Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.

PubMed

Sutcliffe, Siobhan; Nevin, Remington L; Pakpahan, Ratna; Elliott, Debra J; Langston, Marvin E; De Marzo, Angelo M; Gaydos, Charlotte A; Isaacs, William B; Nelson, William G; Sokoll, Lori J; Walsh, Patrick C; Zenilman, Jonathan M; Cersovsky, Steven B; Platz, Elizabeth A

2016-05-01

Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men. © 2015 UICC.

Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial Findings From a Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schreibmann, Eduard, E-mail: eschre2@emory.edu; Schuster, David M.; Rossi, Peter J.

Purpose: {sup 18}F-Fluciclovine (anti-1-amino-3-[{sup 18}F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of {sup 18}F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes. Methods and Materials: We report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the {sup 18}F-fluciclovine arm. All patients underwent {sup 18}F-fluciclovine PET-CT for the detection of metabolic abnormalitiesmore » and high-resolution CT for treatment planning. The 2 datasets were registered first by use of a rigid registration. If soft tissue displacement was observable, the rigid registration was improved with a deformable registration. Each {sup 18}F-fluciclovine abnormality was segmented as a percentage of the maximum standard uptake value (SUV) within a small region of interest around the lesion. The percentage best describing the SUV falloff was integrated in planning by expanding standard target volumes with the PET abnormality. Results: In 21 of 55 abnormalities, a deformable registration was needed to map the {sup 18}F-fluciclovine activity into the simulation CT. The most selected percentage was 50% of maximum SUV, although values ranging from 15% to 70% were used for specific patients, illustrating the need for a per-patient selection of a threshold SUV value. The inclusion of {sup 18}F-fluciclovine changed the planning volumes for 46 abnormalities (83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only 9 PET abnormalities were fully contained in the standard target volumes based on the CT-based segmentations and did not necessitate expansion. Conclusions: The use of {sup 18}F-fluciclovine in postprostatectomy radiation therapy planning was feasible and led to augmentation of the target volumes in the majority (30 of 41) of the patients studied.« less

Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention.

PubMed

Chen, L; Stacewicz-Sapuntzakis, M; Duncan, C; Sharifi, R; Ghosh, L; van Breemen, R; Ashton, D; Bowen, P E

2001-12-19

Human prostate tissues are vulnerable to oxidative DNA damage. The risk of prostate cancer is lower in men reporting higher consumption of tomato products, which contain high levels of the antioxidant lycopene. We examined the effects of consumption of tomato sauce-based pasta dishes on lycopene uptake, oxidative DNA damage, and prostate-specific antigen (PSA) levels in patients already diagnosed with prostate cancer. Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for the 3 weeks (30 mg of lycopene per day) preceding their scheduled radical prostatectomy. Serum and prostate lycopene concentrations, serum PSA levels, and leukocyte DNA oxidative damage (ratio of 8-hydroxy-2'-deoxyguanosine [8-OHdG] to 2'-deoxyguanosine [dG]) were assessed before and after the dietary intervention. DNA oxidative damage was assessed in resected prostate tissue from study participants and from seven randomly selected prostate cancer patients. All statistical tests were two-sided. After the dietary intervention, serum and prostate lycopene concentrations were statistically significantly increased, from 638 nM (95% confidence interval [CI] = 512 to 764 nM) to 1258 nM (95% CI = 1061 to 1455 nM) (P<.001) and from 0.28 nmol/g (95% CI = 0.18 to 0.37 nmol/g) to 0.82 nmol/g (95% CI = 0.57 to 1.11 nmol/g) (P <.001), respectively. Compared with preintervention levels, leukocyte oxidative DNA damage was statistically significantly reduced after the intervention, from 0.61 8-OHdG/10(5) dG (95% CI = 0.45 to 0.77 8-OHdG/10(5) dG) to 0.48 8-OHdG/ 10(5) dG (95% CI = 0.41 to 0.56 8-OHdG/10(5) dG) (P =.005). Furthermore, prostate tissue oxidative DNA damage was also statistically significantly lower in men who had the intervention (0.76 8-OHdG/10(5) dG [95% CI = 0.55 to 0.96 8-OHdG/10(5) dG]) than in the randomly selected patients (1.06 8-OHdG/10(5) dG [95% CI = 0.62 to 1.51 8-OHdG/10(5) dG]; P =.03). Serum PSA levels decreased after the intervention, from 10.9 ng/mL (95% CI = 8.7 to 13.2 ng/mL) to 8.7 ng/mL (95% CI = 6.8 to 10.6 ng/mL) (P<.001). These data indicate a possible role for a tomato sauce constituent, possibly lycopene, in the treatment of prostate cancer and warrant further testing with a larger sample of patients, including a control group.

Evaluation of silodosin in comparison to tamsulosin in benign prostatic hyperplasia: A randomized controlled trial

PubMed Central

Pande, Satabdi; Hazra, Avijit; Kundu, Anup Kumar

2014-01-01

Objectives: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms in elderly men. Selective alfa1-adrenergic antagonists are now first-line drugs in the medical management of BPH. We conducted a single-blind, parallel group, randomized, controlled trial to compare the effectiveness and safety of the new alfa1-blocker silodosin versus the established drug tamsulosin in symptomatic BPH. Materials and Methods: Ambulatory male BPH patients, aged above 50 years, were recruited on the basis of International Prostate Symptom Score (IPSS). Subjects were randomized in 1:1 ratio to receive either tamsulosin 0.4 mg controlled release or silodosin 8 mg once daily after dinner for 12 weeks. Primary outcome measure was reduction in IPSS. Proportion of subjects who achieved IPSS <8, change in prostate size as assessed by ultrasonography and changes in peak urine flow rate and allied uroflowmetry parameters, were secondary effectiveness variables. Treatment emergent adverse events were recorded. Results: Data of 53 subjects – 26 on silodosin and 27 on tamsulosin were analyzed. Final IPSS at 12-week was significantly less than baseline for both groups. However, groups remained comparable in terms of IPSS at all visits. There was a significant impact on sexual function (assessed by IPSS sexual function score) in silodosin arm compared with tamsulosin. Prostate size and uroflowmetry parameters did not change. Both treatments were well-tolerated. Retrograde ejaculation was encountered only with silodosin and postural hypotension only with tamsulosin. Conclusions: Silodosin is comparable to tamsulosin in the treatment of BPH in Indian men. However, retrograde ejaculation may be troublesome for sexually active patients. PMID:25538330

Saw palmetto alters nuclear measurements reflecting DNA content in men with symptomatic BPH: evidence for a possible molecular mechanism.

PubMed

Veltri, Robert W; Marks, Leonard S; Miller, M Craig; Bales, Wes D; Fan, John; Macairan, Maria Luz; Epstein, Jonathan I; Partin, Alan W

2002-10-01

To examine the nuclear chromatin characteristics of epithelial cells, looking for an SPHB-mediated effect on nuclear DNA structure and organization. Saw palmetto herbal blend (SPHB) causes contraction of prostate epithelial cells and suppression of tissue dihydrotestosterone levels in men with symptomatic benign prostatic hyperplasia, but a fundamental mechanism remains unknown. A 6-month randomized trial, comparing prostatic tissue of men treated with SPHB (n = 20) or placebo (n = 20), was performed. At baseline, the two groups were similar in age (65 versus 64 years), symptoms (International Prostate Symptom Score 18 versus 17), uroflow (maximal urinary flow rate 10 versus 11 mL/s), prostate volume (59 versus 58 cm(3)), prostate-specific antigen (4.2 versus 2.7 ng/mL), and percentage of epithelium (17% versus 16%). Prostatic tissue was obtained by sextant biopsy before and after treatment. Five-micron sections were Feulgen stained and quantitatively analyzed using the AutoCyte QUIC-DNA imaging system. Images were captured from 200 randomly selected epithelial cell nuclei, and 60 nuclear morphometric descriptors (NMDs) (eg, size, shape, DNA content, and textural features) were determined for each nucleus. Logistic regression analysis was used to assess the differences in the variances of the NMDs between the treated and untreated prostate epithelial cells. At baseline, the SPHB and placebo groups had similar NMD values. After 6 months of placebo, no significant change from baseline was found in the NMDs. However, after 6 months of SPHB, 25 of the 60 NMDs were significantly different compared with baseline, and a multivariate model for predicting treatment effect using 4 of the 25 was created (P <0.001). The multivariate model had an area under the receiver operating characteristic curve of 94% and an accuracy of 85%. Six months of SPHB treatment appears to alter the DNA chromatin structure and organization in prostate epithelial cells. Thus, a possible molecular basis for tissue changes and therapeutic effect of the compound is suggested.

A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes

ClinicalTrials.gov

2016-07-03

Prostate Cancer; Local Anesthesia; Prostate-Specific Antigen/Blood; Biopsy/Methods; Image-guided Biopsy/Methods; Prostatic Neoplasms/Diagnosis; Prostate/Pathology; Prospective Studies; Humans; Male; Ultrasonography, Interventional/Methods

Diet and dietary supplement intervention trials for the prevention of prostate cancer recurrence: a review of the randomized controlled trial evidence.

PubMed

Van Patten, Cheri L; de Boer, Johan G; Tomlinson Guns, Emma S

2008-12-01

We review the effect of diet and dietary supplement interventions on prostate cancer progression, recurrence and survival. A literature search was conducted in MEDLINE, EMBASE and CINAHL to identify diet and dietary supplement intervention studies in men with prostate cancer using prostate specific antigen or prostate specific antigen doubling time as a surrogate serum biomarker of prostate cancer recurrence and/or survival. Of the 32 studies identified 9 (28%) were randomized controlled trials and the focus of this review. In these studies men had confirmed prostate cancer and elevated or increasing prostate specific antigen. Only 1 trial included men with metastatic disease. When body mass index was reported, men were overweight or obese. A significant decrease in prostate specific antigen was observed in some studies using a low fat vegan diet, soy beverage or lycopene supplement. While not often reported as an end point, a significant increase in prostate specific antigen doubling time was observed in a study on lycopene supplementation. In only 1 randomized controlled trial in men undergoing orchiectomy was a survival end point of fewer deaths with lycopene supplementation reported. A limited number of randomized controlled trials were identified in which diet and dietary supplement interventions appeared to slow disease progression in men with prostate cancer, although results vary. Studies were limited by reliance on the surrogate biomarker prostate specific antigen, sample size and study duration. Well designed trials are warranted to expand knowledge, replicate findings and further assess the impact of diet and dietary supplement interventions on recurrence and treatment associated morbidities.

Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention

PubMed Central

Lance, Peter; Alberts, David S.; Thompson, Patricia A.; Fales, Liane; Wang, Fang; Jose, Jerilyn San; Jacobs, Elizabeth T.; Goodman, Phyllis J.; Darke, Amy K.; Yee, Monica; Minasian, Lori; Thompson, Ian M.; Roe, Denise J.

2017-01-01

Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as alpha tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90–1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared to placebo (RR = 1.03, 95% CI, 0.96–1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. PMID:27777235

Prostatic Response to Supranutritional Selenium Supplementation: Comparison of the Target Tissue Potency of Selenomethionine vs. Selenium-Yeast on Markers of Prostatic Homeostasis

PubMed Central

Waters, David J.; Shen, Shuren; Kengeri, Seema S.; Chiang, Emily C.; Combs, Gerald F.; Morris, J. Steven; Bostwick, David G.

2012-01-01

Prostate cancer is the product of dysregulated homeostasis within the aging prostate. Supplementation with selenium in the form of selenized yeast (Se-yeast) significantly reduced prostate cancer incidence in the Nutritional Prevention of Cancer Trial. Conversely, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no such cancer-protective advantage using selenomethionine (SeMet). The possibility that SeMet and Se-yeast are not equipotent in promoting homeostasis and cancer risk reduction in the aging prostate has not been adequately investigated; no direct comparison has ever been reported in man or animals. Here, we analyzed data on prostatic responses to SeMet or Se-yeast from a controlled feeding trial of 49 elderly beagle dogs—the only non-human species to frequently develop prostate cancer during aging—randomized to one of five groups: control; low-dose SeMet, low-dose Se-yeast (3 μg/kg); high-dose SeMet, high-dose Se-yeast (6 μg/kg). After seven months of supplementation, we found no significant selenium form-dependent differences in toenail or intraprostatic selenium concentration. Next, we determined whether SeMet or Se-yeast acts with different potency on six markers of prostatic homeostasis that likely contribute to prostate cancer risk reduction—intraprostatic dihydrotestosterone (DHT), testosterone (T), DHT:T, and epithelial cell DNA damage, proliferation, and apoptosis. By analyzing dogs supplemented with SeMet or Se-yeast that achieved equivalent intraprostatic selenium concentration after supplementation, we showed no significant differences in potency of either selenium form on any of the six parameters over three different ranges of target tissue selenium concentration. Our findings, which represent the first direct comparison of SeMet and Se-yeast on a suite of readouts in the aging prostate that reflect flux through multiple gene networks, do not further support the notion that the null results of SELECT are attributable to differences in prostatic consequences achievable through daily supplementation with SeMet, rather than Se-yeast. PMID:23201838

Inflammation on Prostate Needle Biopsy is Associated with Lower Prostate Cancer Risk: A Meta-Analysis.

PubMed

Vasavada, Shaleen R; Dobbs, Ryan W; Kajdacsy-Balla, André A; Abern, Michael R; Moreira, Daniel M

2018-05-01

We performed a comprehensive literature review and meta-analysis to evaluate the association of inflammation on prostate needle biopsies and prostate cancer risk. We searched Embase®, PubMed® and Web of Science™ from January 1, 1990 to October 1, 2016 for abstracts containing the key words prostate cancer, inflammation and biopsy. Study inclusion criteria were original research, adult human subjects, cohort or case-control study design, histological inflammation on prostate needle biopsy and prostate cancer on histology. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. Combined ORs and 95% CIs of any, acute and chronic inflammation were calculated using the random effects method. Of the 1,030 retrieved abstracts 46 underwent full text review and 25 were included in the final analysis, comprising a total of 20,585 subjects and 6,641 patients with prostate cancer. There was significant heterogeneity among studies (I 2 = 84.4%, p <0.001). The presence of any inflammation was significantly associated with a lower prostate cancer risk in 25 studies (OR 0.455, 95% CI 0.337-0.573). There was no evidence of publication bias (p >0.05). When subanalyzed by inflammation type, acute inflammation in 4 studies and chronic inflammation in 15 were each associated with a lower prostate cancer risk (OR 0.681, 95% CI 0.450-0.913 and OR 0.499, 95% CI 0.334-0.665, respectively). In a meta-analysis of 25 studies inflammation on prostate needle biopsy was associated with a lower prostate cancer risk. Clinically the presence of inflammation on prostate needle biopsy may lower the risk of a subsequent prostate cancer diagnosis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

To treat or not to treat with testosterone replacement therapy: a contemporary review of management of late-onset hypogonadism and critical issues related to prostate cancer.

PubMed

Kava, Bruce R

2014-07-01

Over the last 10 years there has been a dramatic increase in the number of patients identified and treated with testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH). By virtue of age, race, and family history, many of these patients are concurrently at risk for harboring indolent prostate cancer. Other men are at increased risk for prostate cancer as a result of an elevated serum PSA level or having had a prior prostate biopsy showing prostatic intraepithelial neoplasia (PIN) or atypical small acinar proliferation (ASAP). The clinician is often challenged with the decision whether to initiate TRT in these patients. This review presents a contemporary overview of the rationale for TRT, as well as the relationship between testosterone (endogenous and exogenous) and premalignant and malignant lesions of the prostate. We will discuss preliminary data from several recent series demonstrating that TRT may be safely administered in select patients with certain premalignant and bona fide malignant tumors of the prostate. In the absence of a large randomized clinical trial with long-term outcome data evaluating TRT, we hope that this overview will provide clinicians with an evidence-based approach to managing these anxiety-provoking - and often frustrating - clinical scenarios.

Pharmacodynamic and pharmacokinetic studies and prostatic tissue distribution of fosfomycin tromethamine in bacterial prostatitis or normal rats.

PubMed

Fan, L; Shang, X; Zhu, J; Ma, B; Zhang, Q

2018-05-02

In this study, we assessed the therapeutic effects of fosfomycin tromethamine (FT) in a bacterial prostatitis (BP) rat model. The BP model was induced by Escherichia coli and was demonstrated after 7 days microbiologically and histologically. Then, 25 BP rats selected were randomly divided into five treatment groups: model group, positive group, FT-3 day group, FT-7 day group and FT-14 day group. Ventral lobes of prostate from all animals were removed, and the serum samples were collected at the end of the experiments. Microbiological cultures and histological findings of the prostate samples demonstrated reduced bacterial growth and improved inflammatory responses in FT-treatment groups compared with the model group, indicating that FT against prostatic infection induced by E. coli showed good antibacterial effects. Moreover, plasma pharmacokinetics and prostatic distribution of fosfomycin were studied and compared in BP and normal rats. The concentrations of fosfomycin in samples were analysed by liquid chromatography-tandem mass spectrometry. There were no differences in plasma pharmacokinetic parameters between two groups. But significantly higher penetration of fosfomycin into prostatic tissues was found in BP rats. We therefore suggested that FT had a good therapeutic effect on BP and it might be used in curing masculine reproductive system diseases. © 2018 Blackwell Verlag GmbH.

Cranberry intervention in patients with prostate cancer prior to radical prostatectomy. Clinical, pathological and laboratory findings.

PubMed

Student, Vladimir; Vidlar, Ales; Bouchal, Jan; Vrbkova, Jana; Kolar, Zdenek; Kral, Milan; Kosina, Pavel; Vostalova, Jitka

2016-12-01

Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.

Moving a randomized clinical trial into an observational cohort.

PubMed

Goodman, Phyllis J; Hartline, Jo Ann; Tangen, Catherine M; Crowley, John J; Minasian, Lori M; Klein, Eric A; Cook, Elise D; Darke, Amy K; Arnold, Kathryn B; Anderson, Karen; Yee, Monica; Meyskens, Frank L; Baker, Laurence H

2013-02-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute (NCI) and conducted by the Southwest Oncology Group (SWOG). A total of 35,533 men were assigned randomly to one of the four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, and placebo + placebo). The independent Data and Safety Monitoring Committee (DSMC) recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-Up (CFU) study. The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada, and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures to close Study Sites, and revision of data collection procedures and the process by which to contact participants. At the time of the publication of the primary SELECT results in December 2008, there were 32,569 men alive and currently active in the trial. As of 31 December 2011, 17,761 participants had been registered to the CFU study. This number is less than had been anticipated due to unforeseen difficulties with local Study Site institutional review boards (IRBs). However, from this cohort, we estimate that an additional 580 prostate cancer cases and 215 Gleason 7 or higher grade cancers will be identified. Over 109,000 individual items have been mailed to participants. Active SELECT ancillary studies have continued. The substantial SELECT biorepository is available to researchers; requests to use the specimens are reviewed for feasibility and scientific merit. As of April 2012, 12 proposals had been approved. The accrual goal of the follow-up study was not met, limiting our power to address the study objectives satisfactorily. The CFU study is also dependent on a number of factors including continued funding, continued interest of investigators in the biorepository, and the continued contribution of the participants. Our experience may be less pertinent to investigators who wish to follow participants in a treatment trial or participants in prevention trials in other medical areas. Extended follow-up of participants in prevention research is important to study the long-term effects of the interventions, such as those used in SELECT. The approach taken by SELECT investigators was to continue to follow participants centrally via an annual questionnaire and with a web-based option. The participants enrolled in the CFU study represent a large, well-characterized, generally healthy cohort. The CFU has enabled us to collect additional prostate and other cancer endpoints and longer follow-up on the almost 18,000 participants enrolled. The utility of the extensive biorepository that was developed during the course of the SELECT is enhanced by longer follow-up.

Moving a Randomized Clinical Trial into an Observational Cohort

PubMed Central

Goodman, Phyllis J.; Hartline, Jo Ann; Tangen, Catherine M.; Crowley, John J.; Minasian, Lori M.; Klein, Eric A.; Cook, Elise D.; Darke, Amy K.; Arnold, Kathryn B.; Anderson, Karen; Yee, Monica; Meyskens, Frank L.; Baker, Laurence H.

2013-01-01

Background The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo. The independent Data and Safety Monitoring Committee recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. Purpose A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-up (CFU) study. Methods The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures to close Study Sites, and revision of data collection procedures and the process by which to contact participants. Results At the time of the publication of the primary SELECT results in December 2008, there were 32,569 men alive and currently active in the trial. As of December 31, 2011, 17,761 participants had been registered to the CFU study. This number is less than had been anticipated due to unforeseen difficulties with local Study Site IRBs. However, from this cohort we estimate that an additional 580 prostate cancer cases and 215 Gleason 7 or higher cancers will be identified. Over 109,000 individual items have been mailed to participants. Active SELECT ancillary studies have continued. The substantial SELECT biorepository is available to researchers; requests to use the specimens are reviewed for feasibility and scientific merit. As of April 2012, 12 proposals had been approved. Limitations The accrual goal of the follow-up study was not met, limiting our power to address the study objectives satisfactorily. The CFU study is also dependent on a number of factors including continued funding, continued interest of investigators in the biorepository and the continued contribution of the participants. Our experience may be less pertinent to investigators who wish to follow participants in a treatment trial or participants in prevention trials in other medical areas. Conclusions Extended follow-up of participants in prevention research is important to study the long-term effects of the interventions, such as those used in SELECT. The approach taken by SELECT investigators was to continue to follow participants centrally via an annual questionnaire and with a web-based option. The participants enrolled in the CFU study represent a large, well-characterized, generally healthy cohort. The CFU has enabled us to collect additional prostate and other cancer endpoints and longer follow-up on the almost 18,000 participants enrolled. The utility of the extensive biorepository that was developed during the course of the SELECT is enhanced by longer follow-up. PMID:23064404

The Association between Statin Use and the Diagnosis of Prostate Cancer in a Population-Based Cohort

PubMed Central

Breau, Rodney H.; Karnes, R. Jeffrey; Jacobson, Debra J.; McGree, Michaela E.; Jacobsen, Steven J.; Nehra, Ajay; Lieber, Michael M.; St. Sauver, Jennifer L.

2011-01-01

Purpose The effect of statin medication use on risk of prostate cancer is unknown. Materials and Methods We examined data from a longitudinal, population-based cohort of 2447 men between the ages of 40 and 79 that were followed from 1990 to 2007. Information on statin use was self-reported and obtained by biennial questionnaires. A randomly selected subset of men (634; 26%) completed biennial urologic examinations that included serum PSA measurements. Information on prostate biopsy and prostate cancer was obtained through review of community medical records. Results Of 634 statin users, 38 (6%) were diagnosed with prostate cancer compared to 186 (10%) of 1813 non-statin users. Statin use was associated with a decreased risk of receiving a prostate biopsy (HR: 0.31; 95% CI: 0.24, 0.40), prostate cancer diagnosis (HR: 0.36; 95% CI: 0.25, 0.53) and high-grade (Gleason ≥7) prostate cancer diagnosis (HR: 0.25; 95% CI: 0.11, 0.58). Statin use was also associated with a non-significant decreased risk of exceeding a PSA threshold of 4.0 ng/mL (HR: 0.63; 95% CI: 0.35, 1.13). In addition, longer duration of statin use was associated with lower risk of these outcomes (all tests for trend p<0.05). Conclusions Statin use is associated with a decreased risk of prostate cancer diagnosis. This association may be explained by decreased detection or cancer prevention. PMID:20620405

Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life.

PubMed

Lane, Athene; Metcalfe, Chris; Young, Grace J; Peters, Tim J; Blazeby, Jane; Avery, Kerry N L; Dedman, Daniel; Down, Liz; Mason, Malcolm D; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L

2016-12-01

To present the baseline patient-reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external-beam conformal radiotherapy for localized prostate cancer and to compare results with other populations. A total of 1643 randomized men, aged 50-69 years and diagnosed with clinically localized disease identified by prostate-specific antigen (PSA) testing, in nine UK cities in the period 1999-2009 were included. Validated PROMs for disease-specific (urinary, bowel and sexual function) and condition-specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire-Urinary Incontinence [ICIQ-UI], 2001 onwards; the International Continence Society short-form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12-item short-form health survey [SF-12]; EuroQol quality-of-life survey, the EQ-5D-3L) were assessed at prostate biopsy clinics before randomization. Descriptive statistics are presented by treatment allocation and by men's age at biopsy and PSA testing time points for selected measures. A total of 1438 participants completed biopsy questionnaires (88%) and 77-88% of these were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65-70 years), whilst urinary bother and physical health were somewhat worse than in younger men (49-54 years, all P < 0.001). Bowel health, urinary function and depression were unaltered by age, whilst mental health and anxiety were better in older men (P < 0.001). Only minor differences existed in mental or physical health, anxiety and depression between PSA testing and biopsy assessments. The ProtecT trial baseline PROMs response rates were high. Symptom frequencies and generic quality of life were similar to those observed in populations screened for prostate cancer and control subjects without cancer. © 2016 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention.

PubMed

Lance, Peter; Alberts, David S; Thompson, Patricia A; Fales, Liane; Wang, Fang; San Jose, Jerilyn; Jacobs, Elizabeth T; Goodman, Phyllis J; Darke, Amy K; Yee, Monica; Minasian, Lori; Thompson, Ian M; Roe, Denise J

2017-01-01

Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as α-tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative Risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90-1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared with placebo (RR = 1.03; 95% CI, 0.96-1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. Cancer Prev Res; 10(1); 45-54. ©2016 AACR. ©2016 American Association for Cancer Research.

Prophylactic sildenafil citrate improves select aspects of sexual function in men treated with radiotherapy for prostate cancer.

PubMed

Zelefsky, Michael J; Shasha, Daniel; Branco, Rebekah Dunn; Kollmeier, Marisa; Baser, Raymond E; Pei, Xin; Ennis, Ronald; Stock, Richard; Bar-Chama, Natan; Mulhall, John P

2014-09-01

We studied adjuvant daily sildenafil citrate during and after radiotherapy for prostate cancer for erectile function preservation. We performed a randomized, prospective trial of 279 patients with localized prostate cancer treated with radiotherapy who received sildenafil citrate (50 mg daily) or placebo (2:1 randomization). Medication/placebo was initiated 3 days before treatment and continued daily for 6 months. Before therapy and 3, 6, 9, 12, 18 and 24 months after radiotherapy patients completed the IIEF questionnaire, including the erectile function domain, the I-PSS questionnaire and the RAND SF-36®. All IIEF domains were scored. At 12 months erectile function scores were better for sildenafil citrate than placebo (p = 0.018), 73% of patients on sildenafil citrate vs 50% on placebo had mild/no erectile dysfunction (p = 0.024) and the sildenafil citrate arm had superior overall satisfaction (p = 0.027) and IIEF total scores (p = 0.043). At 24 months erectile function and IIEF scores were no longer significantly better for sildenafil citrate (p = 0.172 and 0.09, respectively) and yet overall satisfaction scores were higher (p = 0.033). Sexual desire scores in patients who received sildenafil citrate were higher at 24 months although they had completed drug therapy 18 months previously (p = 0.049). At 24 months 81.6% of patients on sildenafil citrate and 56.0% of those on placebo achieved functional erection with or without erectile dysfunction medication (p = 0.045). Daily sildenafil citrate during and after radiotherapy for prostate cancer was associated with improved overall sexual function compared with placebo for various sexual function domains. To our knowledge this is the largest randomized, prospective, controlled trial to show the usefulness of a phosphodiesterase-5 inhibitor as a rehabilitation strategy in patients with prostate cancer who received radiation therapy. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Potential surrogate endpoints for prostate cancer survival: analysis of a phase III randomized trial.

PubMed

Ray, Michael E; Bae, Kyounghwa; Hussain, Maha H A; Hanks, Gerald E; Shipley, William U; Sandler, Howard M

2009-02-18

The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial. Patients (n = 1554 randomly assigned and 1521 evaluable for this analysis) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent androgen deprivation therapy with external beam radiation therapy and then randomly assigned to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm). Data from landmark analyses at 3 and 5 years for general clinical treatment failure (defined as documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy) and/or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice's four criteria. All statistical tests were two-sided. At 3 years, 1364 patients were alive and contributed data for analysis. Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years. At 5 years, 1178 patients were alive and contributed data for analysis. Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years (P = .08), both endpoints were consistent with Prentice's remaining criteria. Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years. These endpoints, however, must be validated in other datasets.

Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis in Biopsy-naive Men with Suspected Prostate Cancer Based on Elevated Prostate-specific Antigen Values: Results from a Randomized Prospective Blinded Controlled Trial.

PubMed

Tonttila, Panu P; Lantto, Juha; Pääkkö, Eija; Piippo, Ulla; Kauppila, Saila; Lammentausta, Eveliina; Ohtonen, Pasi; Vaarala, Markku H

2016-03-01

Multiparametric magnetic resonance imaging (MP-MRI) may improve the detection of clinically significant prostate cancer (PCa). To compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided random biopsy for overall and clinically significant PCa detection among patients with suspected PCa based on prostate-specific antigen (PSA) values. This institutional review board-approved, single-center, prospective, randomized controlled trial (April 2011 to December 2014) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values (PSA <20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA <10 ng/ml). Patients were randomized 1:1 to the MP-MRI or control group. Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided random biopsy and cognitive MRI/TRUS fusion targeted biopsy. The control group underwent TRUS-guided random biopsy alone. MP-MRI 3-T phased-array surface coil. The primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups. Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinically significant PCa in the MP-MRI and control groups. Between-group analyses were performed. Overall, 53 and 60 patients were evaluable in the MP-MRI and control groups, respectively. The overall PCa detection rate and the clinically significant cancer detection rate were similar between the MP-MRI and control groups, respectively (64% [34 of 53] vs 57% [34 of 60]; 7.5% difference [95% confidence interval (CI), -10 to 25], p=0.5, and 55% [29 of 53] vs 45% [27 of 60]; 9.7% difference [95% CI, -8.5 to 27], p=0.8). The PCa detection rate was higher than assumed during the planning of this single-center trial. MP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values. In this randomized clinical trial, additional prostate magnetic resonance imaging (MRI) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound-guided random biopsy in the diagnosis of prostate cancer. Similar numbers of cancers were detected with and without MRI. ClinicalTrials.gov identifier: NCT01357512. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

PubMed

Soon, Yu Yang; Chen, Desiree; Tan, Teng Hwee; Tey, Jeremy

2018-06-07

Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

Adjuvant androgen-deprivation therapy following prostate total cryoablation in high-risk localized prostate cancer patients - Open-labeled randomized clinical trial.

PubMed

Chen, Chung-Hsin; Pu, Yeong-Shiau

2018-06-01

To investigate the efficacy and safety profile of 12-month adjuvant androgen-deprivation therapy (ADT) following total-gland cryoablation (TGC) in patients with high-risk localized prostate cancer (HRLPC). This open-label randomized trial included 38 HRLPC patients who received TGC between July 2011 and March 2013. Within 4 weeks after TGC, subjects were randomly assigned (1:1) to either the 12-month adjuvant ADT or non-adjuvant ADT group. The primary outcome was biochemical failure measured by the Phoenix definition. Adverse events were measured at month 1, 2, 3, 6, 9 and 12. In addition, a cohort of 145 HRLPC patients was selected retrospectively for outcome validation. The adjuvant ADT and non-adjuvant ADT groups did't differ in peri-operative characters, such as age, preoperative PSA, tumor stages, Gleason score, prostate size and cryoprobe number. Four patients with adjuvant ADT withdrew from this trial for personal reasons (N = 2), elevated liver function (N = 1) and poorly controlled hyperglycemia (N = 1). In contrast, none in non-adjuvant ADT group experienced adverse events. Biochemical failures were identified in 5 (26%) patients in each group during a median follow-up duration of 45 months. The median times to biochemical failure were 25 and 5.5 months for adjuvant ADT and non-adjuvant ADT groups, respectively. Biochemical-failure survival curves converged 24 months after TGC. Univariable and multivariable analyses revealed adjuvant ADT was not associated with biochemical recurrences in the validation cohort. Adjuvant ADT does not reduce biochemical failure for HRPLC patients undergoing TGC. It should be further confirmed by a larger cohort. Copyright © 2018. Published by Elsevier Inc.

Simulating intrafraction prostate motion with a random walk model.

PubMed

Pommer, Tobias; Oh, Jung Hun; Munck Af Rosenschöld, Per; Deasy, Joseph O

2017-01-01

Prostate motion during radiation therapy (ie, intrafraction motion) can cause unwanted loss of radiation dose to the prostate and increased dose to the surrounding organs at risk. A compact but general statistical description of this motion could be useful for simulation of radiation therapy delivery or margin calculations. We investigated whether prostate motion could be modeled with a random walk model. Prostate motion recorded during 548 radiation therapy fractions in 17 patients was analyzed and used for input in a random walk prostate motion model. The recorded motion was categorized on the basis of whether any transient excursions (ie, rapid prostate motion in the anterior and superior direction followed by a return) occurred in the trace and transient motion. This was separately modeled as a large step in the anterior/superior direction followed by a returning large step. Random walk simulations were conducted with and without added artificial transient motion using either motion data from all observed traces or only traces without transient excursions as model input, respectively. A general estimate of motion was derived with reasonable agreement between simulated and observed traces, especially during the first 5 minutes of the excursion-free simulations. Simulated and observed diffusion coefficients agreed within 0.03, 0.2 and 0.3 mm 2 /min in the left/right, superior/inferior, and anterior/posterior directions, respectively. A rapid increase in variance at the start of observed traces was difficult to reproduce and seemed to represent the patient's need to adjust before treatment. This could be estimated somewhat using artificial transient motion. Random walk modeling is feasible and recreated the characteristics of the observed prostate motion. Introducing artificial transient motion did not improve the overall agreement, although the first 30 seconds of the traces were better reproduced. The model provides a simple estimate of prostate motion during delivery of radiation therapy.

The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer.

PubMed

Wilt, Timothy J; Brawer, Michael K; Barry, Michael J; Jones, Karen M; Kwon, Young; Gingrich, Jeffrey R; Aronson, William J; Nsouli, Imad; Iyer, Padmini; Cartagena, Ruben; Snider, Glenn; Roehrborn, Claus; Fox, Steven

2009-01-01

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. Ninety percent of men with prostate cancer are over aged 60 years, diagnosed by early detection with the prostate specific antigen (PSA) blood test and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting surgery to remove the prostate gland (radical prostatectomy), external beam radiation therapy and interstitial radiation therapy (brachytherapy) and androgen deprivation. Little is known about the relative effectiveness and harms of treatments due to the paucity of randomized controlled trials. The VA/NCI/AHRQ Cooperative Studies Program Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy versus watchful waiting conducted in Scandinavia. We screened 13,022 men with prostate cancer at 52 United States medical centers for potential enrollment. From these, 5023 met initial age, comorbidity and disease eligibility criteria and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African-American. Approximately 85% reported they were fully active. The median prostate specific antigen (PSA) was 7.8 ng/mL (mean 10.2 ng/mL). In three-fourths of men the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade and tumor stage, approximately 43% had low risk, 36% had medium risk and 20% had high-risk prostate cancer. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the U.S. and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared to watchful waiting for men with predominately PSA detected clinically localized prostate cancer.

15-year followup of a population based prostate cancer screening study.

PubMed

Kjellman, Anders; Akre, Olof; Norming, Ulf; Törnblom, Magnus; Gustafsson, Ove

2009-04-01

We evaluated long-term survival in attendees and nonattendees of a 1-time screening for prostate cancer. A total of 2,400 men 55 to 70 years old in 1988 were randomly selected and invited to a screening for prostate cancer. Of the invited men 1,782 (74%) attended. Screening attendees were examined with digital rectal examination, transrectal ultrasound and prostate specific antigen analysis. When cancer was suspected, prostate biopsies were taken. A total of 65 men with prostate cancer were detected by this procedure. The entire source population comprising 27,204 men, including 618 nonattendees (26%), was followed for prostate cancer diagnosis and survival for 15 years. Incidence rate ratios were calculated using Poisson regression models. We found no effect of this screening procedure on the risk of death from prostate cancer and other causes of death (incidence rate ratio 1.10, 95% CI 0.83-1.46 and 0.98, 95% CI 0.92-1.05, respectively) when comparing all invited men with the source population. However, attending the screening program was associated with a significantly decreased risk of death from causes other than prostate cancer (vs source population incidence rate ratio 0.82, 95% CI 0.76-0.90). In contrast, the corresponding incidence rate ratio in nonattendees was 1.53 (95% CI 1.37-1.71). We found no evidence of a beneficial effect of this specific screening procedure but strong evidence of a difference in overall survival in screening attendees and nonattendees. These findings should be considered when interpreting previous and upcoming studies of the effect of screening programs.

Cultural factors associated with the intent to be screened for prostate cancer among adult men in a rural Kenyan community.

PubMed

Mutua, Kinyao; Pertet, Anne M; Otieno, Careena

2017-11-23

The aim of this study was to determine cultural factors associated with prostate cancer screening intent among adult Kenyan African men. A cross-sectional quantitative study with an analytic design was carried out in a randomly selected sample of 155 adult men aged 25-98 years living in a rural community in Kenya. Constructs from the Theory of Planned Behaviour were used to guide this study. A 5 -point Likert scale was used to assess fatalistic beliefs, fear, perceived benefits, and family influence. A structured questionnaire was used to collect quantitative data at the household level. Only 2.4% of the study participants had been screened for prostate cancer. About 2/3rd (64%) of the participants felt that they were at risk of getting prostate cancer; 44% intended to be screened within the following 6 months. Mean scores on a 5-point Likert scale indicated: strong beliefs in the benefits of prostate screening (4.2 (±SD .8), men aged over 40 were not perceived to be at risk of getting prostate cancer (1.3 ± .6), relatively high fatalistic beliefs of prostate cancer screening (3.6 (±SD .8), high degree of fear or apprehension of prostate cancer screening (3.2 (±SD 1.2), and a high level of influence of family members in prostate cancer screening (3.9 (±SD 1.0). The Wald criterion demonstrated that only family influence made a significant contribution to the intent to screen for prostate cancer (p = 0.031). Age, education, marital status, fatalism, fear, and benefit of screening were not associated with the intent to screen for prostate cancer. Strong beliefs of the benefits of prostate screening tended to be surpassed by relatively high fatalistic beliefs and fear or apprehension in prostate cancer screening. The family plays an important role in influencing decision making related to prostate cancer screening in Africans.

Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor.

PubMed

Clark, Richard V; Hermann, David J; Cunningham, Glenn R; Wilson, Timothy H; Morrill, Betsy B; Hobbs, Stuart

2004-05-01

Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5alpha-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperplasia (BPH), and reduction in its level with 5alpha-reductase inhibitors improves the symptoms associated with BPH and reduces the risk of acute urinary retention and prostate surgery. A selective inhibitor of the type 2 isoenzyme (finasteride) has been shown to decrease serum DHT by about 70%. We hypothesized that inhibition of both isoenzymes with the dual inhibitor dutasteride would more effectively suppress serum DHT levels than selective inhibition of only the type 2 isoenzyme. A total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4 +/- 1.2% with 5.0 mg dutasteride and 94.7 +/- 3.3% with 0.5 mg dutasteride, significantly lower (P < 0.001) and with less variability than the 70.8 +/- 18.3% suppression observed with 5 mg finasteride. Mean testosterone levels increased but remained in the normal range for all treatment groups. Dutasteride appeared to be well tolerated with an adverse event profile similar to placebo.

Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

PubMed Central

Mason, Malcolm D.; Parulekar, Wendy R.; Sydes, Matthew R.; Brundage, Michael; Kirkbride, Peter; Gospodarowicz, Mary; Cowan, Richard; Kostashuk, Edmund C.; Anderson, John; Swanson, Gregory; Parmar, Mahesh K.B.; Hayter, Charles; Jovic, Gordana; Hiltz, Andrea; Hetherington, John; Sathya, Jinka; Barber, James B.P.; McKenzie, Michael; El-Sharkawi, Salah; Souhami, Luis; Hardman, P.D. John; Chen, Bingshu E.; Warde, Padraig

2015-01-01

Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer. PMID:25691677

The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer.

PubMed

Wilt, Timothy J

2012-12-01

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. In the United States, 90% of men with prostate cancer are more than age 60 years, diagnosed by early detection with the prostate-specific antigen (PSA) blood test, and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting (WW), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy and interstitial radiation therapy (brachytherapy), and androgen deprivation. Little is known about the relative effectiveness and harms of treatments because of the paucity of randomized controlled trials. The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study #407:Prostate Cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy with WW in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods, and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy vs WW conducted in Scandinavia. We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment. From these, 5023 met initial age, comorbidity, and disease eligibility criteria, and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African American. Approximately 85% reported that they were fully active. The median PSA was 7.8ng/mL (mean 10.2ng/mL). In three-fourths of men, the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade, and tumor stage, it was found that approximately 40% had low-risk, 34% had medium-risk, and 21% had high-risk prostate cancer based on local histopathology. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinically localized prostate cancer.

Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

PubMed Central

Lippman, Scott M.; Klein, Eric A.; Goodman, Phyllis J.; Lucia, M. Scott; Thompson, Ian M.; Ford, Leslie G.; Parnes, Howard L.; Minasian, Lori M.; Gaziano, J. Michael; Hartline, Jo Ann; Parsons, J. Kellogg; Bearden, James D.; Crawford, E. David; Goodman, Gary E.; Claudio, Jaime; Winquist, Eric; Cook, Elise D.; Karp, Daniel D.; Walther, Philip; Lieber, Michael M.; Kristal, Alan R.; Darke, Amy K.; Arnold, Kathryn B.; Ganz, Patricia A.; Santella, Regina M.; Albanes, Demetrius; Taylor, Philip R.; Probstfield, Jeffrey L.; Jagpal, T. J.; Crowley, John J.; Meyskens, Frank L.; Baker, Laurence H.; Coltman, Charles A.

2013-01-01

Context Secondary analyses of two randomized controlled trials (RCTs) and supportive epidemiologic and preclinical indicated the potential of selenium and vitamin E for preventing prostate cancer. Objective To determine whether selenium or vitamin E or both could prevent prostate cancer with little or no toxicity in relatively healthy men. Design, Setting, and Participants Randomization of a planned 32,400 men to selenium, vitamin E, selenium plus vitamin E, and placebo in a double-blinded fashion. Participants were recruited and followed in community practices, local hospitals and HMOs, and tertiary cancer centers in the United States, Canada and Puerto Rico. Baseline eligibility included 50 years or older (African American) or 55 years or older (all others), a serum prostate-specific antigen (PSA) ≤ 4 ng/mL, and a digital rectal examination (DRE) not suspicious for prostate cancer. Between 2001 and 2004, 35,533 men (10% more than planned because of a faster-than-expected accrual rate) were randomly assigned to the four study arms, which were well balanced with respect to all potentially important risk factors. Interventions Oral selenium (200 µg/day from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/day of all rac-α-tocopheryl acetate) and matched selenium placebo, or the two combined or placebo plus placebo for a planned minimum of 7 and maximum of 12 years. Main Outcome Measures Prostate cancer (as determined by routine community diagnostic standards) and prespecified secondary outcomes including lung, colorectal and overall cancer. Results Study supplements were discontinued at the recommendation of the Data and Safety Monitoring Committee at a planned 7-year interim analysis because the evidence convincingly demonstrated no benefit from either study agent (p < 0.0001) and no possibility of a benefit to the planned degree with additional follow-up. As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17 and 7.33). Hazard ratios (number of prostate cancers, 99% confidence intervals [CIs]) for prostate cancer were 1.13 for vitamin E (n=473; CI, 0.91–1.41), 1.04 for selenium (n=432; CI, 0.83–1.30), and 1.05 for the combination (n=437; CI, 0.83–1.31) compared with placebo (n=416). There were no significant differences (all p-values > 0.15) in any prespecified cancer endpoints. There were nonsignificant increased risks of prostate cancer in the vitamin E arm (p=0.06; relative risk [RR]=1.13; 99% CI, 0l95–1.35) and of Type 2 diabetes mellitus in the selenium arm (p=0.16; RR=1.07; 99% CI, 0.94–1.22), but they were not observed in the combination arm. Conclusion Selenium or vitamin E, alone or in combination, did not prevent prostate cancer in this population at the doses and formulations used. PMID:19066370

Estimating bias in causes of death ascertainment in the Finnish Randomized Study of Screening for Prostate Cancer.

