The Benign Prostatic Hyperplasia Registry and Patient Survey: study design, methods and patient baseline characteristics

To describe the design and baseline cohort characteristics of the Benign Prostatic Hyperplasia (BPH) Registry and Patient Survey, an ongoing, prospective, observational, disease registry documenting management practices and patient outcomes in men in the USA with lower urinary tract symptoms associated with BPH (LUTS/BPH) in actual clinical practice settings. PATIENTS AND METHODS Men with LUTS/BPH who were either untreated or treated with Α 1 -adrenergic blockers (ABs), 5Α-reductase inhibitors (5ARIs), a combination of these medications, or anticholinergics, and who met selection criteria, were enrolled at sites throughout the USA. At each visit, standardized forms and validated questionnaires were completed to assess the physicians’ management practices and patients’ clinical characteristics, sexual function, and health-related quality of life. RESULTS At the close of recruitment (February 2005), 6909 men (mean age 66.0 years) were enrolled at 402 sites by urologists and primary-care physicians. Before enrolment, 49% of the men were managed with watchful waiting (WW), 21% with uroselective AB monotherapy, 11% with non-uroselective AB monotherapy, 6% with 5ARI monotherapy, 11% with AB + 5ARI, and 2% with anticholinergics. After enrolment, 42% were on WW and 26% were on selective AB monotherapy; changes in other management groups were minimal. Overall, 33% of the men had mild, 52% had moderate and 15% had severe LUTS. The most common comorbidities were hypertension (53%), high cholesterol (45%) and sexual dysfunction (36%). CONCLUSION The BPH Registry and Patient Survey will provide information on physician management practices and outcomes of men with LUTS/BPH, while examining the effects of demographics, socio-economics, comorbidities, and medical therapies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73286/1/j.1464-410X.2007.07061.x.pd

Current status of 5α-reductase inhibitors in the management of lower urinary tract symptoms and BPH

Benign prostatic hyperplasia (BPH) is a progressive disease that is commonly associated with bothersome lower urinary tract symptoms (LUTS) and might result in complications, such as acute urinary retention and BPH-related surgery. Therefore, the goals of therapy for BPH are not only to improve LUTS in terms of symptoms and urinary flow, but also to identify those patients at a risk of unfavorable disease progression and to optimize their management. This article reviews the current status of therapy with 5 alpha-reductase inhibitors (5ARIs), namely fiasteride and dutasteride, for men with LUTS and BPH. Data from key randomized controlled trials (Oxford level 1b) on the use of 5ARIs are analyzed. The efficacy of 5ARIs either as monotherapy or in combination with alpha(1)-adrenoceptor antagonists in the management of LUTS and the impact of monotherapy and combined therapy on BPH progression are discussed. Further promises, including the withdrawal of the alpha-blocker from the combined medical treatment and the potential clinical implications from the use of 5ARIs for prostate cancer chemoprevention in patients receiving 5ARIs for symptomatic BPH are highlighted. Current evidence shows that 5ARIs are effective in treating LUTS and preventing disease progression and represent a recommended option in treatment guidelines for men who have moderate to severe LUTS and enlarged prostates

Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the Human Prostate

Introduction: alpha(1)-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further alpha(1)-adrenoceptor functions besides contraction. Here, we investigated whether alpha(1)-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 mu M) or phenylephrine (10 mu M) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 mu M) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: alpha(1)-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of alpha(1)-adrenoceptors in the regulation of prostate growth. Copyright (C) 2011 S. Karger AG, Base

Serum Dioxin, Testosterone, and Subsequent Risk of Benign Prostatic Hyperplasia: A Prospective Cohort Study of Air Force Veterans

BACKGROUND: Operation Ranch Hand veterans were involved in spraying herbicides, including Agent Orange, during the Vietnam War in 1962–1971; Agent Orange was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been hypothesized that dioxins may be partially responsible for an increase of male reproductive tract disorders such as testicular cancer, cryptorchidism, and hypospadias. OBJECTIVES: In this study, our objective was to assess the effect of serum TCDD concentration on the risk of development of benign prostatic hyperplasia (BPH) and on serum testosterone levels. METHODS: This study was a longitudinal, prospective cohort study made up of U.S. Air Force veterans involved in Operation Ranch Hand. Other Air Force veterans who did not spray herbicides were included as comparisons. BPH was determined by medical record review and by medical examinations conducted during the study. Data were available for 971 Ranch Hand and 1,266 comparison veterans. We investigated the relationship between BPH and serum TCDD level using the Cox proportional hazards models adjusted for testosterone levels, body mass index (BMI), and the percentage change in BMI per year. RESULTS: In univariate and multivariate analyses, the risk of BPH decreased with increasing serum TCDD in the comparison group. The multivariate risk ratio for BPH in the comparison group was 0.84 (95% confidence interval, 0.73–0.98). Excluding men with prostate cancer, inflammatory or other prostatic diseases did not substantially alter the association. Serum testosterone levels were inversely associated with serum TCDD levels in both Ranch Hand and comparison groups. CONCLUSIONS: TCDD exposure at general population levels is associated with a decreasing risk of BPH with higher exposure levels. TCDD exposure is also negatively associated with serum testosterone levels

