Body size throughout the life-course and incident benign prostatic hyperplasia-related outcomes and nocturia.

BACKGROUND: Existing evidence suggests that there is an association between body size and prevalent Benign Prostatic Hyperplasia (BPH)-related outcomes and nocturia. However, there is limited evidence on the association between body size throughout the life-course and incident BPH-related outcomes. METHODS: Our study population consisted of men without histories of prostate cancer, BPH-related outcomes, or nocturia in the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (n = 4710). Associations for body size in early- (age 20), mid- (age 50) and late-life (age ≥ 55, mean age 60.7 years) and weight change with incident BPH-related outcomes (including self-reported nocturia and physician diagnosis of BPH, digital rectal examination-estimated prostate volume ≥ 30 cc, and prostate-specific antigen [PSA] concentration > 1.4 ng/mL) were examined using Poisson regression with robust variance estimation. RESULTS: Men who were obese in late-life were 25% more likely to report nocturia (Relative Risk (RR): 1.25, 95% Confidence Interval (CI): 1.11-1.40; p-trendfor continuous BMI < 0.0001) and men who were either overweight or obese in late-life were more likely to report a prostate volume ≥ 30 cc (RRoverweight: 1.13, 95% CI 1.07-1.21; RRobese: 1.10, 95% CI 1.02-1.19; p-trendfor continuous BMI = 0.017) as compared to normal weight men. Obesity at ages 20 and 50 was similarly associated with both nocturia and prostate volume ≥ 30 cc. Considering trajectories of body size, men who were normal weight at age 20 and became overweight or obese by later-life had increased risks of nocturia (RRnormal to overweight: 1.09, 95% CI 0.98-1.22; RRnormal to obese: 1.28, 95% CI 1.10-1.47) and a prostate volume ≥ 30 cc (RRnormal to overweight: 1.12, 95% CI 1.05-1.20). Too few men were obese early in life to examine the independent effect of early-life body size. Later-life body size modified the association between physical activity and nocturia. CONCLUSIONS: We found that later-life body size, independent of early-life body size, was associated with adverse BPH outcomes, suggesting that interventions to reduce body size even late in life can potentially reduce the burden of BPH-related outcomes and nocturia.

Baseline Basal Cell Hyperplasia Is not Associated With Baseline Lower Urinary Tract Symptoms, Baseline Clinical Prostatitis or Prostate Cancer in Repeat Biopsies.

OBJECTIVES: To evaluate whether the presence of basal cell hyperplasia (BCH) in negative biopsies is associated with concurrent lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH), clinical prostatitis, and future prostate cancer (PCa) in repeat prostate biopsy. METHODS: We performed a retrospective analysis of 6471 men, 50-75 years old with prostate-specific antigen between 2.5 and 10 ng/ml and prior negative biopsy who were enrolled in the Reduction by Dutasteride of PCa Events trial and underwent a 2-year repeat biopsy. The association between baseline BCH and risk of PCa, BPH/LUTS and clinical prostatitis measured at baseline were evaluated with logistic regression in uni/multivariable analysis, controlling for baseline patient characteristics. RESULTS: Among 6471 men enrolled, 84 (1.3%) had BCH in the baseline prostate biopsy. BCH was associated less chronic inflammation and more prostate atrophy (P < 0.05) and was unrelated to baseline patient characteristics. In both uni/multivariable analyses, BCH was not associated with PCa in repeat biopsy (univariable odds ratio [OR] = 0.98, 95% confidence interval [CI] = 0.53-1.82, P > 0.05; multivariable OR=1.15, 95% CI = 0.61-2.16, P > 0.05), BPH/LUTS (univariable OR = 1.13, 95% CI = 0.71-1.81, P > 0.05; multivariable OR = 1.20, 95% CI = 0.74-1.94, P > 0.05), or clinical prostatitis (univariable OR = 0.56, 95% CI = 0.18-1.81, P > 0.05; multivariable OR = 0.57, 95% CI = 0.18-1.83, P > 0.05). CONCLUSION: Among men undergoing repeat prostate biopsy with a baseline negative biopsy, BCH was associated with more histological atrophy and less chronic prostatitis, but was unrelated to LUTS/BPH, clinical prostatitis or future PCa risk.