PubMed

Kilpeläinen, Tuomas P; Mäkinen, Tuukka; Karhunen, Pekka J; Aro, Jussi; Lahtela, Jorma; Taari, Kimmo; Talala, Kirsi; Tammela, Teuvo L J; Auvinen, Anssi

2016-12-01

Precise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial. Our trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men. Randomly selected deaths in men with PCa (N=442/2568 cases, 17.2%) were reviewed by an independent CoD committee. Median follow-up was 16.8 years in both arms. Overdiagnosis of PCa was present in the SA as the risk ratio for PCa incidence was 1.19 (95% confidence interval (CI) 1.14-1.24). The hazard ratio (HR) for PCa mortality was 0.94 (95%CI 0.82-1.08) in favor of the SA. Agreement with official CoD registry was 94.6% (κ=0.88) in the SA and 95.4% (κ=0.91) in the CA. Altogether 14 PCa deaths were estimated as false-positive in both arms and exclusion of these resulted in HR 0.92 (95% CI 0.80-1.06). A small differential misclassification bias in ascertainment of CoD was present, most likely due to attribution bias (overdiagnosis in the SA). Maximum precision in CoD ascertainment can only be achieved with independent review of all deaths in the diseased population. However, this is cumbersome and expensive and may provide little benefit compared to random sampling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Management Options for Biochemically Recurrent Prostate Cancer.

PubMed

Fakhrejahani, Farhad; Madan, Ravi A; Dahut, William L

2017-05-01

Prostate cancer is the most common solid tumor malignancy in men worldwide. Treatment with surgery and radiation can be curative in organ-confined disease. Unfortunately, about one third of men develop biochemically recurrent disease based only on rising prostate-specific antigen (PSA) in the absence of visible disease on conventional imaging. For these patients with biochemical recurrent prostate cancer, there is no uniform guideline for subsequent management. Based on available data, it seems prudent that biochemical recurrent prostate cancer should initially be evaluated for salvage radiation or prostatectomy, with curative intent. In selected cases, high-intensity focused ultrasound and cryotherapy may be considered in patients that meet very narrow criteria as defined by non-randomized trials. If salvage options are not practical or unsuccessful, androgen deprivation therapy (ADT) is a standard option for disease control. While some patients prefer ADT to manage the disease immediately, others defer treatment because of the associated toxicity. In the absence of definitive randomized data, patients may be followed using PSA doubling time as a trigger to initiate ADT. Based on retrospective data, a PSA doubling time of less than 3-6 months has been associated with near-term development of metastasis and thus could be used signal to initiate ADT. Once treatment is begun, patients and their providers can choose between an intermittent and continuous ADT strategy. The intermittent approach may limit side effects but in patients with metastatic disease studies could not exclude a 20% greater risk of death. In men with biochemical recurrence, large studies have shown that intermittent therapy is non-inferior to continuous therapy, thus making this a reasonable option. Since biochemically recurrent prostate cancer is defined by technological limitations of radiographic detection, as new imaging (i.e., PSMA) strategies are developed, it may alter how the disease is monitored and perhaps managed. Furthermore, patients have no symptoms related to their disease and thus many prefer options that minimize toxicity. For this reason, herbal agents and immunotherapy are under investigation as potential alternatives to ADT and its accompanying side effects. New therapeutic options combined with improved imaging to evaluate the disease may markedly change how biochemically recurrent prostate cancer is managed in the future.

Informed Decision Making About Prostate Cancer Testing in Predominantly Immigrant Black Men: A Randomized Controlled Trial

PubMed Central

Lepore, Stephen J.; Wolf, Randi L.; Basch, Charles E.; Godfrey, Melissa; McGinty, Emma; Shmukler, Celia; Ullman, Ralph; Thomas, Nigel; Weinrich, Sally

2012-01-01

Background Decision support interventions have been developed to help men clarify their values and make informed decisions about prostate cancer testing, but they seldom target high-risk black and immigrant men. Purpose This study evaluated the efficacy of a decision support intervention focused on prostate cancer testing in a sample of predominantly immigrant black men. Methods Black men (N = 490) were randomized to tailored telephone education about prostate cancer testing or a control condition. Results Post-intervention, the intervention group had significantly greater knowledge, lower decision conflict, and greater likelihood of talking with their physician about prostate cancer testing than the control group. There were no significant intervention effects on prostate specific antigen testing, congruence between testing intention and behavior, or anxiety. Conclusions A tailored telephone decision support intervention can promote informed decision making about prostate cancer testing in black and predominantly immigrant men without increasing testing or anxiety. Clinical trial Registered in clinicaltrials.gov (NCT01415375) PMID:22825933

[Laservaporization of the prostate: current status of the greenlight and diode laser].

PubMed

Rieken, M; Bachmann, A; Gratzke, C

2013-03-01

In the last decade laser vaporization of the prostate has emerged as a safe and effective alternative to transurethral resection of the prostate (TURP). This was facilitated in particular by the introduction of photoselective vaporization of the prostate (PVP) with a 532 nm 80 W KTP laser in 2002. Prospective randomized trials comparing PVP and TURP with a maximum follow-up of 3 years mostly demonstrated comparable functional results. Cohort studies showed a safe application of PVP in patients under oral anticoagulation and with large prostates. Systems from various manufacturers with different maximum power output and wavelengths are now available for diode laser vaporization of the prostate. Prospective randomized trials comparing diode lasers and TURP are not yet available. In cohort studies and comparative studies PVP diode lasers are characterized by excellent hemostatic properties but functional results vary greatly with some studies reporting high reoperation rates.

Screening for Prostate Cancer Starting at Age 50-54. A Population-based Cohort Study

PubMed Central

Carlsson, Sigrid; Assel, Melissa; Ulmert, David; Gerdtsson, Axel; Hugosson, Jonas; Vickers, Andrew; Lilja, Hans

2016-01-01

Background Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening. Objective To evaluate the effect of prostate-specific antigen (PSA) screening, versus zero screening, starting at age 50-54, on prostate cancer mortality. Design, Setting, and Participants This is a population-based cohort study comparing 3,479 men aged 50 through 54 randomized to PSA-screening in the Göteborg population-based prostate cancer screening trial, initiated in 1995, versus 4,060 unscreened men aged 51 to 55 providing cryopreserved blood in the population-based Malmö Preventive Project in the pre-PSA era, during 1982-1985. Outcome measures and Statistical Analysis Cumulative incidence and incidence rate ratios of prostate cancer diagnosis, metastasis, and prostate cancer death. Results and Limitation At 17 years, regular PSA-screening in Göteborg of men in their early 50s carried a more than 2-fold higher risk of prostate cancer diagnosis compared to the unscreened men in Malmö (IRR 2.56, 95% CI 2.18, 3.02), but resulted in a substantial decrease in risk of metastases (IRR 0.43, 95% CI 0.22, 0.79) and prostate cancer death (IRR 0.29, 95% CI 0.11, 0.67). There were 57 fewer prostate cancer deaths per 10,000 men (95% CI 22, 92) in the screened group. At 17 years, the number needed to invite to PSA-screening and the number needed to diagnose to prevent one prostate cancer death was 176 and 16, respectively. The study is limited by lack of treatment information and the comparison of two different birth cohorts. Conclusions PSA screening for prostate cancer can decrease prostate cancer mortality among men aged 50–54, with NNI and NND comparable to those previously reported from the European Randomized Study of Screening for Prostate Cancer for men aged 55-69 years, at similar follow-up. Guideline groups could consider whether guidelines for PSA screening should recommend starting no later than at ages 50-54. Trial registration The Göteborg randomized population-based prostate cancer screening trial is registered with the ISRCTN registry (isrctn.com). Identifier: ISRCTN54449243. PMID:27084245

Web-Based Versus Usual Care and Other Formats of Decision Aids to Support Prostate Cancer Screening Decisions: Systematic Review and Meta-Analysis.

PubMed

Baptista, Sofia; Teles Sampaio, Elvira; Heleno, Bruno; Azevedo, Luís Filipe; Martins, Carlos

2018-06-26

Prostate cancer is a leading cause of cancer among men. Because screening for prostate cancer is a controversial issue, many experts in the field have defended the use of shared decision making using validated decision aids, which can be presented in different formats (eg, written, multimedia, Web). Recent studies have concluded that decision aids improve knowledge and reduce decisional conflict. This meta-analysis aimed to investigate the impact of using Web-based decision aids to support men's prostate cancer screening decisions in comparison with usual care and other formats of decision aids. We searched PubMed, CINAHL, PsycINFO, and Cochrane CENTRAL databases up to November 2016. This search identified randomized controlled trials, which assessed Web-based decision aids for men making a prostate cancer screening decision and reported quality of decision-making outcomes. Two reviewers independently screened citations for inclusion criteria, extracted data, and assessed risk of bias. Using a random-effects model, meta-analyses were conducted pooling results using mean differences (MD), standardized mean differences (SMD), and relative risks (RR). Of 2406 unique citations, 7 randomized controlled trials met the inclusion criteria. For risk of bias, selective outcome reporting and participant/personnel blinding were mostly rated as unclear due to inadequate reporting. Based on seven items, two studies had high risk of bias for one item. Compared to usual care, Web-based decision aids increased knowledge (SMD 0.46; 95% CI 0.18-0.75), reduced decisional conflict (MD -7.07%; 95% CI -9.44 to -4.71), and reduced the practitioner control role in the decision-making process (RR 0.50; 95% CI 0.31-0.81). Web-based decision aids compared to printed decision aids yielded no differences in knowledge, decisional conflict, and participation in decision or screening behaviors. Compared to video decision aids, Web-based decision aids showed lower average knowledge scores (SMD -0.50; 95% CI -0.88 to -0.12) and a slight decrease in prostate-specific antigen screening (RR 1.12; 95% CI 1.01-1.25). According to this analysis, Web-based decision aids performed similarly to alternative formats (ie, printed, video) for the assessed decision-quality outcomes. The low cost, readiness, availability, and anonymity of the Web can be an advantage for increasing access to decision aids that support prostate cancer screening decisions among men. ©Sofia Baptista, Elvira Teles Sampaio, Bruno Heleno, Luís Filipe Azevedo, Carlos Martins. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.06.2018.

Comparative randomized pilot study of azithromycin and doxycycline efficacy and tolerability in the treatment of prostate infection caused by Ureaplasma urealyticum.

PubMed

Skerk, Visnja; Mareković, Ivana; Markovinović, Leo; Begovac, Josip; Skerk, Vedrana; Barsić, Neven; Majdak-Gluhinić, Vida

2006-01-01

A total of 1,442 patients with symptoms of chronic prostatitis were examined over a 4-year period at the Outpatient Department for Urogenital Infections, University Hospital for Infectious Diseases Dr. Fran Mihaljević, Zagreb, Croatia. The inclusion criteria for chronic prostatitis caused by Ureaplasma urealyticum were the presence of clinical symptoms, presence of U. urealyticum in expressed prostatic secretion (EPS) or voided urine collected immediately after prostatic massage (VB(3)), absence of U. urealyticum in urethral swabs and absence of other possible pathogens of chronic prostatitis in EPS or VB(3). A total of 63 patients with prostate infection caused by U. urealyticum were available for this pilot study. The patients were randomized according to a computer randomization list to receive a total dose of 4.5 g of azithromycin given as a 3-day therapy of 1 x 500 mg weekly for 3 weeks or doxycyline 100 mg b.i.d. for 21 days. Patients' sexual partners were treated at the same time. Clinical efficacy and tolerability of the administered drug as well as possible adverse events were evaluated during, at the end and 4-6 weeks after completion of therapy. Bacteriological efficacy was evaluated 4-6 weeks after completion of therapy. Treatment groups did not differ regarding age, distribution of urethral, prostatic, sexual and other symptoms, or digitorectal prostatic examination. Five patients treated with doxycycline had nausea. In the group of patients with prostate infection caused by U. urealyticum, the eradication rate was not significantly different with regard to the administered azithromycin (25/32) or doxycycline (23/31). Clinical cure did not significantly differ with regard to the administered azithromycin (22/32) or doxycycline (21/31). Copyright 2006 S. Karger AG, Basel.

Digoxin and prostate cancer survival in the Finnish Randomized Study of Screening for Prostate Cancer.

PubMed

Kaapu, Kalle J; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo Lj; Auvinen, Anssi

2016-11-22

Protective effects have been suggested for digoxin against prostate cancer risk. However, few studies have evaluated the possible effects on prostate cancer-specific survival. We studied the association between use of digoxin or beta-blocker sotalol and prostate cancer-specific survival as compared with users of other antiarrhythmic drugs in a retrospective cohort study. Our study population consisted of 6537 prostate cancer cases from the Finnish Randomized Study of Screening for Prostate Cancer diagnosed during 1996-2009 (485 digoxin users). The median exposure for digoxin was 480 DDDs (interquartile range 100-1400 DDDs). During a median follow-up of 7.5 years after diagnosis, 617 men (48 digoxin users) died of prostate cancer. We collected information on antiarrhythmic drug purchases from the national prescription database. Both prediagnostic and postdiagnostic drug usages were analysed using the Cox regression method. No association was found for prostate cancer death with digoxin usage before (HR 1.00, 95% CI 0.56-1.80) or after (HR 0.81, 95% CI 0.43-1.51) prostate cancer diagnosis. The results were also comparable for sotalol and antiarrhythmic drugs in general. Among men not receiving hormonal therapy, prediagnostic digoxin usage was associated with prolonged prostate cancer survival (HR 0.20, 95% CI 0.05-0.86). No general protective effects against prostate cancer were observed for digoxin or sotalol usage.

Absolute Effect of Prostate Cancer Screening: Balance of benefits and harms by center within the European Randomized Study of Prostate Cancer Screening

PubMed Central

Auvinen, Anssi; Moss, Sue M; Tammela, Teuvo L J; Taari, Kimmo; Roobol, Monique J; Schröder, Fritz H; Bangma, Chris H; Carlsson, Sigrid; Aus, Gunnar; Zappa, Marco; Puliti, Donella; Denis, Louis J; Nelen, Vera; Kwiatkowski, Maciej; Randazzo, Marco; Paez, Alvaro; Lujan, Marcos; Hugosson, Jonas

2016-01-01

Purpose The balance of benefits and harms in prostate cancer screening has not been sufficiently characterized. We related indicators of mortality reduction and overdetection by center within the European Randomized Study of Prostate Cancer Screening. Experimental Design We analyzed the absolute mortality reduction expressed as number needed to invite (NNI=1/absolute risk reduction; indicating how many men had to be randomized to screening arm to avert a prostate cancer death) for screening and the absolute excess of prostate cancer detection as number needed for overdetection (NNO=1/absolute excess incidence; indicating the number of men invited per additional prostate cancer case), and compared their relationship across the seven ERSPC centers. Results Both absolute mortality reduction (NNI) and absolute overdetection (NNO) varied widely between the centers: NNI 200-7000 and NNO 16-69. Extent of overdiagnosis and mortality reduction were closely associated (correlation coefficient r=0.76, weighted linear regression coefficient β=33, 95% 5-62, R2=0.72). For an averted prostate cancer death at 13 years of follow-up, 12-36 excess cases had to be detected in various centers. Conclusions The differences between the ERSPC centers likely reflect variations in prostate cancer incidence and mortality, as well as in screening protocol and performance. The strong interrelation between the benefits and harms suggests that efforts to maximize the mortality effect are bound to increase overdiagnosis, and might be improved by focusing on high-risk populations. The optimal balance between screening intensity and risk of overdiagnosis remains unclear. PMID:26289069

Shared decision making for prostate cancer screening: the results of a combined analysis of two practice-based randomized controlled trials.

PubMed

Sheridan, Stacey L; Golin, Carol; Bunton, Audrina; Lykes, John B; Schwartz, Bob; McCormack, Lauren; Driscoll, David; Bangdiwala, Shrikant I; Harris, Russell P

2012-11-13

Professional societies recommend shared decision making (SDM) for prostate cancer screening, however, most efforts have promoted informed rather than shared decision making. The objective of this study is to 1) examine the effects of a prostate cancer screening intervention to promote SDM and 2) determine whether framing prostate information in the context of other clearly beneficial men's health services affects decisions. We conducted two separate randomized controlled trials of the same prostate cancer intervention (with or without additional information on more clearly beneficial men's health services). For each trial, we enrolled a convenience sample of 2 internal medicine practices, and their interested physicians and male patients with no prior history of prostate cancer (for a total of 4 practices, 28 physicians, and 128 men across trials). Within each practice site, we randomized men to either 1) a video-based decision aid and researcher-led coaching session or 2) a highway safety video. Physicians at each site received a 1-hour educational session on prostate cancer and SDM. To assess intervention effects, we measured key components of SDM, intent to be screened, and actual screening. After finding that results did not vary by trial, we combined data across sites, adjusting for the random effects of both practice and physician. Compared to an attention control, our prostate cancer screening intervention increased men's perceptions that screening is a decision (absolute difference +41%; 95% CI 25 to 57%) and men's knowledge about prostate cancer screening (absolute difference +34%; 95% CI 19% to 50%), but had no effect on men's self-reported participation in shared decisions or their participation at their preferred level. Overall, the intervention decreased screening intent (absolute difference -34%; 95% CI -50% to -18%) and actual screening rates (absolute difference -22%; 95% CI -38 to -7%) with no difference in effect by frame. SDM interventions can increase men's knowledge, alter their perceptions of prostate cancer screening, and reduce actual screening. However, they may not guarantee an increase in shared decisions. #NCT00630188.

Reduction of prostate intrafraction motion using gas-release rectal balloons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su Zhong; Zhao Tianyu; Li Zuofeng

2012-10-15

Purpose: To analyze prostate intrafraction motion using both non-gas-release (NGR) and gas-release (GR) rectal balloons and to evaluate the ability of GR rectal balloons to reduce prostate intrafraction motion. Methods: Twenty-nine patients with NGR rectal balloons and 29 patients with GR balloons were randomly selected from prostate patients treated with proton therapy at University of Florida Proton Therapy Institute (Jacksonville, FL). Their pretreatment and post-treatment orthogonal radiographs were analyzed, and both pretreatment setup residual error and intrafraction-motion data were obtained. Population histograms of intrafraction motion were plotted for both types of balloons. Population planning target-volume (PTV) margins were calculated withmore » the van Herk formula of 2.5{Sigma}+ 0.7{sigma} to account for setup residual errors and intrafraction motion errors. Results: Pretreatment and post-treatment radiographs indicated that the use of gas-release rectal balloons reduced prostate intrafraction motion along superior-inferior (SI) and anterior-posterior (AP) directions. Similar patient setup residual errors were exhibited for both types of balloons. Gas-release rectal balloons resulted in PTV margin reductions from 3.9 to 2.8 mm in the SI direction, 3.1 to 1.8 mm in the AP direction, and an increase from 1.9 to 2.1 mm in the left-right direction. Conclusions: Prostate intrafraction motion is an important uncertainty source in radiotherapy after image-guided patient setup with online corrections. Compared to non-gas-release rectal balloons, gas-release balloons can reduce prostate intrafraction motion in the SI and AP directions caused by gas buildup.« less

Intra-fraction motion of the prostate is a random walk

NASA Astrophysics Data System (ADS)

Ballhausen, H.; Li, M.; Hegemann, N.-S.; Ganswindt, U.; Belka, C.

2015-01-01

A random walk model for intra-fraction motion has been proposed, where at each step the prostate moves a small amount from its current position in a random direction. Online tracking data from perineal ultrasound is used to validate or reject this model against alternatives. Intra-fraction motion of a prostate was recorded by 4D ultrasound (Elekta Clarity system) during 84 fractions of external beam radiotherapy of six patients. In total, the center of the prostate was tracked for 8 h in intervals of 4 s. Maximum likelihood model parameters were fitted to the data. The null hypothesis of a random walk was tested with the Dickey-Fuller test. The null hypothesis of stationarity was tested by the Kwiatkowski-Phillips-Schmidt-Shin test. The increase of variance in prostate position over time and the variability in motility between fractions were analyzed. Intra-fraction motion of the prostate was best described as a stochastic process with an auto-correlation coefficient of ρ = 0.92  ±  0.13. The random walk hypothesis (ρ = 1) could not be rejected (p = 0.27). The static noise hypothesis (ρ = 0) was rejected (p < 0.001). The Dickey-Fuller test rejected the null hypothesis ρ = 1 in 25% to 32% of cases. On average, the Kwiatkowski-Phillips-Schmidt-Shin test rejected the null hypothesis ρ = 0 with a probability of 93% to 96%. The variance in prostate position increased linearly over time (r2 = 0.9  ±  0.1). Variance kept increasing and did not settle at a maximum as would be expected from a stationary process. There was substantial variability in motility between fractions and patients with maximum aberrations from isocenter ranging from 0.5 mm to over 10 mm in one patient alone. In conclusion, evidence strongly suggests that intra-fraction motion of the prostate is a random walk and neither static (like inter-fraction setup errors) nor stationary (like a cyclic motion such as breathing, for example). The prostate tends to drift away from the isocenter during a fraction, and this variance increases with time, such that shorter fractions are beneficial to the problem of intra-fraction motion. As a consequence, fixed safety margins (which would over-compensate at the beginning and under-compensate at the end of a fraction) cannot optimally account for intra-fraction motion. Instead, online tracking and position correction on-the-fly should be considered as the preferred approach to counter intra-fraction motion.

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2011-09-01

placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 3 of the...risk. Our study is nested within the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to determine if finasteride

Deformable segmentation of 3D MR prostate images via distributed discriminative dictionary and ensemble learning

PubMed Central

Guo, Yanrong; Gao, Yaozong; Shao, Yeqin; Price, True; Oto, Aytekin; Shen, Dinggang

2014-01-01

Purpose: Automatic prostate segmentation from MR images is an important task in various clinical applications such as prostate cancer staging and MR-guided radiotherapy planning. However, the large appearance and shape variations of the prostate in MR images make the segmentation problem difficult to solve. Traditional Active Shape/Appearance Model (ASM/AAM) has limited accuracy on this problem, since its basic assumption, i.e., both shape and appearance of the targeted organ follow Gaussian distributions, is invalid in prostate MR images. To this end, the authors propose a sparse dictionary learning method to model the image appearance in a nonparametric fashion and further integrate the appearance model into a deformable segmentation framework for prostate MR segmentation. Methods: To drive the deformable model for prostate segmentation, the authors propose nonparametric appearance and shape models. The nonparametric appearance model is based on a novel dictionary learning method, namely distributed discriminative dictionary (DDD) learning, which is able to capture fine distinctions in image appearance. To increase the differential power of traditional dictionary-based classification methods, the authors' DDD learning approach takes three strategies. First, two dictionaries for prostate and nonprostate tissues are built, respectively, using the discriminative features obtained from minimum redundancy maximum relevance feature selection. Second, linear discriminant analysis is employed as a linear classifier to boost the optimal separation between prostate and nonprostate tissues, based on the representation residuals from sparse representation. Third, to enhance the robustness of the authors' classification method, multiple local dictionaries are learned for local regions along the prostate boundary (each with small appearance variations), instead of learning one global classifier for the entire prostate. These discriminative dictionaries are located on different patches of the prostate surface and trained to adaptively capture the appearance in different prostate zones, thus achieving better local tissue differentiation. For each local region, multiple classifiers are trained based on the randomly selected samples and finally assembled by a specific fusion method. In addition to this nonparametric appearance model, a prostate shape model is learned from the shape statistics using a novel approach, sparse shape composition, which can model nonGaussian distributions of shape variation and regularize the 3D mesh deformation by constraining it within the observed shape subspace. Results: The proposed method has been evaluated on two datasets consisting of T2-weighted MR prostate images. For the first (internal) dataset, the classification effectiveness of the authors' improved dictionary learning has been validated by comparing it with three other variants of traditional dictionary learning methods. The experimental results show that the authors' method yields a Dice Ratio of 89.1% compared to the manual segmentation, which is more accurate than the three state-of-the-art MR prostate segmentation methods under comparison. For the second dataset, the MICCAI 2012 challenge dataset, the authors' proposed method yields a Dice Ratio of 87.4%, which also achieves better segmentation accuracy than other methods under comparison. Conclusions: A new magnetic resonance image prostate segmentation method is proposed based on the combination of deformable model and dictionary learning methods, which achieves more accurate segmentation performance on prostate T2 MR images. PMID:24989402

Deformable segmentation of 3D MR prostate images via distributed discriminative dictionary and ensemble learning.

PubMed

Guo, Yanrong; Gao, Yaozong; Shao, Yeqin; Price, True; Oto, Aytekin; Shen, Dinggang

2014-07-01

Automatic prostate segmentation from MR images is an important task in various clinical applications such as prostate cancer staging and MR-guided radiotherapy planning. However, the large appearance and shape variations of the prostate in MR images make the segmentation problem difficult to solve. Traditional Active Shape/Appearance Model (ASM/AAM) has limited accuracy on this problem, since its basic assumption, i.e., both shape and appearance of the targeted organ follow Gaussian distributions, is invalid in prostate MR images. To this end, the authors propose a sparse dictionary learning method to model the image appearance in a nonparametric fashion and further integrate the appearance model into a deformable segmentation framework for prostate MR segmentation. To drive the deformable model for prostate segmentation, the authors propose nonparametric appearance and shape models. The nonparametric appearance model is based on a novel dictionary learning method, namely distributed discriminative dictionary (DDD) learning, which is able to capture fine distinctions in image appearance. To increase the differential power of traditional dictionary-based classification methods, the authors' DDD learning approach takes three strategies. First, two dictionaries for prostate and nonprostate tissues are built, respectively, using the discriminative features obtained from minimum redundancy maximum relevance feature selection. Second, linear discriminant analysis is employed as a linear classifier to boost the optimal separation between prostate and nonprostate tissues, based on the representation residuals from sparse representation. Third, to enhance the robustness of the authors' classification method, multiple local dictionaries are learned for local regions along the prostate boundary (each with small appearance variations), instead of learning one global classifier for the entire prostate. These discriminative dictionaries are located on different patches of the prostate surface and trained to adaptively capture the appearance in different prostate zones, thus achieving better local tissue differentiation. For each local region, multiple classifiers are trained based on the randomly selected samples and finally assembled by a specific fusion method. In addition to this nonparametric appearance model, a prostate shape model is learned from the shape statistics using a novel approach, sparse shape composition, which can model nonGaussian distributions of shape variation and regularize the 3D mesh deformation by constraining it within the observed shape subspace. The proposed method has been evaluated on two datasets consisting of T2-weighted MR prostate images. For the first (internal) dataset, the classification effectiveness of the authors' improved dictionary learning has been validated by comparing it with three other variants of traditional dictionary learning methods. The experimental results show that the authors' method yields a Dice Ratio of 89.1% compared to the manual segmentation, which is more accurate than the three state-of-the-art MR prostate segmentation methods under comparison. For the second dataset, the MICCAI 2012 challenge dataset, the authors' proposed method yields a Dice Ratio of 87.4%, which also achieves better segmentation accuracy than other methods under comparison. A new magnetic resonance image prostate segmentation method is proposed based on the combination of deformable model and dictionary learning methods, which achieves more accurate segmentation performance on prostate T2 MR images.

The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy.

PubMed

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2015-02-01

For many years it was believed that higher total testosterone contributed to prostate cancer and caused rapid cancer growth. International guidelines consider that adequate data are not available to determine whether there is additional risk of prostate cancer from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between total testosterone and prostate cancer development. To establish current knowledge in this field we reviewed the literature on total testosterone and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a history of prostate cancer. We searched the literature to identify articles from 1994 to 2014 related to the relationship between total testosterone and prostate cancer. Emphasis was given to prospective studies, series with observational data and randomized, controlled trials. Case reports were excluded. Articles on testosterone replacement safety were selected by patient population (under active surveillance or with a prostate cancer history). We organized our results according to the relationship between total testosterone and prostate cancer, including 1) the possible link between low total testosterone and prostate cancer, 2) the effect of high levels and 3) the absence of any link. Finally, we summarized studies of the risk of exogenous testosterone administration in patients already diagnosed with prostate cancer, treated or on active surveillance. We selected 45 articles of the relationship between total testosterone and prostate cancer, of which 18 and 17 showed a relationship to low and high total testosterone, respectively, and 10 showed no relation. Total testosterone was defined according to the definition in each article. Contradictory findings have been reported, largely due to the disparate methodologies used in many studies. Most studies did not adhere to professional society guidelines on total testosterone measurements. One of 18 series of low total testosterone and prostate cancer adhered to published guidelines while none of 17 showing a relationship of high total testosterone to prostate cancer and only 1 of 10 that identified no relationship between total testosterone and prostate cancer adhered to measurements recommended in the guidelines. In 11 studies the risk of exogenous testosterone was examined in patients with a prostate cancer history. Many studies were limited by small cohort size and brief followup. However, overall this literature suggests that the risk of exogenous testosterone replacement in patients with prostate cancer appears to be small. The relationship between total testosterone and prostate cancer has been an area of interest among physicians for decades. Conflicting results have been reported on the relationship between total testosterone and subsequent prostate cancer. Much of this controversy appears to be based on conflicting study designs, definitions and methodologies. To date no prospective study with sufficient power has been published to unequivocally resolve the issue. The preponderance of studies of the safety of exogenous testosterone in men with a prostate cancer history suggests that there is little if any risk. However, because the risk has not proved to be zero, the most prudent course is to follow such men with regular prostate specific antigen measurements and digital rectal examinations. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Intermittent vs Continuous Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-analysis.

PubMed

Magnan, Sindy; Zarychanski, Ryan; Pilote, Laurie; Bernier, Laurence; Shemilt, Michèle; Vigneault, Eric; Fradet, Vincent; Turgeon, Alexis F

2015-12-01

Androgen deprivation is the standard therapy for patients with advanced or recurrent prostate cancer. However, this treatment causes adverse effects, alters quality of life, and may lead to castration-resistant disease. Intermittent androgen deprivation has been studied as an alternative. To conduct a systematic review and meta-analysis comparing the efficacy and tolerability of intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. We searched Cochrane CENTRAL, Medline, Embase, Web of Science, Biosis, National Technical Information Service, OpenSIGLE, and Google Scholar from inception of each database through March 2014. References from published guidelines, reviews, and other relevant articles were also considered. We selected randomized clinical trials comparing intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated hazard ratios (HRs) with the inverse variance method and risk ratios with the Mantel-Haenszel method, using random effect models. A noninferiority analysis was conducted for overall survival with a margin of 1.15 for the upper boundary of the HR. We assessed heterogeneity using the I2 index. Primary outcomes were overall survival and quality of life. Secondary outcomes were cancer-specific survival, progression-free survival, time to castration resistance, skeletal-related events, and adverse effects. From 10 510 references, we included 22 articles from 15 trials (6856 patients) published between 2000 and 2013. All but 1 study had an unclear or high risk of bias. We observed no significant difference between intermittent and continuous therapy for overall survival (HR, 1.02; 95% CI, 0.93-1.11; 8 trials, 5352 patients), cancer-specific survival (HR, 1.02; 95% CI, 0.87-1.19; 5 trials, 3613 patients), and progression-free survival (HR, 0.94; 95% CI, 0.84-1.05; 4 trials, 1774 patients). There was minimal difference in patients' self-reported quality of life between the 2 interventions. Most trials observed an improvement in physical and sexual functioning with intermittent therapy. Intermittent androgen deprivation was not inferior to continuous therapy with respect to the overall survival. Some quality-of-life criteria seemed improved with intermittent therapy. Intermittent androgen deprivation can be considered as an alternative option in patients with recurrent or metastatic prostate cancer.

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2012-09-01

micrometastases that may be targeted with radioimmunotherapy. Prostate specific membrane antigen (PSMA) is the single, most well-established, highly restricted...Radiolabeled anti- prostate specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu-J591) for nonmetastatic castration-resistant prostate cancer...rationale for systemic salvage targeted anti- prostate specific membrane antigen radioimmunotherapy. Adv Urol 2012, Article ID 921674, doi:10.1155

A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lips, Irene M., E-mail: i.m.lips@umcutrecht.nl; Gils, Carla H. van; Kotte, Alexis N.T.J.

2012-06-01

Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondarymore » outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.« less

Feasibility of Prostate Cancer Diagnosis by Transrectal Photo-acoustic Imaging

DTIC Science & Technology

2013-03-01

prostate. Transrectal ultrasound has been used as a guiding tool to direct tissue needle biopsy for prostate cancer diagnosis; it cannot be utilized for...tool currently available for prostate cancer detection; needle biopsy is the current practice for diagnosis of the disease, aiming randomly in the...developing an integrated approach between ultrasound and optical tomography, namely, transrectal ultrasound - guided diffuse optical tomography (TRUS

Poster — Thur Eve — 59: Atlas Selection for Automated Segmentation of Pelvic CT for Prostate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mallawi, A; Farrell, T; Diamond, K

2014-08-15

Automated atlas-based segmentation has recently been evaluated for use in planning prostate cancer radiotherapy. In the typical approach, the essential step is the selection of an atlas from a database that best matches the target image. This work proposes an atlas selection strategy and evaluates its impact on the final segmentation accuracy. Prostate length (PL), right femoral head diameter (RFHD), and left femoral head diameter (LFHD) were measured in CT images of 20 patients. Each subject was then taken as the target image to which all remaining 19 images were affinely registered. For each pair of registered images, the overlapmore » between prostate and femoral head contours was quantified using the Dice Similarity Coefficient (DSC). Finally, we designed an atlas selection strategy that computed the ratio of PL (prostate segmentation), RFHD (right femur segmentation), and LFHD (left femur segmentation) between the target subject and each subject in the atlas database. Five atlas subjects yielding ratios nearest to one were then selected for further analysis. RFHD and LFHD were excellent parameters for atlas selection, achieving a mean femoral head DSC of 0.82 ± 0.06. PL had a moderate ability to select the most similar prostate, with a mean DSC of 0.63 ± 0.18. The DSC obtained with the proposed selection method were slightly lower than the maximums established using brute force, but this does not include potential improvements expected with deformable registration. Atlas selection based on PL for prostate and femoral diameter for femoral heads provides reasonable segmentation accuracy.« less

Chronic bacterial prostatitis and irritable bowel syndrome: effectiveness of treatment with rifaximin followed by the probiotic VSL#3.

PubMed

Vicari, Enzo; La Vignera, Sandro; Castiglione, Roberto; Condorelli, Rosita A; Vicari, Lucia O; Calogero, Aldo E

2014-01-01

This study was undertaken to evaluate the influence of treatment with rifaximin followed by the probiotic VSL#3 versus no treatment on the progression of chronic prostatitis toward chronic microbial prostate-vesiculitis (PV) or prostate-vesiculo-epididymitis (PVE). A total of 106 selected infertile male patients with bacteriologically cured chronic bacterial prostatitis (CBP) and irritable bowel syndrome (IBS) were randomly prescribed rifaximin (200 mg, 2 tablets bid, for 7 days monthly for 12 months) and probiotic containing multiple strains VSL#3 (450 × 10(9) FU per day) or no treatment. Ninety-five of them (89.6%) complied with the therapeutic plan and were included in this study. Group A = "6Tx/6-": treatment for the initial 6 and no treatment for the following 6 months (n = 26); Group B = "12Tx": 12 months of treatment (n = 22); Group C = "6-/6Tx": no treatment for the initial 6 months and treatment in the last 6 months (n = 23); Group D = "12-": no treatment (n = 24). The patients of Groups A = "6Tx/6-" and B = "12Tx" had the highest frequency of chronic prostatitis (88.5% and 86.4%, respectively). In contrast, group "12-": patients had the lowest frequency of prostatitis (33.4%). The progression of prostatitis into PV in groups "6Tx/6-" (15.5%) and "6-/6Tx" (13.6%) was lower than that found in the patients of group "12-" (45.8%). Finally, no patient of groups "6Tx/6-" and "6-/6Tx" had PVE, whereas it was diagnosed in 20.8% of group "12-" patients. Long-term treatment with rifaximin and the probiotic VSL#3 is effective in lowering the progression of prostatitis into more complicated forms of male accessory gland infections in infertile patients with bacteriologically cured CBP plus IBS.

Chronic bacterial prostatitis and irritable bowel syndrome: effectiveness of treatment with rifaximin followed by the probiotic VSL#3

PubMed Central

Vicari, Enzo; Vignera, La Sandro; Castiglione, Roberto; Condorelli, Rosita A; Vicari, Lucia O; Calogero, Aldo E

2014-01-01

This study was undertaken to evaluate the influence of treatment with rifaximin followed by the probiotic VSL#3 versus no treatment on the progression of chronic prostatitis toward chronic microbial prostate-vesiculitis (PV) or prostate-vesiculo-epididymitis (PVE). A total of 106 selected infertile male patients with bacteriologically cured chronic bacterial prostatitis (CBP) and irritable bowel syndrome (IBS) were randomly prescribed rifaximin (200 mg, 2 tablets bid, for 7 days monthly for 12 months) and probiotic containing multiple strains VSL#3 (450 × 109 CFU per day) or no treatment. Ninety-five of them (89.6%) complied with the therapeutic plan and were included in this study. Group A = “6Tx/6-”: treatment for the initial 6 and no treatment for the following 6 months (n = 26); Group B = “12Tx”: 12 months of treatment (n = 22); Group C = “6-/6Tx”: no treatment for the initial 6 months and treatment in the last 6 months (n = 23); Group D = “12-”: no treatment (n = 24). The patients of Groups A = “6Tx/6-” and B = “12Tx” had the highest frequency of chronic prostatitis (88.5% and 86.4%, respectively). In contrast, group “12-”: patients had the lowest frequency of prostatitis (33.4%). The progression of prostatitis into PV in groups “6Tx/6-” (15.5%) and “6-/6Tx” (13.6%) was lower than that found in the patients of group “12-” (45.8%). Finally, no patient of groups “6Tx/6-” and “6-/6Tx” had PVE, whereas it was diagnosed in 20.8% of group “12-” patients. Long-term treatment with rifaximin and the probiotic VSL#3 is effective in lowering the progression of prostatitis into more complicated forms of male accessory gland infections in infertile patients with bacteriologically cured CBP plus IBS. PMID:24969056

Pittsburgh-Tuskegee Prostate Training Program

DTIC Science & Technology

2013-05-01

February 2012, Tuskegee University sophomore trainees will be selected as “Prostate Cancer Scholars” for summer internship at the University of...selected as “Prostate Cancer Scholars” for summer internship at the University of Pittsburgh. This is being reported on as the second group of... internship at the University of Pittsburgh. February – April 2012, Trainees will be selectively paired with University of Pittsburgh Faculty

Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Qaisieh, Bashar; Mason, Josh, E-mail: joshua.mason@nhs.net; Bownes, Peter

2015-07-15

Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focalmore » (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable reduction to organs at risk. Treating smaller targets makes seed positioning more critical.« less

American Brachytherapy Society Task Group Report: Combination of brachytherapy and external beam radiation for high-risk prostate cancer.

PubMed

Spratt, Daniel E; Soni, Payal D; McLaughlin, Patrick W; Merrick, Gregory S; Stock, Richard G; Blasko, John C; Zelefsky, Michael J

To review outcomes for high-risk prostate cancer treated with combined modality radiation therapy (CMRT) utilizing external beam radiation therapy (EBRT) with a brachytherapy boost. The available literature for high-risk prostate cancer treated with combined modality radiation therapy was reviewed and summarized. At this time, the literature suggests that the majority of high-risk cancers are curable with multimodal treatment. Several large retrospective studies and three prospective randomized trials comparing CMRT to dose-escalated EBRT have demonstrated superior biochemical control with CMRT. Longer followup of the randomized trials will be required to determine if this will translate to a benefit in metastasis-free survival, disease-specific survival, and overall survival. Although greater toxicity has been associated with CMRT compared to EBRT, recent studies suggest that technological advances that allow better definition and sparing of critical adjacent structures as well as increasing experience with brachytherapy have improved implant quality and the toxicity profile of brachytherapy. The role of androgen deprivation therapy is well established in the external beam literature for high-risk disease, but there is controversy regarding the applicability of these data in the setting of dose escalation. At this time, there is not sufficient evidence for the omission of androgen deprivation therapy with dose escalation in this population. Comparisons with surgery remain limited by differences in patient selection, but the evidence would suggest better disease control with CMRT compared to surgery alone. Due to a series of technological advances, modern combination series have demonstrated unparalleled rates of disease control in the high-risk population. Given the evidence from recent randomized trials, combination therapy may become the standard of care for high-risk cancers. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Combination of Tramadol and Lidocaine for Pain Control During Transrectal Ultrasound-guided Prostate Biopsy: A Randomized Double-blinded Study.

PubMed

Sen, Haluk; Seckiner, Ilker; Bayrak, Omer; Sen, Elzem; Erturhan, Sakip; Yagci, Faruk

2015-06-01

To evaluate the efficacy of tramadol, lidocaine, and a combination of tramadol with lidocaine in pain relief using periprostatic nerve block technique by guidance of transrectal ultrasound (TRUS) before the prostate biopsy (PBx). For the indication of TRUS-PBx, the patients with a prostate-specific antigen (PSA) level >4.0 ng/mL or abnormal digital examination findings were selected. The patients were randomized through random method. Group 1: patients were administered 5 mL of 2% lidocaine; group 2: patients were administered 5 mL of 25-mg tramadol; and group 3: patients were administered 5 mL of 2% lidocaine + 25-mg tramadol. The procedures were completed in 10 minutes, and a visual pain scale was administered to the patients to question the pain severity. TRUS-guided PBx was performed in 60 patients with an age range of 57-77 years (mean age, 66.2 ± 7.49 years) and a PSA range of 1-1000 ng/mL. The mean PSA level of the groups was 28.5 (±7.5), 16.1 (±5.0), and 14.9 (±2.9) ng/mL, respectively. The postprocedural pain scores by visual pain scale were 4.6 ± 1.2, 5.4 ± 1.2, and 3.6 ± 0.9 in lidocaine, tramadol, and lidocaine + tramadol groups, respectively. Periprostatic nerve block is the current golden standard method owing to pain management and comfort provided, independent of the patient age and the number of core biopsies. We suggest that tramadol may also be used in this field to achieve better pain management by improving lidocaine's effect or as an alternative to lidocaine. Copyright © 2015 Elsevier Inc. All rights reserved.

Feasibility of Prostate Cancer Diagnosis by Transrectal Photoacoustic Imaging

DTIC Science & Technology

2012-03-01

cancer detection; needle biopsy is the current practice for diagnosis of the disease, aiming randomly in the prostate. Transrectal ultrasound has...been used as a guiding tool to direct tissue needle biopsy for prostate cancer diagnosis; it cannot be utilized for detecting prostate cancer due to...Research Systems, CA) and used as a reference signal. The sample and the ultrasound transducer (UST, Olympus NDT, one inch in focal length) are

The Complex Interplay Between Cholesterol and Prostate Malignancy

PubMed Central

Solomon, Keith R.; Freeman, Michael R.

