Effects of the oral testosterone undecanoate Kyzatrex™ on ambulatory blood pressure in hypogonadal men.

Testosterone replacement therapies have been shown to increase blood pressure (BP) in hypogonadal men. We studied the effects of a new formulation of testosterone undecanoate (Kyzatrex™) on ambulatory blood pressure (ABP) and heart rate, in 155 men with hypogonadism (mean age, 50.5 years, 76.

Molecular profiling of ETS gene rearrangements in patients with prostate cancer registered in REDEEM clinical trial.

Objective: Androgen-induced E26 transformation-specific (ETS) gene fusion-positive tumors have been associated with aggressive prostate cancer. The aim is to evaluate the ETS gene rearrangement status on initial biopsy of patients registered in the Reduction by Dutasteride of Clinical Progression Events in Expectant Management trial study and determine if gene fusion status was associated with disease progression.

Materials And Methods: Initial biopsy material from 146 men registered in Reduction by Dutasteride of Clinical Progression Events in Expectant Management trial study treated with dutasteride (73/146, 50%) and as placebo (73/146, 50%) were reviewed, and ERG and SPINK1 immunohistochemistry was performed.

Comparison of Classic and International Society of Urological Pathology 2005 Modified Gleason grading using needle biopsies from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Context: Use of the International Society of Urological Pathology (ISUP) 2005 modified Gleason score may result in higher scores compared with the classic Gleason scoring system.

Objective: To compare scores derived using the 2 scoring systems.

Design: On-study and for-cause biopsies were centrally reviewed and assigned a classic Gleason score in the Reduction by Dutasteride of prostate Cancer Events trial.

Genome-wide association study identifies genetic determinants of urine PCA3 levels in men.

Prostate cancer gene 3 (PCA3) is a non-coding gene specifically overexpressed in prostate cancer (PCa) that has great potential as a clinical biomarker for predicting prostate biopsy outcome. However, genetic determinants of PCA3 expression level remain unknown. To investigate the association between genetic variants and PCA3 mRNA level, a genome-wide association study was conducted in 1371 men of European descent in the REduction by DUtasteride of prostate Cancer Events trial.

Genome-wide association study identifies loci at ATF7IP and KLK2 associated with percentage of circulating free PSA.

Background: Percentage of free-to-total prostate-specific antigen (%fPSA) is an independent predictor of risk for prostate cancer among men with modestly elevated level of total PSA (tPSA) in blood. Physiological and pathological factors have been shown to influence the %fPSA value and diagnostic accuracy.

Materials/methods: To evaluate genetic determinants of %fPSA, we conducted a genome-wide association study of serum %fPSA by genotyping 642,584 single nucleotide polymorphisms (SNPs) in 3192 men of European ancestry, each with a tPSA level of 2.

Genome-wide association study identifies a new locus JMJD1C at 10q21 that may influence serum androgen levels in men.

Circulating androgen levels are often used as indicators of physiological or pathological conditions. More than half of the variance for circulating androgen levels is thought to be genetically influenced. A genome-wide association study (GWAS) has identified two loci, SHBG at 17p13 and FAM9B at Xp22, for serum testosterone (T) levels; however, these explain only a small fraction of inter-individual variability.

A comparison of Bayesian and frequentist approaches to incorporating external information for the prediction of prostate cancer risk.

We present the most comprehensive comparison to date of the predictive benefit of genetics in addition to currently used clinical variables, using genotype data for 33 single-nucleotide polymorphisms (SNPs) in 1,547 Caucasian men from the placebo arm of the REduction by DUtasteride of prostate Cancer Events (REDUCE®) trial. Moreover, we conducted a detailed comparison of three techniques for incorporating genetics into clinical risk prediction. The first method was a standard logistic regression model, which included separate terms for the clinical covariates and for each of the genetic markers.

Potential impact of adding genetic markers to clinical parameters in predicting prostate biopsy outcomes in men following an initial negative biopsy: findings from the REDUCE trial.

Background: Several germline single nucleotide polymorphisms (SNPs) have been consistently associated with prostate cancer (PCa) risk.

Objective: To determine whether there is an improvement in PCa risk prediction by adding these SNPs to existing predictors of PCa.

Design, Setting, And Participants: Subjects included men in the placebo arm of the randomized Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial in whom germline DNA was available.