Spondin-2 (SPON2), a More Prostate-Cancer-Specific Diagnostic Biomarker

BACKGROUND: Prostate-specific antigen (PSA) screening, although common, has recently been called into question. To find prostate cancer (PCa) diagnostic biomarkers that can make up for the defects of PSA, we compared the secretomes of several benign and PCa cell lines, selected candidate molecules, and then confirmed their clinical value. METHODOLOGY/PRINCIPAL FINDINGS: We first identified extracellular proteins by two-dimensional gel electrophoresis (2-DE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification. We then validated the secreted proteins on a cellular level, and finally determined whether they could be used as PCa diagnostic biomarkers using prostate tissue and serum specimens of Chinese volunteers by immunohistostaining and sandwich ELISA. We obtained credible extracellular protein 2-DE graphs of prostate cell lines. The 5 spots that showed superior repeatability were selected for LC-MS/MS analysis, which identified seven candidate molecules. One of the candidate molecules, spondin-2 (SPON2), was only expressed in the conditioned media (CM) of androgen receptor (AR) positive PCa cell lines. Using tissue microarray by immunohistostaining, we found SPON2 to be over-expressed in PCa. SPON2 staining was more intense in Gleason score sum 7-8 and in PCa patients with metastasis. By receiver operator characteristic (ROC) curve analysis, we found that the serum SPON2 level was elevated in PCa patients, showing sensitivity and specificity suitable for diagnostic use. We also found that SPON2 could be used to identify PCa patients with serum PSA levels no higher than 10 ng/ml from healthy elderly men. CONCLUSION/SIGNIFICANCE: SPON2 is a new serum and histological diagnostic biomarker for PCa. It can avoid some of the problems of PSA testing and was here found to offer relatively high sensitivity and specificity relative to PSA

Method for evaluating prediction models that apply the results of randomized trials to individual patients

<p>Abstract</p> <p>Introduction</p> <p>The clinical significance of a treatment effect demonstrated in a randomized trial is typically assessed by reference to differences in event rates at the group level. An alternative is to make individualized predictions for each patient based on a prediction model. This approach is growing in popularity, particularly for cancer. Despite its intuitive advantages, it remains plausible that some prediction models may do more harm than good. Here we present a novel method for determining whether predictions from a model should be used to apply the results of a randomized trial to individual patients, as opposed to using group level results.</p> <p>Methods</p> <p>We propose applying the prediction model to a data set from a randomized trial and examining the results of patients for whom the treatment arm recommended by a prediction model is congruent with allocation. These results are compared with the strategy of treating all patients through use of a net benefit function that incorporates both the number of patients treated and the outcome. We examined models developed using data sets regarding adjuvant chemotherapy for colorectal cancer and Dutasteride for benign prostatic hypertrophy.</p> <p>Results</p> <p>For adjuvant chemotherapy, we found that patients who would opt for chemotherapy even for small risk reductions, and, conversely, those who would require a very large risk reduction, would on average be harmed by using a prediction model; those with intermediate preferences would on average benefit by allowing such information to help their decision making. Use of prediction could, at worst, lead to the equivalent of an additional death or recurrence per 143 patients; at best it could lead to the equivalent of a reduction in the number of treatments of 25% without an increase in event rates. In the Dutasteride case, where the average benefit of treatment is more modest, there is a small benefit of prediction modelling, equivalent to a reduction of one event for every 100 patients given an individualized prediction.</p> <p>Conclusion</p> <p>The size of the benefit associated with appropriate clinical implementation of a good prediction model is sufficient to warrant development of further models. However, care is advised in the implementation of prediction modelling, especially for patients who would opt for treatment even if it was of relatively little benefit.</p