2011-01-01

Research into the topic of the role of cholesterol and prostate disease has been ongoing for many years, however our mechanistic and translational understanding is still poor. Recent evidence indicates that cholesterol lowering drugs reduce the risk of aggressive prostate cancer, however the studies in this area, performed over many years, reflect much controversy and uncertainty. Here we explore the entire literature on the relationship between circulating cholesterol and prostate cancer, with consideration and criticism of the older as well as the newer studies. We consider why low cholesterol is associated with both increased and decreased risk of advanced prostate cancer, and explain why both observations are probably correct. We discuss the conflicting results of randomized placebo-controlled trials of statin drugs vs. observational studies and demonstrate that a predominance of pravastatin in the randomized trials paints a distorted view of statin effects. Lastly, we discuss new data suggesting that a critical aspect of the role of cholesterol in prostate cancer progression is through its role in intratumoral steroidogenesis. With these points addressed, the data strongly point to hypercholesterolemia as a risk factor for prostate cancer progression and suggest clinical opportunities for the use of cholesterol lowering therapies to alter disease course. PMID:21798387

Deformable segmentation of 3D MR prostate images via distributed discriminative dictionary and ensemble learning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Yanrong; Shao, Yeqin; Gao, Yaozong

Purpose: Automatic prostate segmentation from MR images is an important task in various clinical applications such as prostate cancer staging and MR-guided radiotherapy planning. However, the large appearance and shape variations of the prostate in MR images make the segmentation problem difficult to solve. Traditional Active Shape/Appearance Model (ASM/AAM) has limited accuracy on this problem, since its basic assumption, i.e., both shape and appearance of the targeted organ follow Gaussian distributions, is invalid in prostate MR images. To this end, the authors propose a sparse dictionary learning method to model the image appearance in a nonparametric fashion and further integratemore » the appearance model into a deformable segmentation framework for prostate MR segmentation. Methods: To drive the deformable model for prostate segmentation, the authors propose nonparametric appearance and shape models. The nonparametric appearance model is based on a novel dictionary learning method, namely distributed discriminative dictionary (DDD) learning, which is able to capture fine distinctions in image appearance. To increase the differential power of traditional dictionary-based classification methods, the authors' DDD learning approach takes three strategies. First, two dictionaries for prostate and nonprostate tissues are built, respectively, using the discriminative features obtained from minimum redundancy maximum relevance feature selection. Second, linear discriminant analysis is employed as a linear classifier to boost the optimal separation between prostate and nonprostate tissues, based on the representation residuals from sparse representation. Third, to enhance the robustness of the authors' classification method, multiple local dictionaries are learned for local regions along the prostate boundary (each with small appearance variations), instead of learning one global classifier for the entire prostate. These discriminative dictionaries are located on different patches of the prostate surface and trained to adaptively capture the appearance in different prostate zones, thus achieving better local tissue differentiation. For each local region, multiple classifiers are trained based on the randomly selected samples and finally assembled by a specific fusion method. In addition to this nonparametric appearance model, a prostate shape model is learned from the shape statistics using a novel approach, sparse shape composition, which can model nonGaussian distributions of shape variation and regularize the 3D mesh deformation by constraining it within the observed shape subspace. Results: The proposed method has been evaluated on two datasets consisting of T2-weighted MR prostate images. For the first (internal) dataset, the classification effectiveness of the authors' improved dictionary learning has been validated by comparing it with three other variants of traditional dictionary learning methods. The experimental results show that the authors' method yields a Dice Ratio of 89.1% compared to the manual segmentation, which is more accurate than the three state-of-the-art MR prostate segmentation methods under comparison. For the second dataset, the MICCAI 2012 challenge dataset, the authors' proposed method yields a Dice Ratio of 87.4%, which also achieves better segmentation accuracy than other methods under comparison. Conclusions: A new magnetic resonance image prostate segmentation method is proposed based on the combination of deformable model and dictionary learning methods, which achieves more accurate segmentation performance on prostate T2 MR images.« less

A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol.

PubMed

Hofman, Michael S; Murphy, Declan G; Williams, Scott G; Nzenza, Tatenda; Herschtal, Alan; Lourenco, Richard De Abreu; Bailey, Dale L; Budd, Ray; Hicks, Rodney J; Francis, Roslyn J; Lawrentschuk, Nathan

2018-05-03

Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

PubMed Central

Hellwinkel, Olaf J. C.; Sellier, Christina; Sylvester, Yu-Mi Jessica; Brase, Jan C.; Isbarn, Hendrik; Erbersdobler, Andreas; Steuber, Thomas; Sültmann, Holger; Schlomm, Thorsten; Wagner, Christina

2013-01-01

We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ. PMID:23459235

Different lasers in the treatment of benign prostatic hyperplasia: a network meta-analysis

PubMed Central

Zhang, Xingming; Shen, Pengfei; He, Qiying; Yin, Xiaoxue; Chen, Zhibin; Gui, Haojun; Shu, Kunpeng; Tang, Qidun; Yang, Yaojing; Pan, Xiuyi; Wang, Jia; Chen, Ni; Zeng, Hao

2016-01-01

All available surgical treatments for benign prostatic hyperplasia (BPH) have their individual advantages or disadvantages. However, the lack of head-to-head studies comparing different surgeries makes it unavailable to conduct direct analysis. To compare the efficacy and safety among different lasers and transurethral resection of prostate (TURP) for BPH, randomized controlled trials were searched in MEDLINE, EMBASE, Cochrane library, WHO International Clinical Trial Registration Platform, and Clinical Trial.gov by 2015.5; and the effectiveness-, perioperation- and complication-related outcomes were assessed by network meta-analysis. 36 studies involving 3831 patients were included. Holmium laser through resection and enucleation had the best efficacy in maximum flow rate. Thulium laser through vapo-resection was superior in improving international prostate symptom score and holmium laser through enucleation was the best for post-voiding residual volume improvement. Diode laser through vaporization was the rapidest in removing postoperative indwelling catheter, while TURP was the longest. TURP required the longest hospitalization and thulium laser through vapo-resection was relatively shorter. Holmium and thulium lasers seem to be relatively better in surgical efficacy and safety, so that these two lasers might be preferred in selection of optimal laser surgery. Actually, more large-scale and high quality head-to-head RCTs are suggested to validate the conclusions. PMID:27009501

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial.

PubMed

Martin, Richard M; Donovan, Jenny L; Turner, Emma L; Metcalfe, Chris; Young, Grace J; Walsh, Eleanor I; Lane, J Athene; Noble, Sian; Oliver, Steven E; Evans, Simon; Sterne, Jonathan A C; Holding, Peter; Ben-Shlomo, Yoav; Brindle, Peter; Williams, Naomi J; Hill, Elizabeth M; Ng, Siaw Yein; Toole, Jessica; Tazewell, Marta K; Hughes, Laura J; Davies, Charlotte F; Thorn, Joanna C; Down, Elizabeth; Davey Smith, George; Neal, David E; Hamdy, Freddie C

2018-03-06

Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality. The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66). Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening. ISRCTN Identifier: ISRCTN92187251.

Once-weekly versus every-other-day stereotactic body radiotherapy in patients with prostate cancer (PATRIOT): A phase 2 randomized trial.

PubMed

Quon, Harvey C; Ong, Aldrich; Cheung, Patrick; Chu, William; Chung, Hans T; Vesprini, Danny; Chowdhury, Amit; Panjwani, Dilip; Pang, Geordi; Korol, Renee; Davidson, Melanie; Ravi, Ananth; McCurdy, Boyd; Zhang, Liying; Mamedov, Alexandre; Deabreu, Andrea; Loblaw, Andrew

2018-05-01

Prostate stereotactic body radiotherapy (SBRT) regimens differ in time, dose, and fractionation. We completed a multicentre, randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL). Men with low and intermediate-risk prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered once per week (QW) vs. every other day (EOD). QOL was assessed using the Expanded Prostate Cancer Index Composite. The primary endpoint was the proportion with a minimum clinically important change (MCIC) in bowel QOL during the acute (≤12 week) period, and analysis was by intention-to-treat. ClinicalTrials.gov NCT01423474. 152 men from 3 centres were randomized with median follow-up of 47 months. Patients treated QW had superior acute bowel QOL with 47/69 (68%) reporting a MCIC compared to 63/70 (90%) treated EOD (p = 0.002). Fewer patients treated QW reported moderate-severe problems with bowel QOL during the acute period compared with EOD (14/70 [20%] vs. 40/70 [57%], p < 0.001). Acute urinary QOL was also better in the QW arm, with 52/67 (78%) vs 65/69 (94%) experiencing a MCIC (p = 0.006). There were no significant differences in late urinary or bowel QOL at 2 years or last follow-up. Prostate SBRT delivered QW improved acute bowel and urinary QOL compared to EOD. Patients should be counselled regarding the potential for reduced short-term toxicity and improved QOL with QW prostate SBRT. Copyright © 2018 Elsevier B.V. All rights reserved.

Computerized transrectal ultrasound (C-TRUS) of the prostate: detection of cancer in patients with multiple negative systematic random biopsies.

PubMed

Loch, Tillmann

2007-08-01

This study was designed to compare the diagnostic yield of computerized transrectal ultrasound (C-TRUS) guided biopsies in the detection of prostate cancer in a group of men with a history of multiple systematic random biopsies with no prior evidence of prostate cancer. The question was asked: Can we detect cancer by C-TRUS that has been overlooked by multiple systematic biopsies? The entrance criteria for this study were prior negative systematic random biopsies regardless of number of biopsy sessions or number of individual biopsy cores. Serial static TRUS images were evaluated by C-TRUS, which assessed signal information independent of visual gray scale. Five C-TRUS algorithms were utilized to evaluate the information of the ultrasound signal. Interpretation of the results were documented and the most suspicious regions marked by C-TRUS were biopsied by guiding the needle to the marked location. Five hundred and forty men were biopsied because of an elevated PSA or abnormal digital rectal exam. 132 had a history of prior negative systematic random biopsies (1-7 sessions, median: 2 and between 6 and 72 individual prostate biopsies, median: 12 cores). Additionally, a diagnostic TUR-P of the prostate with benign result was performed in four patients. The PSA ranged from 3.1-36 ng/ml with a median of 9.01 ng/ml. The prostate volume ranged from 6-203 ml with a median of 42 ml. Of the 132 patients with prior negative systematic random biopsies, cancer was found in 66 (50%) by C-TRUS targeted biopsies. In this group the median number of negative biopsy sessions was two and a median of 12 biopsy cores were performed. From literature we would expect a cancer detection rate in this group with systematic biopsies of approximately 7%. We only found five carcinomas with a Gleason Score (GS) of 5, 25 with GS 6, 22 with GS 7, 8 with GS 8 and even 7 with GS 9. The results of this prospective clinical trail indicates that the additional use of the C-TRUS identifies clinical significant cancerous lesions that could not been visualized or detected by systematic random biopsies in a very high percentage. In addition, the results of the study support the efforts to search for strategies that utilize expertise and refinement of imaging modalities rather than elevating the number of random biopsies (f.e. 141 cores in one session) in the detection of prostate cancer.

Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the ‘FC Prostate’ randomized controlled trial

PubMed Central

2013-01-01

Background Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The ‘Football Club (FC) Prostate’ study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. Methods/Design Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2–3 times/week for 45–60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. Discussion The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. Trial registration ClinicalTrials.gov: NCT01711892 PMID:24330570

Effect of Soy Protein Isolate Supplementation on Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy

PubMed Central

Bosland, Maarten C; Kato, Ikuko; Zeleniuch-Jacquotte, Anne; Schmoll, Joanne; Rueter, Erika Enk; Melamed, Jonathan; Xiangtian Kong, Max; Macias, Virgilia; Kajdacsy-Balla, Andre; Lumey, L. H.; Xie, Hui; Gao, Weihua; Walden, Paul; Lepor, Herbert; Taneja, Samir S.; Randolph, Carla; Schlicht, Michael J.; Meserve-Watanabe, Hiroko; Deaton, Ryan J.; Davies, Joanne A.

2013-01-01

IMPORTANCE Soy consumption has been suggested to reduce risk or recurrence of prostate cancer, but this has not been tested in a randomized trial with prostate cancer as the end point. OBJECTIVE To determine whether daily consumption of a soy protein isolate supplement for 2 years reduces the rate of biochemical recurrence of prostate cancer after radical prostatectomy or delays such recurrence. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial conducted from July 1997 to May 2010 at 7 US centers comparing daily consumption of a soy protein supplement vs placebo in 177 men at high risk of recurrence after radical prostatectomy for prostate cancer. Supplement intervention was started within 4 months after surgery and continued for up to 2 years, with prostate-specific antigen (PSA) measurements made at 2-month intervals in the first year and every 3 months thereafter. INTERVENTION Participants were randomized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate (n=87)or, as placebo, calcium caseinate (n=90). MAIN OUTCOMES AND MEASURES Biochemical recurrence rate of prostate cancer (defined as development of a PSA level of ≥0.07 ng/mL) over the first 2 years following randomization and time to recurrence. RESULTS The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group. Overall, 28.3% of participants developed biochemical recurrence within 2 years of entering the trial (close to the a priori predicted recurrence rate of 30%). Among these, 22 (27.2%) occurred in the intervention group and 23 (29.5%) in the placebo group. The resulting hazard ratio for active treatment was 0.96 (95% CI, 0.53–1.72; log-rank P = .89). Adherence was greater than 90% and there were no apparent adverse events related to supplementation. CONCLUSION AND RELEVANCE Daily consumption of a beverage powder supplement containing soy protein isolate for 2 years following radical prostatectomy did not reduce biochemical recurrence of prostate cancer in men at high risk of PSA failure. PMID:23839751

COX-2 and Prostate Cancer Angiogenesis

DTIC Science & Technology

2001-03-01

the optimal dosing and timing of a COX-2 inhibitor (NS398) in an animal model of human prostate cancer, (2)and (3) the mechanisms underlying the...cancer tissues (14) and that a COX-2 inhibitor selectively induces apoptosis in a prostate cancer cell line (15). We also demonstrated that treatment of...human prostate tumor-bearing mice with a selective COX-2 inhibitor (NS-398) significantly reduces tumor size, microvessel density and levels of a

Specific probe selection from landscape phage display library and its application in enzyme-linked immunosorbent assay of free prostate-specific antigen.

PubMed

Lang, Qiaolin; Wang, Fei; Yin, Long; Liu, Mingjun; Petrenko, Valery A; Liu, Aihua

2014-03-04

Probes against targets can be selected from the landscape phage library f8/8, displaying random octapeptides on the pVIII coat protein of the phage fd-tet and demonstrating many excellent features including multivalency, stability, and high structural homogeneity. Prostate-specific antigen (PSA) is usually determined by immunoassay, by which antibodies are frequently used as the specific probes. Herein we found that more advanced probes against free prostate-specific antigen (f-PSA) can be screened from the landscape phage library. Four phage monoclones were selected and identified by the specificity array. One phage clone displaying the fusion peptide ERNSVSPS showed good specificity and affinity to f-PSA and was used as a PSA capture probe in a sandwich enzyme-linked immunosorbent assay (ELISA) array. An anti-human PSA monoclonal antibody (anti-PSA mAb) was used to recognize the captured antigen, followed by horseradish peroxidase-conjugated antibody (HRP-IgG) and o-phenylenediamine, which were successively added to develop plate color. The ELISA conditions such as effect of blocking agent, coating buffer pH, phage concentration, antigen incubation time, and anti-PSA mAb dilution for phage ELISA were optimized. On the basis of the optimal phage ELISA conditions, the absorbance taken at 492 nm on a microplate reader was linear with f-PSA concentration within 0.825-165 ng/mL with a low limit of detection of 0.16 ng/mL. Thus, the landscape phage is an attractive biomolecular probe in bioanalysis.

Development of a computer aided diagnosis model for prostate cancer classification on multi-parametric MRI

NASA Astrophysics Data System (ADS)

Alfano, R.; Soetemans, D.; Bauman, G. S.; Gibson, E.; Gaed, M.; Moussa, M.; Gomez, J. A.; Chin, J. L.; Pautler, S.; Ward, A. D.

2018-02-01

Multi-parametric MRI (mp-MRI) is becoming a standard in contemporary prostate cancer screening and diagnosis, and has shown to aid physicians in cancer detection. It offers many advantages over traditional systematic biopsy, which has shown to have very high clinical false-negative rates of up to 23% at all stages of the disease. However beneficial, mp-MRI is relatively complex to interpret and suffers from inter-observer variability in lesion localization and grading. Computer-aided diagnosis (CAD) systems have been developed as a solution as they have the power to perform deterministic quantitative image analysis. We measured the accuracy of such a system validated using accurately co-registered whole-mount digitized histology. We trained a logistic linear classifier (LOGLC), support vector machine (SVC), k-nearest neighbour (KNN) and random forest classifier (RFC) in a four part ROI based experiment against: 1) cancer vs. non-cancer, 2) high-grade (Gleason score ≥4+3) vs. low-grade cancer (Gleason score <4+3), 3) high-grade vs. other tissue components and 4) high-grade vs. benign tissue by selecting the classifier with the highest AUC using 1-10 features from forward feature selection. The CAD model was able to classify malignant vs. benign tissue and detect high-grade cancer with high accuracy. Once fully validated, this work will form the basis for a tool that enhances the radiologist's ability to detect malignancies, potentially improving biopsy guidance, treatment selection, and focal therapy for prostate cancer patients, maximizing the potential for cure and increasing quality of life.

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy.

PubMed

Szabó, J; Hegedûs, G; Bartók, K; Kerényi, T; Végh, A; Romics, I; Szende, B

2000-01-01

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pommier, Pascal, E-mail: Pascal.pommier@lyon.unicancer.fr; Chabaud, Sylvie; Lagrange, Jean-Leon

Purpose: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Patients and Methods: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: “low risk” (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus “high risk” (T3 or Gleason score >6 ormore » prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. Results: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Conclusion: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.« less

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2009-03-01

a randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer... finasteride  (an inhibitor of androgen bioactivation) could  prevent prostate cancer. Included in our study are approximately 1,800 case‐control pairs

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2015-09-01

Award Number: W81XWH-09-1-0596 TITLE: A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti- PSMA Monoclonal Antibody J591 in Patients With High...1-0596 A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti- PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrat Biochemically Relapsed...in December 2014 with approval to proceed without modifications. 15. SUBJECT TERMS Prostate cancer, PSA, PSMA , monoclonal antibody

Selective Activation of a Perforin-Granzyme B Fusion Protein Toxin by PSA as Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2016-10-01

Prostate Cancer PRINCIPAL INVESTIGATOR: Samuel Denmeade RECIPIENT: Johns Hopkins University Baltimore, MD 21218 REPORT DATE: October 2016 TYPE...PSA as Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0382 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Samuel R Denmeade...cytotoxic agent that can selectively kill both proliferating and non-proliferating prostate cancer cells within a metastatic site without significant host

An Estimate of the Incidence of Prostate Cancer in Africa: A Systematic Review and Meta-Analysis

PubMed Central

Aderemi, Adewale Victor; Iseolorunkanmi, Alexander; Oyedokun, Ayo; Ayo, Charles K.

2016-01-01

Background Prostate cancer (PCa) is rated the second most common cancer and sixth leading cause of cancer deaths among men globally. Reports show that African men suffer disproportionately from PCa compared to men from other parts of the world. It is still quite difficult to accurately describe the burden of PCa in Africa due to poor cancer registration systems. We systematically reviewed the literature on prostate cancer in Africa and provided a continent-wide incidence rate of PCa based on available data in the region. Methods A systematic literature search of Medline, EMBASE and Global Health from January 1980 to June 2015 was conducted, with additional search of Google Scholar, International Association of Cancer Registries (IACR), International Agency for Research on Cancer (IARC), and WHO African region websites, for studies that estimated incidence rate of PCa in any African location. Having assessed quality and consistency across selected studies, we extracted incidence rates of PCa and conducted a random effects meta-analysis. Results Our search returned 9766 records, with 40 studies spreading across 16 African countries meeting our selection criteria. We estimated a pooled PCa incidence rate of 22.0 (95% CI: 19.93–23.97) per 100,000 population, and also reported a median incidence rate of 19.5 per 100,000 population. We observed an increasing trend in PCa incidence with advancing age, and over the main years covered. Conclusion Effective cancer registration and extensive research are vital to appropriately quantifying PCa burden in Africa. We hope our findings may further assist at identifying relevant gaps, and contribute to improving knowledge, research, and interventions targeted at prostate cancer in Africa. PMID:27073921

Beta-carotene Antioxidant Use During Radiation Therapy and Prostate Cancer Outcome in the Physicians' Health Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Margalit, Danielle N., E-mail: dmargalit@lroc.harvard.edu; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts

2012-05-01

Purpose: The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro-oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians' Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases. Methods and Materials: PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined asmore » prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT. Results: With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42-1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87-95%) in the beta-carotene group and 89% (95% CI, 84-93%) in the placebo group. Conclusion: The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer.« less

Comparison of the Pharmacological Effects of a Novel Selective Androgen Receptor Modulator, the 5α-Reductase Inhibitor Finasteride, and the Antiandrogen Hydroxyflutamide in Intact Rats: New Approach for Benign Prostate Hyperplasia

PubMed Central

Gao, Wenqing; Kearbey, Jeffrey D.; Nair, Vipin A.; Chung, Kiwon; Parlow, A. F.; Miller, Duane D.; Dalton, James T.

2007-01-01

Tissue-selective androgen receptor modulators (SARMs) demonstrate tissue selectivity in both castrated and intact male rats, behaving as partial agonists in androgenic tissues (i.e. prostate and seminal vesicle), but full agonists in anabolic tissues (i.e. levator ani muscle). The partial agonist activity of SARMs (compounds S-1 and S-4) in the prostate of intact rats suggested that SARM could be used for androgen suppression in the treatment of benign prostate hyperplasia (BPH). This study was designed to explore the mechanisms of action of SARM and to characterize the tissue selectivity of S-1 in intact male rats compared with that of hydroxyflutamide (antiandrogen) and finasteride (5α-reductase inhibitor), two major drugs used for androgen suppression treatment of BPH. In intact male rats, S-1 (5, 10, and 25 mg/kg) selectively decreased the prostate weight with similar efficacy to finasteride (5 mg/kg), without affecting the levator ani muscle or increasing the plasma levels of testosterone, LH, and FSH. Hydroxyflutamide (0.5, 1, 5, 10, and 25 mg/kg), however, decreased both the prostate and levator ani muscle weights without any selectivity and increased plasma hormone levels in a dose-dependent manner. Furthermore, S-1 and S-4 showed very weak inhibitory effects toward transiently expressed type I and II human 5α-reductase (Ki, >20 µM) during in vitro assays. Therefore, although S-1 and finasteride showed very similar suppressive effects in the prostate of intact male rats, they decreased prostate size via different mechanisms of action. S-1 simply worked as androgen receptor partial agonist, whereas finasteride inhibited prostatic 5α-reductase. These studies indicate that SARMs may demonstrate clinical utility as single agent or combination therapy for BPH. PMID:15308613

Fish Oil Supplementation and Fatty Acid Synthase Expression in the Prostate: A Randomized Controlled Trial

DTIC Science & Technology

2009-03-01

AD_________________ Award Number: W81XWH-04-1-0296 TITLE: Fish Oil Supplementation and Fatty Acid...TITLE AND SUBTITLE Fish Oil Supplementation and Fatty Acid Synthase Expression in the Prostate: A 5a. CONTRACT NUMBER...Randomized Controlled Trial 5b. GRANT NUMBER W81XWH-04-1-0296 5c. PROGRAM ELEMENT NUMBER 6 . AUTHOR(S) Jackilen Shannon, Ph.D. 5d. PROJECT NUMBER

Transurethral plasmakinetic resection of the prostate is a reliable minimal invasive technique for benign prostate hyperplasia: a meta-analysis of randomized controlled trials.

PubMed

Wang, Kai; Li, Yao; Teng, Jing-Fei; Zhou, Hai-Yong; Xu, Dan-Feng; Fan, Yi

2015-01-01

To evaluate the efficacy and safety of plasmakinetic resection of the prostate (PKRP) versus transurethral resection of the prostate (TURP) for the treatment of patients with benign prostate hyperplasia (BPH), a meta-analysis of randomized controlled trials was carried out. We searched PubMed, Embase, Web of Science and the Cochrane Library. The pooled estimates of maximum flow rate, International Prostate Symptom Score, operation time, catheterization time, irrigated volume, hospital stay, transurethral resection syndrome, transfusion, clot retention, urinary retention and urinary stricture were assessed. There was no notable difference in International Prostate Symptom Score between TURP and PKRP groups during the 1-month, 3 months, 6 months and 12 months follow-up period, while the pooled Q max at 1-month favored PKRP group. PKRP group was related to a lower risk rate of transurethral resection syndrome, transfusion and clot retention, and the catheterization time and operation time were also shorter than that of TURP. The irrigated volume, length of hospital stay, urinary retention and urinary stricture rate were similar between groups. In conclusion, our study suggests that the PKRP is a reliable minimal invasive technique and may anticipatorily prove to be an alternative electrosurgical procedure for the treatment of BPH.

Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium.

PubMed

Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Garcia, Sara Benlloch; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Giles, Graham G; Fitzgerald, Liesel M; Southey, Melissa C; Pharoah, Paul; Pashayan, Nora; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Stanford, Janet L; Brenner, Hermann; Dieffenbach, Aida K; Arndt, Volker; Park, Jong Y; Lin, Hui-Yi; Sellers, Thomas; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A; Easton, Douglas; Eeles, Rosalind A; Muir, Kenneth

2017-08-22

Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm are at a 22% increased risk as compared to men with height <173 cm (OR 1.22, 95% CI 1.01-1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. There was no evidence of gene-environment interaction between height and the selected candidate SNPs.Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.

ProCare Trial: a phase II randomized controlled trial of shared care for follow-up of men with prostate cancer.

PubMed

Emery, Jon D; Jefford, Michael; King, Madeleine; Hayne, Dickon; Martin, Andrew; Doorey, Juanita; Hyatt, Amelia; Habgood, Emily; Lim, Tee; Hawks, Cynthia; Pirotta, Marie; Trevena, Lyndal; Schofield, Penelope

2017-03-01

To test the feasibility and efficacy of a multifaceted model of shared care for men after completion of treatment for prostate cancer. Men who had completed treatment for low- to moderate-risk prostate cancer within the previous 8 weeks were eligible. Participants were randomized to usual care or shared care. Shared care entailed substituting two hospital visits with three visits in primary care, a survivorship care plan, recall and reminders, and screening for distress and unmet needs. Outcome measures included psychological distress, prostate cancer-specific quality of life, satisfaction and preferences for care and healthcare resource use. A total of 88 men were randomized (shared care n = 45; usual care n = 43). There were no clinically important or statistically significant differences between groups with regard to distress, prostate cancer-specific quality of life or satisfaction with care. At the end of the trial, men in the intervention group were significantly more likely to prefer a shared care model to hospital follow-up than those in the control group (intervention 63% vs control 24%; P<0.001). There was high compliance with prostate-specific antigen monitoring in both groups. The shared care model was cheaper than usual care (shared care AUS$1411; usual care AUS$1728; difference AUS$323 [plausible range AUS$91-554]). Well-structured shared care for men with low- to moderate-risk prostate cancer is feasible and appears to produce clinically similar outcomes to those of standard care, at a lower cost. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

No Effect of Music on Anxiety and Pain During Transrectal Prostate Biopsies: A Randomized Trial.

PubMed

Packiam, Vignesh T; Nottingham, Charles U; Cohen, Andrew J; Eggener, Scott E; Gerber, Glenn S

2018-07-01

To investigate the effect of ambient music on anxiety and pain in men undergoing prostate biopsies. Between September 2015 and June 2016, men undergoing office transrectal prostate biopsy at our institution were randomly assigned to music (n = 85) or control (n = 97) groups. We examined clinical characteristics, pathologic variables, and baseline anxiety using the Trait Instrument of State-Trait Anxiety Inventory. Primary outcomes included anxiety assessed by State Instrument of STAI (STAI-S) and pain using a visual analog scale. There were no significant differences in baseline characteristics between the music and control groups, including median age, prostate-specific antigen, use of magnetic resonance imaging-guided biopsies, or Trait Instrument of State-Trait Anxiety Inventory. The majority (93%) of patients indicated they desired music in their prebiopsy survey. There were no significant differences in STAI-S (33.7 ± 8.9 vs 34.4 ± 9.9, P = .6), pain score (2.3 ± 2.1 vs 2.0 ± 2.1, P = .3), or vital signs between the music and control groups, respectively. There were also no differences in STAI-S, visual analog scale, or vital signs between groups when stratified by age, prostate-specific antigen, or number of previous biopsies. Men who received music were more likely to request music for future prostate biopsy, compared to men who did not (93% vs 83%, P = .07, respectively). This randomized study showed no difference in anxiety or pain scores for patients who had ambient music during transrectal prostate biopsy. Future studies are needed to discern the influence of details including method of music delivery, music type, and utilization of adjunct relaxation tools. Copyright © 2018 Elsevier Inc. All rights reserved.

The Influence of decision aids on prostate cancer screening preferences: A randomized survey study.

PubMed

Weiner, Adam B; Tsai, Kyle P; Keeter, Mary-Kate; Victorson, David E; Schaeffer, Edward M; Catalona, William J; Kundu, Shilajit D

2018-05-28

Shared decision making is recommended regarding prostate cancer screening. Decision aids may facilitate this process; however, the impact of decision aids on screening preferences is poorly understood. In an online survey, a national sample of adults were randomized to one of six different professional societies' online decision aids. We compared pre- and post-decision aid responses. The primary outcome was change in participant likelihood to undergo or recommend prostate cancer screening on a scale of 1 (unlikely) to 100 (extremely likely). Secondary outcomes included change in participant comfort with prostate cancer screening based on the average of six, five-point Likert-scale questions. Median age was 53 years for the 1,336 participants, and 50% were men. Randomized groups did not differ significantly by race, age, gender, income, marital status, or education level. Likelihood to undergo or recommend prostate cancer screening decreased from 83 to 78 following decision aid exposure (p<0.001; Figure). Reviewing the decision aid from the Centers for Disease Control or American Academy of Family Physicians did not alter likelihood (both p>0.2), while the decision aid from the United States Preventive Services Task Force was associated with the largest decrease in screening preference (-16.0, p<0.001). Participants reported increased comfort with the decision-making process for prostate cancer screening from 3.5 to 4.1 (out of 5, p<0.001) following exposure to a decision aid. Exposure to a decision aid decreased participant likelihood to undergo or recommend prostate cancer screening and increased comfort with the screening process. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) in prostate cancer patients undergoing androgen deprivation therapy: study protocol for a randomized controlled trial.

PubMed

Focht, Brian C; Lucas, Alexander R; Grainger, Elizabeth; Simpson, Christina; Thomas-Ahner, Jennifer M; Clinton, Steven K

2014-09-09

Androgen deprivation therapy (ADT) is the foundation of treatment for men with metastatic prostate cancer and is now frequently incorporated into multimodality strategies for the curative treatment of locally advanced prostate cancer. Nevertheless, the catabolic effects of ADT result in meaningful adverse effects on physiological and quality of life outcomes, which may, in turn, increase the risk of functional decline, frailty, cardiovascular disease, and metabolic syndrome. Recent evidence demonstrates that lifestyle intervention promoting change in exercise and dietary behaviors is a promising approach, and may offset, or even reverse, the adverse effects accompanying ADT. Unfortunately, the limited existing studies of the effects of exercise and dietary interventions targeting patients with prostate cancer on ADT are characterized by high attrition rates and poor postintervention maintenance of treatment effects. Consequently, the Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is designed to contrast the effects of a lifestyle intervention designed to promote independent self-management of exercise and dietary behavior with those of standard care disease management approach in the treatment of prostate cancer. A total of 40 patients with prostate cancer undergoing ADT will be randomly assigned to lifestyle intervention or standard care. Outcomes of interest in IDEA-P include changes in self-reported and objectively assessed physical function and physical activity, dietary behavior, body composition, muscular strength, and quality of life. Outcomes will be obtained at baseline, 2-month, and 3-month assessments by trial personnel blinded to participants' randomization assignment. Findings from this study will establish the feasibility and preliminary efficacy of an innovative lifestyle intervention designed to promote progressively independent self-regulated exercise and dietary behavior change in the treatment of patients with prostate cancer undergoing ADT. ClinicalTrials.gov NCT02050906.

Randomized Clinical Trial of Brewed Green and Black Tea in Men with Prostate Cancer Prior to Prostatectomy

PubMed Central

Henning, Susanne M.; Wang, Piwen; Said, Jonathan W.; Huang, Min; Grogan, Tristan; Elashoff, David; Carpenter, Catherine L.; Heber, David; Aronson, William J.

2014-01-01

Background Preclinical and epidemiologic studies suggest chemopreventive effects of green tea (GT) and black tea (BT) in prostate cancer. In the current study we determined the effect of GT and BT consumption on biomarkers related to prostate cancer development and progression. Methods In this exploratory, open label, phase II trial 113 men diagnosed with prostate cancer were randomized to consume six cups daily of brewed GT, BT or water (control) prior to radical prostatectomy (RP). The primary endpoint was prostate tumor markers of cancer development and progression determined by tissue immunostaining of proliferation (Ki67), apoptosis (Bcl-2, Bax, Tunel), inflammation [nuclear and cytoplasmic nuclear factor kappa B (NFκB)] and oxidation [8-hydroxydeoxy- guanosine (8OHdG)]. Secondary endpoints of urinary oxidation, tea polyphenol uptake in prostate tissue, and serum prostate specific antigen (PSA) were evaluated by high performance liquid chromatography and ELISA analysis. Results Ninety three patients completed the intervention. There was no significant difference in markers of proliferation, apoptosis and oxidation in RP tissue comparing GT and BT to water control. Nuclear staining of NFkB was significantly decreased in RP tissue of men consuming GT (p=0.013) but not BT (p=0.931) compared to water control. Tea polyphenols were detected in prostate tissue from 32 of 34 men consuming GT but not in the other groups. Evidence of a systemic antioxidant effect was observed (reduced urinary 8OHdG) only with GT consumption (p=0.03). GT, but not BT or water, also led to a small but statistically significant decrease in serum prostate-specific antigen (PSA) levels (p=0.04). Conclusion Given the GT-induced changes in NFkB and systemic oxidation, and uptake of GT polyphenols in prostate tissue, future longer-term studies are warranted to further examine the role of GT for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis. PMID:25545744

Thulium vapoenucleation of the prostate versus holmium laser enucleation of the prostate for the treatment of large volume prostates: preliminary 6-month safety and efficacy results of a prospective randomized trial.

PubMed

Becker, B; Herrmann, T R W; Gross, A J; Netsch, C

2018-05-05

We compared the perioperative and postoperative characteristics of thulium vapoenucleation and holmium laser enucleation of the prostate for the treatment of large volume benign prostatic hyperplasia. A total of 94 patients with benign prostatic hyperplasia and a median prostate size of 80 (IQR 46.75-100) cc were either randomized to thulium vapoenucleation or holmium laser enucleation of the prostate. Patients were assessed preoperatively, 1 and 6 months postoperatively. The median operative time was 60 (IQR 41-79) min without significant differences between the groups. There were no significant differences between the groups regarding catheter time [2 (IQR 2-2) days] and postoperative stay [2 (IQR 2-3) days]. Clavien 1 (13.8%), 2 (3.2%), 3a (2.1%), and Clavien 3b (4.3%) complications occurred without significant differences between the groups. At 6-month follow-up, median maximum flow rate (10.7 vs. 25.9 ml/s), post-void residual urine (100 vs. 6.5 ml), I-PSS (20 vs. 5), quality of life (4 vs. 1), PSA (4.14 vs. 0.71 µg/l), and prostate volume (80 vs. 16 ml) had improved significantly (p < 0.001) compared to baseline without significant differences between the groups. Median PSA decrease was 79.7% (58.8-90.6%) and prostate volume reduction was 74.5% (68.57-87.63%) without differences between the groups. The reoperation rate was zero at 6-month follow-up. Thulium vapoenucleation and holmium laser enucleation of the prostate are safe and effective procedures for the treatment of large volume benign prostatic hyperplasia. Both procedures give satisfactory micturition improvement with low morbidity and sufficient prostate volume reduction at 6-month follow-up.

Outcomes of minimally invasive simple prostatectomy for benign prostatic hyperplasia: a systematic review and meta-analysis.

PubMed

Lucca, Ilaria; Shariat, Shahrokh F; Hofbauer, Sebastian L; Klatte, Tobias

2015-04-01

(1) To assess the outcomes of minimally invasive simple prostatectomy (MISP) for the treatment of symptomatic benign prostatic hyperplasia in men with large prostates and (2) to compare them with open simple prostatectomy (OSP). A systematic review of outcomes of MISP for benign prostatic hyperplasia with meta-analysis was conducted. The article selection process was conducted according to the PRISMA guidelines. Twenty-seven observational studies with 764 patients were analyzed. The mean prostate volume was 113.5 ml (95 % CI 106-121). The mean increase in Qmax was 14.3 ml/s (95 % CI 13.1-15.6), and the mean improvement in IPSS was 17.2 (95 % CI 15.2-19.2). Mean duration of operation was 141 min (95 % CI 124-159), and the mean intraoperative blood loss was 284 ml (95 % CI 243-325). One hundred and four patients (13.6 %) developed a surgical complication. In comparative studies, length of hospital stay (WMD -1.6 days, p = 0.02), length of catheter use (WMD -1.3 days, p = 0.04) and estimated blood loss (WMD -187 ml, p = 0.015) were significantly lower in the MISP group, while the duration of operation was longer than in OSP (WMD 37.8 min, p < 0.0001). There were no differences in improvements in Qmax, IPSS and perioperative complications between both procedures. The small study sizes, publication bias, lack of systematic complication reporting and short follow-up are limitations. MISP seems an effective and safe treatment option. It provides similar improvements in Qmax and IPSS as OSP. Despite taking longer, it results in less blood loss and shorter hospital stay. Prospective randomized studies comparing OSP, MISP and laser enucleation are needed to define the standard surgical treatment for large prostates.

Place of residence and primary treatment of prostate cancer: examining trends in rural and nonrural areas in Wisconsin.

PubMed

Cetnar, Jeremy P; Hampton, John M; Williamson, Amy A; Downs, Tracy; Wang, Dian; Owen, Jean B; Crouse, Byron; Jones, Nathan; Wilson, J Frank; Trentham-Dietz, Amy

2013-03-01

To determine whether rural residents were at a disadvantage compared with urban residents with regard to the receipt of curative therapy for prostate cancer. Using the Breast and Prostate Cancer Data Quality and Patterns of Care Study II, patients with prostate cancer who were diagnosed in 2004 were identified. Registrars reviewed the medical records of randomly selected patients with incident prostate cancer (n = 1906). The patients' residential address was geocoded and linked to the census tract from the 2000 U.S. Census. The place of residence was defined as rural or nonrural according to the census tract and rural-urban commuting area categorization. The distance from the residence to the nearest radiation oncology facility was calculated. The odds ratio and 95% confidence intervals associated with receipt of noncurative treatment was calculated from logistic regression models and adjusted for several potential confounders. Of the incident patients, 39.1% lived in urban census tracts, 41.5% lived in mixed tracts, and 19.4% lived in rural tracts. Hormone-only or active surveillance was received by 15.4% of the patients. Relative to the urban patients, the odds ratio for noncurative treatment was 1.01 (95% confidence interval 0.59-1.74) for those living in mixed tracts and 0.96 (95% confidence interval 0.52-1.77) for those living in rural tracts. No association was found for noncurative treatment according to the Rural-Urban Commuting Area categorization. The linear trend was null between noncurative treatment and the distance to nearest radiation oncology facility (P = .92). The choice of curative treatment did not significantly depend on the patient's place of residence, suggesting a lack of geographic disparity for the primary treatment of prostate cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Night shift work, chronotype and prostate cancer risk in the MCC-Spain case-control study.

PubMed

Papantoniou, Kyriaki; Castaño-Vinyals, Gemma; Espinosa, Ana; Aragonés, Nuria; Pérez-Gómez, Beatriz; Burgos, Javier; Gómez-Acebo, Inés; Llorca, Javier; Peiró, Rosana; Jimenez-Moleón, Jose Juan; Arredondo, Francisco; Tardón, Adonina; Pollan, Marina; Kogevinas, Manolis

2015-09-01

Night shift work has been classified as a probable human carcinogen based on experimental studies and limited human evidence on breast cancer. Evidence on other common cancers, such as prostate cancer, is scarce. Chronotype is an individual characteristic that may relate to night work adaptation. We evaluated night shift work with relation to prostate cancer, taking into account chronotype and disease severity in a population based case-control study in Spain. We included 1,095 prostate cancer cases and 1,388 randomly selected population controls. We collected detailed information on shift schedules (permanent vs. rotating, time schedules, duration, frequency), using lifetime occupational history. Sociodemographic and lifestyle factors were assessed by face-to-face interviews and chronotype through a validated questionnaire. We used unconditional logistic regression analysis adjusting for potential confounders. Subjects who had worked at least for one year in night shift work had a slightly higher prostate cancer risk [Odds Ratio (OR) 1.14; 95%CI 0.94, 1.37] compared with never night workers; this risk increased with longer duration of exposure (≥ 28 years: OR 1.37; 95%CI 1.05, 1.81; p-trend = 0.047). Risks were more pronounced for high risk tumors [D'Amico classification, Relative Risk Ratio (RRR) 1.40; 95%CI 1.05, 1.86], particularly among subjects with longer duration of exposure (≥28 years: RRR 1.63; 95%CI 1.08, 2.45; p-trend = 0.027). Overall risk was higher among subjects with an evening chronotype, but also increased in morning chronotypes after long-term night work. In this large population based study, we found an association between night shift work and prostate cancer particularly for tumors with worse prognosis. © 2014 UICC.

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Biochemically Monoclonal Antibody J591 in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2010-09-01

relapsed prostate cancer (PC) after local therapy. J Clin Oncol 28: 15s, 2010 (suppl; Abstr TPS248) Presentation: Poster presentation, 2010 ASCO...Annual Meeting V. Conclusions Biochemical relapse is common after local therapy for prostate cancer. Based on the physical properties of 177Lu...ketoconazole in patients (pts) with high-risk castrate biochemically relapsed prostate cancer (PC) after local therapy. S. T. Tagawa, J. Osborne, P. J

Photodynamic Therapy of the Canine Prostate: Intra-arterial Drug Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Ronald B.; Xiao, Zhengwen; Owen, Richard J.

2008-01-15

Purpose. Interstitial photodynamic therapy (PDT) selectively destroys tissue targeted with a photosensitizer and then exposed to light of a specific wavelength. We report a novel delivery method-intra-arterial drug delivery for PDT of the prostate-in a canine model.Methods. To evaluate drug distribution, the prostatovesical artery was selectively cannulated and photosensitizers alone or in conjunction with 99m-technetium-labeled macro-aggregated albumin ({sup 99m}Tc-MAA) were injected via a 3 Fr microcatheter in 8 animals. One dog was followed for 3 months to determine tolerance and toxicity. The remaining animals were euthanized and imaged with whole-body single photon emission CT and gamma counting for radioactivity distribution.more » Photosensitizer distribution was further analyzed by fluorescence confocal microscopy and tissue chemical extraction. To evaluate PDT, the photosensitizer QLT0074 was infused in 3 animals followed by interstitial illumination with 690 nm laser light. Results. Intra-arterial infusion selectively delivered drugs to the prostate, with both radioactivity and photosensitizer levels significantly higher (up to 18 times) than in the surrounding organs (i.e., rectum). With unilateral injection of {sup 99m}Tc-MAA, only the injected half of the prostate showed activity whereas bilateral administration resulted in drug delivery to the entire prostate. PDT resulted in comprehensive damage to the prostate without severe complications or systemic toxicity. Conclusion. Injection of radiolabeled MAA into the prostatovesical artery results in distribution within the prostate with negligible amounts reaching the adjacent organs. PDT also demonstrates selective damage to the prostate, which warrants clinical application in targeted prostate therapies.« less

The effect of increasing doses of saw palmetto fruit extract on serum prostate specific antigen: analysis of the CAMUS randomized trial.