The association of atrophy in baseline prostate biopsy and lower prostate cancer grade in radical prostatectomy specimens.

INTRODUCTION: To evaluate whether the presence of prostate atrophy (P.A.) in negative prostate biopsy is associated with prostate cancer (P.C.a) grade at surgical pathology among men who are ultimately diagnosed with P.C.a and undergo radical prostatectomy (R.P.). METHODS: A retrospective analysis was performed of 136 men from the placebo arm of the Reduction by Dutasteride of P.C.a Events (R.E.D.U.C.E.) trial who had a baseline prostate biopsy negative for P.C.a, and were later diagnosed with P.C.a on biopsy and underwent radical prostatectomy over the 4-year study period. The association of baseline P.A. (present/absent) with P.C.a grade (W.H.O./I.S.U.P. grade group 1 or ≥2) at surgical pathology was evaluated with logistic regression in uni- and multivariable analyses, controlling for baseline patient characteristics. RESULTS: P.A. was observed in 74 prostate biopsies (54%). P.A. was not associated with baseline characteristics (age, body mass index, prostate-specific antigen level, prostate volume, race, family history of P.C.a, and digital rectal exam), except for chronic inflammation (p = 0.001). The presence of P.A. in baseline prostate biopsies was associated with lower risk of W.H.O./I.S.U.P. grade group ≥2 P.C.a in R.P. specimens on both univariable (O.R. = 0.39, 95% C.I. = 0.19-0.78, p = 0.008) and multivariable (O.R. = 0.43, 95% C.I. = 0.20-0.92, p = 0.029) analyses. CONCLUSIONS: Among men with a baseline prostate biopsy negative for P.C.a who were later found to have P.C.a and underwent R.P., baseline P.A. is independently associated with lower risk of W.H.O./I.S.U.P. grade group ≥2 P.C.a on surgical pathology. P.A. may be used to identify subjects at lower risk for W.H.O./I.S.U.P. ≥ 2 P.C.a and select optimal candidates for active surveillance.

The combination of histological prostate atrophy and inflammation is associated with lower risk of prostate cancer in biopsy specimens.

BACKGROUND: To evaluate whether the presence of both prostate atrophy (PA) and chronic prostate inflammation (CPI) in the same biopsy and in the same biopsy core are associated with prostate cancer (PCa) risk and grade in repeat biopsies. METHODS: Retrospective analyses of 6132 men who were 50-75 years old undergoing 2-year repeat prostate biopsy after a negative baseline biopsy for PCa in the REduction by DUtasteride of prostate Cancer Events (REDUCE) study. PA, CPI and PCa were determined by central pathology. The association of baseline PA and CPI with 2-year repeat biopsy cancer status and grade was evaluated with χ2 test and logistic regression controlling clinicopathological features. RESULTS: PA, CPI and both were detected in 583 (9.5%), 1063 (17.4%) and 3675 (59.9%) baseline biopsies, respectively. Compared with biopsies with neither PA nor CPI, the presence of PA (odds ratio (OR)=0.73, 95% confidence interval (CI)=0.57-0.93), CPI (OR=0.72, 95% CI=0.58-0.88) and both (OR=0.54, 95% CI=0.45-0.64) were associated with lower PCa risk in the 2-year repeat prostate biopsy. Results were similar in multivariable analysis. Among subjects with both PA and CPI, those with both findings in the same core had even lower PCa risk compared with PA and CPI in different cores (univariable OR=0.68, 95% CI=0.51-0.91; multivariable OR=0.73, 95% CI=0.54-0.99). Combination of PA and CPI was associated with lower risk of high-grade PCa. CONCLUSIONS: The presence of both PA and CPI in baseline biopsies, especially in the same core, was associated with lower PCa risk and grade. The presence and topographical distribution of PA and CPI may be used in PCa risk stratification.

Baseline subject characteristics predictive of compliance with study-mandated prostate biopsy in men at risk of prostate cancer: results from REDUCE.

