) with silodosin rapidly provided significant improvement of urinary symptoms. Results of these studies were discussed in a podium session at the AUA meeting. The lead author of a post-hoc analysis of the trials was Leonard S. Marks, MD, Clinical Associate Professor in the Department of Surgery/Urology at the University of California, Los Angeles School of Medicine.

Silodosin is a highly selective alpha1A-adrenoceptor antagonist. The post-hoc analysis examined changes in International Prostate Symptom Score (IPSS) subscales by individual IPSS question. The two trials were randomized, placebo-controlled, double-blind clinical studies in men ≥ 50 years with BPH and IPSS ≥ 13. Patients enrolled in the trials were assigned to receive either silodosin or placebo.

There were 466 patients randomized to receive silodosin 8 mg and 457 patients who received placebo once daily for 12 weeks. Symptom improvement was assessed based on seven questions of the IPSS, evaluating both irritative and obstructive symptoms. IPSS scores for incomplete emptying (Q1), frequency (Q2), intermittency (Q3), urgency (Q4), weak stream (Q5), straining (Q6), and nocturia (Q7) were determined during clinical visits at baseline and weeks 1, 2, 4, and 12, and by telephone interview at day 3 or 4 of treatment.

Questions 1 to 6 were scored on a 6-point scale, from “not at all” to “almost always.” Question 7 was scored from 0 (none) to 5 (≥ 5 times). The significance of treatment effects comparing patients who received silodosin or placebo was assessed by analysis of covariance.

The authors reported that combined results of the mean baseline values for patients receiving silodosin and those receiving placebo were identical in all IPSS subcategories (Q1, 3.1; Q2, 3.5; Q3, 3.1; Q4, 3.0; Q5, 3.6; Q6, 2.2; Q7, 2.8). At the last observation, the mean change (standard deviation) in score from baseline in all IPSS subcategories was significantly greater with silodosin than with placebo. Except for Q7 (nocturia), the difference in symptom improvement between silodosin and placebo was already statistically significant at week 0.5, the earliest postbaseline measurement.

Improvement in nocturia with silodosin versus placebo was significant at week 1 of treatment (silodosin, −0.5 [1.07] vs placebo, −0.3 [1.05]; P = 0.0091). The change from baseline to the last observation for Q2 was −0.9 for the silodosin group versus −0.5 for the placebo group (P < 0.0001); for Q4, the change was −0.8 for silodosin versus −0.4 for placebo (P < 0.0001); for Q7, the change was −0.6 for silodosin versus −0.4 for placebo (P = 0.0037); for Q1, the change was −0.9 for silodosin versus −0.6 for placebo (P < 0.0001); for Q3, the change was −1.1 for silodosin versus −0.6 for placebo (P < 0.0001); for Q5 the change was −1.1 for silodosin versus −0.5 for placebo (P < 0.0001); and for Q6, the change was −0.9 for silodosin versus −0.5 for placebo (P < 0.0001).

The authors concluded that in the combined results of the two clinical trials, silodosin promoted rapid and sustained improvement in irritative and obstructive symptoms of BPH. These improvements were statistically significant after 3-7 days of treatment.
__________________________________________________________________________________________________________________

Prebiopsy Reduction of Prostate Volume Achieved with Dutasteride

Chicago, IL—A group of researchers at a single institution has quantified treatment times needed for patients diagnosed with prostate cancer to achieve prostate volume reduction with dutasteride prior to 3-dimensional mapping biopsies (MBx). Dutasteride is a 5-alpha-reductase inhibitor. The lead author was Daniel J. Tandberg, MD, of Aurora, Colorado, and results were presented at a podium presentation during the AUA meeting.

According to the study authors, prostate volume reduction is desirable in certain subsets of men undergoing targeted focal therapy for prostate cancer, including brachytherapy and cryotherapy. It is becoming more common for men diagnosed with prostate cancer to undergo saturation or MBx to evaluate the extent of their prostate cancer before treatment decisions are made. Treatment options also include surveillance, or watchful waiting.