PubMed

Andriole, Gerald L; McCullum-Hill, Christie; Sandhu, Gurdarshan S; Crawford, E David; Barry, Michael J; Cantor, Alan

2013-02-01

Saw palmetto extracts are used to treat lower urinary tract symptoms in men despite level I evidence that saw palmetto is ineffective in reducing these lower urinary tract symptoms. We determined whether higher doses of saw palmetto as studied in the CAMUS (Complementary and Alternative Medicine for Urologic Symptoms) trial affect serum prostate specific antigen levels. The CAMUS trial was a randomized, placebo controlled, double-blind, multicenter, North American trial conducted between June 5, 2008 and October 10, 2012, in which 369 men older than 45 years with an AUA symptom score of 8 to 24 were randomly assigned to placebo or dose escalation of saw palmetto, which consisted of 320 mg for the first 24 weeks, 640 mg for the next 24 weeks and 960 mg for the last 24 weeks of this 72-week trial. Serum prostate specific antigen levels were obtained at baseline and at weeks 24, 48 and 72, and were compared between treatment groups using the pooled t test and Fisher's exact test. Serum prostate specific antigen was similar at baseline for the placebo (mean ± SD 1.93 ± 1.59 ng/ml) and saw palmetto groups (2.20 ± 1.95, p = 0.16). Changes in prostate specific antigen during the study were similar, with a mean change in the placebo group of 0.16 ± 1.08 ng/ml and 0.23 ± 0.83 ng/ml in the saw palmetto group (p = 0.50). In addition, no differential effect on serum prostate specific antigen was observed between treatment arms when the groups were stratified by baseline prostate specific antigen. Saw palmetto extract does not affect serum prostate specific antigen more than placebo, even at relatively high doses. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

CD8+ T-cell responses rapidly select for antigen-negative tumor cells in the prostate.

PubMed

Bak, S Peter; Barnkob, Mike Stein; Wittrup, K Dane; Chen, Jianzhu

2013-12-01

Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8(+) T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell-treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8(+) T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells. ©2013 AACR.

PSA velocity does not aid the detection of prostate cancer in men with a prior negative biopsy: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden and Rotterdam, Netherlands

PubMed Central

Vickers, Andrew J.; Wolters, Tineke; Savage, Caroline J.; Cronin, Angel M.; O’Brien, M. Frank; Roobol, Monique J.; Aus, Gunnar; Scardino, Peter T.; Hugosson, Jonas; Schröder, Fritz H.; Lilja, Hans

2012-01-01

Purpose Prostate specific antigen (PSA) velocity has been proposed as a marker to aid detection of prostate cancer. We sought to determine whether PSA velocity could predict the results of repeat biopsy in men with persistently elevated PSA after initial negative biopsy. Materials and Methods We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer (ERSPC), and who had one or more subsequent prostate biopsies after an initial negative finding. We evaluated whether PSA velocity improved predictive accuracy beyond that of PSA alone. Results There were a total of 2579 repeat biopsies, of which 363 (14%) were positive for prostate cancer, and 44 (1.7%) were high grade (Gleason score ≥7). Although PSA velocity was statistically associated with cancer risk (p<0.001), it had very low predictive accuracy (area-under-the-curve [AUC] of 0.55). There was some evidence that PSA velocity improved AUC compared to PSA for high grade cancer. However, the small increase in risk associated with high PSA velocity – from 1.7 % to 2.8% as velocity increased from 0 to 1 ng / ml / year - is of questionable clinical relevance. Conclusions Men with a prior negative biopsy have a lower risk for prostate cancer at subsequent biopsies, with high grade disease particularly rare. We found little evidence to support the use of PSA velocity to aid decisions about repeat biopsy for prostate cancer. PMID:20643434

[Prostate cancer: Quality assessment of clinical management in the Midi-Pyrenean region in 2011].

PubMed

Daubisse-Marliac, L; Lamy, S; Lunardi, P; Tollon, C; Thoulouzan, M; Latorzeff, I; Bauvin, E; Grosclaude, P

2017-02-01

Assessing the quality of the clinical management of prostate cancer in the Midi-Pyrenean region in 2011. The study population was randomly selected among new cases of prostate cancer presented in Multidisciplinary Team Meeting (MTM) in 2011. The indicators defined with the professionals have evaluated the quality of the diagnostic care, when treatment started and at the time of the MTM. Six hundred and thirty-three new patients were included (median age at diagnosis=69years, min: 48; max: 93). In diagnostic period, 92% of patients had a prostate biopsy. Performing a pelvic MRI, an abdomino-pelvic CT and bone scintigraphy concerned respectively 53%, 55% and 61% of intermediate or high-risk patients. The Gleason score, surgical margins and pathological stage were included in over 98% patient records treated by radical prostatectomy. A PSA assay in 3months after prostatectomy was found in 59% of surgical patients. The MTM was performed before treatment to 83% of patients. About three-quarters of surgical patients with stage pT≥3 or pN1 or with no healthy margins were discussed in MTM after surgery. Most of the studied indicators reach a high level. However, the lower level of realization of complementary examinations may question about their real place, accessibility and traceability. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Informing men about prostate cancer screening: a randomized controlled trial of patient education materials.

PubMed

Ilic, Dragan; Egberts, Kristine; McKenzie, Joanne E; Risbridger, Gail; Green, Sally

2008-04-01

Patient education materials can assist patient decision making on prostate cancer screening. To explore the effectiveness of presenting health information on prostate cancer screening using video, internet, and written interventions on patient decision making, attitudes, knowledge, and screening interest. Randomized controlled trial. A total of 161 men aged over 45, who had never been screened for prostate cancer, were randomized to receive information on prostate cancer screening. Participants were assessed at baseline and 1-week postintervention for decisional conflict, screening interest, knowledge, anxiety, and decision-making preference. A total of 156 men were followed-up at 1-week postintervention. There was no statistical, or clinical, difference in mean change in decisional conflict scores between the 3 intervention groups (video vs internet -0.06 [95% CI -0.24 to 0.12]; video vs pamphlet 0.04 [95%CI -0.15 to 0.22]; internet vs pamphlet 0.10 [95%CI -0.09 to 0.28]). There was also no statistically significant difference in mean knowledge, anxiety, decision-making preference, and screening interest between the 3 intervention groups. Results from this study indicate that there are no clinically significant differences in decisional conflict when men are presented health information on prostate cancer screening via video, written materials, or the internet. Given the equivalence of the 3 methods, other factors need to be considered in deciding which method to use. Health professionals should provide patient health education materials via a method that is most convenient to the patient and their preferred learning style.

[A magnetic therapy apparatus with an adaptable electromagnetic spectrum for the treatment of prostatitis and gynecopathies].

PubMed

Kuz'min, A A; Meshkovskiĭ, D V; Filist, S A

2008-01-01

Problems of engineering and algorithm development of magnetic therapy apparatuses with pseudo-random radiation spectrum within the audio range for treatment of prostatitis and gynecopathies are considered. A typical design based on a PIC 16F microcontroller is suggested. It includes a keyboard, LCD indicator, audio amplifier, inducer, and software units. The problem of pseudo-random signal generation within the audio range is considered. A series of rectangular pulses is generated on a random-length interval on the basis of a three-component random vector. This series provides the required spectral characteristics of the therapeutic magnetic field and their adaptation to the therapeutic conditions and individual features of the patient.

Identification of Prostate Cancer-Specific microDNAs

DTIC Science & Technology

2016-02-01

circular DNA by rolling circle amplification (RCA) and then amplified DNA fragments were subject to deep sequencing. Deep sequencing of the...demonstrate the existence of microDNAs in prostate cancer. We adopted multiple displacement amplification (MDA) with random 2 primers for enriched...prostate cancer cells through multiple displacement amplification and next generation sequencing. R e la ti v e c e ll g ro w th ( % ) 0 20

Results of vardenafil mediated power Doppler ultrasound, contrast enhanced ultrasound and systematic random biopsies to detect prostate cancer.

PubMed

Morelli, Girolamo; Pagni, Riccardo; Mariani, Chiara; Minervini, Riccardo; Morelli, Andrea; Gori, Francesco; Ferdeghini, Ezio Maria; Paterni, Marco; Mauro, Eva; Guidi, Elisa; Armillotta, Nicola; Canale, Domenico; Vitti, Paolo; Caramella, Davide; Minervini, Andrea

2011-06-01

We evaluated the ability of the phosphodiesterase-5 inhibitor vardenafil to increase prostate microcirculation during power Doppler ultrasound. We also evaluated the results of contrast and vardenafil enhanced targeted biopsies compared to those of standard 12-core random biopsies to detect cancer. Between May 2008 and January 2010, 150 consecutive patients with prostate specific antigen more than 4 ng/ml at first diagnosis with negative digital rectal examination and transrectal ultrasound, and no clinical history of prostatitis underwent contrast enhanced power Doppler ultrasound (bolus injection of 2.4 ml SonoVue® contrast agent), followed by vardenafil enhanced power Doppler ultrasound (1 hour after oral administration of vardenafil 20 mg). All patients underwent standard 12-core transrectal ultrasound guided random prostate biopsy plus 1 further sampling from each suspected hypervascular lesion detected by contrast and vardenafil enhanced power Doppler ultrasound. Prostate cancer was detected in 44 patients (29.3%). Contrast and vardenafil enhanced power Doppler ultrasound detected suspicious, contrast enhanced and vardenafil enhanced areas in 112 (74.6%) and 110 patients (73.3%), and was diagnostic for cancer in 32 (28.5%) and 42 (38%), respectively. Analysis of standard technique, and contrast and vardenafil enhanced power Doppler ultrasound findings by biopsy core showed significantly higher detection using vardenafil vs contrast enhanced power Doppler ultrasound and standard technique (41.2% vs 22.7% and 8.1%, p <0.005 and <0.001, respectively). The detection rate of standard plus contrast or vardenafil enhanced power Doppler ultrasound was 10% and 11.7% (p not significant). Vardenafil enhanced power Doppler ultrasound enables excellent visualization of the microvasculature associated with cancer and can improve the detection rate compared to contrast enhanced power Doppler ultrasound and the random technique. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Predicting Classifier Performance with Limited Training Data: Applications to Computer-Aided Diagnosis in Breast and Prostate Cancer

PubMed Central

Basavanhally, Ajay; Viswanath, Satish; Madabhushi, Anant

2015-01-01

Clinical trials increasingly employ medical imaging data in conjunction with supervised classifiers, where the latter require large amounts of training data to accurately model the system. Yet, a classifier selected at the start of the trial based on smaller and more accessible datasets may yield inaccurate and unstable classification performance. In this paper, we aim to address two common concerns in classifier selection for clinical trials: (1) predicting expected classifier performance for large datasets based on error rates calculated from smaller datasets and (2) the selection of appropriate classifiers based on expected performance for larger datasets. We present a framework for comparative evaluation of classifiers using only limited amounts of training data by using random repeated sampling (RRS) in conjunction with a cross-validation sampling strategy. Extrapolated error rates are subsequently validated via comparison with leave-one-out cross-validation performed on a larger dataset. The ability to predict error rates as dataset size increases is demonstrated on both synthetic data as well as three different computational imaging tasks: detecting cancerous image regions in prostate histopathology, differentiating high and low grade cancer in breast histopathology, and detecting cancerous metavoxels in prostate magnetic resonance spectroscopy. For each task, the relationships between 3 distinct classifiers (k-nearest neighbor, naive Bayes, Support Vector Machine) are explored. Further quantitative evaluation in terms of interquartile range (IQR) suggests that our approach consistently yields error rates with lower variability (mean IQRs of 0.0070, 0.0127, and 0.0140) than a traditional RRS approach (mean IQRs of 0.0297, 0.0779, and 0.305) that does not employ cross-validation sampling for all three datasets. PMID:25993029

Diagnostic performance of power doppler and ultrasound contrast agents in early imaging-based diagnosis of organ-confined prostate cancer: Is it possible to spare cores with contrast-guided biopsy?

PubMed

Delgado Oliva, F; Arlandis Guzman, S; Bonillo García, M; Broseta Rico, E; Boronat Tormo, F

2016-10-01

To evaluate the diagnostic performance of gray scale transrectal ultrasound-B-mode US (BMUS), power Doppler (PDUS), and sonographic contrast (CEUS) in early imaging-based diagnosis of localized prostate cancer (PCa) and to compare the diagnostic profitability of randomized biopsy (RB), US-targeted prostate biopsy by means of PDUS and CEUS. A single-center, prospective, transversal, epidemiological study was conducted from January 2010 to January 2014. We consecutively included patients who an imaging study of the prostate with BMUS, PDUS, and CEUS was performed, followed by prostate biopsy due to clinical suspicion of prostate cancer (PSA 4-20ng/mL and/or rectal exam suggestive of malignancy). The diagnostic performance of BMUS, PDUS, and CEUS was determined by calculating the Sensitivity (S), Specificity (Sp), Predictive values (PV), and diagnostic odds ratio (OR) of the diagnosis tests and, for these variables, in the population general and based on their clinical stage according to rectal exam (cT1 and cT2). PCa detection rates determined by means of a randomized 10-core biopsy scheme were compared with detection rates of CEUS-targeted (SonoVue) 2-core biopsies. Of the initial 984 patients, US contrast SonoVue was administered to 179 (18.2%). The PCa detection rate by organ of BMUS/PDUS in the global population was 38% versus 43% in the subpopulation with CEUS. The mean age of the patients was 64.3±7.01years (95% CI, 63.75-64.70); mean total PSA was 8.9±3.61ng/mL (95% CI, 8.67-9.13) and the mean prostate volume was 56.2±29cc (95% CI, 54.2-58.1). The detection rate by organ of targeted biopsy with BMUS, PDUS, and CEUS were as follows: Global population (10.6, 8.2, 24.5%), stage cT1 (5.6, 4.2, 16.4%), and stage cT2 (32.4, 22.3, 43.5%). Comparing the detection rates of the CEUS-targeted biopsy and randomized biopsy, the following results were obtained: Global population (24.5% vs. 41.8%), stage cT1 (16% vs. 35%), and stage cT2 (43.5% vs. 66.6%), with a p value<0.05. Following the "core-by-core" analysis, the detection rates by core of CEUS-targeted biopsy versus randomized biopsy were: Global population (16% vs. 13%), stage cT1 (30.3% vs. 28%), and stage cT2 (48% vs. 37%), with a p value>0.05. The NNT for CEUS-targeted biopsy was 83.3. The low sensitivity, specificity, positive predictive and negative predictive values of gray scale-B-mode, PDUS and CEUS represent scant diagnostic performance of these variables in prostate cancer detection. Prostate cancer detection rates yielded by randomized biopsy were superior than the detection rate of targeted biopsy using B-mode, PDUS and CEUS; as a result, randomized biopsy versus CEUS-targeted biopsies cannot be excluded from biopsy strategy plans for the diagnosis of prostate cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Lower urinary tract symptoms are associated with low levels of serum serotonin, high levels of adiponectin and fasting glucose, and benign prostatic enlargement.

PubMed

Haghsheno, Mohammad-Ali; Mellström, Dan; Peeker, Ralph; Hammarsten, Jan; Lorentzon, Mattias; Sundh, Valter; Karlsson, Magnus; Ohlsson, Claes; Damber, Jan-Erik

2015-04-01

The aim of this study was to test whether lower urinary tract symptoms (LUTS) and urinary incontinence are associated with the metabolic syndrome (MetS). The association between LUTS and benign prostatic enlargement (BPE) was also investigated. A cross-sectional, representative risk factor analysis of LUTS, as measured by the International Prostate Symptom Score (IPSS), and urinary incontinence was conducted. Among 950 representative individuals, aged 69-81 years, the association between clinical, anthropometric, endocrine, metabolic and inflammatory factors on the one hand, as both major and minor aspects of MetS, and LUTS and urinary incontinence, on the other hand, was analysed. The prostate gland volume was measured in a subgroup of 155 randomly selected individuals and the association between LUTS and BPE was estimated. No significant association was found between LUTS or urinary incontinence and the major aspects of the MetS. However, in a multivariate analysis, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. Furthermore, in a subgroup of 155 individuals, the prostate gland volume correlated positively with LUTS. The study did not show an association between LUTS or urinary incontinence and the major components of the MetS. However, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. The data confirm the general knowledge that BPE may be one of the causative factors of LUTS.

The prevention of fragility fractures in patients with non-metastatic prostate cancer: a position statement by the international osteoporosis foundation

PubMed Central

Cianferotti, Luisella; Bertoldo, Francesco; Carini, Marco; Kanis, John A.; Lapini, Alberto; Longo, Nicola; Martorana, Giuseppe; Mirone, Vincenzo; Reginster, Jean-Yves; Rizzoli, Rene; Brandi, Maria Luisa

2017-01-01

Androgen deprivation therapy is commonly employed for the treatment of non-metastatic prostate cancer as primary or adjuvant treatment. The skeleton is greatly compromised in men with prostate cancer during androgen deprivation therapy because of the lack of androgens and estrogens, which are trophic factors for bone. Men receiving androgen deprivation therapy sustain variable degrees of bone loss with an increased risk of fragility fractures. Several bone antiresorptive agents have been tested in randomized controlled trials in these patients. Oral bisphosphonates, such as alendronate and risedronate, and intravenous bisphosphonates, such as pamidronate and zoledronic acid, have been shown to increase bone density and decrease the risk of fractures in men receiving androgen deprivation therapy. Denosumab, a fully monoclonal antibody that inhibits osteoclastic-mediated bone resorption, is also effective in increasing bone mineral density and reducing fracture rates in these patients. The assessment of fracture risk, T-score and/or the evaluation of prevalent fragility fractures are mandatory for the selection of patients who will benefit from antiresorptive therapy. In the future, new agents modulating bone turnover and skeletal muscle metabolism will be available for testing in these subjects. PMID:29088899

The prevention of fragility fractures in patients with non-metastatic prostate cancer: a position statement by the international osteoporosis foundation.

PubMed

Cianferotti, Luisella; Bertoldo, Francesco; Carini, Marco; Kanis, John A; Lapini, Alberto; Longo, Nicola; Martorana, Giuseppe; Mirone, Vincenzo; Reginster, Jean-Yves; Rizzoli, Rene; Brandi, Maria Luisa

2017-09-26

Androgen deprivation therapy is commonly employed for the treatment of non-metastatic prostate cancer as primary or adjuvant treatment. The skeleton is greatly compromised in men with prostate cancer during androgen deprivation therapy because of the lack of androgens and estrogens, which are trophic factors for bone. Men receiving androgen deprivation therapy sustain variable degrees of bone loss with an increased risk of fragility fractures. Several bone antiresorptive agents have been tested in randomized controlled trials in these patients. Oral bisphosphonates, such as alendronate and risedronate, and intravenous bisphosphonates, such as pamidronate and zoledronic acid, have been shown to increase bone density and decrease the risk of fractures in men receiving androgen deprivation therapy. Denosumab, a fully monoclonal antibody that inhibits osteoclastic-mediated bone resorption, is also effective in increasing bone mineral density and reducing fracture rates in these patients. The assessment of fracture risk, T-score and/or the evaluation of prevalent fragility fractures are mandatory for the selection of patients who will benefit from antiresorptive therapy. In the future, new agents modulating bone turnover and skeletal muscle metabolism will be available for testing in these subjects.

SU-E-T-571: Prostate IMRT QA: Prediction of the Range of Rectal NTCP Using a 2D Field Approach Based on Variations of the Rectal Wall Motion and Thickness.

PubMed

Grigorov, G; Chow, J; Foster, K

2012-06-01

The aims of this study is to (1) introduce a 2D field of possible rectal normal tissue complication probability (NTCP) in prostate intensity modulated radiotherapy (IMRT) plan, so that based on a given prescribed dose the rectal NTCP is merely a function of the rectal wall thickness and rectal motion; and (2) separate the 2D field of rectal NTCP into area of low risk and area of high risk for rectal toxicity < Grade II, based on the threshold rectal NTCP. The 2D field of NTCP model was developed using ten randomly selected prostate IMRT plans. The clinical rectal geometry was initially represented by the cylindrical contour in the treatment planning system. Different combinations of rectal motions, rectal wall thicknesses, planning target volume margins and prescribed doses were used to determine the NTCP in prostate IMRT plans. It was found that the functions bordering the 2D field for the given AP, LR and SI direction can be described as exponential, quadratic and linear equations, respectively. A ratio of the area of 2D field containing data of the low risk NTCP to the entire area of the field was introduced and calculated. Although our method is based on the Kutcher's dose response model and published tissue parameters, other mathematical models can be used in our approach. The 2D field of rectal NTCP is useful to estimate the rectal NTCP range in the prostate pre-treatment and treatment QA. Our method can determine the patient's threshold immobilization for a given rectal wall thickness so that prescribed dose can be delivered to the prostate to avoid rectal complication. Our method is also applicable to multi-phase prostate IMRT, and can be adapted to any treatment planning systems. © 2012 American Association of Physicists in Medicine.

Correlation of Prostate Gland Size and Uroflowmetry in Patients with Lower Urinary Tract Symptoms.

PubMed

Sundaram, Deepak; Sankaran, Ponnusamy Kasirajan; Raghunath, Gunapriya; Vijayalakshmi, S; Vijayakumar, J; Yuvaraj, Maria Francis; Kumaresan, Munnusamy; Begum, Zareena

2017-05-01

Benign Prostatic Hyperplasia (BPH) is a common entity among men over 40 years of age with significant disability. It is a condition that occurs when the enlarged prostate gland compresses the urethra leading to Bladder Outlet Obstruction (BOO). To correlate the size of the prostate gland and uroflowmetry parameters in patients with Lower Urinary Tract Symptoms (LUTS). One hundred and twenty randomly selected male patients, from the ages of 41 to 70 years, with LUTS, and underwent trans abdominal sonogram and uroflowmetry were included in the study. The samples were divided into three groups according to the age; Group 1: 41 to 50 years, Group 2: 51 to 60 years, Group 3: 61 to 70 years. In Group 1 (41 to 50 years), there were totally 28 patients with LUTS, out of which seven patients had BPH, indicating that about 5% of patients with LUTS have BPH. In Group 2 (51-60 years) there were totally 31 patients with LUTS, out of which 10 patients had BPH, indicating that 8% of patients with LUTS have BPH. In Group 3 (61-70 years) there were totally 61 patients with LUTS, out of which 33 patients had BPH, indicating that 27% of patients with LUTS had BPH. The mean age of patients with LUTS was 60 years with mean prostate size of 45 cm 3 . Enlarged prostate gland was present in 41% of patients with mean Q max of 14 ml/sec and post voidal volume of 48 ml. This study concludes that the LUTS in older patients are mostly due to BPH leading to BOO. Also, patients with BPH in early ages can lead to increased Post voidal Residual Volume (PVR) following uroflowmetry. Thus, screening male patients with LUTS, at 40 years and above, is an ideal way to detect prostatic problems at an early stage.

Correlation of Prostate Gland Size and Uroflowmetry in Patients with Lower Urinary Tract Symptoms

PubMed Central

Sankaran, Ponnusamy Kasirajan; Raghunath, Gunapriya; Vijayalakshmi, S; Vijayakumar, J; Yuvaraj, Maria Francis; Kumaresan, Munnusamy; begum, Zareena

2017-01-01

Introduction Benign Prostatic Hyperplasia (BPH) is a common entity among men over 40 years of age with significant disability. It is a condition that occurs when the enlarged prostate gland compresses the urethra leading to Bladder Outlet Obstruction (BOO). Aim To correlate the size of the prostate gland and uroflowmetry parameters in patients with Lower Urinary Tract Symptoms (LUTS). Materials and Methods One hundred and twenty randomly selected male patients, from the ages of 41 to 70 years, with LUTS, and underwent trans abdominal sonogram and uroflowmetry were included in the study. The samples were divided into three groups according to the age; Group 1: 41 to 50 years, Group 2: 51 to 60 years, Group 3: 61 to 70 years. Results In Group 1 (41 to 50 years), there were totally 28 patients with LUTS, out of which seven patients had BPH, indicating that about 5% of patients with LUTS have BPH. In Group 2 (51-60 years) there were totally 31 patients with LUTS, out of which 10 patients had BPH, indicating that 8% of patients with LUTS have BPH. In Group 3 (61-70 years) there were totally 61 patients with LUTS, out of which 33 patients had BPH, indicating that 27% of patients with LUTS had BPH. The mean age of patients with LUTS was 60 years with mean prostate size of 45 cm3. Enlarged prostate gland was present in 41% of patients with mean Q max of 14 ml/sec and post voidal volume of 48 ml. Conclusion This study concludes that the LUTS in older patients are mostly due to BPH leading to BOO. Also, patients with BPH in early ages can lead to increased Post voidal Residual Volume (PVR) following uroflowmetry. Thus, screening male patients with LUTS, at 40 years and above, is an ideal way to detect prostatic problems at an early stage. PMID:28658743

Chemotherapy of prostate cancer: present and future.

PubMed

Trump, Donald; Lau, Yiu-Keung

2003-06-01

The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer.

PubMed

Carducci, Michael A; Saad, Fred; Abrahamsson, Per-Anders; Dearnaley, David P; Schulman, Claude C; North, Scott A; Sleep, Darryl J; Isaacson, Jeffrey D; Nelson, Joel B

2007-11-01

The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone-refractory prostate cancer (HRPC). This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P = .136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P < .05 for each). The median time to BAP progression (>/=50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P < .01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.

Targeting MTA1/HIF-1alpha Signaling by Pterostilbene in Combination with Histone Deacetylase Inhibitor Attenuates Prostate Cancer Progression (Open Access)

DTIC Science & Technology

2017-08-30

stained cells in five randomly selected fields for each slide. ELISA Conditioned media from cell lines or mice sera diluted in carbonate coating buffer... ELISA . Our results showed that Pter/SAHA combination treat- ment was more effective in suppressing VEGF- c and IL- 1β circulating levels compared to...3) SAHA (50 mg/kg; n = 5), and (4) Pter + SAHA (10 mg/kg and 50 mg/kg; n = 7) by i.p. injections for 10 weeks were quantitatively analyzed by ELISA

Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy

PubMed Central

Greenspan, Susan L.; Nelson, Joel B.; Trump, Donald L.; Wagner, Julie M.; Miller, Megan E.; Perera, Subashan; Resnick, Neil M.

2008-01-01

Purpose Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. Patients and Methods A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. Results Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% ± 0.7) and hip (mean, 1.3% ± 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, −1.9% ± 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (± 1.2%) increase at the spine and a 3.2% (± 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. Conclusion Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health. PMID:18802155

Targeting the prostate for destruction through a vascular address

PubMed Central

Arap, Wadih; Haedicke, Wolfgang; Bernasconi, Michele; Kain, Renate; Rajotte, Daniel; Krajewski, Stanislaw; Ellerby, H. Michael; Bredesen, Dale E.; Pasqualini, Renata; Ruoslahti, Erkki

2002-01-01

Organ specific drug targeting was explored in mice as a possible alternative to surgery to treat prostate diseases. Peptides that specifically recognize the vasculature in the prostate were identified from phage-displayed peptide libraries by selecting for phage capable of homing into the prostate after an i.v. injection. One of the phage selected in this manner homed to the prostate 10–15 times more than to other organs. Unselected phage did not show this preference. The phage bound also to vasculature in the human prostate. The peptide displayed by the prostate-homing phage, SMSIARL (single letter code), was synthesized and shown to inhibit the homing of the phage when co-injected into mice with the phage. Systemic treatment of mice with a chimeric peptide consisting of the SMSIARL homing peptide, linked to a proapoptotic peptide that disrupts mitochondrial membranes, caused tissue destruction in the prostate, but not in other organs. The chimeric peptide delayed the development of the cancers in prostate cancer-prone transgenic mice (TRAMP mice). These results suggest that it may be possible to develop an alternative to surgical prostate resection and that such a treatment may also reduce future cancer risk. PMID:11830668

Alfuzosin and symptoms of chronic prostatitis-chronic pelvic pain syndrome.

PubMed

Nickel, J Curtis; Krieger, John N; McNaughton-Collins, Mary; Anderson, Rodney U; Pontari, Michel; Shoskes, Daniel A; Litwin, Mark S; Alexander, Richard B; White, Paige C; Berger, Richard; Nadler, Robert; O'Leary, Michael; Liong, Men Long; Zeitlin, Scott; Chuai, Shannon; Landis, J Richard; Kusek, John W; Nyberg, Leroy M; Schaeffer, Anthony J

2008-12-18

In men with chronic prostatitis-chronic pelvic pain syndrome, treatment with alpha-adrenergic receptor blockers early in the course of the disorder has been reported to be effective in some, but not all, relatively small randomized trials. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of alfuzosin, an alpha-adrenergic receptor blocker, in reducing symptoms in men with chronic prostatitis-chronic pelvic pain syndrome. Participation in the study required diagnosis of the condition within the preceding 2 years and no previous treatment with an alpha-adrenergic receptor blocker. Men were randomly assigned to treatment for 12 weeks with either 10 mg of alfuzosin per day or placebo. The primary outcome was a reduction of at least 4 points (from baseline to 12 weeks) in the score on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (range, 0 to 43; higher scores indicate more severe symptoms). A 4-point decrease is the minimal clinically significant difference in the score. A total of 272 eligible participants underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least 4 points in their total NIH-CPSI score (rate difference associated with alfuzosin, 0.1%; 95% confidence interval, -11.2 to 11.0; P=0.99). In addition, a global response assessment showed similar response rates at 12 weeks: 33.6% in the placebo group and 34.8% in the alfuzosin group (P=0.90). The rates of adverse events in the two groups were also similar. Our findings do not support the use of alfuzosin to reduce the symptoms of chronic prostatitis-chronic pelvic pain syndrome in men who have not received prior treatment with an alpha-blocker. (ClinicalTrials.gov number, NCT00103402.) 2008 Massachusetts Medical Society

Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials

PubMed Central

Tsodikov, Alex; Gulati, Roman; Heijnsdijk, Eveline AM; Pinsky, Paul F; Moss, Sue M; Qiu, Sheng; de Carvalho, Tiago M; Hugosson, Jonas; Berg, Christine D; Auvinen, Anssi; Andriole, Gerald L; Roobol, Monique J; Crawford, E David; Nelen, Vera; Kwiatkowski, Maciej; Zappa, Marco; Luján, Marcos; Villers, Arnauld; Feuer, Eric J; de Koning, Harry J; Mariotto, Angela B; Etzioni, Ruth

2017-01-01

Background The European Randomized Study of Screening for Prostate Cancer (ERSPC) found screening reduced prostate cancer (PC) mortality, but the Prostate, Lung, Colorectal, and Ovarian trial (PLCO) found no reduction. Objective To evaluate whether effects of screening on PC mortality relative to no screening differed between the ERSPC and PLCO. Design Cox regression of PC death in each trial arm adjusted for age and trial, and extended analyses that accounted for increased incidence due to screening and diagnostic workup on each arm via mean lead times (MLTs). MLTs were estimated empirically and using analytic or microsimulation models. Setting Randomized controlled trials in Europe and the US. Participants Men aged 55–69 (ERSPC) or 55–74 (PLCO) at randomization. Intervention Prostate cancer screening. Measurements PC incidence and survival from randomization; PC incidence in the US before screening began. Results Estimated MLTs were similar in the ERSPC and PLCO intervention arms but were longer in the PLCO control arm than the ERSPC control arm. Extended analyses found no evidence that effects of screening differed between trials (P=0.37–0.47, range across MLT estimation approaches) but strong evidence that benefit increased with MLT (P=0.0027–0.0032). Screening was estimated to confer a 7–9% reduction in PC death per year of MLT. This translated into an estimated 25–31% and 27–32% lower risk of PC death under screening as performed in the ERSPC and PLCO intervention arms, respectively, relative to no screening. Limitations MLT is a simple metric of screening and diagnostic workup. Conclusion After accounting for differences in implementation and settings, the ERSPC and PLCO provide compatible evidence that screening reduces PC mortality. PMID:28869989

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2012-11-01

randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer...and that this risk differed between men who took finasteride versus those who took the placebo. The strongest association was seen for a cluster of 9...SNPs in NPAS2, which was associated with total prostate cancer risk in the finasteride group but not in the placebo group. The most significant NPAS2

Association between variants in genes involved in the immune response and prostate cancer risk in men randomized to the finasteride Arm in the Prostate Cancer Prevention Trial*

PubMed Central

Winchester, Danyelle; Till, Cathee; Goodman, Phyllis J.; Tangen, Catherine M.; Santella, Regina M.; Johnson-Pais, Teresa L.; Leach, Robin J.; Xu, Jianfeng; Zheng, S. Lilly; Thompson, Ian M.; Lucia, M. Scott; Lippman, Scott M.; Parnes, Howard L.; Isaacs, William B.; De Marzo, Angelo M.; Drake, Charles G.; Platz, Elizabeth A.

2017-01-01

BACKGROUND We reported that some, but not all single nucleotide polymorphisms (SNPs) in select immune response genes are associated with prostate cancer, but not individually with the prevalence of intraprostatic inflammation in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Here, we investigated whether these same SNPs are associated with risk of lower- and higher-grade prostate cancer in men randomized to finasteride, and with prevalence of intraprostatic inflammation among controls. METHODS 16 candidate SNPs in IL1β, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, and TNFA and 7 tagSNPs in IL10 were genotyped in 625 white prostate cancer cases, and 532 white controls negative for cancer on an end-of-study biopsy nested in the PCPT finasteride arm. We used logistic regression to estimate log-additive odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history. RESULTS Minor alleles of rs2243250 (T) in IL4 (OR=1.46, 95% CI 1.03–2.08, P-trend=0.03), rs1800896 (G) in IL10 (OR=0.77, 95% CI 0.61–0.96, P-trend=0.02), rs2430561 (A) in IFNG (OR=1.33, 95% CI 1.02–1.74; P-trend=0.04), rs3747531 (C) in MSR1 (OR=0.55, 95% CI 0.32–0.95; P-trend=0.03), and possibly rs4073 (A) in IL8 (OR=0.81, 95% CI 0.64–1.01, P-trend=0.06) were associated with higher- (Gleason 7–10; N=222), but not lower- (Gleason 2–6; N=380) grade prostate cancer. In men with low PSA (<2 ng/mL), these higher-grade disease associations were attenuated and/or no longer significant, whereas associations with higher-grade disease were apparent for minor alleles of rs1800795 (C: OR=0.70, 95% CI 0.51–0.94, P-trend=0.02) and rs1800797 (A: OR=0.72, 95% CI 0.53–0.98, P-trend=0.04) in IL6. While some IL10 tagSNPs were associated with lower- and higher-grade prostate cancer, distributions of IL10 haplotypes did not differ, except possibly between higher-grade cases and controls among those with low PSA (P=0.07). We did not observe an association between the studied SNPs and intraprostatic inflammation in the controls. CONCLUSION In the PCPT finasteride arm, variation in genes involved in the immune response, including possibly IL8 and IL10 as in the placebo arm, may be associated with prostate cancer, especially higher-grade disease, but not with intraprostatic inflammation. We cannot rule out PSA-associated detection bias or chance due to multiple testing. PMID:28317149

Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial.

PubMed

Lane, J Athene; Donovan, Jenny L; Davis, Michael; Walsh, Eleanor; Dedman, Daniel; Down, Liz; Turner, Emma L; Mason, Malcolm D; Metcalfe, Chris; Peters, Tim J; Martin, Richard M; Neal, David E; Hamdy, Freddie C

2014-09-01

Prostate cancer is a major public health problem with considerable uncertainties about the effectiveness of population screening and treatment options. We report the study design, participant sociodemographic and clinical characteristics, and the initial results of the testing and diagnostic phase of the Prostate testing for cancer and Treatment (ProtecT) trial, which aims to investigate the effectiveness of treatments for localised prostate cancer. In this randomised phase 3 trial, men aged 50-69 years registered at 337 primary care centres in nine UK cities were invited to attend a specialist nurse appointment for a serum prostate-specific antigen (PSA) test. Prostate biopsies were offered to men with a PSA concentration of 3·0 μg/L or higher. Consenting participants with clinically localised prostate cancer were randomly assigned to active monitoring (surveillance strategy), radical prostatectomy, or three-dimensional conformal external-beam radiotherapy by a computer-generated allocation system. Randomisation was stratified by site (minimised for differences in participant age, PSA results, and Gleason score). The primary endpoint is prostate cancer mortality at a median 10-year follow-up, ascertained by an independent committee, which will be analysed by intention to treat in 2016. This trial is registered with ClinicalTrials.gov, number NCT02044172, and as an International Standard Randomised Controlled Trial, number ISRCTN20141297. Between Oct 1, 2001, and Jan 20, 2009, 228,966 men were invited to attend an appointment with a specialist nurse. Of the invited men, 100,444 (44%) attended their initial appointment and 82,429 (82%) of attenders had a PSA test. PSA concentration was below the biopsy threshold in 73,538 (89%) men. Of the 8566 men with a PSA concentration of 3·0-19·9 μg/L, 7414 (87%) underwent biopsies. 2896 men were diagnosed with prostate cancer (4% of tested men and 39% of those who had a biopsy), of whom 2417 (83%) had clinically localised disease (mostly T1c, Gleason score 6). With the addition of 247 pilot study participants recruited between 1999 and 2001, 2664 men were eligible for the treatment trial and 1643 (62%) agreed to be randomly assigned (545 to active monitoring, 545 to radiotherapy, and 553 to radical prostatectomy). Clinical and sociodemographic characteristics of randomly assigned participants were balanced across treatment groups. The ProtecT trial randomly assigned 1643 men with localised prostate cancer to active monitoring, radiotherapy, or surgery. Participant clinicopathological features are more consistent with contemporary patient characteristics than in previous prostate cancer treatment trials. UK National Institute for Health Research Health Technology Assessment Programme. Copyright © 2014 Lane et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

A functional variant in NKX3.1 associated with prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

PubMed Central

Martinez, Erin E.; Darke, Amy K.; Tangen, Catherine M.; Goodman, Phyllis J.; Fowke, Jay H.; Klein, Eric A.; Abdulkadir, Sarki A.

2014-01-01

NKX3.1 is an androgen-regulated prostate tumor suppressor protein. We previously found that antioxidant administration (N-acetylcysteine) in the Nkx3.1 knock-out mouse model promoted prostate epithelial proliferation, suggesting that NKX3.1 activity modifies the effect of antioxidant administration on prostate carcinogenesis. Interestingly, administration of the antioxidant vitamin E significantly increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), suggesting our animal experiments may be relevant to humans. To determine whether NKX3.1 played a role in increased human prostate cancer risk associated with antioxidant administration in SELECT, we investigated the joint risk of antioxidant administration and NKX3.1 genotypes previously found to be associated with decreased NKX3.1 mRNA expression (rs11781886) or DNA-binding activity in vitro (rs2228013) in the SELECT biomarker case-cohort sub-study (1,866 cases; 3135 non-cases). Multivariable COX regression models were developed to determine the joint association of NKX3.1 genotypes with administration of vitamin E, selenium, or the combination, compared to placebo. The CC genotype at rs11781886 combined with selenium administration was associated with increased overall prostate cancer risk (HR 1.676, 95% CI 1.011-2.777, p=0.045) and low grade prostate cancer risk (HR 1.811, 95% CI 1.016-3.228, p=0.0441). Similarly, the rs11781886 minor allele (CC+CT) combined with vitamin E administration was significantly associated with increased prostate cancer risk (HR 1.450, 95% CI 1.117-1.882, p=0.0052). Our results indicate that variation in NKX3.1 expression combined with selenium or vitamin E treatment modifies the risk of prostate cancer. Genetic background may modulate the effects of antioxidant supplementation thought to act as chemoprevention agents. PMID:24894197

Prostate Enlargement: Benign Prostatic Hyperplasia (BPH)

MedlinePlus

... such as ultrasound, a computerized tomography scan, or magnetic resonance imaging to guide the biopsy needle into ... heats and destroys selected portions of prostate tissue. Shields protect the urethra from heat damage. Transurethral microwave ...

The Influence of a Dietary Protocol on Cone Beam CT-Guided Radiotherapy for Prostate Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smitsmans, Monique H.P.; Pos, Floris J.; Bois, Josien de

2008-07-15

Purpose: To evaluate the influence of a dietary protocol on cone beam computed tomography (CBCT) image quality, which is an indirect indicator for short-term (intrafraction) prostate motion, and on interfraction motion. Image quality is affected by motion (e.g., moving gas) during imaging and influences the performance of automatic prostate localization on CBCT scans. Methods and Materials: Twenty-six patients (336 CBCT scans) followed the dietary protocol and 23 patients (240 CBCT scans) did not. Prostates were automatically localized by using three dimensional (3D) gray-value registration (GR). Feces and (moving) gas occurrence in the CBCT scans, the success rate of 3D-GR, andmore » the statistics of prostate motion data were assessed. Results: Feces, gas, and moving gas significantly decreased from 55%, 61%, and 43% of scans in the nondiet group to 31%, 47%, and 28% in the diet group (all p < 0.001). Since there is a known relation between gas and short-term prostate motion, intrafraction prostate motion probably also decreased. The success rate of 3D-GR improved from 83% to 94% (p < 0.001). A decrease in random interfraction prostate motion also was found, which was not significant after Bonferroni's correction. Significant deviations from planning CT position for rotations around the left-right axis were found in both groups. Conclusions: The dietary protocol significantly decreased the incidence of feces and (moving) gas. As a result, CBCT image quality and the success rate of 3D-GR significantly increased. A trend exists that random interfraction prostate motion decreases. Using a dietary protocol therefore is advisable, also without CBCT-based image guidance.« less

A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden

PubMed Central

Vickers, Andrew J; Cronin, Angel M; Aus, Gunnar; Pihl, Carl-Gustav; Becker, Charlotte; Pettersson, Kim; Scardino, Peter T; Hugosson, Jonas; Lilja, Hans

2008-01-01

Background Prostate-specific antigen (PSA) is widely used to detect prostate cancer. The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies. We set out to determine whether a multivariable model including four kallikrein forms (total, free, and intact PSA, and human kallikrein 2 (hK2)) could predict prostate biopsy outcome in previously unscreened men with elevated total PSA. Methods The study cohort comprised 740 men in Göteborg, Sweden, undergoing biopsy during the first round of the European Randomized study of Screening for Prostate Cancer. We calculated the area-under-the-curve (AUC) for predicting prostate cancer at biopsy. AUCs for a model including age and PSA (the 'laboratory' model) and age, PSA and digital rectal exam (the 'clinical' model) were compared with those for models that also included additional kallikreins. Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and clinical models respectively. Using a 20% risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 (57%) and missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers. Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA. A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening, but defer biopsy until there was stronger evidence of malignancy. PMID:18611265

[Comparative oncologic and functional outcomes of prostate cancer surgery with other curative treatments].

PubMed

Soulié, M; Salomon, L

2015-11-01

Review of the comparative results of different treatment strategies (surgery, radiotherapy, ultrasound, surveillance) of prostate cancer, in which the main goal is the local control and the second target is the tolerance of the side effects of those treatments. Review of literature using Medline databases selected based on scientific relevance. Clinical keys centered on the oncological and functional outcomes of comparative series between different curative treatments. The numerous comparative series between surgery and other therapeutic modalities are essentially retrospective with significant methodological bias that is difficult to overcome in order to formulate the optimal thesis. However, there is a clear tendency toward surgery usually with young patients who have intermediate risk tumors without important comorbidity. In the absence of randomized comparative series with significant power, the oncological and functional results of the radical prostatectomy with or without adjuvant treatment seem at least the same, in a selected population of patients, compared with the combination of radiotherapy-hormonotherapy in terms of survival, without biochemical recurrence, disease-specific survival and overall survival, for the aggressive tumors necessitating curative local treatments. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication.

