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The Persistence of Silodosin Monotherapy and the Reasons for Withdrawal from Treatment of Previously Untreated Japanese Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia.

ABSTRACT: The persistence of silodosin and the reasons for withdrawal from treatment of previously untreated Japanese patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) were evaluated in real-life clinical practice.A total of 81 previously untreated Japanese patients diagnosed with LUTS/BPH were treated with silodosin monotherapy and prospectively followed for 4 years. The persistence rate was estimated using the Kaplan-Meier method. If silodosin had to be terminated or a patient did not come to the hospital, the reason was determined.The 6-month, 1-year, 2-year, 3-year, and 4-year persistence rates were 63.0%, 56.8%, 50.6%, 44.4%, and 35.8%, respectively. The most frequent reason (22.2%) for withdrawal was symptom resolution. After silodosin treatment, the international prostate symptom score and the quality of life index were significantly improved and maintained for 4 years.35.8% of previously untreated Japanese patients continued silodosin for 4 years. Many patients terminated silodosin for various reasons, the most frequent of which was symptom resolution. The effects of silodosin were maintained when the patients continued treatment.This study was approved by the institutional review board of Hokkaido Prefectural Esashi Hospital (number 2007-2) and was registered in a public trial registry (UMIN000026910).

SUBMITTER: Tanaka Y

PROVIDER: S-EPMC5485276 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:BackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.

Project description:BackgroundAlthough combination therapy with 5 alpha-reductase inhibitor (5ARI) and alpha-blocker is one of the standard interventions in symptomatic benign prostatic hyperplasia (BPH), 5ARI monotherapy is seldom the focus of attention. Adverse events associated with 5ARI include depression and suicidal attempts in addition to persistent erectile dysfunction. The aim of this study is to update our knowledge of clinical efficacy and incidence of adverse events associated with 5ARI treatment in symptomatic BPH.Methods and findingsA meta-analysis of randomized controlled clinical trials (RCTs) from 1966 until March, 2017 was performed using database from PubMed, Cochrane Collaboration and Embase. A total of 23395 patients were included in this study and the inclusion criteria were: RCTs with 5ARI and placebo in symptomatic BPH patients. Parameters included prostate specific antigen (PSA), prostate volume (PV), International Prostate Symptom Score (IPPS), post-void residual urine (PVR), voiding symptoms of IPSS (voiding IPSS), maximum urinary flow rate (Qmax), and adverse events (AEs). A meta-analysis with meta-regression was performed for each effect size and adverse events, sensitivity analysis, cumulative analysis along with the analysis of ratio of means (ROM) in the placebo group. A total of 42 studies were included in this study for review, and a total of 37 studies were included in the meta-analysis, including a total of 23395 patients (treatment group: 11392, placebo group: 12003). The effect size of all variables except PVR showed a significant improvement following 5ARI treatment compared with placebo. However, the effect size of differences showed declining trend in PV, IPSS and Qmax according to recent years of publication. In ROM analysis, PV showed no significant increase in the placebo group, with a ROM of 1.00 (95% CI, 0.88, 1.14). The 5ARI treatment resulted in a significantly higher incidence of decreased libido (OR = 1.7; 95% CI, 1.36, 2.13), ejaculatory disorder (OR = 2.94; 95% CI, 2.15, 4.03), gynecomastia (OR = 2.32; 95% CI, 1.41, 3.83), and impotence (OR = 1.74; 95% CI, 1.32, 2.29). Our study has the following limitations: included studies were heterogeneous and direct comparison of efficacy between alpha blocker and 5ARI was not performed. Adverse events including depression or suicidal attempt could not be analyzed in this meta-analysis setting.ConclusionsAlthough there was a significant clinical benefit of 5ARI monotherapy compared with placebo, the effective size was small. Moreover, the risk of adverse events including sexually related complications were high. Additional head-to-head studies are needed to re-evaluate the clinical efficacy of 5ARI compared with alpha-adrenergic receptor blockers.

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The Persistence of Silodosin Monotherapy and the Reasons for Withdrawal from Treatment of Previously Untreated Japanese Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia.

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