The study population included patients in whom large prostate volume was deemed to be secondary to benign prostatic hypertrophy and not prostate cancer. The authors stated that in their experience, prostate size is related to postbiopsy complications such as urinary retention and bleeding. The study involved treating men who had large-volume prostates with dutasteride 0.5 mg daily prior to MBx. From 2005 until the time of the presentation, the authors said that 146 men have had MBx at their institution. They treated men with enlarged prostates with dutasteride to reduce their prostate volume before MBx. Prostate volumes were evaluated using transrectal ultrasound at baseline and after treatment.

Dutasteride treatment was administered to 39 men prior to MBx. The mean prostate volume was 55.1 cc prior to dutasteride therapy and 38.3 cc after therapy. The average treatment time was 19 weeks. The average reduction in volume size was 16.7 cc, or an average decrease of 28.0% in prostate volume.

The authors compiled a graph to show prostate volume change before and after dutasteride treatment by length of treatment in weeks. They also categorized the information by initial prostate size: ≤ 49 cc, 50-69 cc, and ≥ 70 cc. The graph enables clinicians to determine the length of treatment needed to reduce the prostate gland to the desired size based on initial prostate volume.

The authors said that the trial was one of the first reviews to demonstrate volume reduction in men with prostate cancer taking dutasteride over a varied length of time, and that the graph presented will aid clinicians in determining the length of therapy needed to reach a desired volume reduction.
____________________________________________________________________________________________________________________________ 

New Study Shows Nocturia Increases Mortality Risk in the Elderly

Chicago, IL—A new prospective study examining nocturia in an elderly population found that ≥ 2 episodes of nocturia a night significantly increased the risk of mortality in the study participants. The results of the analysis were presented during a poster session at the AUA meeting.

Nocturia is a common condition affecting the elderly and can be either the result of an overproduction of urine at night or an indication of a more serious ailment, such as cardiovascular disease, diabetes mellitus, sleep apnea, renal dysfunction, lower urinary tract dysfunction, or a sleep disorder. It has been previously reported that nocturia increases the mortality rate among elderly patients and patients with coronary heart disease; however, it is not clear whether the increased mortality rate is due to nocturia itself or the associated ailments.

In this prospective cohort study, researchers conducted a comprehensive geriatric assessment to evaluate the association between nocturia and mortality in a community-dwelling elderly population. Researchers conducted a population-based cross-sectional survey of persons age ≥ 70 in Sendai, Japan, by completing extensive health interviews with each participant. Mortality figures over the 3-year study period were investigated using data in the national health insurance system. The primary outcome of the study was rate of mortality.

During the analysis of 788 participants (mean age [± standard deviation] 74.9 ± 4.77 [range, 70-97]), researchers reported that there was a significant increase in the risk of morality with ≥ 2 episodes of nocturia each night. According to study findings, of the 426 patients in the group without nocturia, there were 7 deaths as compared with 24 deaths in the 362 participants who had nocturia (P < 0.001) at least twice a night. Researchers reported an odds ratio of 3.32 from the multivariate analysis of those with nocturia as compared with those without it (95% CI, 1.42-8.74; P = 0.008).

The study’s authors also determined that the multivariate hazard ratios for mortality with nocturia ≥ 2 times a night were 2.68 (1.12-6.43). Based on the findings of the Cox proportional hazards model used in the study, nocturia was found to be an independent risk factor for increasing mortality.

Data on mortality and its risk factors in the study also show a difference in mortality based on patient age. Of the 477 patients between the ages of 70 and 74 years, there were 8 deaths (1.7%), as compared with the group of 311 patients age ≥ 75 who experienced 23 deaths (7.4%) during the course of the study (P < 0.001). Researchers also looked at other possible mortality risk factors, including hypertension, coronary disease, nephropathy, diabetes, stroke, liver disease, malignant disease, and alcohol consumption.

Researchers concluded that findings of the study indicate that nocturia is not only a quality-of-life issue, but is a serious problem among the elderly.