PubMed

Bellera, Carine; Proust-Lima, Cécile; Joseph, Lawrence; Richaud, Pierre; Taylor, Jeremy; Sandler, Howard; Hanley, James; Mathoulin-Pélissier, Simone

2018-04-01

Background Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure. Objective Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework. For this purpose, we monitored the prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. We focused on the assessment of the prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure. Methods We used a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. We modeled prostate-specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability was expressed as a function of prostate-specific antigens concentration. Covariates in the survival model included hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process. Results We showed positive associations between an increased prostate-specific antigens nadir, an earlier changepoint and a steeper post-nadir slope with an increased risk of failure. Importantly, we highlighted a significant benefit of hormone therapy, an effect that was not observed when the prostate-specific antigens trajectory was not accounted for in the survival model. Conclusion Our modeling strategy was particularly flexible and accounted for multiple complex features of longitudinal and survival data, including the presence of a random changepoint and a time-dependent covariate.

Development and external multicenter validation of Chinese Prostate Cancer Consortium prostate cancer risk calculator for initial prostate biopsy.

PubMed

Chen, Rui; Xie, Liping; Xue, Wei; Ye, Zhangqun; Ma, Lulin; Gao, Xu; Ren, Shancheng; Wang, Fubo; Zhao, Lin; Xu, Chuanliang; Sun, Yinghao

2016-09-01

Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men. Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals. Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa. CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared with Western risk calculators. CPCC-RC may aid in decision-making of prostate biopsy in Chinese or in other Asian populations with similar genetic and environmental backgrounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial

PubMed Central

Brundage, Michael; Sydes, Matthew R.; Parulekar, Wendy R.; Warde, Padraig; Cowan, Richard; Bezjak, Andrea; Kirkbride, Peter; Parliament, Matthew; Moynihan, Clare; Bahary, Jean-Paul; Parmar, Mahesh K.B.; Sanders, Karen; Chen, Bingshu E.; Mason, Malcolm D.

2015-01-01

Purpose The NCIC CTG PR3/MRC PR07 randomized phase III trial compared androgen-deprivation therapy (ADT) alone versus ADT with radiotherapy (RT) for patients with locally advanced prostate cancer. This article reports the health-related quality-of-life (HRQOL) outcomes of this trial. Patients and Methods A total of 1,205 patients were randomly allocated to either ADT alone or ADT with RT. HRQOL was assessed at baseline and every 6 months thereafter using the European Organisation for Research and Treatment of Cancer Core Questionnaire and a prostate cancer–specific checklist or the Functional Assessment of Cancer Therapy–Prostate questionnaire. Mean changes from baseline scores for five function domains and nine symptom domains were analyzed as those most relevant to ADT and RT. The proportions of patients with improved, stable, or worsened HRQOL scores according to instrument-specific minimal important differences were calculated. Results Baseline questionnaires were completed by 1,028 patients (88%). At 6 months, RT had a statistically significant impact on mean score for bowel symptoms (P = .02), diarrhea (P < .001), urinary function (P = .003), and erectile dysfunction (P = .008); by 3 years, however, there were no significant between-group differences in any domain. Generalized linear mixed modeling revealed no significant between-arm differences in any of the function scales but showed significant deterioration in both arms over time for Functional Assessment of Cancer Therapy–Prostate total score, treatment outcome index, and physical and functional well-being. Conclusion The addition of RT to ADT for patients with locally advanced prostate cancer significantly improved overall survival and had only modest and transient negative impact on relevant domains of HRQOL. PMID:26014295

State-of-the-art: prostate LDR brachytherapy.

PubMed

Voulgaris, S; Nobes, J P; Laing, R W; Langley, S E M

2008-01-01

This article on low dose rate (LDR) prostate brachytherapy reviews long-term results, patient selection and quality of life issues. Mature results from the United States and United Kingdom are reported and issues regarding definitions of biochemical failure are discussed. Latest data comparing brachytherapy with radical prostatectomy or no definitive treatment and also the risk of secondary malignancies after prostate brachytherapy are presented. Urological parameters of patient selection and quality of life issues concerning urinary, sexual and bowel function are reviewed. The position of prostate brachytherapy next to surgery as a first-line treatment modality is demonstrated.

Radiotherapy for Prostate Cancer: is it 'what you do' or 'the way that you do it'? A UK Perspective on Technique and Quality Assurance.

PubMed

Mason, M D; Moore, R; Jones, G; Lewis, G; Donovan, J L; Neal, D E; Hamdy, F C; Lane, J A; Staffurth, J N

2016-09-01

The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history of prostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial. The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localised prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n = 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era. There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outlining review showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of the prostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints in ProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent. The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials. Copyright © 2016. Published by Elsevier Ltd.

Active for Life After Cancer: a randomized trial examining a lifestyle physical activity program for prostate cancer patients.

PubMed

Carmack Taylor, Cindy L; Demoor, Carl; Smith, Murray A; Dunn, Andrea L; Basen-Engquist, Karen; Nielsen, Ingrid; Pettaway, Curtis; Sellin, Rena; Massey, Pamela; Gritz, Ellen R

2006-10-01

Active for Life After Cancer is a randomized trial evaluating the efficacy of a 6-month group-based lifestyle physical activity program (Lifestyle) for prostate cancer patients to improve quality of life (QOL) including physical and emotional functioning compared to a group-based Educational Support Program and a Standard Care Program (no group). A total of 134 prostate cancer patients receiving continuous androgen-ablation were randomly assigned to one of the three study conditions. Results indicated no significant improvements in QOL at 6 or 12 months. Both group-based programs were positively received and yielded good attendance and retention. Lifestyle participants demonstrated significant improvements in most theoretical mediators proposed by the Transtheoretical Model and Social Cognitive Theory to affect physical activity. Despite these improvements, no significant changes were found for most physical activity measures. Results suggest a lifestyle program focusing on cognitive-behavioral skills training alone is insufficient for promoting routine physical activity in these patients.

Sexual dysfunction in subjects treated with inhibitors of 5α-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis.

PubMed

Corona, G; Tirabassi, G; Santi, D; Maseroli, E; Gacci, M; Dicuio, M; Sforza, A; Mannucci, E; Maggi, M

2017-07-01

Despite their efficacy in the treatment of benign prostatic hyperplasia, the popularity of inhibitors of 5α-reductase (5ARIs) is limited by their association with adverse sexual side effects. The aim of this study was to review and meta-analyze currently available randomized clinical trials evaluating the rate of sexual side effects in men treated with 5ARIs. An extensive Medline Embase and Cochrane search was performed including the following words: 'finasteride', 'dutasteride', 'benign prostatic hyperplasia'. Only placebo-controlled randomized clinical trials evaluating the effect of 5ARI in subjects with benign prostatic hyperplasia were considered. Of 383 retrieved articles, 17 were included in this study. Randomized clinical trials enrolled 24,463 in the active and 22,270 patients in the placebo arms, respectively, with a mean follow-up of 99 weeks and mean age of 64.0 years. No difference was observed between trials using finasteride or dutasteride as the active arm considering age, trial duration, prostate volume or International Prostatic Symptoms Score at enrollment. Overall, 5ARIs determined an increased risk of hypoactive sexual desire [OR = 1.54 (1.29; 1.82); p < 0.0001] and erectile dysfunction [OR = 1.47 (1.29; 1.68); p < 0.0001]. No difference between finasteride and dutasteride regarding the risk of hypoactive sexual desire and erectile dysfunction was observed. Meta-regression analysis showed that the risk of hypoactive sexual desire and erectile dysfunction was higher in subjects with lower Q max at enrollment and decreased as a function of trial follow-up. Conversely, no effect of age, low urinary tract symptom or prostate volume at enrollment as well as Q max at end-point was observed. In conclusion, present data show that the use of 5ARI significantly increases the risk of erectile dysfunction and hypoactive sexual desire in subjects with benign prostatic hyperplasia. Patients should be adequately informed before 5ARIs are prescribed. © 2017 American Society of Andrology and European Academy of Andrology.

Configuration and validation of a novel prostate disease nomogram predicting prostate biopsy outcome: A prospective study correlating clinical indicators among Filipino adult males with elevated PSA level.

PubMed

Chua, Michael E; Tanseco, Patrick P; Mendoza, Jonathan S; Castillo, Josefino C; Morales, Marcelino L; Luna, Saturnino L

2015-04-01

To configure and validate a novel prostate disease nomogram providing prostate biopsy outcome probabilities from a prospective study correlating clinical indicators and diagnostic parameters among Filipino adult male with elevated serum total prostate specific antigen (PSA) level. All men with an elevated serum total PSA underwent initial prostate biopsy at our institution from January 2011 to August 2014 were included. Clinical indicators, diagnostic parameters, which include PSA level and PSA-derivatives, were collected as predictive factors for biopsy outcome. Multiple logistic-regression analysis involving a backward elimination selection procedure was used to select independent predictors. A nomogram was developed to calculate the probability of the biopsy outcomes. External validation of the nomogram was performed using separate data set from another center for determination of sensitivity and specificity. A receiver-operating characteristic (ROC) curve was used to assess the accuracy in predicting differential biopsy outcome. Total of 552 patients was included. One hundred and ninety-one (34.6%) patients had benign prostatic hyperplasia, and 165 (29.9%) had chronic prostatitis. The remaining 196 (35.5%) patients had prostate adenocarcinoma. The significant independent variables used to predict biopsy outcome were age, family history of prostate cancer, prior antibiotic intake, PSA level, PSA-density, PSA-velocity, echogenic findings on ultrasound, and DRE status. The areas under the receiver-operating characteristic curve for prostate cancer using PSA alone and the nomogram were 0.688 and 0.804, respectively. The nomogram configured based on routinely available clinical parameters, provides high predictive accuracy with good performance characteristics in predicting the prostate biopsy outcome such as presence of prostate cancer, high Gleason prostate cancer, benign prostatic hyperplasia, and chronic prostatitis.

Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.

PubMed

Guimond, Marie-Odile; Battista, Marie-Claude; Nikjouitavabi, Fatemeh; Carmel, Maude; Barres, Véronique; Doueik, Alexandre A; Fazli, Ladan; Gleave, Martin; Sabbagh, Robert; Gallo-Payet, Nicole

2013-07-01

Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture. AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate. AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells. AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance. Copyright © 2013 Wiley Periodicals, Inc.

The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer.

PubMed

Navarro-Pelayo Láinez, M M; Rodríguez-Fernández, A; Gómez-Río, M; Vázquez-Alonso, F; Cózar-Olmo, J M; Llamas-Elvira, J M

2014-11-01

prostate cancer is the most frequent solid malignant tumor in Western Countries. Positron emission tomography/x-ray computed tomography imaging with radiolabeled choline analogues is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. a MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer» and «Choline-PET/CT». Other search terms were «Biochemical failure» and/or «Staging» and/or «PSA kinetics». English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. according to available data, radiolabeled choline analogues plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Synthesis of magnetic molecularly imprinted polymers with excellent biocompatibility for the selective separation and inhibition of testosterone in prostate cancer cells.

PubMed

Tang, Xiaoshuang; Li, Feng; Jia, Jing; Yang, Chao; Liu, Wei; Jin, Ben; Wang, Xinyang; Gao, Ruixia; He, Dalin; Guo, Peng

2017-01-01

Androgen plays an important role in the progression of prostate cancer. In the present study, novel magnetic molecularly imprinted polymers (MMIPs) with good biocompatibility were produced for the selective separation and inhibition of testosterone in prostate cancer cells. MMIPs were prepared by using magnetic nanospheres, gelatin, and testosterone as the supporting materials, functional monomer, and the template molecule, respectively. The characterization of the resultant products was investigated by transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometry. To test whether MMIPs can remove testosterone in biologic samples, human LNCaP (androgen-dependent) and C4-2 (androgen-independent) prostate cancer cells were selected as cell models. The translocation of androgen receptor (AR) was detected by immunofluorescence assay, and the expression of PSA mRNA was detected by real-time quantitative polymerase chain reaction analysis. Cell flow cytometry analysis was performed to detect cell cycle arrest. The synthesized nanomaterials (MMIPs) possessed high crystallinity, satisfactory superparamagnetic properties, and uniform imprinted shell, and exhibited high adsorption capacity, fast kinetics, and high selectivity for testosterone. Moreover, the obtained imprinted nanomaterials could selectively enrich and detect testosterone in the LNCaP cell samples as a solid-phase extractant coupled with high-performance liquid chromatography. In addition, the MMIPs could freely enter prostate cancer cells and suppress the translocation of AR into the cell nucleus. We further found that MMIPs inhibited upregulation of AR downstream target genes in LNCaP and C4-2 cells; also, MMIPs inhibited cell growth and induced obvious cell cycle arrest in androgen-dependent LNCaP cells, but had no obvious effect on androgen-independent C4-2 cells. Our results indicate that the obtained imprinted nanomaterials can specifically and effectively bind testosterone and recover it from prostate cancer cells. Moreover, the MMIPs can freely enter prostate cancer cells and block the activation of testosterone-AR pathway. Thus, the MMIPs may be a new option for antiandrogen therapy in prostate cancer.

Inhibition of Adrenergic and Non-Adrenergic Smooth Muscle Contraction in the Human Prostate by the Phosphodiesterase 10-Selective Inhibitor TC-E 5005.

PubMed

Hennenberg, Martin; Schott, Melanie; Kan, Aysenur; Keller, Patrick; Tamalunas, Alexander; Ciotkowska, Anna; Rutz, Beata; Wang, Yiming; Strittmatter, Frank; Herlemann, Annika; Yu, Qingfeng; Stief, Christian G; Gratzke, Christian

2016-11-01

The phosphodiesterase (PDE) 5 inhibitor tadalafil is available for treatment of male lower urinary tract symptoms (LUTS), while the role of other PDE isoforms for prostate smooth muscle tone is still unknown. Here, we examined effects of the PDE10-selective inhibitor TC-E 5005 on smooth muscle contraction in human prostate tissue. Prostate samples were obtained from patients undergoing radical prostatectomy. Expression of PDE10 was addressed by RT-PCR, Western blot, and fluorescence staining with different markers. Effects of TC-E 5005 and tadalafil on contraction, and relaxation of prostate strips were studied via organ bath. PDE10A was detectable by RT-PCR, Western blot, and fluorescence staining in prostate tissues. Colocalization with markers suggested expression of PDE10A in smooth muscle cells and catecholaminergic nerves. Norepinephrine, the α1 -adrenergic agonist phenylephrine, the thromboxane A2 analogue U46619, and endothelins 1-3 induced concentration-dependent contractions of prostate strips, while electric field stimulation (EFS) induced frequence-dependent contractions. Application of TC-E 5005 (500 nM) caused significant inhibition of norepinephrine-, phenylephrine-, and endothelin-3-induced contractions. Inhibition of EFS-induced contractions by TC-E 5005 ranged around 50%, resembling inhibition of EFS-induced contractions by tadalafil (10 μM). The prostacyclin analog treprostinil and the nitric oxide donor DEA NONOate induced relaxations of precontracted prostate strips, which were significantly amplified by TCE 5005. The PDE10-selective inhibitor TC-E 5005 inhibits adrenergic and neurogenic smooth muscle contractions in the human prostate. TC-E 5005 inhibits neurogenic contractions with similar efficacy than tadalafil, so that urodynamic effects in vivo appear possible. Prostate 76:1364-1374, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Impact of Contextual Factors on Prostate Cancer Risk and Outcomes

DTIC Science & Technology

2013-07-01

framework with random effects (“frailty models”) while the case-control analyses (Aim 4) will use multilevel unconditional logistic regression models...contextual-level SES on prostate cancer risk within racial/ethnic groups. The survival analyses (Aims 1-3) will utilize a proportional hazards regression

Altered prostate epithelial development and IGF-1 signal in mice lacking the androgen receptor in stromal smooth muscle cells.

PubMed

Yu, Shengqiang; Zhang, Caixia; Lin, Chiu-Chun; Niu, Yuanjie; Lai, Kuo-Pao; Chang, Hong-chiang; Yeh, Shauh-Der; Chang, Chawnshang; Yeh, Shuyuan

2011-04-01

Androgens and the androgen receptor (AR) play critical roles in the prostate development via mesenchymal-epithelial interactions. Smooth muscle cells (SMC), differentiated from mesenchyme, are one of the basic components of the prostate stroma. However, the roles of smooth muscle AR in prostate development are still obscure. We established the smooth muscle selective AR knockout (SM-ARKO) mouse model using the Cre-loxP system, and confirmed the ARKO efficiency at RNA, DNA and protein levels. Then, we observed the prostate morphology changes, and determined the epithelial proliferation, apoptosis, and differentiation. We also knocked down the AR in a prostate smooth muscle cell line (PS-1) to confirm the in vivo findings and to probe the mechanism. The AR was selectively and efficiently knocked out in the anterior prostates of SM-ARKO mouse. The SM-ARKO prostates have defects with loss of infolding structures, and decrease of epithelial proliferation, but with little change of apoptosis and differentiation. The mechanism studies showed that IGF-1 expression level decreased in the SM-ARKO prostates and AR-knockdown PS-1 cells. The decreased IGF-1 expression might contribute to the defective development of SM-ARKO prostates. The AR in SMCs plays important roles in the prostate development via the regulation of IGF-1 signal. Copyright © 2010 Wiley-Liss, Inc.

Commentary on "randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and Ki67 labeling in prostate cancer patients." Wagner D, Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo S, Hersey K, Klotz L, Finelli A, Fleshner N, Vieth R, Department of Nutritional Sciences, University of Toronto, Ontario, Canada.: J Clin Endocrinol Metab 2013;98(4):1498-507 [Epub 2013 Mar 5].

PubMed

Olumi, Aria F

2014-02-01

Vitamin D3 might benefit prostate cancer (PCa) patients because prostate cells can locally synthesize the active hormone calcitriol. Our objective was to determine the effects of oral vitamin D3 on vitamin D metabolites and PCa proliferative activity in prostate tissue. We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada. PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol. Vitamin D3 (400, 10000, or 40000 IU/d) was orally administered before radical prostatectomy. We evaluated vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety measures, PTH, and prostate-specific antigen (PSA) were also assessed. Prostate tissue and serum levels of vitamin D metabolites, including calcitriol, increased dose dependently (P<.03) and were significantly higher in the 40000-IU/d group than in every other dose group (P<.03). Prostate vitamin D metabolites correlated positively with serum levels (P<.0001). Ki67 measures did not differ significantly among vitamin D dose groups. However, cross-sectional analysis indicated that the calcitriol level attained in prostate was inversely associated with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign tissue (P<.05). Safety measures did not change adversely with dosing. Compared with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose groups at the end of the study (P< .02). Oral vitamin D3 raised prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and PTH. Although Ki67 expression did not differ among dose groups, its levels correlated inversely with prostate calcitriol. These suggestions of clinical benefit justify continued clinical research. Copyright © 2014 Elsevier Inc. All rights reserved.

Residual Prostate Cancer in Patients Treated With Endocrine Therapy With or Without Radical Radiotherapy: A Side Study of the SPCG-7 Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solberg, Arne, E-mail: arne.solberg@stolav.n; Haugen, Olav A.; Department of Pathology and Medical Genetics, St. Olav's Hospital, Trondheim University Hospital, Trondheim

2011-05-01

Purpose: The Scandinavian Prostate Cancer Group-7 randomized trial demonstrated a survival benefit of combined endocrine therapy and external-beam radiotherapy over endocrine therapy alone in patients with high-risk prostate cancer. In a subset of the study population, the incidence and clinical implications of residual prostate cancer in posttreatment prostate biopsy specimens was evaluated. Methods and Materials: Biopsy specimens were obtained from 120 of 875 men in the Scandinavian Prostate Cancer Group-7 study. Results: Biopsies were performed at median of 45 months follow-up. In 63 patients receiving endocrine treatment only and 57 patients receiving combined treatment, residual cancer was found in 66%more » (n = 41) and 22% (n = 12), respectively (p < 0.0001). The vast majority of residual tumors were poorly differentiated (Gleason score {>=}8). Endocrine therapy alone was predictive of residual prostate cancer: odds ratio 7.49 (3.18-17.7), p < 0.0001. In patients with positive vs. negative biopsy the incidences of clinical events were as follows: biochemical recurrence 74% vs. 27% (p < 0.0001), local progression 26% vs. 4.7% (p = 0.002), distant recurrence 17% vs. 9.4% (p = 0.27), clinical recurrence 36% vs. 13% (p = 0.006), cancer-specific death 19% vs. 9.7% (p = 0.025). In multivariable analysis, biochemical recurrence was significantly associated with residual cancer: hazard ratio 2.69 (1.45-4.99), p = 0.002, and endocrine therapy alone hazard ratio 3.45 (1.80-6.62), p < 0.0001. Conclusions: Radiotherapy combined with hormones improved local tumor control in comparison with endocrine therapy alone. Residual prostate cancer was significantly associated with serum prostate-specific antigen recurrence, local tumor progression, clinical recurrence, and cancer-specific death in univariable analysis. Residual cancer was predictive of prostate-specific antigen recurrence in multivariable analysis.« less

Finasteride accelerates prostate wound healing after thulium laser resection through DHT and AR signalling.

PubMed

Zhao, Ruizhe; Wang, Xingjie; Jiang, Chenyi; Shi, Fei; Zhu, Yiping; Yang, Boyu; Zhuo, Jian; Jing, Yifeng; Luo, Guangheng; Xia, Shujie; Han, Bangmin

2018-06-01

Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post-operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling. TmLRP beagles were randomly distributed into different treatment groups. Serum and intra-prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re-epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF-α on prostate epithelium and stromal cells were also investigated. Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF-α secretion through AR signalling. TNF-α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF-α also played a pivotal role in suppressing fibroblasts activation and contraction. Testosterone treatment repressed re-epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re-epithelialization. © 2017 John Wiley & Sons Ltd.

Impact of pelvic nodal irradiation with intensity-modulated radiotherapy on treatment of prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, Robert A.; Hannoun-Levi, Jean-Michel; Horwitz, Eric

2006-10-01

Purpose: The aim of this study was to evaluate the feasibility of treating the pelvic lymphatic regions during prostate intensity-modulated radiotherapy (IMRT) with respect to our routine acceptance criteria. Methods and Materials: A series of 10 previously treated prostate patients were randomly selected and the pelvic lymphatic regions delineated on the fused magnetic resonance/computed tomography data sets. A targeting progression was formed from the prostate and proximal seminal vesicles only to the inclusion of all pelvic lymphatic regions and presacral region resulting in 5 planning scenarios of increasing geometric difficulty. IMRT plans were generated for each stage for two acceleratormore » manufacturers. Dose volume histogram data were analyzed with respect to dose to the planning target volumes, rectum, bladder, bowel, and normal tissue. Analysis was performed for the number of segments required, monitor units, 'hot spots,' and treatment time. Results: Both rectal endpoints were met for all targets. Bladder endpoints were not met and the bowel endpoint was met in 40% of cases with the inclusion of the extended and presacral lymphatics. A significant difference was found in the number of segments and monitor units with targeting progression and between accelerators, with the smaller beamlets yielding poorer results. Treatment times between the 2 linacs did not exhibit a clinically significant difference when compared. Conclusions: Many issues should be considered with pelvic lymphatic irradiation during IMRT delivery for prostate cancer including dose per fraction, normal structure dose/volume limits, planning target volumes generation, localization, treatment time, and increased radiation leakage. We would suggest that, at a minimum, the endpoints used in this work be evaluated before beginning IMRT pelvic nodal irradiation.« less

Transrectal-ultrasound prostatic biopsy preparation: rectal enema vs. mechanical bowel preparation.

PubMed

De Nunzio, Cosimo; Lombardo, Riccardo; Presicce, Fabrizio; Bellangino, Mariangela; Finazzi Agro, Enrico; Gambrosier, Matteo Bonetto; Trucchi, Alberto; Petta, Stefano; Tubaro, Andrea

2015-01-01

Transrectal prostate biopsy (TRUSbx) is the standard for the diagnosis of prostate cancer. Different bowel preparations are used for patients undergoing TRUSbx. The aim of our study was to compare two different bowel preparations for TRUSbx. From May 2012 and onwards, a selected group of men undergoing TRUS 12-core prostate biopsy were enrolled into a prospective database. Patients were randomized 1:1 to receive a rectal enema (Group A) the night before the procedure or polyethylene glycol 34.8 grams/4 liters of water the day before the procedure (Group B). A VAS scale to evaluate the patients' discomfort according to the two preparations was collected. The same antibiotic prophylaxis was performed in both groups. All complications were prospectively recorded and graded according to the Clavien Classification System (CCS). A total of 198 patients were consecutively enrolled. Mean age was 67.5 ±7.9 years, mean body mass index (BMI) was 27.1 ±4.2 Kg/m(2), mean PSA value was 9.3 ±12.6 ng/ml and the mean prostatic volume was 60.6 ±29 ml. 97 patients were enrolled in Group A and 101 in Group B. Overall post-biopsy morbidity rate was 60%. No significant differences for low-grade and high-grade complications was observed between the two groups. Patients receiving the rectal enema presented with a significantly lower VAS score (3.1 ±1.1 vs. 5.9 ±1.7; p = 0.02). Our study confirmed that a rectal enema should be considered as the standard bowel preparation in patients undergoing a TRUS biopsy; it is as effective as PEG and associated with less discomfort.

Dosimetric effects of weight loss or gain during volumetric modulated arc therapy and intensity-modulated radiation therapy for prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pair, Matthew L.; Du, Weiliang; Rojas, Hector D.

Weight loss or gain during the course of radiation therapy for prostate cancer can alter the planned dose to the target volumes and critical organs. Typically, source-to-surface distance (SSD) measurements are documented by therapists on a weekly basis to ensure that patients' exterior surface and isocenter-to-skin surface distances remain stable. The radiation oncology team then determines whether the patient has undergone a physical change sufficient to require a new treatment plan. The effect of weight change (SSD increase or decrease) on intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) dosimetry is not well known, and it is unclearmore » when rescanning or replanning is needed. The purpose of this study was to determine the effects of weight change (SSD increase or decrease) on IMRT or VMAT dose delivery in patients with prostate cancer and to determine the SSD change threshold for replanning. Whether IMRT or VMAT provides better dose stability under weight change conditions was also determined. We generated clinical IMRT and VMAT prostate and seminal vesicle treatment plans for varying SSDs for 10 randomly selected patients with prostate cancer. The differences due to SSD change were quantified by a specific dose change for a specified volume of interest. The target mean dose, decreased or increased by 2.9% per 1-cm SSD decrease or increase in IMRT and by 3.6% in VMAT. If the SSD deviation is more than 1 cm, the radiation oncology team should determine whether to continue treatment without modifications, to adjust monitor units, or to resimulate and replan.« less

Selective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities

PubMed Central

Montecinos, Viviana P; Morales, Claudio H; Fischer, Thomas H; Burns, Sarah; San Francisco, Ignacio F; Godoy, Alejandro S; Smith, Gary J

2015-01-01

Androgen deprivation therapy (ADT) provides palliation for most patients with advanced prostate cancer (CaP); however, greater than 80% subsequently fail ADT. ADT has been indicated to induce an acute but transient destabilization of the prostate vasculature in animal models and humans. Human re-hydrated lyophilized platelets (hRL-P) were investigated as a prototype for therapeutic agents designed to target selectively the tumour-associated vasculature in CaP. The ability of hRL-P to bind the perturbed endothelial cells was tested using thrombin- and ADP-activated human umbilical vein endothelial cells (HUVEC), as well as primary xenografts of human prostate tissue undergoing acute vascular involution in response to ADT. hRL-P adhered to activated HUVEC in a dose-responsive manner. Systemically administered hRL-P, and hRL-P loaded with super-paramagnetic iron oxide (SPIO) nanoparticles, selectively targeted the ADT-damaged human microvasculature in primary xenografts of human prostate tissue. This study demonstrated that hRL-P pre-loaded with chemo-therapeutics or nanoparticles could provide a new paradigm for therapeutic modalities to prevent the rebound/increase in prostate vasculature after ADT, inhibiting the transition to castration-recurrent growth. PMID:25736582

Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study.

PubMed

Doria, Carlo; Leali, Paolo Tranquilli; Solla, Federico; Maestretti, Gianluca; Balsano, Massimo; Scarpa, Robero Mario

2016-01-01

Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. The best defense against osteoporosis in prostate cancer is to identify patients with a high risk for fracture during the first clinical visit, select an effective anti-osteoporosis agent, and advise the patient to change his lifestyle and diet to prevent further bone loss. New agents include denosumab, a human monoclonal antibody that inhibits the RANK ligand (RANKL). RANKL promotes the formation, activity, and survival of osteoclasts and, thus, supports the breakdown of bone. This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT in prostate cancer patients in three European countries (Italy, France, Switzerland). In this 24-month observation study we enrolled 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer. All patients aged ≥55 years and had a dual-energy X-ray absorptiometry (DEXA) T-score <-1.0 (hip or spine, measured within last 2 years) and ≥ 1 fragility fracture. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg weekly) for 2 years. All patient received supplemental vitamin D (600 IU per day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), Bone Mineral Density (BMD), fracture incidence, Visual Analogue Scale (VAS) score for back pain, and Short Form-8 (SF-8TM) health survey score for health-related quality of life (HRQoL). Percent changes from baseline in BTMs and BMD were assessed using the paired t test; a P-value 0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs -1.1% with alendronate (P<0.001). New vertebral fractures developed in fewer patients in the denosumab group than in the alendronate group during the 24-month period, although this difference was not significant (P=0.10). Back pain significantly (P<0.001) improved from baseline at all time points during the study in both study groups. SF-8 health survey scores significantly improved following treatment with both drugs. Incidence of adverse drug reactions were similar in both groups. In our study denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.

Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study

PubMed Central

Doria, Carlo; Leali, Paolo Tranquilli; Solla, Federico; Maestretti, Gianluca; Balsano, Massimo; Scarpa, Robero Mario

2016-01-01

Summary Introduction Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. The best defense against osteoporosis in prostate cancer is to identify patients with a high risk for fracture during the first clinical visit, select an effective anti-osteoporosis agent, and advise the patient to change his lifestyle and diet to prevent further bone loss. New agents include denosumab, a human monoclonal antibody that inhibits the RANK ligand (RANKL). RANKL promotes the formation, activity, and survival of osteoclasts and, thus, supports the breakdown of bone. Purpose This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT in prostate cancer patients in three European countries (Italy, France, Switzerland). Patients and methods In this 24-month observation study we enrolled 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer. All patients aged ≥55 years and had a dual-energy X-ray absorptiometry (DEXA) T-score <−1.0 (hip or spine, measured within last 2 years) and ≥ 1 fragility fracture. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg weekly) for 2 years. All patient received supplemental vitamin D (600 IU per day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), Bone Mineral Density (BMD), fracture incidence, Visual Analogue Scale (VAS) score for back pain, and Short Form-8 (SF-8TM) health survey score for health-related quality of life (HRQoL). Percent changes from baseline in BTMs and BMD were assessed using the paired t test; a P-value 0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs −1.1% with alendronate (P<0.001). New vertebral fractures developed in fewer patients in the denosumab group than in the alendronate group during the 24-month period, although this difference was not significant (P=0.10). Back pain significantly (P<0.001) improved from baseline at all time points during the study in both study groups. SF-8 health survey scores significantly improved following treatment with both drugs. Incidence of adverse drug reactions were similar in both groups. Conclusion In our study denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures. PMID:28228781

A randomized, phase II study of pazopanib in castrate-sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study.

PubMed

Ward, J E; Karrison, T; Chatta, G; Hussain, M; Shevrin, D; Szmulewitz, R Z; O'Donnell, P H; Stadler, W M; Posadas, E M

2012-03-01

Intermittent androgen suppression (IAS) is an increasingly popular treatment option for castrate-sensitive prostate cancer. On the basis of previous data with anti-angiogenic strategies, we hypothesized that pan-inhibition of the vascular endothelial growth factor receptor using pazopanib during the IAS off period would result in prolonged time to PSA failure. Men with biochemically recurrent prostate cancer, whose PSA was <0.5 ng ml(-1) after 6 months of androgen deprivation therapy were randomized to pazopanib 800 mg daily or observation. The planned primary outcome was time to PSA progression >4.0 ng ml(-1). Thirty-seven patients were randomized. Of 18 patients randomized to pazopanib, at the time of study closure, 4 had progressive disease, 1 remained on treatment and 13 (72%) electively disenrolled, the most common reason being patient request due to grade 1/2 toxicity (8 patients). Two additional patients were removed from treatment due to adverse events. Of 19 patients randomized to observation, at the time of study closure, 4 had progressive disease, 7 remained under protocol-defined observation and 8 (42%) had disenrolled, most commonly due to non-compliance with protocol visits (3 patients). Because of high dropout rates in both arms, the study was halted. IAS is a treatment approach that may facilitate investigation of novel agents in the hormone-sensitive state. This trial attempted to investigate the role of antiangiogenic therapy in this setting, but encountered several barriers, including toxicities and patient non-compliance, which can make implementation of such a study difficult. Future investigative efforts in this arena should carefully consider drug toxicity and employ a design that maximizes patient convenience to reduce the dropout rate.

Thulium laser VapoResection of the prostate versus traditional transurethral resection of the prostate or transurethral plasmakinetic resection of prostate for benign prostatic obstruction: a systematic review and meta-analysis.

PubMed

Deng, Zheng; Sun, Menghao; Zhu, Yiping; Zhuo, Jian; Zhao, Fujun; Xia, Shujie; Han, Bangmin; Herrmann, Thomas R W

2018-04-12

To compare the efficacy and safety of thulium laser VapoResection of the prostate (ThuVaRP) versus standard traditional transurethral resection of the prostate (TURP) or plasmakinetic resection of prostate (PKRP) for benign prostatic obstruction. Systematic searches were performed in the Medline, EMBASE, the Cochrane Library, Web of Science, and CNKI in December 2017. The outcomes of demographic and clinical characteristics, perioperative variables, complications, and postoperative efficacy including International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), and postvoid residual (PVR) were assessed. 16 studies were selected in the meta-analysis including nine randomized controlled trials (RCTs) and seven non-RCTs. Among of them, nine studies compared ThuVaRP with PKRP, while seven studies compared ThuVaRP with TURP. It seemed that ThuVaRP needed longer operation time than TURP (WMD = 6.41, 95% CI 1.38-11.44, p = 0.01) and PKRP (WMD = 10.15, 95% CI 5.20-15.10, p < 0.0001). ThuVaRP was associated with less serum hemoglobin decreased, catheterization time, and the length of hospital stay compared with TURP (WMD = - 0.58, 95% CI - 0.77 to 0.38, p < 0.00001; WMD = - 1.89, 95% CI - 2.67 to 1.11, p < 0.00001; WMD = - 2.25, 95% CI - 2.91 to 1.60, p < 0.00001) and PKRP (WMD = - 0.28, 95% CI - 0.46 to 0.10, p = 0.002; WMD = - 1.88, 95% CI - 2.87 to 0.89, p = 0.0002; WMD = - 2.08, 95% CI - 2.63 to 1.54, p<0.00001). According to our assessment, there was no significantly difference in postoperative efficacy. The pooled data indicated that ThuVaRP had a nearly efficacy to TURP and PKRP based on IPSS, QoL, Qmax, and PVR. Although ThuVaRP was associated with longer operation time, it got distinct superiority on serum hemoglobin decreased, catheterization time, and hospital stay.

Effectiveness of Educational Intervention on the Congruence of Prostate and Rectal Contouring as Compared With a Gold Standard in Three-Dimensional Radiotherapy for Prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szumacher, Ewa, E-mail: Ewa.Szumacher@sunnybrook.c; Harnett, Nicole; Warner, Saar

Purpose: To examine effects of a teaching intervention on precise delineation of the prostate and rectum during planning of three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Methods and Materials: A pretest, posttest, randomized controlled group design was used. During pretest all participants contoured prostate and rectum on planning CT. Afterward, they participated in two types of workshops. The experimental group engaged in an interactive teaching session focused on prostate and rectum MR anatomy compared with CT anatomy. The control group focused on 3D-CRT planning without mention of prostate or rectal contouring. The experimental group practiced on fused MR-CT images, whereasmore » the control group practiced on CT images. All participants completed the posttest. Results: Thirty-one trainees (12 male, 19 female) were randomly assigned to two groups, 17 in the experimental arm, and 14 in the control group. Seventeen felt familiar or very familiar with pelvic organ contouring, 12 somewhat, and 2 had never done it. Thirteen felt confident with organ contouring, 13 somewhat, and 5 not confident. The demographics and composition of groups were analyzed with chi{sup 2} and repeated-measures analysis of variance with the two groups (experimental or control) and two tests (pre- or posttest) as factors. Satisfaction with the course and long-term effects of the course on practice were assessed with immediate and delayed surveys. All performance variables showed a similar pattern of results. Conclusions: The training sessions improved the technical performance similarly in both groups. Participants were satisfied with the course content, and the delayed survey reflected that cognitively participants felt more confident with prostate and rectum contouring and would investigate opportunities to learn more about organ contouring.« less

Pharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy.

PubMed

Ross, Ashley E; Hughes, Robert M; Glavaris, Stephanie; Ghabili, Kamyar; He, Ping; Anders, Nicole M; Harb, Rana; Tosoian, Jeffrey J; Marchionni, Luigi; Schaeffer, Edward M; Partin, Alan W; Allaf, Mohamad E; Bivalacqua, Trinity J; Chapman, Carolyn; O'Neal, Tanya; DeMarzo, Angelo M; Hurley, Paula J; Rudek, Michelle A; Antonarakis, Emmanuel S

2017-11-28

To determine the pharmacodynamic effects of Sonidegib (LDE-225) in prostate tumor tissue from men with high-risk localized prostate cancer, by comparing pre-surgical core-biopsy specimens to tumor tissue harvested post-treatment at prostatectomy. We conducted a prospective randomized (Sonidegib vs. observation) open-label translational clinical trial in men with high-risk localized prostate cancer undergoing radical prostatectomy. The primary endpoint was the proportion of patients in each arm who achieved at least a two-fold reduction in GLI1 mRNA expression in post-treatment versus pre-treatment tumor tissue. Secondary endpoints included the effect of pre-surgical treatment with Sonidegib on disease progression following radical prostatectomy, and safety. Fourteen men were equally randomized (7 per arm) to either neoadjuvant Sonidegib or observation for 4 weeks prior to prostatectomy. Six of seven men (86%) in the Sonidegib arm (and none in the control group) achieved a GLI1 suppression of at least two-fold. In the Sonidegib arm, drug was detectable in plasma and in prostatic tissue; and median intra-patient GLI1 expression decreased by 63-fold, indicating potent suppression of Hedgehog signaling. Sonidegib was well tolerated, without any Grade 3-4 adverse events observed. Disease-free survival was comparable among the two arms (HR = 1.50, 95% CI 0.26-8.69, P = 0.65). Hedgehog pathway activity (as measured by GLI1 expression) was detectable at baseline in men with localized high-risk prostate cancer. Sonidegib penetrated into prostatic tissue and induced a >60-fold suppression of the Hedgehog pathway. The oncological benefit of Hedgehog pathway inhibition in prostate cancer remains unclear.

Listening to music during transrectal ultrasound-guided prostate biopsy decreases anxiety, pain and dissatisfaction in patients: a pilot randomized controlled trial.

PubMed

Chang, Yun Hee; Oh, Tae Hoon; Lee, Jae Whan; Park, Seung Chol; Seo, Ill Young; Jeong, Hee Jong; Kwon, Whi-An

2015-01-01

To determine whether listening to music during transrectal ultrasound (TRUS)-guided 12-core needle prostate biopsy decreases anxiety, pain and dissatisfaction among patients and results in a more comfortable and better tolerated procedure. 76 male patients who underwent TRUS-guided prostate biopsy between March 2013 and June 2014 were randomized into the following groups: no music (group I, n = 38) or classical music (group II, n = 38) during the procedure. Before TRUS-guided prostate biopsy, lidocaine gel was instilled into the rectum. Patient anxiety levels were quantified using the State-Trait Anxiety Inventory. A visual analog scale (0-10) was used for self-assessment of satisfaction, discomfort and willingness among patients to have a repeat TRUS-guided prostate biopsy. Demographic characteristics, mean age, procedure duration and procedure indications did not differ statistically between the two groups. The mean anxiety level and mean pain score of group II were significantly lower than those of group I (p = 0.001 and p = 0.003, respectively). Group II also had a significantly higher mean satisfaction score than group I (p = 0.007). Before the procedure, heart rate and systolic blood pressure were similar in groups I and II; however, after the procedure, levels were lower in group II than in group I (heart rate, p = 0.014; systolic blood pressure, p = 0.011). Listening to music during TRUS-guided prostate biopsy significantly reduced patients' feelings of pain, discomfort and dissatisfaction. Music can serve as a simple, inexpensive and effective adjunct to sedation during TRUS-guided prostate biopsy. We recommend playing music during TRUS-guided prostate biopsy. 2014 S. Karger AG, Basel

Saw Palmetto for Symptom Management During Radiation Therapy for Prostate Cancer.

PubMed

Wyatt, Gwen K; Sikorskii, Alla; Safikhani, Abolfazl; McVary, Kevin T; Herman, James

2016-06-01

Lower urinary tract symptoms (LUTSs) affect 75%-80% of men undergoing radiation therapy (RT) for prostate cancer. To determine the safety, maximum tolerated dose (MTD), and preliminary efficacy of Serenoa repens commonly known as saw palmetto (SP) for management of LUTS during RT for prostate cancer. The dose finding phase used the time-to-event continual reassessment method to evaluate safety of three doses (320, 640, and 960 mg) of SP. Dose-limiting toxicities were assessed for 22 weeks using the Common Terminology Criteria for Adverse Events for nausea, gastritis, and anorexia. The exploratory randomized controlled trial phase assessed preliminary efficacy of the MTD against placebo. The primary outcome of LUTS was measured over 22 weeks using the International Prostate Symptom Score. Additional longitudinal assessments included quality of life measured with the Functional Assessment of Cancer Therapy-Prostate. The dose finding phase was completed by 27 men who reported no dose-limiting toxicities and with 20 participants at the MTD of 960 mg daily. The exploratory randomized controlled trial phase included 21 men, and no statistically significant differences in the International Prostate Symptom Score were observed. The prostate-specific concerns score of the Functional Assessment of Cancer Therapy-Prostate improved in the SP group (P = 0.03). Of 11 men in the placebo group, two received physician-prescribed medications to manage LUTS compared with none of the 10 men in the SP group. SP at 960 mg may be a safe herbal supplement, but its efficacy in managing LUTS during RT needs further investigation. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Prospective Randomized Phase 2 Trial of Intensity Modulated Radiation Therapy With or Without Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Intermediate-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freytag, Svend O., E-mail: sfreyta1@hfhs.org; Stricker, Hans; Lu, Mei

Purpose: To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer. Methods and Materials: Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival. Results: Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis,more » neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer. Conclusions: Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer.« less

Adding Celecoxib With or Without Zoledronic Acid for Hormone-Naïve Prostate Cancer: Long-Term Survival Results From an Adaptive, Multiarm, Multistage, Platform, Randomized Controlled Trial

PubMed Central

Mason, Malcolm D.; Clarke, Noel W.; James, Nicholas D.; Dearnaley, David P.; Spears, Melissa R.; Ritchie, Alastair W.S.; Attard, Gerhardt; Cross, William; Jones, Rob J.; Parker, Christopher C.; Russell, J. Martin; Thalmann, George N.; Schiavone, Francesca; Cassoly, Estelle; Matheson, David; Millman, Robin; Rentsch, Cyrill A.; Barber, Jim; Gilson, Clare; Ibrahim, Azman; Logue, John; Lydon, Anna; Nikapota, Ashok D.; O’Sullivan, Joe M.; Porfiri, Emilio; Protheroe, Andrew; Srihari, Narayanan Nair; Tsang, David; Wagstaff, John; Wallace, Jan; Walmsley, Catherine; Parmar, Mahesh K.B.; Sydes, Matthew R.