BACKGROUND: Study compliance is crucial when the study outcome is determined by an invasive procedure, such as prostate biopsy. To investigate predictors of compliance in study-mandated prostate biopsies, we analyzed demographic, clinical and reported lifestyle data from the REDUCE trial. METHODS: We retrospectively identified 8025 men from REDUCE with at least 2 years of follow-up, and used multivariable logistic regression to test the association between baseline demographic and clinical characteristics and undergoing the study-mandated prostate biopsy at 2 years. We then examined whether missing any of these data was associated with undergoing a biopsy. RESULTS: In REDUCE, 22% of men did not undergo a 2-year biopsy. On multivariable analysis, the non-North American region was predictive of 42-44% increased likelihood of undergoing a 2-year biopsy (P⩽0.001). Being enrolled at a center that enrolled >10 subjects (2nd and 3rd tertile) was associated with a 42-48% increased likelihood of undergoing a 2-year biopsy (P<0.001). In addition, black race predicted 44% lower rate of on-study 2-year biopsy (odds ratio (OR)=0.56; P=0.001). Finally, missing one or more baseline variables was associated with a 32% decreased likelihood of undergoing a 2-year biopsy (OR=0.68; P<0.001). CONCLUSIONS: In REDUCE, men outside North America, those at higher volume centers and those with complete baseline data were more likely to undergo study-mandated 2-year biopsies. Given prostate biopsy is becoming increasingly utilized as an endpoint in trials that are often multi-national, regional differences in compliance should be considered when designing future trials. Likewise, efforts are needed to ensure compliance in low-volume centers or among subjects missing baseline data.

Greater extent of prostate inflammation in negative biopsies is associated with lower risk of prostate cancer on repeat biopsy: results from the REDUCE study.

BACKGROUND: To evaluate whether the extent of baseline acute prostate inflammation (API) and chronic prostate inflammation (CPI) was associated with risk of prostate cancer (PCa) at 2-year repeat prostate biopsy in a clinical trial with systematic biopsies independent of PSA. METHODS: A retrospective analysis of 6065 men with a negative baseline biopsy in the reduction by dutasteride of PCa events (REDUCE) trial undergoing 2-year biopsy. API and CPI extent (percentage of cores involved) and PCa (present or absent) were assessed by central pathology. The association of baseline API and CPI with PCa at the 2-year biopsy was evaluated with logistic regression in uni- and multivariable analyses. RESULTS: API extent was classified as absent or involving 1-25%, 26-50%, 51-75% and >75% cores in 5140 (85%), 742 (12%), 151 (2%), 17 (<1%) and 15 (<1%) cases, respectively. CPI extent was classified as absent or involving 1-25%, 26-50%, 51-75% and >75% cores in 1367 (22%), 2532 (42%), 1474 (24%), 397 (7%) and 295 (5%) cases, respectively. More extensive API was associated with younger age, lower PSA and lower prostate volume, while more extensive CPI was associated with older age, lower PSA and higher prostate volume (all P<0.01). In both uni- and multivariable analyses, API and CPI extent were associated with lower risk of PCa at the 2-year biopsy (both P<0.01). CONCLUSIONS: In a cohort of men undergoing repeat prostate biopsy 2 years after a negative baseline biopsy, a greater extent of baseline API and CPI was independently associated with lower PCa risk.

NFATc1 promotes prostate tumorigenesis and overcomes PTEN loss-induced senescence.