Prostate cancer risk in men with baseline history of coronary artery disease: results from the REDUCE Study.

Background: Coronary artery disease (CAD) and prostate cancer (PCa) are not only common diseases, but share many risk factors. To date, only a few studies have explored the relationship between CAD and PCa risk, with conflicting results.

Methods: The four-year REDUCE study tested dutasteride 0.

Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial.

Background: We aimed to investigate the safety and efficacy of dutasteride, a 5α-reductase inhibitor, on prostate cancer progression in men with low-risk disease who chose to be followed up with active surveillance.

Methods: In our 3 year, randomised, double-blind, placebo-controlled study, undertaken at 65 academic medical centres or outpatient clinics in North America, we enrolled men aged 48-82 years who had low-volume, Gleason score 5-6 prostate cancer and had chosen to be followed up with active surveillance. We randomly allocated participants in a one-to-one ratio, stratified by site and in block sizes of four, to receive once-daily dutasteride 0·5 mg or matching placebo.

Dutasteride reduces prostatitis symptoms compared with placebo in men enrolled in the REDUCE study.

Purpose: Men at risk for prostate cancer may concurrently experience chronic prostatitis or pelvic pain. We evaluated the effect of dutasteride on prostatitis-like symptoms in the REDUCE study population.

Materials And Methods: REDUCE was a 4-year, randomized, double-blind, placebo controlled study of prostate cancer risk reduction with 0.

Prostate cancer gene 3 score predicts prostate biopsy outcome in men receiving dutasteride for prevention of prostate cancer: results from the REDUCE trial.

Objectives: To examine the ability of the urinary prostate cancer gene 3 (PCA3) assay to predict biopsy-detected cancers in men receiving dutasteride in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study cohort.

Methods: Urine and serum samples from 930 men in the active arm were acquired at years 2 and 4 of the biopsy visits. In addition to univariate logistic regression and receiver operating characteristic analysis, multivariate analysis for association with biopsy outcome was performed for PCA3 score in the presence of serum prostate-specific antigen (PSA), age, prostate volume, and family history of prostate cancer.

Dutasteride improves outcomes of benign prostatic hyperplasia when evaluated for prostate cancer risk reduction: secondary analysis of the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial.

Objective: To investigate the effect of dutasteride versus placebo on the symptoms and associated complications of male lower urinary tract symptoms and benign prostatic hyperplasia (BPH) across a range of prostate volumes and BPH symptoms in men evaluated for prostate cancer risk reduction in the 4-year REduction by DUtasteride of prostate Cancer Events (REDUCE) trial.

Methods: REDUCE was a multicenter, randomized, double-blind, placebo-controlled study of prostate cancer risk reduction with daily dutasteride 0.5 mg or placebo.

Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study.

Objectives: To determine if dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostate-specific antigen (PSA) level for detecting high grade cancers.

Patients And Methods: The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether dutasteride (0.

Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS).

Objective: • To assess the efficacy and safety of dutasteride compared with finasteride in treating men with symptomatic benign prostatic hyperplasia (BPH) for 12 months.

Patients And Methods: • The Enlarged Prostate International Comparator Study was a multicentre, randomized, double-blind, 12-month, parallel-group study. • Men aged ≥ 50 years with a clinical diagnosis of BPH received once-daily treatment with dutasteride 0.

Chemoprevention of prostate cancer.

Over the past two decades, many more men are diagnosed with prostate cancer then die of the disease. This increase in diagnosis has led to aggressive treatment of indolent disease in many individuals and has been the impetus for finding a means of reducing the risk of prostate cancer. In the past decade, there have been eight large trials of prostate cancer risk reduction using dietary supplements, 5α-reductase inhibitors, or anti-estrogens.

Biopsy misidentification identified by DNA profiling in a large multicenter trial.

Purpose: The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) prostate cancer risk reduction study randomly assigned 8,231 men to dutasteride or placebo for 4 years. Protocol-mandated biopsies were obtained after 2 and 4 years. After the discovery of three cases of biopsy sample misidentification in the first 2 years, all protocol-mandated biopsy samples were DNA tested to verify biopsy identity.

Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the Combination of Avodart and Tamsulosin trial.