2017-01-01

Purpose Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy is a randomized controlled trial using a multiarm, multistage, platform design. It recruits men with high-risk, locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy. We report survival data for two celecoxib (Cel)-containing comparisons, which stopped accrual early at interim analysis on the basis of failure-free survival. Patients and Methods Standard of care (SOC) was hormone therapy continuously (metastatic) or for ≥ 2 years (nonmetastatic); prostate (± pelvic node) radiotherapy was encouraged for men without metastases. Cel 400 mg was administered twice a day for 1 year. Zoledronic acid (ZA) 4 mg was administered for six 3-weekly cycles, then 4-weekly for 2 years. Stratified random assignment allocated patients 2:1:1 to SOC (control), SOC + Cel, or SOC + ZA + Cel. The primary outcome measure was all-cause mortality. Results were analyzed with Cox proportional hazards and flexible parametric models adjusted for stratification factors. Results A total of 1,245 men were randomly assigned (Oct 2005 to April 2011). Groups were balanced: median age, 65 years; 61% metastatic, 14% N+/X M0, 25% N0M0; 94% newly diagnosed; median prostate-specific antigen, 66 ng/mL. Median follow-up was 69 months. Grade 3 to 5 adverse events were seen in 36% SOC-only, 33% SOC + Cel, and 32% SOC + ZA + Cel patients. There were 303 control arm deaths (83% prostate cancer), and median survival was 66 months. Compared with SOC, the adjusted hazard ratio was 0.98 (95% CI, 0.80 to 1.20; P = .847; median survival, 70 months) for SOC + Cel and 0.86 (95% CI, 0.70 to 1.05; P =.130; median survival, 76 months) for SOC + ZA + Cel. Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 (95% CI, 0.62 to 0.98; P = .033) for SOC + ZA + Cel. Conclusion These data show no overall evidence of improved survival with Cel. Preplanned subgroup analyses provide hypotheses for future studies. PMID:28300506

Adding Celecoxib With or Without Zoledronic Acid for Hormone-Naïve Prostate Cancer: Long-Term Survival Results From an Adaptive, Multiarm, Multistage, Platform, Randomized Controlled Trial.

PubMed

Mason, Malcolm D; Clarke, Noel W; James, Nicholas D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Attard, Gerhardt; Cross, William; Jones, Rob J; Parker, Christopher C; Russell, J Martin; Thalmann, George N; Schiavone, Francesca; Cassoly, Estelle; Matheson, David; Millman, Robin; Rentsch, Cyrill A; Barber, Jim; Gilson, Clare; Ibrahim, Azman; Logue, John; Lydon, Anna; Nikapota, Ashok D; O'Sullivan, Joe M; Porfiri, Emilio; Protheroe, Andrew; Srihari, Narayanan Nair; Tsang, David; Wagstaff, John; Wallace, Jan; Walmsley, Catherine; Parmar, Mahesh K B; Sydes, Matthew R

2017-05-10

Purpose Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy is a randomized controlled trial using a multiarm, multistage, platform design. It recruits men with high-risk, locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy. We report survival data for two celecoxib (Cel)-containing comparisons, which stopped accrual early at interim analysis on the basis of failure-free survival. Patients and Methods Standard of care (SOC) was hormone therapy continuously (metastatic) or for ≥ 2 years (nonmetastatic); prostate (± pelvic node) radiotherapy was encouraged for men without metastases. Cel 400 mg was administered twice a day for 1 year. Zoledronic acid (ZA) 4 mg was administered for six 3-weekly cycles, then 4-weekly for 2 years. Stratified random assignment allocated patients 2:1:1 to SOC (control), SOC + Cel, or SOC + ZA + Cel. The primary outcome measure was all-cause mortality. Results were analyzed with Cox proportional hazards and flexible parametric models adjusted for stratification factors. Results A total of 1,245 men were randomly assigned (Oct 2005 to April 2011). Groups were balanced: median age, 65 years; 61% metastatic, 14% N+/X M0, 25% N0M0; 94% newly diagnosed; median prostate-specific antigen, 66 ng/mL. Median follow-up was 69 months. Grade 3 to 5 adverse events were seen in 36% SOC-only, 33% SOC + Cel, and 32% SOC + ZA + Cel patients. There were 303 control arm deaths (83% prostate cancer), and median survival was 66 months. Compared with SOC, the adjusted hazard ratio was 0.98 (95% CI, 0.80 to 1.20; P = .847; median survival, 70 months) for SOC + Cel and 0.86 (95% CI, 0.70 to 1.05; P =.130; median survival, 76 months) for SOC + ZA + Cel. Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 (95% CI, 0.62 to 0.98; P = .033) for SOC + ZA + Cel. Conclusion These data show no overall evidence of improved survival with Cel. Preplanned subgroup analyses provide hypotheses for future studies.

Prostate cancer prevention agent development: Criteria and pipeline for candidate chemoprevention agents.

PubMed

Nelson, W G; Wilding, G

2001-04-01

Epidemiologic data suggest that prostate cancer morbidity and mortality ought to be preventable. New insights into the molecular pathogenesis of prostate cancer offer new opportunities for the discovery of prostate cancer chemoprevention drugs and new challenges for their development. Established pathways that lead to US Food and Drug Administration (FDA) approval of drugs for advanced prostate cancer may not be appropriate for the development of drugs for prostate cancer chemoprevention. For example, large randomized clinical trials designed to test the efficacy of new chemoprevention drugs on prostate cancer survival in the general population are likely to be conducted at great expense and take many years, threatening to increase commercial development risks while decreasing exclusive marketing revenues. As a consequence, to accelerate progress in research, new validated surrogate and strategic clinical trial endpoints, and new clinical trial designs featuring more precisely defined high-risk clinical trial cohorts, are needed. In this review, 10 criteria for prostate cancer chemoprevention agent development are offered and the pipeline of new prostate cancer chemoprevention drug candidates is considered.

Cancer among farmers in central Italy.

PubMed

Forastiere, F; Quercia, A; Miceli, M; Settimi, L; Terenzoni, B; Rapiti, E; Faustini, A; Borgia, P; Cavariani, F; Perucci, C A

1993-12-01

This case-referent study evaluated cancer risks among farmers in central Italy. Cancer cases (N = 1674, 17 sites) were selected from all deceased men aged 35-80 years; a random sample of 480 decedents formed the reference series. Farmers had a decreased risk of lung and bladder cancer and melanoma and nonsignificant excess risks for stomach, rectal, kidney, and nonmelanoma skin cancer. Stomach and kidney cancer were significantly increased among the farmers with > 10 years' experience, and stomach, rectal, and pancreatic cancer were increased among licensed pesticide users with > 10 years' experience. Possible relationships emerged between specific crops and cancer: fruit and colon and bladder cancer, wheat and prostate cancer, olives and kidney cancer, and potato and kidney cancer. The results regarding stomach, pancreatic, lung, bladder, and prostate cancer and melanoma congrue with earlier results. The kidney cancer excess, the association of colon and bladder cancer with orchard farming, and the excess of rectal cancer among licensed farmers are new and unexpected findings.

Survivin and NAIP in Human Benign Prostatic Hyperplasia: Protective Role of the Association of Serenoa repens, Lycopene and Selenium from the Randomized Clinical Study.

PubMed

Morgia, Giuseppe; Micali, Antonio; Rinaldi, Mariagrazia; Irrera, Natasha; Marini, Herbert; Puzzolo, Domenico; Pisani, Antonina; Privitera, Salvatore; Russo, Giorgio I; Cimino, Sebastiano; Ieni, Antonio; Trichilo, Vincenzo; Altavilla, Domenica; Squadrito, Francesco; Minutoli, Letteria

2017-03-22

Benign prostatic hyperplasia (BPH) treatment includes the apoptosis machinery modulation through the direct inhibition of caspase cascade. We previously demonstrated that Serenoa repens (Ser) with lycopene (Ly) and selenium (Se) reawakened apoptosis by reducing survivin and neuronal apoptosis inhibitory protein (NAIP) levels in rats. The aim of this study was to evaluate the effectiveness of Ser-Se-Ly association on survivin and NAIP expression in BPH patients. Ninety patients with lower urinary tract symptoms (LUTS) due to clinical BPH were included in this randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive placebo (Group BPH + placebo, n = 45) or Ser-Se-Ly association (Group BPH + Ser-Se-Ly; n = 45) for 3 months. At time 0, all patients underwent prostatic biopsies. After 3 months of treatment, they underwent prostatic re-biopsy and specimens were collected for molecular, morphological, and immunohistochemical analysis. After 3 months, survivin and NAIP were significantly decreased, while caspase-3 was significantly increased in BPH patients treated with Ser-Se-Ly when compared with the other group. In BPH patients treated with Ser-Se-Ly for 3 months, the glandular epithelium was formed by a single layer of cuboidal cells. PSA showed high immunoexpression in all BPH patients and a focal positivity in Ser-Se-Ly treated patients after 3 months. Evident prostate specific membrane antigen (PSMA) immunoexpression was shown in all BPH patients, while no positivity was present after Ser-Se-Ly administration. Ser-Se-Ly proved to be effective in promoting apoptosis in BPH patients.

Perceptions of Radiation Oncologists and Urologists on Sources and Type of Evidence to Inform Prostate Cancer Treatment Decisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Leona C.; Delpe, Sophia; Shah, Nilay D.

2014-06-01

Purpose: To perform a national survey of radiation oncologists and urologists about the type of resources used and the level of evidence needed to change clinical practice in localized prostate cancer. Methods and Materials: From a random sample, 1422 physicians were mailed a survey assessing the types of information used and what level of evidence could alter their clinical practice in prostate cancer. Multivariable logistic regression models were used to identify differences in physician characteristics for each outcome. Results: Survey response rates were similar for radiation oncologists and urologists (44% vs 46%; P=.46). Specialty-specific journals represented the most commonly usedmore » resource for informing the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to report utilizing top-tier medical journals (25% vs 39%; adjusted odds ratio [OR] 0.50; P=.01) or cancer journals (22% vs 51%; adjusted OR 0.50; P<.001) but more likely to rely on clinical guidelines (46% vs 38%; adjusted OR 1.6; P=.006). Both radiation oncologists and urologists most commonly reported large randomized, clinical trials as the level of evidence to change treatment recommendations for localized prostate cancer (85% vs 77%; P=.009). Conclusions: Both specialties rely on their own specialty-specific journals and view randomized, clinical trials as the level of evidence needed to change clinical practice. Our study provides a context on meaningful ways of disseminating evidence for localized prostate cancer.« less

Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract.

PubMed

Li, Gongbo; Petiwala, Sakina M; Pierce, Dana R; Nonn, Larisa; Johnson, Jeremy J

2013-01-01

The increased proliferation of cancer cells is directly dependent on the increased activity of the endoplasmic reticulum (ER) machinery which is responsible for protein folding, assembly, and transport. In fact, it is so critical that perturbations in the endoplasmic reticulum can lead to apoptosis. This carefully regulated organelle represents a unique target of cancer cells while sparing healthy cells. In this study, a standardized mangosteen fruit extract (MFE) was evaluated for modulating ER stress proteins in prostate cancer. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells (PrECs) procured from two patients undergoing radical prostatectomy were treated with MFE. Flow cytometry, MTT, BrdU and Western blot were used to evaluate cell apoptosis, viability, proliferation and ER stress. Next, we evaluated MFE for microsomal stability and anti-cancer activity in nude mice. MFE induced apoptosis, decreased viability and proliferation in prostate cancer cells. MFE increased the expression of ER stress proteins. Interestingly, MFE selectively promotes ER stress in prostate cancer cells while sparing PrECs. MFE suppressed tumor growth in a xenograft tumor model without obvious toxicity. Mangosteen fruit extract selectively promotes endoplasmic reticulum stress in cancer cells while sparing non-tumorigenic prostate epithelial cells. Furthermore, in an in vivo setting mangosteen fruit extract significantly reduces xenograft tumor formation.

Selective Modulation of Endoplasmic Reticulum Stress Markers in Prostate Cancer Cells by a Standardized Mangosteen Fruit Extract

PubMed Central

Li, Gongbo; Petiwala, Sakina M.; Pierce, Dana R.; Nonn, Larisa; Johnson, Jeremy J.

2013-01-01

The increased proliferation of cancer cells is directly dependent on the increased activity of the endoplasmic reticulum (ER) machinery which is responsible for protein folding, assembly, and transport. In fact, it is so critical that perturbations in the endoplasmic reticulum can lead to apoptosis. This carefully regulated organelle represents a unique target of cancer cells while sparing healthy cells. In this study, a standardized mangosteen fruit extract (MFE) was evaluated for modulating ER stress proteins in prostate cancer. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells (PrECs) procured from two patients undergoing radical prostatectomy were treated with MFE. Flow cytometry, MTT, BrdU and Western blot were used to evaluate cell apoptosis, viability, proliferation and ER stress. Next, we evaluated MFE for microsomal stability and anti-cancer activity in nude mice. MFE induced apoptosis, decreased viability and proliferation in prostate cancer cells. MFE increased the expression of ER stress proteins. Interestingly, MFE selectively promotes ER stress in prostate cancer cells while sparing PrECs. MFE suppressed tumor growth in a xenograft tumor model without obvious toxicity. Mangosteen fruit extract selectively promotes endoplasmic reticulum stress in cancer cells while sparing non-tumorigenic prostate epithelial cells. Furthermore, in an in vivo setting mangosteen fruit extract significantly reduces xenograft tumor formation. PMID:24367485

Brachytherapy Boost Utilization and Survival in Unfavorable-risk Prostate Cancer.

PubMed

Johnson, Skyler B; Lester-Coll, Nataniel H; Kelly, Jacqueline R; Kann, Benjamin H; Yu, James B; Nath, Sameer K

2017-11-01

There are limited comparative survival data for prostate cancer (PCa) patients managed with a low-dose rate brachytherapy (LDR-B) boost and dose-escalated external-beam radiotherapy (DE-EBRT) alone. To compare overall survival (OS) for men with unfavorable PCa between LDR-B and DE-EBRT groups. Using the National Cancer Data Base, we identified men with unfavorable PCa treated between 2004 and 2012 with androgen suppression (AS) and either EBRT followed by LDR-B or DE-EBRT (75.6-86.4Gy). Treatment selection was evaluated using logistic regression and annual percentage proportions. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards, and propensity score matching. We identified 25038 men between 2004 and 2012, during which LDR-B boost utilization decreased from 29% to 14%. LDR-B was associated with better OS on univariate (7-yr OS: 82% vs 73%; p<0.001) and multivariate analyses (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.64-0.77). Propensity score matching verified an OS benefit associated with LDR-B boost (HR 0.74, 95% CI 0.66-0.89). The OS benefit of LDR-B boost persisted when limited to men aged <60 yr with no comorbidities. On subset analysis, there was no interaction between treatment and age, risk group, or radiation dose. Limitations include the retrospective design, nonrandomized selection bias, and the absence of treatment toxicity, hormone duration, and cancer-specific outcomes. Between 2004 and 2012, LDR-B boost utilization declined and was associated with better OS compared to DE-EBRT alone. LDR-B boost is probably the ideal treatment option for men with unfavorable PCa, pending long-term results of randomized trials. We compared radiotherapy utilization and survival for prostate cancer (PCa) patients using a national database. We found that low-dose rate brachytherapy (LDR-B) boost, a method being used less frequently, was associated with better overall survival when compared to dose-escalated external-beam radiotherapy alone for men with unfavorable PCa. Randomized trials are needed to confirm that LDR-B boost is the ideal treatment. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Prospective Evaluation of Intraprostatic Inflammation and Focal Atrophy as a Predictor of Risk of High-Grade Prostate Cancer and Recurrence after Prostatectomy

DTIC Science & Technology

2015-08-01

average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data ...SELECT data (incident prostate cancer). We found that the odds of low-grade prostate cancer tended to increase with the number of biopsy cores with...merged pathology-PCPT-SELECT data from the review of the H&E stained slide images (Task 7a), and performed the statistical analysis of the merged

A Double Blind, Randomized, Neoadjuvant Study of the Tissue effects of POMx Pills in Men with Prostate Cancer Prior to Radical Prostatectomy

PubMed Central

Freedland, Stephen J.; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A.; Zhang, Yanjun; Heber, David; Pantuck, Allan J.

2013-01-01

Pomegranates slow prostate cancer xenograft growth and prolong PSA doubling times in single-arm human studies. Pomegranates’ effects on human prostate tissue are understudied. We hypothesized orally administered pomegranate extract (POMx; PomWonderful, Los Angeles, CA) would lower tissue 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker. 70 men were randomized to 2 tablets POMx or placebo daily up to 4 weeks prior to radical prostatectomy. Tissue was analyzed for intra-prostatic Urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NFκB, and Ki67. Primary end-point was differences in 8-OHdG powered to detect 30% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (p=0.095), which was not statistically significant. POMx was well-tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21/33 patient in the POMx group vs. 12/35 in the placebo group (p=0.031). Cancer pS6 kinase, NFκB, Ki67, and serum PSA changes were similar between arms. POMx prior to surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary end-point in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitely test whether POMx reduces prostate oxidative stress as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology. PMID:23985577

Association between variants in genes involved in the immune response and prostate cancer risk in men randomized to the finasteride arm in the Prostate Cancer Prevention Trial.

PubMed

Winchester, Danyelle A; Till, Cathee; Goodman, Phyllis J; Tangen, Catherine M; Santella, Regina M; Johnson-Pais, Teresa L; Leach, Robin J; Xu, Jianfeng; Zheng, S Lilly; Thompson, Ian M; Lucia, M Scott; Lippman, Scott M; Parnes, Howard L; Isaacs, William B; De Marzo, Angelo M; Drake, Charles G; Platz, Elizabeth A

2017-06-01

We reported that some, but not all single nucleotide polymorphisms (SNPs) in select immune response genes are associated with prostate cancer, but not individually with the prevalence of intraprostatic inflammation in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Here, we investigated whether these same SNPs are associated with risk of lower- and higher-grade prostate cancer in men randomized to finasteride, and with prevalence of intraprostatic inflammation among controls. Methods A total of 16 candidate SNPs in IL1β, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, and TNFA and 7 tagSNPs in IL10 were genotyped in 625 white prostate cancer cases, and 532 white controls negative for cancer on an end-of-study biopsy nested in the PCPT finasteride arm. We used logistic regression to estimate log-additive odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history. Minor alleles of rs2243250 (T) in IL4 (OR = 1.46, 95% CI 1.03-2.08, P-trend = 0.03), rs1800896 (G) in IL10 (OR = 0.77, 95% CI 0.61-0.96, P-trend = 0.02), rs2430561 (A) in IFNG (OR = 1.33, 95% CI 1.02-1.74; P-trend = 0.04), rs3747531 (C) in MSR1 (OR = 0.55, 95% CI 0.32-0.95; P-trend = 0.03), and possibly rs4073 (A) in IL8 (OR = 0.81, 95% CI 0.64-1.01, P-trend = 0.06) were associated with higher- (Gleason 7-10; N = 222), but not lower- (Gleason 2-6; N = 380) grade prostate cancer. In men with low PSA (<2 ng/mL), these higher-grade disease associations were attenuated and/or no longer significant, whereas associations with higher-grade disease were apparent for minor alleles of rs1800795 (C: OR = 0.70, 95% CI 0.51-0.94, P-trend = 0.02) and rs1800797 (A: OR = 0.72, 95% CI 0.53-0.98, P-trend = 0.04) in IL6. While some IL10 tagSNPs were associated with lower- and higher-grade prostate cancer, distributions of IL10 haplotypes did not differ, except possibly between higher-grade cases and controls among those with low PSA (P = 0.07). We did not observe an association between the studied SNPs and intraprostatic inflammation in the controls. In the PCPT finasteride arm, variation in genes involved in the immune response, including possibly IL8 and IL10 as in the placebo arm, may be associated with prostate cancer, especially higher-grade disease, but not with intraprostatic inflammation. We cannot rule out PSA-associated detection bias or chance due to multiple testing. © 2017 Wiley Periodicals, Inc.

Biorepository for Selenium and Vitamin E Cancer Prevention Trial (SELECT) | Division of Cancer Prevention

Cancer.gov

As the largest prostate cancer prevention trial ever undertaken, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) has assembled a substantial biorepository of specimens. To help make SELECT resources available to a wider research community, NCI and the Southwest Oncology Group are developing a plan for prostate cancer biology and nutritional science and

Prostate specific antigen velocity does not aid prostate cancer detection in men with prior negative biopsy.

PubMed

Vickers, Andrew J; Wolters, Tineke; Savage, Caroline J; Cronin, Angel M; O'Brien, M Frank; Roobol, Monique J; Aus, Gunnar; Scardino, Peter T; Hugosson, Jonas; Schröder, Fritz H; Lilja, Hans

2010-09-01

Prostate specific antigen velocity has been proposed as a marker to aid in prostate cancer detection. We determined whether prostate specific antigen velocity could predict repeat biopsy results in men with persistently increased prostate specific antigen after initial negative biopsy. We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer and who underwent 1 or more subsequent prostate biopsies after an initial negative finding. We evaluated whether prostate specific antigen velocity improved predictive accuracy beyond that of prostate specific antigen alone. Of the 2,579 repeat biopsies 363 (14%) were positive for prostate cancer, of which 44 (1.7%) were high grade (Gleason score 7 or greater). Prostate specific antigen velocity was statistically associated with cancer risk but had low predictive accuracy (AUC 0.55, p <0.001). There was some evidence that prostate specific antigen velocity improved AUC compared to prostate specific antigen for high grade cancer. However, the small increase in risk associated with high prostate specific antigen velocity (from 1.7% to 2.8% as velocity increased from 0 to 1 ng/ml per year) had questionable clinical relevance. Men with prior negative biopsy are at lower risk for prostate cancer at subsequent biopsies with high grade disease particularly rare. We found little evidence to support prostate specific antigen velocity to aid in decisions about repeat biopsy for prostate cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Selective androgen receptor modulators: in pursuit of tissue-selective androgens.

PubMed

Omwancha, Josephat; Brown, Terry R

2006-10-01

The androgen receptor mediates the androgenic and anabolic activity of the endogenous steroids testosterone and 5alpha-dihydrotestosterone. Current knowledge of the androgen receptor protein structure, and the molecular mechanisms surrounding the binding properties and activities of agonists and antagonists has led to the design and development of novel nonsteroidal ligands with selected tissue-specific androgen receptor agonist and antagonist activities. The activity of these compounds, termed selective androgen receptor modulators (SARMs), is directed toward the maintenance or enhancement of anabolic effects on bone and muscle with minimal androgenic effects on prostate growth. SARMs are of potential therapeutic value in the treatment of male hypogonadism, osteoporosis, frailty and muscle wasting, burn injury and would healing, anemia, mood and depression, benign prostatic hyperplasia and prostate cancer.

Current Status of Prostate Artery Embolization for Lower Urinary Tract Symptoms: Review of World Literature.

PubMed

Jones, Patrick; Rai, Bhavan Prasad; Nair, Rajesh; Somani, Bhaskar K

2015-10-01

Prostate artery embolization has emerged as a promising treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. However, although it has gained increasing attention in radiology literature, it remains under-reported from a urologic perspective. We aim at providing an up-to-date review of this minimally invasive technique. Evidence suggests it is a promising and effective option for patients with large prostate volumes, multiple comorbidities, and suboptimal results from pharmacotherapy. Larger, randomized studies with longer follow-up periods are needed for this technique to be formally established in the urology community. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiation Therapy Did Not Induce Long-Term Changes in Rectal Mucosa: Results From the Randomized Scandinavian Prostate Cancer Group 7 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slagsvold, Jens Erik, E-mail: Jens.Erik.Slagsvold@stolav.no; Viset, Trond; Wibe, Arne

Purpose: To investigate long-term changes in the rectal mucosa after curative external beam radiation therapy in the treatment of prostate cancer. Methods and Materials: In the Scandinavian Prostate Cancer Group 7 trial, 880 men with locally advanced prostate cancer were randomized to hormonal therapy alone versus hormonal therapy plus radiation therapy to 70 Gy. A subcohort from this trial being randomized at our center (n=178) was invited to a study on late anorectal side effects during 2003-2005, approximately 5 years after treatment, including measuring health-reported quality of life and physician-assessed toxicity score by the Late Effects Normal Tissue Task Force/Subjective, Objective, Management, Analyticmore » (LENT/SOMA) and European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group score. Sixty-seven patients had a rectal mucosa biopsy. Sixty-four biopsies were included in the final analysis, of which 33 patients were randomized to hormonal treatment and 31 to hormonal treatment plus radiation therapy. The presence of fibrosis, number of capillaries, and lymphocyte infiltration was then evaluated by light microscopy. Results: The group receiving radiation therapy had significantly higher LENT/SOMA and function/bother scale scores than the group that only received hormonal treatment, but there was no significant difference in the presence of fibrosis, ectasia, number of capillaries in the lamina propria, or lymphocyte infiltration between the groups. Conclusion: Radiation therapy to 70 Gy to the prostate does not induce long-term microscopic mucosal changes in the rectum 5 years after treatment. This is in contrast to the general assumption that structural changes, including fibrosis, seen after radiation therapy include the mucosa. We speculate that the main late effects of radiation therapy on the structure of the rectum are located in the deeper layers of the rectal wall than the mucosa.« less

Perspectives on the clinical development of immunotherapy in prostate cancer.

PubMed

Cordes, Lisa M; Gulley, James L; Madan, Ravi A

2018-01-01

Despite impressive survival benefits with immunotherapy in patients with various solid tumors, the full potential of these agents in prostate cancer has yet to be realized. Sipuleucel-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents. A large trial with ipilimumab in prostate cancer failed to meet its primary objective, and small trials with PD-1/PD-L1 inhibitors did not yield a significant improvement in overall response. However, several late-stage clinical trials are underway with other vaccines in prostate cancer. Reports of clinical benefit with immunotherapies, particularly when used in combination or a select population, have provided the framework to develop sound clinical trials. Understanding immunogenic modulation, antigen spread, biomarkers, and DNA-repair defects will also help mold future strategies. Through rational patient selection and evidence-based combination approaches, patients with prostate cancer may soon derive durable survival benefits with immunotherapies.

Protective effect of Acticoa powder, a cocoa polyphenolic extract, on prostate carcinogenesis in Wistar-Unilever rats.

PubMed

Bisson, Jean-François; Guardia-Llorens, Maria-Alba; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

2008-02-01

The effects of Acticoa powder on prostate carcinogenesis were investigated using the N-methylnitrosourea and testosterone propionate prostate tumor model. Sixty male Wistar-Unilever rats were randomly divided in four groups of 15 rats: one control group not induced but treated with vehicle (not induced+vehicle) and three chemo-induced groups. Two weeks before prostate tumor induction and then throughout the experiment, chemo-induced rats were orally treated with Acticoa powder at 24 (chemo-induced+Acticoa powder24) or 48 (chemo-induced+Acticoa powder48) mg/kg or with vehicle (chemo-induced+vehicle), daily from Monday to Friday. Survival, body weight, food and water consumption were recorded throughout the experiment. Six rats per group were randomly killed 9 months after the prostate tumor induction for histopathological analysis of prostates. A reduction in the incidence of prostate tumors was observed for the chemo-induced+Acticoa powder48-treated group in comparison with the chemo-induced+vehicle-treated group and no tumors were observed in the chemo-induced+Acticoa powder24-treated group as in the not induced+vehicle-treated group after 9 months. The nine remaining rats per group were maintained in a long-term survival study. The life span of the chemo-induced+Acticoa powder24-treated group was significantly increased in comparison with the chemo-induced+Acticoa powder48 and the chemo-induced+vehicle-treated groups, close to the one of the not induced+vehicle-treated group. A significant reduction in the incidence of prostate tumors was also observed for the chemo-induced+Acticoa powder24 and chemo-induced+Acticoa powder48-treated groups in comparison with the chemo-induced+vehicle-treated group. In conclusion, Acticoa powder at 24 mg/kg protected rats from prostate carcinogenesis when chronically given before the initiation and promotion phases of induction.

A novel curvilinear approach for prostate seed implantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Podder, Tarun K.; Dicker, Adam P.; Hutapea, Parsaoran

Purpose: A new technique called ''curvilinear approach'' for prostate seed implantation has been proposed. The purpose of this study is to evaluate the dosimetric benefit of curvilinear distribution of seeds for low-dose-rate (LDR) prostate brachytherapy. Methods: Twenty LDR prostate brachytherapy cases planned intraoperatively with VariSeed planning system and I-125 seeds were randomly selected as reference rectilinear cases. All the cases were replanned by using curved-needle approach keeping the same individual source strength and the volume receiving 100% of prescribed dose 145 Gy (V{sub 100}). Parameters such as number of needles, seeds, and the dose coverage of the prostate (D{sub 90},more » V{sub 150}, V{sub 200}), urethra (D{sub 30}, D{sub 10}) and rectum (D{sub 5}, V{sub 100}) were compared for the rectilinear and the curvilinear methods. Statistical significance was assessed using two-tailed student's t-test. Results: Reduction of the required number of needles and seeds in curvilinear method were 30.5% (p < 0.001) and 11.8% (p < 0.49), respectively. Dose to the urethra was reduced significantly; D{sub 30} reduced by 10.1% (p < 0.01) and D{sub 10} reduced by 9.9% (p < 0.02). Reduction in rectum dose D{sub 5} was 18.5% (p < 0.03) and V{sub 100} was also reduced from 0.93 cc in rectilinear to 0.21 cc in curvilinear (p < 0.001). Also the V{sub 150} and V{sub 200} coverage of prostate reduced by 18.8% (p < 0.01) and 33.9% (p < 0.001), respectively. Conclusions: Significant improvement in the relevant dosimetric parameters was observed in curvilinear needle approach. Prostate dose homogeneity (V{sub 150}, V{sub 200}) improved while urethral dose was reduced, which might potentially result in better treatment outcome. Reduction in rectal dose could potentially reduce rectal toxicity and complications. Reduction in number of needles would minimize edema and thereby could improve postimplant urinary incontinence. This study indicates that the curvilinear implantation approach is dosimetrically superior to conventional rectilinear implantation technique.« less

Intermittent androgen suppression in the LuCaP 23.12 prostate cancer xenograft model.

PubMed

Buhler, K R; Santucci, R A; Royai, R A; Whitney, S C; Vessella, R L; Lange, P H; Ellis, W J

2000-04-01

Intermittent androgen suppression (IAS) has been proposed as a method of delaying the onset of androgen-independent growth in prostate cancer. While several pilot studies have demonstrated the feasibility of such a treatment, no study to date has defined the effect of IAS on survival. We developed an IAS protocol for mice bearing the LuCaP 23.12 human prostate cancer xenograft, with each cycle consisting of 1 week of androgen replacement with a testosterone pellet followed by 3 weeks of androgen withdrawal. Mice that responded to castration with a 40% or greater decrease in serum prostate-specific antigen (PSA) were randomized to treatment with either continuous androgen suppression (CAS) or IAS. Serum PSA, tumor volume, and overall survival were monitored. A total of 75 mice met the randomization criteria. There was no significant difference of survival between animals treated with CAS or IAS (185 vs. 239 days, P = 0.1835). Serum PSA showed evidence of cycling with hormonal manipulation. No cycling was noted in tumor volume. IAS is not associated with a decrease in survival compared to CAS, yet in patients may offer quality-of-life improvements. Further studies of IAS in the setting of Institutional Review Board (IRB) approved clinical trials should be encouraged. Prostate 43:63-70, 2000. Published 2000 Wiley-Liss, Inc.

Pim Kinases Promote Migration and Metastatic Growth of Prostate Cancer Xenografts

PubMed Central

Santio, Niina M.; Eerola, Sini K.; Paatero, Ilkka; Yli-Kauhaluoma, Jari; Anizon, Fabrice; Moreau, Pascale; Tuomela, Johanna; Härkönen, Pirkko; Koskinen, Päivi J.

2015-01-01

Background and methods Pim family proteins are oncogenic kinases implicated in several types of cancer and involved in regulation of cell proliferation, survival as well as motility. Here we have investigated the ability of Pim kinases to promote metastatic growth of prostate cancer cells in two xenograft models for human prostate cancer. We have also evaluated the efficacy of Pim-selective inhibitors to antagonize these effects. Results We show here that tumorigenic growth of both subcutaneously and orthotopically inoculated prostate cancer xenografts is enhanced by stable overexpression of either Pim-1 or Pim-3. Moreover, Pim-overexpressing orthotopic prostate tumors are highly invasive and able to migrate not only to the nearby prostate-draining lymph nodes, but also into the lungs to form metastases. When the xenografted mice are daily treated with the Pim-selective inhibitor DHPCC-9, both the volumes as well as the metastatic capacity of the tumors are drastically decreased. Interestingly, the Pim-promoted metastatic growth of the orthotopic xenografts is associated with enhanced angiogenesis and lymphangiogenesis. Furthermore, forced Pim expression also increases phosphorylation of the CXCR4 chemokine receptor, which may enable the tumor cells to migrate towards tissues such as the lungs that express the CXCL12 chemokine ligand. Conclusions Our results indicate that Pim overexpression enhances the invasive properties of prostate cancer cells in vivo. These effects can be reduced by the Pim-selective inhibitor DHPCC-9, which can reach tumor tissues without serious side effects. Thus, Pim-targeting therapies with DHPCC-9-like compounds may help to prevent progression of local prostate carcinomas to fatally metastatic malignancies. PMID:26075720

Bone Marrow-derived Mesenchymal Stem Cells (MSCs) as a Selective Delivery Vehicle for a PSA-Activated Protoxin for Advanced Prostate Cancer

DTIC Science & Technology

2014-04-01

other groups are seeking to develop MSCs as vectors to deliver prostate - specific antigen (PSA)-activated prodrugs (Denmeade et al. 2003) and protoxins...Denmeade SR, Jakobsen CM, Janssen S, Khan SR, Garrett ES, Lilja H, Christensen SB & Isaacs JT 2003 Prostate - specific antigen -activated thapsigargin...cells derived from benign prostatic hyperplasia specimens possess stem cell like property. Prostate 67 1265–1276. (doi:10.1002/ pros .20599) Lin G, Yang R

Altered prostate epithelial development in mice lacking the androgen receptor in stromal fibroblasts.

PubMed

Yu, Shengqiang; Yeh, Chiuan-Ren; Niu, Yuanjie; Chang, Hong-Chiang; Tsai, Yu-Chieh; Moses, Harold L; Shyr, Chih-Rong; Chang, Chawnshang; Yeh, Shuyuan

2012-03-01

Androgens and the androgen receptor (AR) play important roles in the development of male urogenital organs. We previously found that mice with total AR knockout (ARKO) and epithelial ARKO failed to develop normal prostate with loss of differentiation. We have recently knocked out AR gene in smooth muscle cells and found the reduced luminal infolding and IGF-1 production in the mouse prostate. However, AR roles of stromal fibroblasts in prostate development remain unclear. To further probe the stromal fibroblast AR roles in prostate development, we generated tissue-selective knockout mice with the AR gene deleted in stromal fibroblasts (FSP-ARKO). We also used primary culture stromal cells to confirm the in vivo data and investigate mechanisms related to prostate development. The results showed cellular alterations in the FSP-ARKO mouse prostate with decreased epithelial proliferation, increased apoptosis, and decreased collagen composition. Further mechanistic studies demonstrated that FSP-ARKO mice have defects in the expression of prostate stromal growth factors. To further confirm these in vivo findings, we prepared primary cultured mouse prostate stromal cells and found knocking down the stromal AR could result in growth retardation of prostate stromal cells and co-cultured prostate epithelial cells, as well as decrease of some stromal growth factors. Our FSP-ARKO mice not only provide the first in vivo evidence in Cre-loxP knockout system for the requirement of stromal fibroblast AR to maintain the normal development of the prostate, but may also suggest the selective knockdown of stromal AR might become a potential therapeutic approach to battle prostate hyperplasia and cancer. Copyright © 2011 Wiley Periodicals, Inc.

The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model

PubMed Central

Zhang, Xikui; Zhu, Weikun; Lu, Taikun; Chen, Jinchun; Zou, Qiang; Zheng, Qizhong; Chen, Junying; Jiang, Changming; Jin, Guanyu

2017-01-01

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups (n = 12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF-α) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats' prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats' prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF-α levels in the blood serum and inhibited the expression of iNOS in the rats' prostate tissues (P < 0.05). Following YZS treatment, the pathological changes in the rats' prostates were improved compared with those in the model group (P < 0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF-α, and chemokines, such as iNOS, in the rat model of EAP. PMID:29430255

The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model.

PubMed

Deng, Longsheng; Zhang, Xikui; Zhu, Weikun; Lu, Taikun; Chen, Jinchun; Zou, Qiang; Zheng, Qizhong; Chen, Junying; Jiang, Changming; Jin, Guanyu

2017-01-01

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups ( n = 12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF- α ) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats' prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats' prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF- α levels in the blood serum and inhibited the expression of iNOS in the rats' prostate tissues ( P < 0.05). Following YZS treatment, the pathological changes in the rats' prostates were improved compared with those in the model group ( P < 0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF- α , and chemokines, such as iNOS, in the rat model of EAP.

Prostate-specific antigen-based prostate cancer screening: Past and future.

PubMed

Alberts, Arnout R; Schoots, Ivo G; Roobol, Monique J

2015-06-01

Prostate-specific antigen-based prostate cancer screening remains a controversial topic. Up to now, there is worldwide consensus on the statement that the harms of population-based screening, mainly as a result of overdiagnosis (the detection of clinically insignificant tumors that would have never caused any symptoms), outweigh the benefits. However, worldwide opportunistic screening takes place on a wide scale. The European Randomized Study of Screening for Prostate Cancer showed a reduction in prostate cancer mortality through prostate-specific antigen based-screening. These population-based data need to be individualized in order to avoid screening in those who cannot benefit and start screening in those who will. For now, lacking a more optimal screening approach, screening should only be started after the process of shared decision-making. The focus of future research is the reduction of unnecessary testing and overdiagnosis by further research to better biomarkers and the value of the multiparametric magnetic resonance imaging, potentially combined in already existing prostate-specific antigen-based multivariate risk prediction models. © 2015 The Japanese Urological Association.

Dashboard report on performance on select quality indicators to cancer care providers.

PubMed

Stattin, Pär; Sandin, Fredrik; Sandbäck, Torsten; Damber, Jan-Erik; Franck Lissbrant, Ingela; Robinson, David; Bratt, Ola; Lambe, Mats

2016-01-01

Cancer quality registers are attracting increasing attention as important, but still underutilized sources of clinical data. To optimize the use of registers in quality assurance and improvement, data have to be rapidly collected, collated and presented as actionable, at-a-glance information to the reporting departments. This article presents a dashboard performance report on select quality indicators to cancer care providers. Ten quality indicators registered on an individual patient level in the National Prostate Cancer Register of Sweden and recommended by the National Prostate Cancer Guidelines were selected. Data reported to the National Prostate Cancer Register are uploaded within 24 h to the Information Network for Cancer Care platform. Launched in 2014, "What''s Going On, Prostate Cancer" provides rapid, at-a-glance performance feedback to care providers. The indicators include time to report to the National Prostate Cancer Register, waiting times, designated clinical nurse specialist, multidisciplinary conference, adherence to guidelines for diagnostic work-up and treatment, and documentation and outcome of treatment. For each indicator, three performance levels were defined. What's Going On, a dashboard performance report on 10 selected quality indicators to cancer care providers, provides an example of how data in cancer quality registers can be transformed into condensed, at-a-glance information to be used as actionable metrics for quality assurance and improvement.

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.

PubMed

Smith, Matthew R; Saad, Fred; Chowdhury, Simon; Oudard, Stéphane; Hadaschik, Boris A; Graff, Julie N; Olmos, David; Mainwaring, Paul N; Lee, Ji Youl; Uemura, Hiroji; Lopez-Gitlitz, Angela; Trudel, Géralyn C; Espina, Byron M; Shu, Youyi; Park, Youn C; Rackoff, Wayne R; Yu, Margaret K; Small, Eric J

2018-04-12

Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204 .).

A Randomized Phase II Trial of Short-Course Androgen Deprivation Therapy With or Without Bevacizumab for Patients With Recurrent Prostate Cancer After Definitive Local Therapy

PubMed Central

McKay, Rana R.; Zurita, Amado J.; Werner, Lillian; Bruce, Justine Y.; Carducci, Michael A.; Stein, Mark N.; Heath, Elisabeth I.; Hussain, Arif; Tran, Hai T.; Sweeney, Christopher J.; Ross, Robert W.; Kantoff, Philip W.; Slovin, Susan F.

2016-01-01

Purpose Patients with recurrent prostate cancer after local treatment make up a heterogeneous population for whom androgen deprivation therapy (ADT) is the usual treatment. The purpose of this randomized phase II trial was to investigate the efficacy and toxicity of short-course ADT with or without bevacizumab in men with hormone-sensitive prostate cancer. Patients and Methods Eligible patients had an increasing prostate-specific antigen (PSA) of ≤ 50 ng/mL and PSA doubling time of less than 18 months. Patients had either no metastases or low burden, asymptomatic metastases (lymph nodes < 3 cm and five or fewer bone metastases). Patients were randomly assigned 2:1 to a luteinizing hormone-releasing hormone agonist, bicalutamide and bevacizumab or ADT alone, for 6 months. The primary end point was PSA relapse-free survival (RFS). Relapse was defined as a PSA of more than 0.2 ng/mL for prostatectomy patients or PSA of more than 2.0 ng/mL for primary radiation therapy patients. Results Sixty-six patients received ADT + bevacizumab and 36 received ADT alone. Patients receiving ADT + bevacizumab had a statistically significant improvement in RFS compared with patients treated with ADT alone (13.3 months for ADT + bevacizumab v 10.2 months for ADT alone; hazard ratio, 0.47; 95% CI, 0.29 to 0.77; log-rank P = .002). Hypertension was the most common adverse event in patients receiving ADT + bevacizumab (36%). Conclusion ADT combined with bevacizumab resulted in an improved RFS for patients with hormone-sensitive prostate cancer. Long-term follow-up is needed to determine whether some patients have a durable PSA response and are able to remain off ADT for prolonged periods. Our data provide rationale for combining vascular endothelial growth factor–targeting therapy with ADT in hormone-sensitive prostate cancer. PMID:27044933

Detection of prostate cancer using magnetic resonance imaging/ultrasonography image-fusion targeted biopsy in African-American men.

PubMed

Shin, Toshitaka; Smyth, Thomas B; Ukimura, Osamu; Ahmadi, Nariman; de Castro Abreu, Andre Luis; Oishi, Masakatsu; Mimata, Hiromitsu; Gill, Inderbir S

2017-08-01

To assess the diagnostic yield of targeted prostate biopsy in African-American (A-A) men using image fusion of multi-parametric magnetic resonance imaging (mpMRI) with real-time transrectal ultrasonography (US). We retrospectively analysed 661 patients (117 A-A and 544 Caucasian) who had mpMRI before biopsy and then underwent MRI/US image-fusion targeted biopsy (FTB) between October 2012 and August 2015. The mpMRIs were reported on a 5-point Likert scale of suspicion. Clinically significant prostate cancer (CSPC) was defined as biopsy Gleason score ≥7. After controlling for age, prostate-specific antigen level and prostate volume, there were no significant differences between A-A and Caucasian men in the detection rate of overall cancer (35.0% vs 34.2%, P = 0.9) and CSPC (18.8% vs 21.7%, P = 0.3) with MRI/US FTB. There were no significant differences between the races in the location of dominant lesions on mpMRI, and in the proportion of 5-point Likert scoring. In A-A men, MRI/US FTB from the grade 4-5 lesions outperformed random biopsy in the detection rate of overall cancer (70.6% vs 37.2%, P = 0.003) and CSPC (52.9% vs 12.4%, P < 0.001). MRI/US FTB outperformed random biopsy in cancer core length (5.0 vs 2.4 mm, P = 0.001), in cancer rate per core (24.9% vs 6.8%, P < 0.001), and in efficiency for detecting one patient with CSPC (mean number of cores needed 13.3 vs 81.9, P < 0.001), respectively. Our key finding confirms a lack of racial difference in the detection rate of overall prostate cancers and CSPC with MRI/US FTB between A-A and Caucasian men. MRI/US FTB detected more CSPC using fewer cores compared with random biopsy. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

A Multicenter Randomized Noninferiority Trial Comparing GreenLight-XPS Laser Vaporization of the Prostate and Transurethral Resection of the Prostate for the Treatment of Benign Prostatic Obstruction: Two-yr Outcomes of the GOLIATH Study.