Despite recent insights into prostate cancer (PCa)-associated genetic changes, full understanding of prostate tumorigenesis remains elusive owing to complexity of interactions among various cell types and soluble factors present in prostate tissue. We found the upregulation of nuclear factor of activated T cells c1 (NFATc1) in human PCa and cultured PCa cells, but not in normal prostates and non-tumorigenic prostate cells. To understand the role of NFATc1 in prostate tumorigenesis in situ, we temporally and spatially controlled the activation of NFATc1 in mouse prostate and showed that such activation resulted in prostatic adenocarcinoma with features similar to those seen in human PCa. Our results indicate that the activation of a single transcription factor, NFATc1 in prostatic luminal epithelium to PCa can affect expression of diverse factors in both cells harboring the genetic changes and in neighboring cells through microenvironmental alterations. In addition to the activation of oncogenes c-MYC and STAT3 in tumor cells, a number of cytokines and growth factors, such as IL1ß, IL6 and SPP1 (osteopontin, a key biomarker for PCa), were upregulated in NFATc1-induced PCa, establishing a tumorigenic microenvironment involving both NFATc1 positive and negative cells for prostate tumorigenesis. To further characterize interactions between genes involved in prostate tumorigenesis, we generated mice with both NFATc1 activation and Pten inactivation in prostate. We showed that NFATc1 activation led to acceleration of Pten null-driven prostate tumorigenesis by overcoming the PTEN loss-induced cellular senescence through inhibition of p21 activation. This study provides direct in vivo evidence of an oncogenic role of NFATc1 in prostate tumorigenesis and reveals multiple functions of NFATc1 in activating oncogenes, in inducing proinflammatory cytokines, in oncogene addiction, and in overcoming cellular senescence, which suggests calcineurin-NFAT signaling as a potential target in preventing PCa.

Statin use and risk of prostate cancer and high-grade prostate cancer: results from the REDUCE study.

BACKGROUND: Statins are associated with lower PSA levels. As PSA is the primary method for prostate cancer (PC) screening, this confounds any associations between statins and risk of being diagnosed with PC. Thus, we examined the association between statins and cancer and high-grade cancer in REDUCE, where biopsies were largely PSA-independent. METHODS: Post-hoc secondary analysis of REDUCE, which was a prospective multinational randomized controlled trial of dutasteride vs placebo for 4 years among men aged 50-75 years with PSA of 2.5-10.0 ng ml(-1) and a negative biopsy at baseline, and included PSA-independent biopsies mandated at 2- and 4-years. Analyses were limited to men who underwent at least one biopsy while under study (n=6729). The association between baseline statin use and risk of overall, high-grade (Gleason ≥ 7) or low-grade (Gleason ≤ 6) PC vs no cancer was examined using multinomial logistic regression adjusting for age, race, baseline PSA, prostate volume, rectal examination findings, body mass index (BMI), comorbidities, smoking, alcohol intake and treatment arm. RESULTS: Of 6729 men who had at least one biopsy while on study, 1174 (17.5%) were taking a statin at baseline. Men taking statins were older, had lower PSA levels, higher BMI values and lower serum testosterone and dihydrotestosterone levels, though differences, were slight. Statin use was not associated with overall PC diagnosis (multivariable OR 1.05, 95% CI 0.89-1.24, P=0.54). When stratified by grade, statin use was not associated with low-grade (multivariable OR 1.03, 95% CI 0.85-1.25, P=0.75) or high-grade cancer (multivariable OR 1.11, 95% CI 0.85-1.45, P=0.46). The major limitation is the inclusion of only men with a negative baseline biopsy. CONCLUSIONS: Among men with a negative baseline biopsy and follow-up biopsies largely independent of PSA, statins were not associated with cancer or high-grade cancer.

Aspirin but not ibuprofen use is associated with reduced risk of prostate cancer: a PLCO study.

BACKGROUND: Although most epidemiological studies suggest that non-steroidal anti-inflammatory drug use is inversely associated with prostate cancer risk, the magnitude and specificity of this association remain unclear. METHODS: We examined self-reported aspirin and ibuprofen use in relation to prostate cancer risk among 29 450 men ages 55-74 who were initially screened for prostate cancer from 1993 to 2001 in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Men were followed from their first screening exam until 31 December 2009, during which 3575 cases of prostate cancer were identified. RESULTS: After adjusting for potential confounders, the hazard ratios (HRs) of prostate cancer associated with <1 and ≥ 1 pill of aspirin daily were 0.98 (95% confidence interval (CI), 0.90-1.07) and 0.92 (95% CI: 0.85-0.99), respectively, compared with never use (P for trend 0.04). The effect of taking at least one aspirin daily was more pronounced when restricting the analyses to men older than age 65 or men who had a history of cardiovascular-related diseases or arthritis (HR (95% CI); 0.87 (0.78-0.97), 0.89 (0.80-0.99), and 0.88 (0.78-1.00), respectively). The data did not support an association between ibuprofen use and prostate cancer risk. CONCLUSION: Daily aspirin use, but not ibuprofen use, was associated with lower risk of prostate cancer risk.

Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1).

BACKGROUND: To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases. METHODS: Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5-10.0 ng mL(-1) and a negative prestudy biopsy. Among men undergoing at least one on-study biopsy with complete data (n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics. RESULTS: A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22-1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73-1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38-2.15) (P-interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72-3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84-1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region. CONCLUSIONS: In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification.

Diabetes and prostate cancer risk in the REDUCE trial.

Men with diabetes mellitus are less likely to be diagnosed with prostate cancer (PCa). As diabetic men have lower serum PSA, it is unclear if this is due to lower PCa incidence or reflects detection bias from fewer PSA-triggered biopsies. To account for differential biopsy rates, we used multivariate regression to examine the link between diabetes and PCa risk in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which required all subjects to undergo biopsy regardless of PSA. We further tested for interaction between diabetes and obesity. Diabetes status and body mass index (BMI) measurements were obtained at baseline. On multivariate analysis, diabetes was not associated with PCa risk (odds ratio (OR) 1.01, 95% confidence interval 0.79-1.30, P=0.92) or risk of low- or high-grade disease (all P ≥ 0.65). When stratified by obesity, diabetes was also not associated with PCa risk in any BMI category (all P ≥ 0.15). However, there was suggestion of effect modification by obesity for high-grade disease (P-interaction=0.053). Specifically, diabetes was associated with decreased risk of high-grade PCa in normal-weight men but increased risk in obese men (OR 0.35 vs 1.38). In the REDUCE trial, when all men underwent biopsy, diabetes was not associated with lower PCa risk, but rather equal risk of PCa, low-grade PCa and high-grade PCa.

Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia.

OBJECTIVES: To examine the rate of prostate cancer detection in three large randomized placebo-controlled benign prostatic hyperplasia trials of dutasteride. Dutasteride, which lowers serum dihydrotestosterone more than 93% by inhibiting type 1 and type 2 5-alpha-reductase, is effective in the treatment of benign prostatic hyperplasia. However, its effect on the development of prostate cancer is unknown. METHODS: A total of 4325 men with benign prostatic hyperplasia but without a history, or evidence, of prostate cancer, and a serum prostate-specific antigen level of 1.5 to 10 ng/mL, were randomized to 0.5 mg/day dutasteride or placebo for 24 months. The prostate cancer detection rates for subjects were determined by non-protocol-mandated biopsies, either during the double-blind phase of the study or during the first 3 months of the open-label extension. A follow-up questionnaire was administered to a subset of consenting subjects to ascertain the number, outcomes, and reasons for the prostate biopsies. RESULTS: The cumulative incidence of prostate cancer as an adverse event was significantly lower in the dutasteride versus placebo group at 24 months (1.1% versus 1.9%, P = 0.025) and 27 months (1.2% versus 2.5%, P = 0.002). There were no differences in the diagnosis rates of prostate cancer during the first 15 months, after which time the detection rate of prostate cancer increased in the placebo group and remained low in the dutasteride group. CONCLUSIONS: Prostate cancer detection was significantly lower in subjects randomized to dutasteride compared with the placebo group. These results have prompted the initiation of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study, which was designed and powered to test the hypothesis that treatment with dutasteride decreases the incidence and progression of prostate cancer.

Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer.