Background: A 23% relative risk reduction (RRR) in prostate cancer (PCa) was shown in men receiving dutasteride in the 4-yr Reduction by Dutasteride of Prostate Cancer Events study, in whom biopsies were protocol dependent.

Objective: Our aim was to explore PCa risk reduction in men with benign prostatic hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study, in which biopsies were undertaken for cause.

Design, Setting, And Participants: CombAT was a 4-yr randomized double-blind parallel group study in 4844 men ≥50 yr of age with clinically diagnosed moderate to severe BPH, International Prostate Symptom Score ≥12, prostate volume ≥30 ml, and serum prostate-specific antigen (PSA) 1.

The effect of dutasteride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinically relevant prostate cancer in men with a previous negative biopsy: results from the REDUCE study.

Purpose: We assessed whether dutasteride enhances the usefulness of total prostate specific antigen for diagnosing clinically significant prostate cancer.

Materials And Methods: The 4-year REDUCE study evaluated the efficacy and safety of 0.5 mg dutasteride daily for prostate cancer risk reduction in men with a prostate specific antigen of 2.

Low serum testosterone levels are poor predictors of sexual dysfunction.

Objective: • To identify predictors of sexual dysfunction using baseline data from the reduction by dutasteride of prostate cancer events (REDUCE) study.

Patients And Methods: • REDUCE was a 4-year randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of once-daily dutasteride 0.5 mg in over 8000 men aged 50-75 years with a prostate-specific antigen (PSA) level of 2.

PCA3 molecular urine test for predicting repeat prostate biopsy outcome in populations at risk: validation in the placebo arm of the dutasteride REDUCE trial.

Purpose: We determined the performance of PCA3 alone and in the presence of other covariates as an indicator of contemporaneous and future prostate biopsy results in a population with previous negative biopsy and increased serum prostate specific antigen.

Materials And Methods: Urine PCA3 scores were determined before year 2 and year 4 biopsies from patients in the placebo arm of the REDUCE trial, a prostate cancer risk reduction study evaluating men with moderately increased serum prostate specific antigen results and negative biopsy at baseline. PCA3, serum prostate specific antigen and percent free prostate specific antigen results were correlated with biopsy outcome via univariate logistic regression and ROC analyses.

Effect of dutasteride on the risk of prostate cancer.

Background: We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease.

Methods: In this 4-year, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we compared dutasteride, at a dose of 0.5 mg daily, with placebo.

Reduction in the risk of prostate cancer: future directions after the Prostate Cancer Prevention Trial.

The landmark Prostate Cancer Prevention Trial (PCPT) generated interest in the potential health benefits and cost of reducing prostate cancer risk--specifically, the potential role of 5alpha-reductase inhibitors. However, the PCPT raised several unanswered questions, including the cause and significance of the increased incidence of high-grade tumors associated with finasteride. In the present study, we review the PCPT findings and unanswered questions, next steps in this field, and ongoing prostate cancer prevention trials addressing these unanswered questions.

Prostate needle biopsy quality in reduction by dutasteride of prostate cancer events study: worldwide comparison of improvement with investigator training and centralized laboratory processing.

Objectives: To compare biopsy quality factors among study sites worldwide at entry and at year 2 in the reduction by dutasteride of prostate cancer events study. The accuracy of prostate cancer detection is influenced by the length and number of biopsy cores.

Methods: Biopsy quality factors at entry and at year 2 were compared for subjects enrolled from 6 geographic regions: North America, South America, Western Europe, Central/Eastern Europe, Australia, and Africa.

Phase II study of androgen synthesis inhibition with ketoconazole, hydrocortisone, and dutasteride in asymptomatic castration-resistant prostate cancer.

Purpose: Increasing evidence indicates that enhanced intratumoral androgen synthesis contributes to prostate cancer progression after androgen deprivation therapy. This phase II study was designed to assess responses to blocking multiple steps in androgen synthesis with inhibitors of CYP17A1 (ketoconazole) and type I and II 5alpha-reductases (dutasteride) in patients with castration-resistant prostate cancer (CRPC).

Experimental Design: Fifty-seven men with CRPC were continued on gonadal suppression and treated with ketoconazole (400 mg thrice daily), hydrocortisone (30 mg/AM, 10 mg/PM), and dutasteride (0.