PubMed

Thomas, James A; Tubaro, Andrea; Barber, Neil; d'Ancona, Frank; Muir, Gordon; Witzsch, Ulrich; Grimm, Marc-Oliver; Benejam, Joan; Stolzenburg, Jens-Uwe; Riddick, Antony; Pahernik, Sascha; Roelink, Herman; Ameye, Filip; Saussine, Christian; Bruyère, Franck; Loidl, Wolfgang; Larner, Tim; Gogoi, Nirjan-Kumar; Hindley, Richard; Muschter, Rolf; Thorpe, Andrew; Shrotri, Nitin; Graham, Stuart; Hamann, Moritz; Miller, Kurt; Schostak, Martin; Capitán, Carlos; Knispel, Helmut; Bachmann, Alexander

2016-01-01

The GOLIATH study is a 2-yr trial comparing transurethral resection of prostate (TURP) to photoselective vaporization with the GreenLight XPS Laser System (GL-XPS) for the treatment of benign prostatic obstruction (BPO). Noninferiority of GL-XPS to TURP was demonstrated based on a 6-mo follow-up from the study. To determine whether treatment effects observed at 6 mo between GL-XPS and TURP was maintained at the 2-yr follow-up. Prospective randomized controlled trial at 29 centers in nine European countries involving 281 patients with BPO. Photoselective vaporization using the 180-W GreenLight GL-XPS or conventional (monopolar or bipolar) TURP. The primary outcome was the International Prostate Symptom Score for which a margin of three was used to evaluate the noninferiority of GL-XPS. Secondary outcomes included Qmax, prostate volume, prostate specific antigen, Overactive Bladder Questionnaire Short Form, International Consultation on Incontinence Questionnaire Short Form, occurrence of surgical retreatment, and freedom from complications. One hundred and thirty-six patients were treated using GL-XPS and 133 using TURP. Noninferiority of GL-XPS on International Prostate Symptom Score, Qmax, and freedom from complications was demonstrated at 6-mo and was sustained at 2-yr. The proportion of patients complication-free through 24-mo was 83.6% GL-XPS versus 78.9% TURP. Reductions in prostate volume and prostate specific antigen were similar in both arms and sustained over the course of the trial. Compared with the 1(st) yr of the study, very few adverse events or retreatments were reported in either arm. Treatment differences in the Overactive Bladder Questionnaire Short Form observed at 12-mo were not statistically significant at 24-mo. A limitation was that patients and treating physicians were not blinded to the therapy. Twenty-four-mo follow-up data demonstrated that GL-XPS provides a durable surgical option for the treatment of BPO that exhibits efficacy and safety outcomes similar to TURP. The long-term effectiveness and safety of GLP-XLS was similar to conventional TURP for the treatment of prostate enlargement. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The effect of chronic prostatitis on zinc concentration of prostatic fluid and seminal plasma: a systematic review and meta-analysis.

PubMed

Cui, Dong; Han, GuangWei; Shang, YongGang; Mu, LiJun; Long, QingZhi; Du, YueFeng

2015-01-01

Prostatitis is a common disease in urology departments. Prostatic zinc accumulation is connected with the secretory function of the prostate, and zinc concentrations present in prostatic diseases differ greatly from the normal level. Studies have investigated the effect of chronic prostatitis on zinc concentration of prostatic fluid and seminal plasma, but have shown inconsistent results. Hence, we performed a systematic literature review and meta-analysis to assess the effect of chronic prostatitis on the zinc concentration of prostatic fluid and seminal plasma. Systematic literature searches were conducted with PubMed, Embase, Science Direct/Elsevier, CNKI and the Cochrane Library up to March 2015 for case-control studies that involved the relationship between chronic prostatitis and zinc concentration of prostatic fluid and seminal plasma. Meta-analysis was performed with Review Manager and Stata software. Standard mean differences (SMDs) of zinc concentration were identified with 95% confidence intervals (95% CIs) in a random- or fixed-effects model. Our results illustrated that the zinc concentrations in prostatic fluid and seminal plasma from chronic prostatitis patients were significantly lower than normal controls (SMD [95% CI] -246.71 [-347.97, -145.44], -20.74 [-35.11, -6.37], respectively). The sample size of each study was relatively small, and a total of 731 chronic prostatitis patients and 574 normal controls were investigated in all fourteen studies. Several studies related to the subject were excluded due to lack of control data or means and standard deviations. The present study illustrates that there was a significant negative effect of chronic prostatitis on zinc concentrations of prostatic fluid and seminal plasma. Further studies with larger sample sizes are needed to better illuminate the negative impact of chronic prostatitis on zinc concentrations.

Prostate-Specific Antigen-Based Screening for Prostate Cancer: Evidence Report and Systematic Review for the US Preventive Services Task Force.

PubMed

Fenton, Joshua J; Weyrich, Meghan S; Durbin, Shauna; Liu, Yu; Bang, Heejung; Melnikow, Joy

2018-05-08

Prostate cancer is the second leading cause of cancer death among US men. To systematically review evidence on prostate-specific antigen (PSA)-based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk calculators to inform the US Preventive Services Task Force. Searches of PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on February 1, 2018. English-language reports of randomized clinical trials (RCTs) of screening; cohort studies reporting harms; RCTs and cohort studies of active localized cancer treatments vs conservative approaches (eg, active surveillance, watchful waiting); external validations of prebiopsy risk calculators to identify aggressive cancers. One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Prostate cancer and all-cause mortality; false-positive screening results, biopsy complications, overdiagnosis; adverse effects of active treatments. Random-effects meta-analyses were conducted for treatment harms. Sixty-three studies in 104 publications were included (N = 1 904 950). Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a US trial with substantial control group contamination (n = 76 683) or a UK trial with low adherence to a single PSA screen (n = 408 825) but was associated with significantly reduced prostate cancer mortality in a European trial (n = 162 243; relative risk [RR], 0.79 [95% CI, 0.69-0.91]; absolute risk reduction, 1.1 deaths per 10 000 person-years [95% CI, 0.5-1.8]). Of 61 604 men screened in the European trial, 17.8% received false-positive results. In 3 cohorts (n = 15 136), complications requiring hospitalization occurred in 0.5% to 1.6% of men undergoing biopsy after abnormal screening findings. Overdiagnosis was estimated to occur in 20.7% to 50.4% of screen-detected cancers. In an RCT of men with screen-detected prostate cancer (n = 1643), neither radical prostatectomy (hazard ratio [HR], 0.63 [95% CI, 0.21-1.93]) nor radiation therapy (HR, 0.51 [95% CI, 0.15-1.69]) were associated with significantly reduced prostate cancer mortality vs active monitoring, although each was associated with significantly lower risk of metastatic disease. Relative to conservative management, radical prostatectomy was associated with increased risk of urinary incontinence (pooled RR, 2.27 [95% CI, 1.82-2.84]; 3 trials; n = 1796) and erectile dysfunction (pooled RR, 1.82 [95% CI, 1.62-2.04]; 2 trials; n = 883). Relative to conservative management (8 cohort studies; n = 3066), radiation therapy was associated with increased risk of erectile dysfunction (pooled RR, 1.31 [95% CI, 1.20-1.42]). PSA screening may reduce prostate cancer mortality risk but is associated with false-positive results, biopsy complications, and overdiagnosis. Compared with conservative approaches, active treatments for screen-detected prostate cancer have unclear effects on long-term survival but are associated with sexual and urinary difficulties.

Psychosocial and Patient Education Needs of Prostate Cancers Selecting Watchful Waiting

DTIC Science & Technology

2006-05-01

A., van Andel, G.: Psychosocial and educational aspects in prostate cancer patients. Patient Educ Couns, 49: 203, 2003 16. Maliski, S. L., Clerkin ...prostate cancer patients. Patient Educ Couns, 49: 203, 2003 21. Maliski, S. L., Clerkin , B., Letwin, M. S.: Describing a nurse case manager intervention

Pairing Physician Education With Patient Activation to Improve Shared Decisions in Prostate Cancer Screening: A Cluster Randomized Controlled Trial

PubMed Central

Wilkes, Michael S.; Day, Frank C.; Srinivasan, Malathi; Griffin, Erin; Tancredi, Daniel J.; Rainwater, Julie A.; Kravitz, Richard L.; Bell, Douglas S.; Hoffman, Jerome R.

2013-01-01

BACKGROUND Most expert groups recommend shared decision making for prostate cancer screening. Most primary care physicians, however, routinely order a prostate-specific antigen (PSA) test with little or no discussion about whether they believe the potential benefits justify the risk of harm. We sought to assess whether educating primary care physicians and activating their patients to ask about prostate cancer screening had a synergistic effect on shared decision making, rates and types of discussions about prostate cancer screening, and the physician’s final recommendations. METHODS Our study was a cluster randomized controlled trial among primary care physicians and their patients, comparing usual education (control), with physician education alone (MD-Ed), and with physician education and patient activation (MD-Ed+A). Participants included 120 physicians in 5 group practices, and 712 male patients aged 50 to 75 years. The interventions comprised a Web-based educational program for all intervention physicians and MD-Ed+A patients compared with usual education (brochures from the Centers for Disease Control and Prevention). The primary outcome measure was patients’ reported postvisit shared decision making regarding prostate cancer screening; secondary measures included unannounced standardized patients’ reported shared decision making and the physician’s recommendation for prostate cancer screening. RESULTS Patients’ ratings of shared decision making were moderate and did not differ between groups. MD-Ed+A patients reported that physicians had higher prostate cancer screening discussion rates (MD-Ed+A = 65%, MD-Ed = 41%, control=38%; P <.01). Standardized patients reported that physicians seeing MD-Ed+A patients were more neutral during prostate cancer screening recommendations (MD-Ed+A=50%, MD-Ed=33%, control=15%; P <.05). Of the male patients, 80% had had previous PSA tests. CONCLUSIONS Although activating physicians and patients did not lead to significant changes in all aspects of physician attitudes and behaviors that we studied, interventions that involved physicians did have a large effect on their attitudes toward screening and in the discussions they had with patients, including their being more likely than control physicians to engage in prostate cancer screening discussions and more likely to be neutral in their final recommendations. PMID:23835818

Thulium laser enucleation (ThuLEP) versus transurethral resection of the prostate in saline (TURis): A randomized prospective trial to compare intra and early postoperative outcomes.

PubMed

Bozzini, G; Seveso, M; Melegari, S; de Francesco, O; Buffi, N M; Guazzoni, G; Provenzano, M; Mandressi, A; Taverna, G

2017-06-01

To compare clinical intra and early postoperative outcomes between thulium laser transurethral enucleation of the prostate (ThuLEP) and transurethral bipolar resection of the prostate (TURis) for treating benign prostatic hyperplasia (BPH) in a prospective randomized trial. The study randomized 208 consecutive patients with BPH to ThuLEP (n=102) or TURis (n=106). For all patients were evaluated preoperatively with regards to blood loss, catheterization time, irrigation volume, hospital stay and operative time. At 3 months after surgery they were also evaluated by International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and postvoid residual urine volume (PVR). The patients in each study arm each showed no significant difference in preoperative parameters. Compared with TURIS, ThuLEP had same operative time (53.69±31.44 vs 61.66±18.70minutes, P=.123) but resulted in less hemoglobin decrease (0.45 vs 2.83g/dL, P=.005). ThuLEP also needed less catheterization time (1.3 vs 4.8 days, P=.011), irrigation volume (29.4 vs 69.2 L, P=.002), and hospital stay (1.7 vs 5.2 days, P=.016). During the 3 months of follow-up, the procedures did not demonstrate a significant difference in Qmax, IPSS, PVR, and QOLS. ThuLEP and TURis both relieve lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP was statistically superior to TURis in blood loss, catheterization time, irrigation volume, and hospital stay. However, procedures did not differ significantly in Qmax, IPSS, PVR, and QOLS through 3 months of follow-up. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Updated Prognostic Model for Predicting Overall Survival in First-Line Chemotherapy for Patients With Metastatic Castration-Resistant Prostate Cancer

PubMed Central

Halabi, Susan; Lin, Chen-Yen; Kelly, W. Kevin; Fizazi, Karim S.; Moul, Judd W.; Kaplan, Ellen B.; Morris, Michael J.; Small, Eric J.

2014-01-01

Purpose Prognostic models for overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC) are dated and do not reflect significant advances in treatment options available for these patients. This work developed and validated an updated prognostic model to predict OS in patients receiving first-line chemotherapy. Methods Data from a phase III trial of 1,050 patients with mCRPC were used (Cancer and Leukemia Group B CALGB-90401 [Alliance]). The data were randomly split into training and testing sets. A separate phase III trial served as an independent validation set. Adaptive least absolute shrinkage and selection operator selected eight factors prognostic for OS. A predictive score was computed from the regression coefficients and used to classify patients into low- and high-risk groups. The model was assessed for its predictive accuracy using the time-dependent area under the curve (tAUC). Results The model included Eastern Cooperative Oncology Group performance status, disease site, lactate dehydrogenase, opioid analgesic use, albumin, hemoglobin, prostate-specific antigen, and alkaline phosphatase. Median OS values in the high- and low-risk groups, respectively, in the testing set were 17 and 30 months (hazard ratio [HR], 2.2; P < .001); in the validation set they were 14 and 26 months (HR, 2.9; P < .001). The tAUCs were 0.73 (95% CI, 0.70 to 0.73) and 0.76 (95% CI, 0.72 to 0.76) in the testing and validation sets, respectively. Conclusion An updated prognostic model for OS in patients with mCRPC receiving first-line chemotherapy was developed and validated on an external set. This model can be used to predict OS, as well as to better select patients to participate in trials on the basis of their prognosis. PMID:24449231

Comparative randomized study on the efficaciousness of treatment of BOO due to BPH in patients with prostate up to 100 gr by endoscopic gyrus prostate resection versus open prostatectomy. Preliminary data.

PubMed

Giulianelli, Roberto; Brunori, Stefano; Gentile, Barbara Cristina; Vincenti, Giorgio; Nardoni, Stefano; Pisanti, Francesco; Shestani, Teuta; Mavilla, Luca; Albanesi, Luca; Attisani, Francesco; Mirabile, Gabriella; Schettini, Manlio

2011-06-01

With the advent of medical management and minimally techniques for benign prostate hypeplasia (BPH), invasive surgical procedures such open prostatectomy (OPSU) have become less common, although selected patients may still benefit from open prostatectomy. Aim of this study was to evaluate efficacy and safety of Bipolar TURP (Gyrus electro surgical system) versus standard open prostatectomy in patients with lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO) with markedly enlarged glands refractory to medical therapy. From January 2003 to January 2004, 140 patients affected by mild-severe LUTS, secondary to BOO from BPH, refractory to medical therapy, with markedly enlarged glands, were randomized in two groups (1:1), and subjected to open prostatectomy (OPSU) carried out with traditional method (Bracci Thechnique) versus transurethral resection of the prostate (TURP) utilizing the bipolar methodology. Preoperative work-up included IPSS, IIEF-5 and Qol questionnaires. All patients were submitted to uroflowmetry, transrectal ultrasound (TRUS), measurament of postvoidal residual urine and PSA determination. IPSS, IIEF-5 and Qol, uroflowmetry, TRUS, measurement of post-voidal residual urine, PSA determination and number of reoperations were evaluated at 1, 3, 6, 12, 18, 24, 30 and 36 months. Operative time, resected tissue weight and perioperative complications were also registered. Total post-operative catheter time, total postoperative hospital stay, haemoglobin loss were recorded in the 2 groups. Comparative data on IPSS symptom score, IIEF-5 and Qol, PSA, peak urinary flow rates and post-void residual urine volume in the 2 groups were similar but showed a significative improvement with respect to baseline value. Postoperative haemoglobin levels, postoperative catheterization, hospital stay and 3-yr overall surgical re-treatment-free rate were significantly better in the Bipolar group. In the treatment of LUTS due to bladder outlet obstruction (BOO) with markedly enlarged glands refractory to medical therapy, Bipolar TURP has a comparable outcome to open prostatectomy at short and medium term according to both subjective and objective outcome measures.

Prospective randomized trial comparing magnetic resonance imaging (MRI)-guided in-bore biopsy to MRI-ultrasound fusion and transrectal ultrasound-guided prostate biopsy in patients with prior negative biopsies.

PubMed

Arsov, Christian; Rabenalt, Robert; Blondin, Dirk; Quentin, Michael; Hiester, Andreas; Godehardt, Erhard; Gabbert, Helmut E; Becker, Nikolaus; Antoch, Gerald; Albers, Peter; Schimmöller, Lars

2015-10-01

A significant proportion of prostate cancers (PCas) are missed by conventional transrectal ultrasound-guided biopsy (TRUS-GB). It remains unclear whether the combined approach using targeted magnetic resonance imaging (MRI)-ultrasound fusion-guided biopsy (FUS-GB) and systematic TRUS-GB is superior to targeted MRI-guided in-bore biopsy (IB-GB) for PCa detection. To compare PCa detection between IB-GB alone and FUS-GB + TRUS-GB in patients with at least one negative TRUS-GB and prostate-specific antigen ≥4 ng/ml. Patients were prospectively randomized after multiparametric prostate MRI to IB-GB (arm A) or FUS-GB + TRUS-GB (arm B) from November 2011 to July 2014. The study was powered at 80% to demonstrate an overall PCa detection rate of ≥60% in arm B compared to 40% in arm A. Secondary endpoints were the distribution of highest Gleason scores, the rate of detection of significant PCa (Gleason ≥7), the number of biopsy cores to detect one (significant) PCa, the positivity rate for biopsy cores, and tumor involvement per biopsy core. The study was halted after interim analysis because the primary endpoint was not met. The trial enrolled 267 patients, of whom 210 were analyzed (106 randomized to arm A and 104 to arm B). PCa detection was 37% in arm A and 39% in arm B (95% confidence interval for difference, -16% to 11%; p=0.7). Detection rates for significant PCa (29% vs 32%; p=0.7) and the highest percentage tumor involvement per biopsy core (48% vs 42%; p=0.4) were similar between the arms. The mean number of cores was 5.6 versus 17 (p<0.001). A limitation is the limited number of patients because of early cessation of accrual. This trial failed to identify an important improvement in detection rate for the combined biopsy approach over MRI-targeted biopsy alone. A prospective comparison between MRI-targeted biopsy alone and systematic TRUS-GB is justified. Our randomized study showed similar prostate cancer detection rates between targeted prostate biopsy guided by magnetic resonance imaging and the combination of targeted biopsy and systematic transrectal ultrasound-guided prostate biopsy. An important improvement in detection rates using the combined biopsy approach can be excluded. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery

PubMed Central

Demark-Wahnefried, Wendy; Polascik, Thomas J.; George, Stephen L.; Switzer, Boyd R.; Madden, John F.; Ruffin, Mack T.; Snyder, Denise C.; Owzar, Kouros; Hars, Vera; Albala, David M.; Walther, Philip J.; Robertson, Cary N.; Moul, Judd W.; Dunn, Barbara K.; Brenner, Dean; Minasian, Lori; Stella, Philip; Vollmer, Robin T.

2009-01-01

Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol. PMID:19064574

Effect of saw palmetto soft gel capsule on lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized trial in Shanghai, China.

PubMed

Shi, Rong; Xie, Qiungwen; Gang, X; Lun, Jing; Cheng, Life; Pantuck, Allan; Rao, Jianyu

2008-02-01

We determined the effect of Prostataplex in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. A total of 92 Chinese men between 49 and 75 years old with lower urinary tract symptoms were randomly assigned in this double-blind, placebo controlled trial. The 46 patients in the intervention group were given 2 Prostataplex soft gels daily for 12 weeks, while the 46 in the control group were given 2 placebo soft gels for the same time. The treated and control groups appeared to have more than a 95% compliance rate, as judged by counting the remaining pills in the bottle collected at the end of trial months 1 to 3. After 12 weeks of intervention the mean +/- SD maximum urinary flow rate was significantly higher in the treatment group than in the control group (14.07 +/- 2.56 vs 11.74 +/- 1.23 ml per second, p <0.001), while relative urinary resistance was significantly lower in the treatment group than in the control group (2.35 +/- 0.83 vs 3.02 +/- 1.18, p = 0.002). While there was no significant difference in mean prostate volume or International Prostate Symptom Score between the 2 groups, 18 of 46 patients (39.1%) in the treatment group showed an International Prostate Symptom Score improvement (decrease of 3 or greater) after intervention, whereas only 1 of 46 (2.2%) in the control group showed an International Prostate Symptom Score improvement (chi-square test p <0.001). Prostataplex may have short-term effects in improving symptoms and objective measures in Chinese men with lower urinary tract symptoms associated with benign prostatic hyperplasia.

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2010-09-01

determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 2 of the award, we were approved by the...Trial (PCPT), a randomized placebo‐ controlled clinical trial to determine if  finasteride  (an inhibitor of androgen bioactivation) could  prevent

Selenium and Vitamin E for Prostate Cancer: Post-SELECT (Selenium and Vitamin E Cancer Prevention Trial) Status

PubMed Central

Ledesma, Mark C; Jung-Hynes, Brittney; Schmit, Travis L; Kumar, Raj; Mukhtar, Hasan; Ahmad, Nihal

2011-01-01

Various formulations of selenium and vitamin E, both essential human dietary components, have been shown to possess a therapeutic and preventive effect against prostate cancer. Fortuitous results of clinical trials also implied a risk-reduction effect of selenium and vitamin E supplements. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), using oral selenium and vitamin E supplementation in disease-free volunteers, was designed to test a prostate cancer chemoprevention hypothesis. SELECT was terminated early because of both safety concerns and negative data for the formulations and doses given. Here, we review and discuss the studies done before and since the inception of SELECT, as well as the parameters of the trial itself. We believe that there is a lack of appropriate in vivo preclinical studies on selenium and vitamin E despite many promising in vitro studies on these agents. It seems that the most effective doses and formulations of these agents for prostate cancer chemoprevention have yet to be tested. Also, improved understanding of selenium and vitamin E biology may facilitate the discovery of these doses and formulations. PMID:20882260

Management of benign prostatic hyperplasia with silodosin

PubMed Central

Yamanishi, Tomonori; Mizuno, Tomoya; Kamai, Takao; Yoshida, Ken-Ichiro; Sakakibara, Ryuji; Uchiyama, Tomoyuki

2009-01-01

It has been reported that blockade of α1A-adrenoceptor (AR) relieves bladder outlet obstruction, while blockade of α1D-AR is believed to alleviate storage symptoms due to detrusor overactivity. Silodosin, (−)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy) phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7- carboxamide, is a new α1A-AR selective antagonist. Silodosin is highly selective for the α1A-AR subtype, showing an affinity for the α1A-AR that is 583- and 55.5-fold higher than its affinity for the α1B-and α1D-ARs, respectively. In randomized, double-blind, placebo-controlled phase III studies performed in Japan and the United States, silodosin has been shown to be effective for both storage and voiding symptoms associated with benign prostatic hyperplasia. Early effects of silodosin (after 2–6 hours or day 1) on lower urinary tract symptoms have also been reported. In urodynamic studies, detrusor overactivity disappeared in 40% and improved in 35% of patients after administration. In pressure flow studies, the grade of obstruction on the International Continence Society nomogram showed improvement in 56% of patients. The rate of adverse events in the silodosin, tamsulosin and placebo groups was 88.6%, 82.3%, and 71.6%, respectively. The most common adverse event was (mostly mild) abnormal ejaculation (28.1%). However, few patients (2.8%) discontinued silodosin because of abnormal ejaculation. Orthostatic hypotension showed a similar incidence in the silodosin (2.6%) and placebo (1.5%) groups. In conclusion, silodosin improves detrusor overactivity and obstruction and thus may be effective for both storage and voiding symptoms in patients with benign prostatic hyperplasia. PMID:24198606

EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.

PubMed

Kitamura, Tadaichi; Nishimatsu, Hiroaki; Hamamoto, Toshiaki; Tomita, Kyoichi; Takeuchi, Takumi; Ohta, Nobutaka

2002-02-01

Many chemotherapeutic regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25-58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43-77%) with moderate to severe toxicity in the rate of thromboembolic event (5-18%) and of neutropenia (9-41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roper, J; Bradshaw, B; Godette, K

Purpose: To create a knowledge-based algorithm for prostate LDR brachytherapy treatment planning that standardizes plan quality using seed arrangements tailored to individual physician preferences while being fast enough for real-time planning. Methods: A dataset of 130 prior cases was compiled for a physician with an active prostate seed implant practice. Ten cases were randomly selected to test the algorithm. Contours from the 120 library cases were registered to a common reference frame. Contour variations were characterized on a point by point basis using principle component analysis (PCA). A test case was converted to PCA vectors using the same process andmore » then compared with each library case using a Mahalanobis distance to evaluate similarity. Rank order PCA scores were used to select the best-matched library case. The seed arrangement was extracted from the best-matched case and used as a starting point for planning the test case. Computational time was recorded. Any subsequent modifications were recorded that required input from a treatment planner to achieve an acceptable plan. Results: The computational time required to register contours from a test case and evaluate PCA similarity across the library was approximately 10s. Five of the ten test cases did not require any seed additions, deletions, or moves to obtain an acceptable plan. The remaining five test cases required on average 4.2 seed modifications. The time to complete manual plan modifications was less than 30s in all cases. Conclusion: A knowledge-based treatment planning algorithm was developed for prostate LDR brachytherapy based on principle component analysis. Initial results suggest that this approach can be used to quickly create treatment plans that require few if any modifications by the treatment planner. In general, test case plans have seed arrangements which are very similar to prior cases, and thus are inherently tailored to physician preferences.« less

Flexible proton 3D MR spectroscopic imaging of the prostate with low-power adiabatic pulses for volume selection and spiral readout.

PubMed

Steinseifer, Isabell K; Philips, Bart W J; Gagoski, Borjan; Weiland, Elisabeth; Scheenen, Tom W J; Heerschap, Arend

2017-03-01

Cartesian k-space sampling in three-dimensional magnetic resonance spectroscopic imaging (MRSI) of the prostate limits the selection of voxel size and acquisition time. Therefore, large prostates are often scanned at reduced spatial resolutions to stay within clinically acceptable measurement times. Here we present a semilocalized adiabatic selective refocusing (sLASER) sequence with gradient-modulated offset-independent adiabatic (GOIA) refocusing pulses and spiral k-space acquisition (GOIA-sLASER-Spiral) for fast prostate MRSI with enhanced resolution and extended matrix sizes. MR was performed at 3 tesla with an endorectal receive coil. GOIA-sLASER-Spiral at an echo time (TE) of 90 ms was compared to a point-resolved spectroscopy sequence (PRESS) with weighted, elliptical phase encoding at an TE of 145 ms using simulations and measurements of phantoms and patients (n = 9). GOIA-sLASER-Spiral acquisition allows prostate MR spectra to be obtained in ∼5 min with a quality comparable to those acquired with a common Cartesian PRESS protocol in ∼9 min, or at an enhanced spatial resolution showing more precise tissue allocation of metabolites. Extended field of views (FOVs) and matrix sizes for large prostates are possible without compromising spatial resolution or measurement time. The flexibility of spiral sampling enables prostate MRSI with a wide range of resolutions and FOVs without undesirable increases in acquisition times, as in Cartesian encoding. This approach is suitable for routine clinical exams of prostate metabolites. Magn Reson Med 77:928-935, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Thakkinstian, Ammarin; Attia, John; Anothaisintawee, Thunyarat; Nickel, J Curtis

2012-10-01

Study Type - Therapy (systematic review) Level of Evidence 1a. What's known on the subject? and What does the study add? Individual clinical trials evaluating antibiotics, anti-inflammatories and α-blockers for the treatment of chronic prostatitis/chronic pelvic pain syndrome have shown only modest or even no benefits for patients compared with placebo, yet we continue to use these agents in selected patients with some success in clinical practice. This network meta-analysis of current evidence from all available randomized placebo-controlled trials with similar inclusion criteria and outcome measures shows that these '3-As' of chronic prostatitis/chronic pelvic pain syndrome treatment (antibiotics, anti-inflammatories and α-blockers) do offer benefits to some patients, particularly if we use them strategically in selected individuals. To provide an updated network meta-analysis mapping α-blockers, antibiotics and anti-inflammatories (the 3-As) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). • To use the results of this meta-analysis to comment on the role of the 3-As in clinical practice. We updated a previous review including only randomized controlled studies employing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) as one of the outcomes to compare treatment effects in CP/CPPS patients. • A longitudinal mixed regression model (network meta-analysis) was applied to indirectly assess multiple treatment comparisons (i.e. α-blockers, antibiotics, anti-inflammatory/immune modulation therapies, α-blockers plus antibiotics, and placebo). Nineteen studies (1669 subjects) were eligible for analysis. • α-blockers, antibiotics and anti-inflammatory/immune modulation therapies were associated with significant improvement in symptoms when compared with placebo, with mean differences of total CPSI of -10.8 (95% CI -13.2 to -8.3; P < 0.001), -9.7 (95% CI -14.2 to -5.3; P < 0.001) and -1.7 (95% CI -3.2 to -0.2; P= 0.032) respectively, while α-blockers plus antibiotics resulted in the greatest CPSI difference (-13.6, 95% CI -16.7 to -10.6; P < 0.001). • With respect to responder analysis compared with placebo, anti-inflammatories showed the greatest response rates (risk ratio 1.7, 95% CI 1.4-2.1; P < 0.001) followed by α-blockers (risk ratio 1.4, 95% CI 1.1-1.8; P= 0.013) and antibiotics (risk ratio 1.2, 95% CI 0.7-1.9; P= 0.527). α-blockers, antibiotics and/or anti-inflammatory/immune modulation therapy appear to be beneficial for some patients with CP/CPPS. • The magnitude of effect and the disconnect between mean CPSI decrease and response rates compared with placebo suggest that directed multimodal therapy, rather than mono-therapy, with these agents should be considered for optimal management of CP/CPPS. © 2012 BJU INTERNATIONAL.

Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.

PubMed

Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K; Marck, Brett T; Matsumoto, Alvin M

2011-07-01

Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older, hypogonadal men with symptomatic benign prostatic hyperplasia. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Overcoming Drug Resistant Prostate Cancer with APE1/Ref 1 Blockade

DTIC Science & Technology

2016-10-01

prostate cancer specimens. Genetic knockdown of APE1/Ref-1 disrupts prostate cancer cell growth and survival in cell culture. In addition...inhibition of the redox function selectively of Ref-1 results in cell growth inhibition, with this therapy preferentially inhibiting prostate cancer cell... growth above that in non-cancerous cells. Specific blockade of Ref-1 redox activity in tumors is a novel concept in tumor therapy. If we are successful

Novel Biomarker Discovery for Diagnostic and Therapeutic Strategies in Prostate Cancer

DTIC Science & Technology

2014-03-01

aptamers that distinguish between prostate cancers that are likely to remain organ-confined and those with potential to metastasize, The scope of this...pilot is to generate DNA aptamers that selectively react with a prostate cancer cell line that remains confined to the prostate (LNCaP) vs. a...subpopulation of this cell line that has acquired the ability to metastasize aggressively, employing Cell-Selex and Aptamer -Facilitated Biomarker Discovery

Transrectal Near-Infrared Optical Tomography for Prostate Imaging

DTIC Science & Technology

2010-03-01

valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 31-03-2010 2. REPORT TYPE Annual 3...technology of trans-rectal near-infrared (NIR) optical tomography for accurate, selective prostate biopsy. Prostate cancer is the most common non ...mice and recovered/homogenized for injection into the non -immune suppressed dog’s prostate gland. Under general anesthesia, ~2 cc of TVT cells

CT-Guided Transgluteal Biopsy for Systematic Random Sampling of the Prostate in Patients Without Rectal Access.

PubMed

Goenka, Ajit H; Remer, Erick M; Veniero, Joseph C; Thupili, Chakradhar R; Klein, Eric A

2015-09-01

The objective of our study was to review our experience with CT-guided transgluteal prostate biopsy in patients without rectal access. Twenty-one CT-guided transgluteal prostate biopsy procedures were performed in 16 men (mean age, 68 years; age range, 60-78 years) who were under conscious sedation. The mean prostate-specific antigen (PSA) value was 11.4 ng/mL (range, 2.3-39.4 ng/mL). Six had seven prior unsuccessful transperineal or transurethral biopsies. Biopsy results, complications, sedation time, and radiation dose were recorded. The mean PSA values and number of core specimens were compared between patients with malignant results and patients with nonmalignant results using the Student t test. The average procedural sedation time was 50.6 minutes (range, 15-90 minutes) (n = 20), and the mean effective radiation dose was 8.2 mSv (median, 6.6 mSv; range 3.6-19.3 mSv) (n = 13). Twenty of the 21 (95%) procedures were technically successful. The only complication was a single episode of gross hematuria and penile pain in one patient, which resolved spontaneously. Of 20 successful biopsies, 8 (40%) yielded adenocarcinoma (Gleason score: mean, 8; range, 7-9). Twelve biopsies yielded nonmalignant results (60%): high-grade prostatic intraepithelial neoplasia (n = 3) or benign prostatic tissue with or without inflammation (n = 9). Three patients had carcinoma diagnosed on subsequent biopsies (second biopsy, n = 2 patients; third biopsy, n = 1 patient). A malignant biopsy result was not significantly associated with the number of core specimens (p = 0.3) or the mean PSA value (p = 0.1). CT-guided transgluteal prostate biopsy is a safe and reliable technique for the systematic random sampling of the prostate in patients without a rectal access. In patients with initial negative biopsy results, repeat biopsy should be considered if there is a persistent rise in the PSA value.

Diode laser (980 nm) vaporization in comparison with transurethral resection of the prostate for benign prostatic hyperplasia: randomized clinical trial with 2-year follow-up.

PubMed

Razzaghi, Mohammad Reza; Mazloomfard, Mohammad Mohsen; Mokhtarpour, Hooman; Moeini, Aida

2014-09-01

To compare outcomes of diode laser vaporization of prostate with transurethral resection of the prostate (TURP) as a gold-standard treatment. A total number of 115 patients with benign prostatic hyperplasia underwent TURP and 980-nm diode vaporization of prostate in a balanced randomization (1:1) from 2010 to 2012 and were followed up for 24 months. Baseline characteristics of the patients, perioperative data, and postoperative outcomes were compared. The primary end point of the study was assessing the values of International Prostate Symptom Score (IPSS), and maximum flow rate (Qmax) to predict the functional improvement of each group. The trial is registered at http://www.irct.ir (number IRCT201202138146N3). The mean age (± standard deviation) of the patients was 68.2 ± 7.8 years in TURP and 68.5 ± 8.8 in diode groups. In TURP and diode groups, the operation time was 54.9 ± 15.3 vs 60.6 ± 22.6 minutes (P = .14), Foley catheterization time was 88.9 ± 22.5 vs 20.1 ± 4.6 hours (P = .0001) and postoperative hospital stay was 59.9 ± 14.4 vs 25.8 ± 9.2 hours (P = .0001) respectively. Outcome with regard to increase in Qmax, decrease in IPSS, and decrease in postvoid residual urine volume showed a dramatic improvement in both groups during the first 6 months. In the TURP group, the values of IPSS and Qmax were respectively lower and higher than diode patients at 12 and 24 months of follow-up. According to our study, diode laser vaporization (980 nm) offers a safe and feasible procedure in the management of patients with symptomatic benign prostatic hypertrophy; however, at longer follow-up the functional outcome of diode laser vaporization has been less efficient than TURP. Copyright © 2014 Elsevier Inc. All rights reserved.

Low dose oral desmopressin for nocturnal polyuria in patients with benign prostatic hyperplasia: a double-blind, placebo controlled, randomized study.

PubMed

Wang, Chung-Jing; Lin, Yu-Nan; Huang, Shi-Wei; Chang, Chien-Hsing

2011-01-01

We evaluated the long-term efficacy and safety of low dose oral desmopressin in elderly patients with benign prostatic hyperplasia with more than nocturnal voids and nocturnal polyuria more than 30% of total daily urine volume. Eligible patients with benign prostatic hyperplasia older than 65 years with nocturia, nocturnal polyuria and International Prostate Symptom Score 14 or greater were included in the study. All patients received placebo or 0.1 mg desmopressin orally at bedtime. Patients were required to visit the outpatient clinic from the first visit, and after 1, 3, 6 and 12 months of treatment. Patients maintained flow volume charts and used diaries to record voiding data throughout the study. During followup urinalysis, urine sodium, urine osmolality, serum electrolytes, prostate specific antigen, International Prostate Symptom Score, quality of life, transrectal ultrasonography of prostate, uroflowmetry and post-void residual urine volume were performed at each visit. A total of 115 patients were enrolled in the study and randomized as 58 in the placebo group and 57 in the desmopressin group. Desmopressin significantly decreased nocturnal urine output and the number of nocturia episodes, and prolonged the first sleep period (p < 0.01). Compared to before treatment desmopressin gradually decreased serum sodium and induced statistically but not clinically significant hyponatremia after 12 months of treatment. No serious systemic complications were found during medication. Low dose oral desmopressin is an effective and well tolerated treatment for nocturnal polyuria in the lower urinary tract symptoms of patients with benign prostatic hyperplasia. Long-term desmopressin therapy gradually decreases serum sodium and it might induce hyponatremia even in patients without initial hyponatremia. For long-term desmopressin administration serum sodium should be assessed carefully, at least at 1 week after treatment. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia.

PubMed

Marks, L S; Partin, A W; Epstein, J I; Tyler, V E; Simon, I; Macairan, M L; Chan, T L; Dorey, F J; Garris, J B; Veltri, R W; Santos, P B; Stonebrook, K A; deKernion, J B

2000-05-01

We tested the effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled trial. We randomized 44 men 45 to 80 years old with symptomatic BPH into a trial of a saw palmetto herbal blend versus placebo. End points included routine clinical measures (symptom score, uroflowmetry and post-void residual urine volume), blood chemistry studies (prostate specific antigen, sex hormones and multiphasic analysis), prostate volumetrics by magnetic resonance imaging, and prostate biopsy for zonal tissue morphometry and semiquantitative histology studies. Saw palmetto herbal blend and placebo groups had improved clinical parameters with a slight advantage in the saw palmetto group (not statistically significant). Neither prostate specific antigen nor prostate volume changed from baseline. Prostate epithelial contraction was noted, especially in the transition zone, where percent epithelium decreased from 17.8% at baseline to 10.7% after 6 months of saw palmetto herbal blend (p <0.01). Histological studies showed that the percent of atrophic glands increased from 25. 2% to 40.9% after treatment with saw palmetto herbal blend (p <0.01). The mechanism of action appeared to be nonhormonal but it was not identified by tissue studies of apoptosis, cellular proliferation, angiogenesis, growth factors or androgen receptor expression. We noted no adverse effects of saw palmetto herbal blend. When the study was no longer blinded, 41 men elected to continue therapy in an open label extension. Saw palmetto herbal blend appears to be a safe, highly desirable option for men with moderately symptomatic BPH. The secondary outcome measures of clinical effect in our study were only slightly better for saw palmetto herbal blend than placebo (not statistically significant). However, saw palmetto herbal blend therapy was associated with epithelial contraction, especially in the transition zone (p <0.01), indicating a possible mechanism of action underlying the clinical significance detected in other studies.

The role of 68Ga-PSMA PET/CT scan in biochemical recurrence after primary treatment for prostate cancer: a systematic review of literature.

PubMed

Eissa, Ahmed; El Sherbiny, Ahmed; Coelho, Rafael F; Rassweiler, Jens; Davis, John W; Porpiglia, Francesco; Patel, Vipul R; Prandini, Napoleone; Micali, Salvatore; Sighinolfi, Maria C; Puliatti, Stefano; Rocco, Bernardo; Bianchi, Giampaolo

2018-04-17

Recurrence after primary treatment of prostate cancer is one of the major challenges facing urologists. Biochemical recurrence is not rare and occurs in up to one third of the patients undergoing radical prostatectomy. Management of biochemical recurrence is tailored according to the site and the burden of recurrence. Therefore, developing an imaging technique to early detect recurrent lesions represents an urgent need. Positron emission tomography (PET) of 68Ga-labelled prostate-specific membrane antigen (68Ga-PSMA) is an emerging imaging modality that seems to be a promising tool with capability to localize recurrent prostate cancer. Our aim was a systematic review of literature was done to evaluate the role of 68Ga-PSMA PET/CT scan in patients with recurrent prostate cancer after primary radical treatment. A systematic and comprehensive review of literature was performed in September 2017 analyzing the MEDLINE and Cochrane Library following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The following key terms were used for the search "PSMA", "prostate-specific membrane antigen", "positron emission tomography", "PET", "recurrent", "prostate cancer", "prostate neoplasm", "prostate malignancy" and "68Ga". Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Thirty-seven articles met our inclusion criteria and were included in the analysis of this systematic review. Of the 37 articles selected for analysis only four studies were prospective. The overall detection rate of 68Ga PSMA PET scan ranged from 47% up to 96.6%. The main advantage of this imaging technique is its relatively high detection rates at low serum PSA levels below 0.5 ng/ml (ranging from 11.1% to 75%). Higher serum PSA level was strongly associated with increased positivity on 68Ga PSMA PET scan. 68Ga PSMA PET scan was found superior to conventional imaging techniques (CT and MRI) in this setting of patients and even it seems to outperform choline-based PET scan. This technique provided significant changes in the therapeutic management of 28.6% - 87.1% of patients. After biochemical recurrence, the primary goal is to locate the recurrent lesions' site. 68Ga-PSMA PET/CT seems to be effective in identifying recurrence localization also for very low levels of PSA (< 0.5 ng/ml) thus permitting to choose the best therapeutic strategy as early as possible. However, data available cannot be considered exhaustive and prospective randomized trials are needed.

Prostate ultrasound: back in business!

PubMed

Crisan, Nicolae; Andras, Iulia; Radu, Corina; Andras, David; Coman, Radu-Tudor; Tucan, Paul; Pisla, Doina; Crisan, Dana; Coman, Ioan

2017-11-29

The use of grey scale prostate ultrasound decreased after the implementation of magnetic resonance imaging (MRI) for the diagnosis and evaluation of prostate cancer. The new developments, such as multiparametric ultrasound and MRI-ultrasound fusion technology, renewed the interest for this imaging method in the assessment of prostate cancer. The purpose of this paper was to review the current role of prostate ultrasound in the setting of these new applications. A thorough reevaluation of the selection criteria of the patients is required to assess which patients would benefit from multiparametric ultrasound, who wouldbenefit from multiparametric MRI or the combination of both to assist prostate biopsy in order to ensure the balance between overdiagnosis and underdiagnosis of prostate cancer.

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses.

PubMed

Khankari, Nikhil K; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I; Easton, Douglas; Eeles, Rosalind A; Gruber, Stephen B; Haiman, Christopher A; Hunter, David J; Chanock, Stephen J; Pierce, Brandon L; Zheng, Wei

2016-09-01

Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.