PURPOSE: In the prostate testosterone is converted to dihydrotestosterone (DHT) by the enzymes 5alpha-reductase (5alphaR) types 1 and 2 (5alphaR1 and 5alphaR2). Suppression of DHT formation by 5alphaR inhibition may be beneficial in early treatment or prevention of prostate cancer. Although 5alphaR2 is the dominant enzyme in the prostate, evidence indicates that 5alphaR1 may be up-regulated in some prostate cancers. This suggests that dual inhibition of both isoenzymes may be more effective than suppression of 5alphaR2 alone in prostate cancer treatment or prevention. In this short-term pilot study we examined the effect of the dual 5alphaR inhibitor dutasteride on markers of tumor regression. MATERIALS AND METHODS: A total of 46 men with clinically staged T1 or T2 prostate cancer were randomized to receive 5 mg per day of placebo or dutasteride for 6 to 10 weeks before radical prostatectomy. Resected tissues were analyzed to determine the effect of dutasteride on intraprostatic androgen levels, and indices of apoptosis and microvessel density (MVD) in malignant tissue, as well as degree of atrophy in benign tissue. RESULTS: Treatment with dutasteride caused a 97% decrease in intraprostatic DHT and was associated with a trend toward increased apoptosis. In patients receiving dutasteride for 45 days or more, a significant increase in apoptosis and a trend toward decreased MVD in prostate cancer tissue was observed. Dutasteride treatment was also associated with an 18% decrease in mean benign epithelial cell width compared with placebo (p < 0.0001). CONCLUSIONS: In this pilot study dutasteride treatment resulted in almost complete suppression of intraprostatic DHT, increased apoptosis and a trend toward decreased MVD. These findings suggest that short-term treatment with dutasteride can cause regression in some prostate cancers.

Risk behaviours and benign prostatic hyperplasia.

OBJECTIVE: To identify risk factors for benign prostatic hyperplasia (BPH). SUBJECTS AND METHODS: Medical history data, including reported urological conditions and treatments, and risk factor data were collected from 34 694 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial designed to evaluate methods for the early detection of cancer. RESULTS: Asian men had the lowest risks (odds ratio, 95% confidence interval) for nocturia (0.7, 0.5-0.9), physician-diagnosed BPH (0.3, 0.2-0.5) and transurethral prostatectomy (TURP, 0.2, 0.1-0.6), while risks for Whites and Blacks were similar for most measures of BPH. Greater alcohol intake was associated with decreased nocturia (P trend = 0.002), BPH (P trend < 0.001) and TURP (P trend < 0.001). Current tobacco use was associated with decreased nocturia (0.8, 0.7-0.9), BPH (0.7, 0.6-0.8) and TURP (0.6, 0.4-0.8) but dose-response patterns were weak. CONCLUSION: Asian-Americans have the lowest risk of clinical BPH. Alcohol and possibly cigarettes are related to a lower risk for BPH.

Improvements in benign prostatic hyperplasia-specific quality of life with dutasteride, the novel dual 5alpha-reductase inhibitor.

OBJECTIVES: To examine the effect of the dual-action 5alpha-reductase inhibitor dutasteride on benign prostatic hyperplasia (BPH)-specific health status, as measured by the BPH Impact Index (BII), and to identify baseline and treatment risk factors for those most bothered by their BPH symptoms at the end of the protocol. PATIENTS AND METHODS: Data were derived from three randomized, double-blind, placebo-controlled, 2-year studies conducted in 4325 men with lower urinary tract symptoms caused by benign prostatic enlargement. Each study comprised a 1-month single-blind placebo run-in period, followed by randomization to oral dutasteride 0.5 mg once daily or placebo for 2 years. Patients eligible for inclusion were consenting men aged >/= 50 years with moderate to severe symptoms (American Urological Symptom Index, AUA-SI, score >/= 12), a prostate volume of >/= 30 mL, a serum prostate-specific antigen (PSA) level of >/= 1.5 or < 10 ng/mL, and a maximum urinary flow rate (Qmax) of /= 5 (greatest symptomatic burden) treatment with dutasteride improved the scores by 2.41, while the scores in placebo-treated patients only improved by 1.64. Dutasteride-treated patients with a baseline BII score of < 5 (least symptom burden) had a clinically significant improvement in health status, while placebo-treated patients deteriorated. Regression analysis showed that men with a combination of a baseline BII item-3 score of 3 (bothered a lot) and a high symptom score (AUA-SI >/= 20) were more likely to be bothered by their symptoms at the end of the study. Men receiving placebo were also more likely to be bothered at the end of the study than were those receiving dutasteride. CONCLUSIONS: Dutasteride treatment is associated with clinically significant improvements in BII score, reflecting improvements in the quality of life of men with BPH. Taken together with previously reported improvements in prostate volume, lower urinary tract symptoms and urinary flow, and diminution of the risk of acute urinary retention and the need for BPH-related surgery, dutasteride offers demonstrable efficacy in the management of BPH.

Relationship of demographic and clinical factors to free and total prostate-specific antigen.

OBJECTIVES: To characterize the role of demographic and clinical parameters in the measurements of prostate-specific antigen (PSA), free PSA (fPSA), and percent free PSA (%fPSA). METHODS: This was a cohort study of volunteers to a randomized screening trial. A central laboratory determined PSA and fPSA for the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. A baseline evaluation of free and total PSA was done for 7183 white, black, Asian, Hispanic, and other male volunteers, aged 55 to 74 years. Comparisons were made across racial and ethnic groups and across a set of clinical parameters from a baseline questionnaire. RESULTS: The median levels of serum PSA were less than 2.1 ng/mL in each age-race grouping of the study participants. The levels of free and total PSA were higher in black (n = 868, 12%) participants than in white (n = 4995, 70%) and Asian (n = 849, 11.8%) participants. Individuals who identified themselves as ethnically Hispanic (n = 339, 4.7%) had median PSA levels higher than whites who were not Hispanic. The free and total PSA levels increased with age, particularly among men 70 to 74 years old. However, the %fPSA levels showed less variation among the four racial groups or by age. The free and total PSA levels were higher among those who had a history of benign prostatic disease. CONCLUSIONS: Demographic (age and race/ethnicity) and clinical (history of benign prostatic disease) variables had a moderate effect on the measures of PSA and fPSA and very little effect on %fPSA.

Preoperative oral rofecoxib does not decrease postoperative pain or morphine consumption in patients after radical prostatectomy: a prospective, randomized, double-blinded, placebo-controlled trial.

STUDY OBJECTIVES: To evaluate the analgesic efficacy of the rofecoxib po before radical prostatectomy. DESIGN: Prospective, randomized, double-blinded, placebo-controlled trial. SETTING: Teaching hospital. PATIENTS: Anesthetic management was standardized. Patients received either a 50-mg rofecoxib capsule or a placebo capsule po 1 hour before induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Patient-generated 10-cm visual analog scale (VAS) scores for pain were assessed at 1, 2, 4, 6, 8, and 24 hours after surgery. Morphine consumption was recorded from a patient-controlled analgesia device at the same time. A patient-generated overall pain relief score was obtained at 24 hours after surgery. We were unable to detect any differences between study groups with respect to postoperative morphine consumption, VAS score, or overall pain relief score. CONCLUSIONS: When rofecoxib is used po in maximum recommended doses before surgery, it does not provide significant analgesia that results in reduction in pain scores or analgesic requirements for patients after radical prostatectomy.

Periurethral transurethral microwave thermotherapy for the treatment of benign prostatic hyperplasia: an interim 1-year safety and efficacy analysis using the thermatrx TMx-2000.

Transurethral microwave thermotherapy (TUMT) represents an accepted minimally invasive approach to the management of patients with benign prostatic hyperplasia (BPH). The TherMatrx TMx-2000 represents a further evolution in TUMT technique. This device uses periurethral transurethral microwave thermotherapy (P-TUMT) technology to directly target the BPH tissue adjacent to the prostatic urethra by using a catheter without a urethral-cooling surface. This article provides a technical review of the device and describes the results of a randomized, controlled multicenter study of P-TUMT for the treatment of symptomatic BPH. A discussion of the physiologic effects of P-TUMT is presented and compared to conventional TUMT. A comparison of P-TUMT to contemporary TUMT series in relation to efficacy and complications is also described. This study concludes that P-TUMT using the TherMatrx TMx-2000 device represents a minimally invasive, efficacious, and well-tolerated treatment for symptomatic BPH.