TU-H-CAMPUS-JeP3-05: Adaptive Determination of Needle Sequence HDR Prostate Brachytherapy with Divergent Needle-By-Needle Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borot de Battisti, M; Maenhout, M; Lagendijk, J J W

Purpose: To develop a new method which adaptively determines the optimal needle insertion sequence for HDR prostate brachytherapy involving divergent needle-by-needle dose delivery by e.g. a robotic device. A needle insertion sequence is calculated at the beginning of the intervention and updated after each needle insertion with feedback on needle positioning errors. Methods: Needle positioning errors and anatomy changes may occur during HDR brachytherapy which can lead to errors in the delivered dose. A novel strategy was developed to calculate and update the needle sequence and the dose plan after each needle insertion with feedback on needle positioning errors. Themore » dose plan optimization was performed by numerical simulations. The proposed needle sequence determination optimizes the final dose distribution based on the dose coverage impact of each needle. This impact is predicted stochastically by needle insertion simulations. HDR procedures were simulated with varying number of needle insertions (4 to 12) using 11 patient MR data-sets with PTV, prostate, urethra, bladder and rectum delineated. Needle positioning errors were modeled by random normally distributed angulation errors (standard deviation of 3 mm at the needle’s tip). The final dose parameters were compared in the situations where the needle with the largest vs. the smallest dose coverage impact was selected at each insertion. Results: Over all scenarios, the percentage of clinically acceptable final dose distribution improved when the needle selected had the largest dose coverage impact (91%) compared to the smallest (88%). The differences were larger for few (4 to 6) needle insertions (maximum difference scenario: 79% vs. 60%). The computation time of the needle sequence optimization was below 60s. Conclusion: A new adaptive needle sequence determination for HDR prostate brachytherapy was developed. Coupled to adaptive planning, the selection of the needle with the largest dose coverage impact increases chances of reaching the clinical constraints. M. Borot de Battisti is funded by Philips Medical Systems Nederland B.V.; M. Moerland is principal investigator on a contract funded by Philips Medical Systems Nederland B.V.; G. Hautvast and D. Binnekamp are fulltime employees of Philips Medical Systems Nederland B.V.« less

Dihydrotestosterone and testosterone levels in men screened for prostate cancer: a study of a randomized population.

PubMed

Gustafsson, O; Norming, U; Gustafsson, S; Eneroth, P; Aström, G; Nyman, C R

1996-03-01

To investigate the possible relationship between serum levels of prostate specific antigen (PSA), dihydrotestosterone (DHT), testosterone, sexual-hormone binding globulin (SHBG) and tumour stage, grade and ploidy in 65 cases of prostate cancer diagnosed in a screening study compared to 130 controls from the same population. From a population of 26,602 men between the ages of 55 and 70 years, 2400 were selected randomly and invited to undergo screening for prostate cancer using a digital rectal examination, transrectal ultrasonography and PSA analysis. Among the 1782 attendees, 65 cases of prostate cancer were diagnosed. Each case was matched with two control subjects of similar age and prostate volume from the screening population. Frozen serum samples were analysed for PSA, DHT, testosterone and SHBG, and compared to the diagnosis and tumour stage, grade and ploidy. Comparisons between these variables, and multivariate and regression analyses were performed. There were significant differences in PSA level with all variables except tumour ploidy. DHT levels were slightly lower in patients with prostate cancer but the difference was not statistically significant. There was a trend towards lower DHT values in more advanced tumours and the difference for T-stages was close to statistical significance (P = 0.059). Testosterone levels were lower in patients with cancer than in the control group, but the differences were not significant. There was no correlation between testosterone levels, tumour stage and ploidy, but the differences in testosterone level in tumours of a low grade of differentiation compared to those with intermediate and high grade was nearly significant (P = 0.058). The testosterone/DHT ratio tended to be higher in patients with more advanced tumours. SHBG levels were lower in patients with cancer than in controls but the differences were not statistically significant. There were no systematic variations of tumour stage, grade and ploidy. Multivariate analysis showed that if the PSA level was known, then DHT, testosterone or SHBG added no further information concerning diagnosis, stage, grade or ploidy. Regression analysis on T-stage, PSA level and DHT showed an inverse linear relationship between PSA and DHT for stage T-3 (P = 0.035), but there was no relationship between PSA and testosterone. PSA was of value in discriminating between cases and controls and between various tumour stages and grades, but no statistically significant correlation was found for ploidy. If PSA level was known, no other variable added information in individual cases. Within a group, DHT levels tended to be lower among cases and in those with more advanced tumours. There was an inverse relationship between tumour volume, as defined by PSA level, and 5 alpha-reductase activity, as defined by DHT level, and the testosterone/DHT ratio. This trend was most obvious with T-stage. No systematic variation were found in the levels of testosterone or SHBG.

Focal Cryotherapy for Localized Prostate Cancer.

PubMed

Tay, K J; Polascik, T J

2016-07-01

To systematically review the oncological and functional outcomes of contemporary primary prostate focal cryotherapy for localized prostate cancer in the context of current developments in prostate focal therapy. We performed a systematic search of the Pubmed, Cochrane and Embase databases to identify studies where primary prostate focal cryotherapy was performed to treat prostate cancer. These included reports on focal/ lesion/ sector ablation, hemi-ablation and partial prostate ablation. We excluded salvage focal therapy studies. Where multiple reports were published over time from a single cohort, the latest one was used. Our search yielded 290 publications, including 17 primary reports on eight single-center cohort studies and one multi-center registry report. Of 1,595 men identified, mean age was 60.5-69.5 years and mean PSA 5.1-7.8 ng/ml. When stratified by D'Amico risk criteria, 52% of the aggregate total number of men were low-risk, 38% intermediate-risk and 10% high-risk. Besides 12-core TRUS biopsy, 3 cohorts reported using TTMB and one included mpMRI to select men for focal treatment. Median follow-up ranged from 13-63 months. BPFS ranged from 71-98%. The overall post-treatment positive biopsy rate was 8-25%. Among 5 cohorts with a mandatory 6-12 month posttreatment biopsy, 216 of 272 men (79%) did undergo biopsy, with 47 positive (21.8%). Of these, 15 were infield, 26 outfield, 2 bilateral and 4 undeclared. Ten upgraded to Gleason≥7. Overall, two men had metastatic disease and none died of prostate cancer. Post-treatment continence rates were 96-100% and rates of erectile dysfunction ranged from 0-42%. The rate of post-treatment urinary retention ranged from 0-15%. The rate of recto-urethral fistula was 0-0.1%. Focal cryotherapy for localized prostate cancer is a safe and provides good preservation of sexual and urinary function. Accurate cancer localization and risk stratification is key to patient selection. In highly selected patients, focal therapy has good short to medium term oncological efficacy.

The theory of reasoned action and intention to seek cancer information.

PubMed

Ross, Levi; Kohler, Connie L; Grimley, Diane M; Anderson-Lewis, Charkarra

2007-01-01

To evaluate the applicability of the theory of reasoned action to explain men's intentions to seek prostate cancer information. Three hundred randomly selected African American men participated in telephone interviews. Correlational and regression analyses were conducted to examine relationships among measures. All relationships were significant in regression analyses. Attitudes and subjective norm were significantly related to intentions. Indirect measures of beliefs derived from elicitation research were associated with direct measures of attitude and subjective norms. The data are sufficiently clear to support the applicability of the theory for this behavioral domain with African American men and suggest several important areas for future research.

Statistical modeling of interfractional tissue deformation and its application in radiation therapy planning

NASA Astrophysics Data System (ADS)

Vile, Douglas J.

In radiation therapy, interfraction organ motion introduces a level of geometric uncertainty into the planning process. Plans, which are typically based upon a single instance of anatomy, must be robust against daily anatomical variations. For this problem, a model of the magnitude, direction, and likelihood of deformation is useful. In this thesis, principal component analysis (PCA) is used to statistically model the 3D organ motion for 19 prostate cancer patients, each with 8-13 fractional computed tomography (CT) images. Deformable image registration and the resultant displacement vector fields (DVFs) are used to quantify the interfraction systematic and random motion. By applying the PCA technique to the random DVFs, principal modes of random tissue deformation were determined for each patient, and a method for sampling synthetic random DVFs was developed. The PCA model was then extended to describe the principal modes of systematic and random organ motion for the population of patients. A leave-one-out study tested both the systematic and random motion model's ability to represent PCA training set DVFs. The random and systematic DVF PCA models allowed the reconstruction of these data with absolute mean errors between 0.5-0.9 mm and 1-2 mm, respectively. To the best of the author's knowledge, this study is the first successful effort to build a fully 3D statistical PCA model of systematic tissue deformation in a population of patients. By sampling synthetic systematic and random errors, organ occupancy maps were created for bony and prostate-centroid patient setup processes. By thresholding these maps, PCA-based planning target volume (PTV) was created and tested against conventional margin recipes (van Herk for bony alignment and 5 mm fixed [3 mm posterior] margin for centroid alignment) in a virtual clinical trial for low-risk prostate cancer. Deformably accumulated delivered dose served as a surrogate for clinical outcome. For the bony landmark setup subtrial, the PCA PTV significantly (p<0.05) reduced D30, D20, and D5 to bladder and D50 to rectum, while increasing rectal D20 and D5. For the centroid-aligned setup, the PCA PTV significantly reduced all bladder DVH metrics and trended to lower rectal toxicity metrics. All PTVs covered the prostate with the prescription dose.

The expression of β3-adrenoceptors and their function in the human prostate.

PubMed

Suzuki, Takahisa; Otsuka, Atsushi; Matsumoto, Rikiya; Furuse, Hiroshi; Ozono, Seiichiro

2016-02-01

Little is known about β3-adrenoceptor (AR) expression and function in human prostate. We examined the expression and distribution of β-AR subtypes in normal prostate and benign prostatic hyperplasia (BPH) tissues, and investigated which selective β-AR subtype agonist was most involved in the relaxation of isolated human prostate strips. Messenger RNA (mRNA) expression for β1-, β2-, and β3 -ARs was investigated using reverse transcriptase-polymerase chain reactions (RT-PCR). Quantitative analysis of mRNA expression of β-AR subtypes between normal prostate and BPH tissues was performed using quantitative RT-PCR (qPCR). Distributions were examined by immunohistochemistry (IHC). Strips of human normal prostate or BPH were suspended in organ baths and exposed to isoproterenol, dobutamine, procaterol, and TRK-380 to investigate their relaxant effects on KCl-induced contractions, and their inhibitory effects on electrical field stimulation (EFS)-induced contractions. We confirmed the presence of mRNA for β1-, β2-, and β3-ARs both in normal prostate and in BPH tissues. For β3-AR, mRNA expression in BPH tissues was significantly higher than in normal prostate tissues, but there was no significant difference in β1- and β2-AR expression between normal and BPH tissues. IHC revealed differences in staining intensity between smooth muscle cells and glandular cells, with different proportions for different β-AR subtypes. Staining of β3-AR was particularly intense in smooth muscle cells as opposed to glandular cells. Isoproterenol and TRK-380 significantly decreased the tone of KCl-induced contractions of the normal prostate strips. The rank order of relaxant effects was isoproterenol > TRK-380 > procaterol > dobutamine. All selective β-AR agonists significantly decreased the amplitude of EFS-induced contractions of the normal prostate strips. The rank order of inhibitory effects was isoproterenol > dobutamine >TRK-380 > procaterol. In BPH strips, all selective β-AR agonists showed no significant relaxant or inhibitory effects on KCl- or EFS-induced contractions. β3 -AR is abundant in human prostate smooth muscle, whose relaxation is mediated by β1- and β3-AR stimulation. β3-AR agonists may have clinical use in the treatment of male non-BPH patients or neurogenic bladder patients with voiding dysfunction. © 2015 Wiley Periodicals, Inc.

Regressive changes in finasteride-treated human hyperplastic prostates correlate with an upregulation of TGF-beta receptor expression.

PubMed

Sáez, C; González-Baena, A C; Japón, M A; Giráldez, J; Segura, D I; Miranda, G; Rodríguez-Vallejo, J M; González-Esteban, J; Torrubia, F

1998-10-01

Prostatic atrophy has been documented histologically as a consequence of finasteride action on human hyperplastic prostates. An increase in apoptotic rates has also been reported in androgen-deprived hyperplastic prostates. Transforming growth factor beta (TGF-beta) signaling is implicated in apoptotic cell death. TGF-betas have been detected in normal and diseased human prostate. In the normal prostate, TGF-beta acts as a predominantly negative growth regulator. TGF-beta signaling receptors TbetaRI and TbetaRII have been shown to be negatively regulated by androgens. We studied the histological changes in 9 selected finasteride-treated patients with benign prostatic hyperplasia (BPH), and analyzed the levels of expression and localization of TGF-beta receptor types TbetaRI and TbetaRII in these patients as compared to selected BPH controls. The prostatic epithelial compartment seemed to be a primary target site for finasteride action, since we observed moderate to severe glandular atrophy after 4-6 months of treatment. TGF-beta receptors were upregulated in treated cases. We assessed a twofold increase in TbetaRII mRNA levels in treated cases as compared to controls. An increase in both TbetaRI and TbetaRII at the protein level by immunostaining was observed, which also provided a helpful means for detecting glands undergoing regression. We conclude that finasteride may modulate the TGF-beta signaling system to promote changes leading to apoptosis of epithelial cells and prostatic glandular atrophy.

The prospect of gene therapy for prostate cancer: update on theory and status.

PubMed

Koeneman, K S; Hsieh, J T

2001-09-01

Molecularly based novel therapeutic agents are needed to address the problem of locally recurrent, or metastatic, advanced hormone-refractory prostate cancer. Recent basic science advances in mechanisms of gene expression, vector delivery, and targeting have rendered clinically relevant gene therapy to the prostatic fossa and distant sites feasible in the near future. Current research and clinical investigative efforts involving methods for more effective vector delivery and targeting, with enhanced gene expression to selected (specific) sites, are reviewed. These areas of research involve tissue-specific promoters, transgene exploration, vector design and delivery, and selective vector targeting. The 'vectorology' involved mainly addresses selective tissue homing with ligands, mechanisms of innate immune system evasion for durable transgene expression, and the possibility of repeat administration.

The Exercising Together Project: Design and recruitment for a randomized, controlled trial to determine the benefits of partnered strength training for couples coping with prostate cancer

PubMed Central

Winters-Stone, Kerri M.; Lyons, Karen S.; Nail, Lillian M.; Beer, Tomasz M.

2011-01-01

Prostate cancer can threaten quality of life for the patient and his spouse and the quality of his marital relationship. The purpose of our study is to evaluate the effects of “Exercising Together” – a partnered strength training program for married couples coping with prostate cancer – on the physical and emotional health of prostate cancer survivors (PCS) and their spouses and on marital quality. We are conducting a 6-month randomized controlled trial with two groups: 1) Exercising Together - a progressive, supervised strength training program and 2) a usual care control condition. The primary aims of this exploratory study are to: 1) Determine the effect of partnered strength training on physical and emotional health (muscle strength, physical function, body composition and self-report physical and mental health) in PCS, 2) Determine the effect of partnered strength training on physical and emotional health in spouses and 3) Explore the effect of partnered strength training on marital quality (incongruence, communication, relationship quality, intimacy) of the PCS and spouse. Target accrual has been met in this study with 64 couples enrolled and randomized to exercise (n=32) or usual care (n=32) groups. This study is the first to examine the feasibility of this exercise format in both the chronically ill patient and spouse and explore benefits at the individual and couple level. PMID:22101224

The Exercising Together project: design and recruitment for a randomized, controlled trial to determine the benefits of partnered strength training for couples coping with prostate cancer.

PubMed

Winters-Stone, Kerri M; Lyons, Karen S; Nail, Lillian M; Beer, Tomasz M

2012-03-01

Prostate cancer can threaten quality of life for the patient and his spouse and the quality of his marital relationship. The purpose of our study is to evaluate the effects of "Exercising Together" - a partnered strength training program for married couples coping with prostate cancer - on the physical and emotional health of prostate cancer survivors (PCS) and their spouses and on marital quality. We are conducting a 6-month randomized controlled trial with two groups: 1) Exercising Together - a progressive, supervised strength training program and 2) a usual care control condition. The primary aims of this exploratory study are to: 1) Determine the effect of partnered strength training on physical and emotional health (muscle strength, physical function, body composition and self-report physical and mental health) in PCS, 2) Determine the effect of partnered strength training on physical and emotional health in spouses and 3) Explore the effect of partnered strength training on marital quality (incongruence, communication, relationship quality, intimacy) of the PCS and spouse. Target accrual has been met in this study with 64 couples enrolled and randomized to exercise (n=32) or usual care (n=32) groups. This study is the first to examine the feasibility of this exercise format in both the chronically ill patient and spouse and explore benefits at the individual and couple level. Copyright © 2011 Elsevier Inc. All rights reserved.

A Diet, Physical Activity, and Meditation Intervention in Men With Rising Prostate-Specific Antigen (PSA)

DTIC Science & Technology

2006-05-01

AD_________________ Award Number: DAMD17-03-1-0139 TITLE: A Diet , Physical Activity, and...A Diet , Physical Activity, and Meditation Intervention in Men With Rising Prostate- 5a. CONTRACT NUMBER Specific Antigen (PSA...favorably affected by an intensive, vegetable-based diet , plus physical activity and mindfulness-based stress reduction. This randomized trial will

The Potential Role of Lycopene for the Prevention and Therapy of Prostate Cancer: From Molecular Mechanisms to Clinical Evidence

PubMed Central

Holzapfel, Nina Pauline; Holzapfel, Boris Michael; Champ, Simon; Feldthusen, Jesper; Clements, Judith; Hutmacher, Dietmar Werner

2013-01-01

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. PMID:23857058

Update on the use of diode laser in the management of benign prostate obstruction in 2014.

PubMed

Lusuardi, Lukas; Mitterberger, Michael; Hruby, Stephan; Kunit, Thomas; Kloss, Birgit; Engelhardt, Paul F; Sieberer, Manuela; Janetschek, Günter

2015-04-01

To determine the status quo in respect of various diode lasers and present the techniques in use, their results and complications. We assess how these compare with transurethral resection of the prostate and other types of laser in randomized controlled trials (RCTs). When adequate RCTs were not available, case studies and reports were evaluated. Laser for the treatment of benign prostatic hyperplasia (BPH) has aroused the interest and curiosity of urologists as well as patients. The patient associates the term laser with a successful and modern procedure. The journey that started with coagulative necrosis of prostatic adenoma based on neodymium: yttrium-aluminum-garnet (Nd:YAG) laser has culminated in endoscopic "enucleation" with holmium laser. Diode laser is being used in urology for about 10 years now. Various techniques have been employed to relieve bladder outlet obstruction due to BPH. The diode laser scenario is marked by a diversity of surgical techniques and wavelengths. We summarize the current published literature in respect of functional results and complications. More randomized controlled studies are needed to determine the position and the ideal technique of diode laser treatment for BPH.

Dietary intake and development of a quantitative food-frequency questionnaire for the Barbados National Cancer Study.

PubMed

Sharma, Sangita; Cao, Xia; Harris, Rachel; Hennis, Anselm J M; Leske, M Cristina; Wu, Suh-Yuh

2007-05-01

To develop a quantitative food-frequency questionnaire (QFFQ) for the Barbados National Cancer Study (BNCS) that will permit examination of associations of diet with breast and prostate cancer. Population intake data from the year 2000 Barbados Food Consumption and Anthropometric Surveys (BFCAS 2000) were used to derive a list of foods consumed by the population. A 192-item draft QFFQ was developed from this list. Barbados, West Indies provides an ideal environment to understand cancer risk in African-origin populations, with high relevance to African-Americans. The BNCS is a population-based case-control study examining risk factors for breast and prostate cancer in such populations. A total of 1600 persons, 18 years and older, completed a 24-hour recall in the BFCAS 2000. Fifty of 63 randomly selected residents (79% response rate) gave additional updated information on foods consumed. The 50 participants provided a one-time 24-hour recall and completed the draft QFFQ. The final instrument contains 148 items: breads, cakes, cereals = 17; rice, pastas, noodles = 8; dairy = 10; meat, fish, poultry = 42; fruit = 16; vegetables = 26; soft drinks = 14; alcoholic beverages = 5; others = 10. Additional questions include supplement use and food preparation methods such as grilling. The final instrument is concise, complete and the most up-to-date for assessing the food and nutrient intake of African-origin Barbadians and the associations with breast and prostate cancer.

Opportunistic testing versus organized prostate-specific antigen screening: outcome after 18 years in the Göteborg randomized population-based prostate cancer screening trial.

PubMed

Arnsrud Godtman, Rebecka; Holmberg, Erik; Lilja, Hans; Stranne, Johan; Hugosson, Jonas

2015-09-01

It has been shown that organized screening decreases prostate cancer (PC) mortality, but the effect of opportunistic screening is largely unknown. To compare the ability to reduce PC mortality and the risk of overdiagnosis between organized and opportunistic screening. The Göteborg screening study invited 10 000 randomly selected men for prostate-specific antigen (PSA) testing every 2 yr since 1995, with a prostate biopsy recommended for men with PSA ≥2.5 ng/ml. The control group of 10 000 men not invited has been exposed to a previously reported increased rate of opportunistic PSA testing. Both groups were followed until December 31, 2012. Observed cumulative PC incidence and mortality rates in both groups were calculated using the actuarial method. Using historical data from 1990-1994 (pre-PSA era), we calculated expected PC incidence and mortality rates in the absence of any PSA testing. The number needed to invite (NNI) and the number needed to diagnose (NND) were calculated by comparing the expected versus observed incidence and mortality rates. At 18 yr, 1396 men were diagnosed with PC and 79 men died of PC in the screening group, compared to 962 and 122, respectively, in the control group. In the screening group, the observed cumulative PC incidence/mortality was 16%/0.98% compared to expected values of 6.8%/1.7%. The corresponding values for the control group were 11%/1.5% and 6.9%/1.7%. Organized screening was associated with an absolute PC-specific mortality reduction of 0.72% (95% confidence interval [CI] 0.50-0.94%) and relative risk reduction of 42% (95% CI 28-54%). There was an absolute reduction in PC deaths of 0.20% (95% CI -0.06% to 0.47%) and a relative risk reduction of 12% (95% CI -5 to 26%) associated with opportunistic PSA testing. NNI and NND were 139 (95% CI 107-200) and 13 for organized biennial screening and 493 (95% CI 213- -1563) and 23 for opportunistic screening. The extent of opportunistic screening could not be measured; incidence trends were used as a proxy. Organized screening reduces PC mortality but is associated with overdiagnosis. Opportunistic PSA testing had little if any effect on PC mortality and resulted in more overdiagnosis, with almost twice the number of men needed to be diagnosed to save one man from dying from PC compared to men offered an organized biennial screening program. Prostate-specific antigen (PSA) screening within the framework of an organized program seems more effective than unorganized screening. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Ratio of prostate specific antigen to the outer gland volume of prostrate as a predictor for prostate cancer.

PubMed

Zhang, Hai-Min; Yan, Yang; Wang, Fang; Gu, Wen-Yu; Hu, Guang-Hui; Zheng, Jun-Hua

2014-01-01

As a definite diagnosis of prostate cancer, puncture biopsy of the prostate is invasive method. The aim of this study was to evaluate the value of OPSAD (the ratio of PSA to the outer gland volume of prostate) as a non-invasive screening and diagnosis method for prostate cancer in a select population. The diagnosis data of 490 subjects undergoing ultrasound-guided biopsy of the prostate were retrospectively analyzed. This included 133 patients with prostate cancer, and 357 patients with benign prostate hyperplasia (BPH). The OPSAD was significantly greater in patients with prostate cancer (1.87 ± 1.26 ng/ml(2)) than those with BPH (0.44 ± 0.21 ng/ml(2)) (P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the performance of OPSAD as a diagnostic tool is superior to PSA and PSAD for the diagnosis of prostate cancer. In the different groups divided according to the Gleason score of prostate cancer, OPSAD is elevated with the rise of the Gleason score. OPSAD may be used as a new indicator for the diagnosis and prognosis of prostate cancer, and it can reduce the use of unnecessary puncture biopsy of the prostate.

Diagnostic Pathway with Multiparametric Magnetic Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naïve Patients with Suspected Prostate Cancer.

PubMed

Porpiglia, Francesco; Manfredi, Matteo; Mele, Fabrizio; Cossu, Marco; Bollito, Enrico; Veltri, Andrea; Cirillo, Stefano; Regge, Daniele; Faletti, Riccardo; Passera, Roberto; Fiori, Cristian; De Luca, Stefano

2017-08-01

An approach based on multiparametric magnetic resonance imaging (mpMRI) might increase the detection rate (DR) of clinically significant prostate cancer (csPCa). To compare an mpMRI-based pathway with the standard approach for the detection of prostate cancer (PCa) and csPCa. Between November 2014 and April 2016, 212 biopsy-naïve patients with suspected PCa (prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results) were included in this randomized clinical trial. Patients were randomized into a prebiopsy mpMRI group (arm A, n=107) or a standard biopsy (SB) group (arm B, n=105). In arm A, patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy (TB) (n=81). The remaining patients in arm A (n=26) with negative mpMRI results and patients in arm B underwent 12-core SB. The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study; the secondary end point was comparison of the DR between TB and SB. The overall DRs were higher in arm A versus arm B for PCa (50.5% vs 29.5%, respectively; p=0.002) and csPCa (43.9% vs 18.1%, respectively; p<0.001). Concerning the biopsy approach, that is, TB in arm A, SB in arm A, and SB in arm B, the overall DRs were significantly different for PCa (60.5% vs 19.2% vs 29.5%, respectively; p<0.001) and for csPCa (56.8% vs 3.8% vs 18.1%, respectively; p<0.001). The reproducibility of the study could have been affected by the single-center nature. A diagnostic pathway based on mpMRI had a higher DR than the standard pathway in both PCa and csPCa. In this randomized trial, a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) was compared with the standard pathway based on random biopsy. The mpMRI-based pathway had better performance than the standard pathway. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Bipolar plasma enucleation of the prostate vs open prostatectomy in large benign prostatic hyperplasia cases - a medium term, prospective, randomized comparison.

PubMed

Geavlete, Bogdan; Stanescu, Florin; Iacoboaie, Catalin; Geavlete, Petrisor

2013-05-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: According to the EAU Guidelines 2012, large size benign prostatic hyperplasia (BPH) cases (>80 mL) continue to have open prostatectomy as the first line treatment alternative, despite the substantial peri-operative morbidity and extended catheterization and convalescence periods related to this undoubtedly invasive approach. During the past two decades, holmium laser enucleation of the prostate was constantly described as a successful choice for this category of patients. According to rather numerous studies, the technique displayed superior results in terms of surgical safety and postoperative recovery compared with the open procedure. On the other hand, the concept of electrosurgical enucleation of the prostate, using either a monopolar or bipolar cutting current, materialized into several technical applications that eventually failed to gain general acknowledgement as reliable alternatives to the BPH transurethral approach. While keeping in mind the already proved advantage of enucleating substantial quantities of BPH tissue, bipolar plasma enucleation of the prostate was introduced as a novel endoscopic approach in cases of large prostates. The present trial represents the first prospective, medium-term, randomized comparison to be published of this innovative technique with standard open prostatectomy. Basically, the premises for a viable alternative relied on the practical advantages provided by the 'button' electrode, mainly the large surface creating the conditions for a fast enucleation process, continuous vaporization and concomitant haemostasis. Eventually, it was concluded that the plasma enucleation procedure distinguished itself as a successful treatment option in large BPH patients, characterized by good surgical efficiency, significantly reduced complications, faster postoperative recovery, similar prostatic tissue ablation capabilities and satisfactory follow-up results compared with the open technique. Most importantly, plasma-button enucleation patients benefited from a similar 12 months' outcome from the perspectives of symptom scores and voiding parameters when drawing a parallel with open surgery results, thus underlining the reliable viability of this type of endoscopic approach. To evaluate the viability of bipolar plasma enucleation of the prostate (BPEP) by comparison with open transvesical prostatectomy (OP) in cases of large prostates with regard to surgical efficacy and peri-operative morbidity. To compare the medium-term follow-up parameters specific for the two methods. A total of 140 benign prostatic hyperplasia (BPH) patients with prostate volume >80 mL, maximum flow rate (Qmax ) <10 mL/s and International Prostate Symptom Score (IPSS) >19 were randomized in the two study arms. All cases were assessed preoperatively and at 1, 3, 6 and 12 months after surgery by IPSS, Qmax , quality of life score (QoL) and post-voiding residual urinary volume (PVR). The prostate volume and prostate specific antigen (PSA) level were measured at 6 and 12 months. The BPEP and OP techniques emphasized similar mean operating durations (91.4 vs 87.5 min) and resected tissue weights (108.3 vs 115.4 g). The postoperative haematuria rate (2.9% vs 12.9%) as well as the mean haemoglobin drop (1.7 vs 3.1 g/dL), catheterization period (1.5 vs 5.8 days) and hospital stay (2.1 vs 6.9 days) were significantly improved for BPEP. Recatheterization for acute urinary retention was more frequent in the OP group (8.6% vs 1.4%), while the rates of early irritative symptoms were similar for BPEP and OP (11.4% vs 7.1%). During the follow-up period, no statistically significant difference was determined in terms of IPSS, Qmax , QoL, PVR, PSA level and postoperative prostate volume between the two series. BPEP represents a promising endoscopic approach in large BPH cases, characterized by good surgical efficiency and similar BPH tissue removal capabilities compared with standard transvesical prostatectomy. BPEP patients benefited from significantly reduced complications, shorter convalescence and satisfactory follow-up symptom scores and voiding parameters. © 2013 BJU International.

Molecular biomarkers to guide precision medicine in localized prostate cancer.

PubMed

Smits, Minke; Mehra, Niven; Sedelaar, Michiel; Gerritsen, Winald; Schalken, Jack A

2017-08-01

Major advances through tumor profiling technologies, that include next-generation sequencing, epigenetic, proteomic and transcriptomic methods, have been made in primary prostate cancer, providing novel biomarkers that may guide precision medicine in the near future. Areas covered: The authors provided an overview of novel molecular biomarkers in tissue, blood and urine that may be used as clinical tools to assess prognosis, improve selection criteria for active surveillance programs, and detect disease relapse early in localized prostate cancer. Expert commentary: Active surveillance (AS) in localized prostate cancer is an accepted strategy in patients with very low-risk prostate cancer. Many more patients may benefit from watchful waiting, and include patients of higher clinical stage and grade, however selection criteria have to be optimized and early recognition of transformation from localized to lethal disease has to be improved by addition of molecular biomarkers. The role of non-invasive biomarkers is challenging the need for repeat biopsies, commonly performed at 1 and 4 years in men under AS programs.

Precision Medicine and Men's Health.

PubMed

Mata, Douglas A; Katchi, Farhan M; Ramasamy, Ranjith

2017-07-01

Precision medicine can greatly benefit men's health by helping to prevent, diagnose, and treat prostate cancer, benign prostatic hyperplasia, infertility, hypogonadism, and erectile dysfunction. For example, precision medicine can facilitate the selection of men at high risk for prostate cancer for targeted prostate-specific antigen screening and chemoprevention administration, as well as assist in identifying men who are resistant to medical therapy for prostatic hyperplasia, who may instead require surgery. Precision medicine-trained clinicians can also let couples know whether their specific cause of infertility should be bypassed by sperm extraction and in vitro fertilization to prevent abnormalities in their offspring. Though precision medicine's role in the management of hypogonadism has yet to be defined, it could be used to identify biomarkers associated with individual patients' responses to treatment so that appropriate therapy can be prescribed. Last, precision medicine can improve erectile dysfunction treatment by identifying genetic polymorphisms that regulate response to medical therapies and by aiding in the selection of patients for further cardiovascular disease screening.

Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model

PubMed Central

Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

2016-01-01

Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID:26840261

Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model.

PubMed

Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

2016-03-01

Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer.

Classification of prostate cancer grade using temporal ultrasound: in vivo feasibility study

NASA Astrophysics Data System (ADS)

Ghavidel, Sahar; Imani, Farhad; Khallaghi, Siavash; Gibson, Eli; Khojaste, Amir; Gaed, Mena; Moussa, Madeleine; Gomez, Jose A.; Siemens, D. Robert; Leveridge, Michael; Chang, Silvia; Fenster, Aaron; Ward, Aaron D.; Abolmaesumi, Purang; Mousavi, Parvin

2016-03-01

Temporal ultrasound has been shown to have high classification accuracy in differentiating cancer from benign tissue. In this paper, we extend the temporal ultrasound method to classify lower grade Prostate Cancer (PCa) from all other grades. We use a group of nine patients with mostly lower grade PCa, where cancerous regions are also limited. A critical challenge is to train a classifier with limited aggressive cancerous tissue compared to low grade cancerous tissue. To resolve the problem of imbalanced data, we use Synthetic Minority Oversampling Technique (SMOTE) to generate synthetic samples for the minority class. We calculate spectral features of temporal ultrasound data and perform feature selection using Random Forests. In leave-one-patient-out cross-validation strategy, an area under receiver operating characteristic curve (AUC) of 0.74 is achieved with overall sensitivity and specificity of 70%. Using an unsupervised learning approach prior to proposed method improves sensitivity and AUC to 80% and 0.79. This work represents promising results to classify lower and higher grade PCa with limited cancerous training samples, using temporal ultrasound.

Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

PubMed

Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng

2017-08-15

This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017. Published by Elsevier B.V.

Prostate-specific membrane antigen-targeted liposomes specifically deliver the Zn(2+) chelator TPEN inducing oxidative stress in prostate cancer cells.

PubMed

Stuart, Christopher H; Singh, Ravi; Smith, Thomas L; D'Agostino, Ralph; Caudell, David; Balaji, K C; Gmeiner, William H

2016-05-01

To evaluate the potential use of zinc chelation for prostate cancer therapy using a new liposomal formulation of the zinc chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN). TPEN was encapsulated in nontargeted liposomes or liposomes displaying an aptamer to target prostate cancer cells overexpression prostate-specific membrane antigen. The prostate cancer selectivity and therapeutic efficacy of liposomal (targeted and nontargeted) and free TPEN were evaluated in vitro and in tumor-bearing mice. TPEN chelates zinc and results in reactive oxygen species imbalance leading to cell death. Delivery of TPEN using aptamer-targeted liposomes results in specific delivery to targeted cells. In vivo experiments show that TPEN-loaded, aptamer-targeted liposomes reduce tumor growth in a human prostate cancer xenograft model.

Comparison of Single-Agent Androgen Suppression for Advanced Prostate Cancer

PubMed Central

Lepor, Herbert

2005-01-01

Gonadotropin-releasing hormone (GnRH) agonists are the agents of choice for achieving androgen suppression in men with advanced prostate cancer. The GnRH agonists that have been developed and marketed for prostate cancer are leuprolide, goserelin, triptorelin, and histrelin. So far, there have been few randomized studies directly comparing these single-agent therapies; however, the literature and the data on file with the Food and Drug Administration suggest that triptorelin may be more reliable than leuprolide in maintaining castration levels of serum testosterone. The clinical significance of this benefit remains to be proven. PMID:16985882

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial.

PubMed

Blanchard, Pierre; Faivre, Laura; Lesaunier, François; Salem, Naji; Mesgouez-Nebout, Nathalie; Deniau-Alexandre, Elisabeth; Rolland, Frédéric; Ferrero, Jean-Marc; Houédé, Nadine; Mourey, Loïc; Théodore, Christine; Krakowski, Ivan; Berdah, Jean-François; Baciuchka, Marjorie; Laguerre, Brigitte; Davin, Jean-Louis; Habibian, Muriel; Culine, Stéphane; Laplanche, Agnès; Fizazi, Karim

2016-01-01

The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, Maryam, E-mail: mmoteabbed@partners.org; Trofimov, Alexei; Sharp, Gregory C.

Purpose: To quantify and compare the impact of interfractional setup and anatomic variations on proton therapy (PT) and intensity modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Twenty patients with low-risk or intermediate-risk prostate cancer randomized to receive passive-scattering PT (n=10) and IMRT (n=10) were selected. For both modalities, clinical treatment plans included 50.4 Gy(RBE) to prostate and proximal seminal vesicles, and prostate-only boost to 79.2 Gy(RBE) in 1.8 Gy(RBE) per fraction. Implanted fiducials were used for prostate localization and endorectal balloons were used for immobilization. Patients in PT and IMRT arms received weekly computed tomography (CT) and cone beam CTmore » (CBCT) scans, respectively. The planned dose was recalculated on each weekly image, scaled, and mapped onto the planning CT using deformable registration. The resulting accumulated dose distribution over the entire treatment course was compared with the planned dose using dose-volume histogram (DVH) and γ analysis. Results: The target conformity index remained acceptable after accumulation. The largest decrease in the average prostate D{sub 98} was 2.2 and 0.7 Gy for PT and IMRT, respectively. On average, the mean dose to bladder increased by 3.26 ± 7.51 Gy and 1.97 ± 6.84 Gy for PT and IMRT, respectively. These values were 0.74 ± 2.37 and 0.56 ± 1.90 for rectum. Differences between changes in DVH indices were not statistically significant between modalities. All volume indices remained within the protocol tolerances after accumulation. The average pass rate for the γ analysis, assuming tolerances of 3 mm and 3%, for clinical target volume, bladder, rectum, and whole patient for PT/IMRT were 100/100, 92.6/99, 99.2/100, and 97.2/99.4, respectively. Conclusion: The differences in target coverage and organs at risk dose deviations for PT and IMRT were not statistically significant under the guidelines of this protocol.« less

Elevated serum progastrin-releasing peptide (31-98) in metastatic and androgen-independent prostate cancer patients.

PubMed

Yashi, Masahiro; Muraishi, Osamu; Kobayashi, Yutaka; Tokue, Akihiko; Nanjo, Hiroshi

2002-05-01

Increases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin-releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of precursors for gastrin-releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor. In 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate-specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow-up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin-A (CgA) in tissue samples from several subjects. We found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P < 0.0001), especially in the androgen-independent group (P < 0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen-dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA. The clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen-independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone. Copyright 2002 Wiley-Liss, Inc.

Targeting the Human Complement Membrane Attack Complex to Selectively Kill Prostate Cancer Cells

DTIC Science & Technology

2013-10-01

prostate cancer cells in vitro . Evaluate CD59 expression in human prostate cancer microarrays. Aim 4: Evaluate toxicity and efficacy of the lead PAC5...fragment in vitro . Since PSA is the major chymotrypsin-like serine protease in the seminal plasma and prostatic fluid, we hypothesized that PSA was...that the evolution -related complement protein C5, but not C4, is a substrate of PSA as well. *Department of Pharmacology and Molecular Sciences, The

Targeting the Human Complement Membrane Attack Complex to Selectively Kill Prostate Cancer Cells

DTIC Science & Technology

2012-10-01

prostate cancer cells in vitro . Evaluate CD59 expression in human prostate cancer microarrays. Aim 4: Evaluate toxicity and efficacy of the lead...findings suggest PSA may also have immunoregulatory activity in the seminal plasma to aid in normal fertility that may have been co-opted by prostate...cleavage fragments have not been described. PSA can cleave C3 and generate the 37 kDa fragment in vitro . PSA is the major chymotrypsin-like serine

Effect of Tripterygium Wilfordii Polyglycoside on Experimental Prostatitis Caused by Ureaplasma Urealyticum in Rats

PubMed Central

Shan, Pingnan; Lu, Zhiyong; Ye, Lihong; Fang, Yaqin; Tan, Suhong; Xuan, Guohong; Ru, Jincheng; Mao, Liming

2016-01-01

Background Prostatitis is a common and refractory urological disease with complicated etiology. Ureaplasma urealyticum (UU) has a close relationship with human urinary tract infection that can induce nonbacterial prostatitis. Tripterygium wilfordii polyglycoside (TWP) is a non-steroidal immune inhibitor that causes significant immune suppression and anti-inflammatory effects. Its role in prostatitis caused by UU has not yet been established. The aim of this study was to investigate the effect of TWP on UU-infected prostatitis in a rat model. Material/Methods UU-infected prostatitis SD model rats were randomly divided into 2 groups: the prostatitis group (model group) and the TWP treatment group (treatment group). At 7 days after treatment, prostate weight, leucocyte count, lecithin corpuscles, UU infection rate, and UU microbe count were compared between the 2 groups. Serum inflammatory cytokines TNF-α was determined by ELISA, and ICAM-1 and NF-κB expression were detected. Results UU infection rate was 80% after modeling. The rat prostate weight and leucocyte count in the model group increased significantly, while lecithin corpuscles decreased. Compared with controls, inflammatory factor TNF-α, ICAM-1, and NF-κB expression were obviously higher (P<0.05). TWP markedly reduced prostate weight and leucocyte count, increased lecithin corpuscles, and decreased UU microbe count and TNF-α, ICAM-1, and NF-κB expression (P<0.05). Conclusions TWP can inhibit expression of inflammatory factors and may be useful in treating UU-infected prostatitis through reducing UU infection rate. PMID:27743513

Effect of Tripterygium Wilfordii Polyglycoside on Experimental Prostatitis Caused by Ureaplasma Urealyticum in Rats.

PubMed

Shan, Pingnan; Lu, Zhiyong; Ye, Lihong; Fang, Yaqin; Tan, Suhong; Xuan, Guohong; Ru, Jincheng; Mao, Liming

2016-10-15

BACKGROUND Prostatitis is a common and refractory urological disease with complicated etiology. Ureaplasma urealyticum (UU) has a close relationship with human urinary tract infection that can induce nonbacterial prostatitis. Tripterygium wilfordii polyglycoside (TWP) is a non-steroidal immune inhibitor that causes significant immune suppression and anti-inflammatory effects. Its role in prostatitis caused by UU has not yet been established. The aim of this study was to investigate the effect of TWP on UU-infected prostatitis in a rat model. MATERIAL AND METHODS UU-infected prostatitis SD model rats were randomly divided into 2 groups: the prostatitis group (model group) and the TWP treatment group (treatment group). At 7 days after treatment, prostate weight, leucocyte count, lecithin corpuscles, UU infection rate, and UU microbe count were compared between the 2 groups. Serum inflammatory cytokines TNF-α was determined by ELISA, and ICAM-1 and NF-κB expression were detected. RESULTS UU infection rate was 80% after modeling. The rat prostate weight and leucocyte count in the model group increased significantly, while lecithin corpuscles decreased. Compared with controls, inflammatory factor TNF-α, ICAM-1, and NF-κB expression were obviously higher (P<0.05). TWP markedly reduced prostate weight and leucocyte count, increased lecithin corpuscles, and decreased UU microbe count and TNF-α, ICAM-1, and NF-κB expression (P<0.05). CONCLUSIONS TWP can inhibit expression of inflammatory factors and may be useful in treating UU-infected prostatitis through reducing UU infection rate.

Epigenetic Regulation in Prostate Cancer Progression.

PubMed

Ruggero, Katia; Farran-Matas, Sonia; Martinez-Tebar, Adrian; Aytes, Alvaro

2018-01-01

An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity. Chromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

[Studies on localized low-risk prostate cancer : Do we know enough?

PubMed

Weißbach, L; Roloff, C

2018-06-05

Treatment of localized low-risk prostate cancer (PCa) is undergoing a paradigm shift: Invasive treatments such as surgery and radiation therapy are being replaced by defensive strategies such as active surveillance (AS) and watchful waiting (WW). The aim of this work is to evaluate the significance of current studies regarding defensive strategies (AS and WW). The best-known AS studies are critically evaluated for their significance in terms of input criteria, follow-up criteria, and statistical significance. The difficulties faced by randomized studies in answering the question of the best treatment for low-risk cancer in two or even more study groups with known low tumor-specific mortality are clearly shown. Some studies fail because of the objective, others-like PIVOT-are underpowered. ProtecT, a renowned randomized, controlled trial (RCT), lists systematic and statistical shortcomings in detail. The time and effort required for RCTs to answer the question of which therapy is best for locally limited low-risk cancer is very large because the low specific mortality rate requires a large number of participants and a long study duration. In any case, RCTs create hand-picked cohorts for statistical evaluation that have little to do with care in daily clinical practice. The necessary randomization is also offset by the decision-making of the informed patient. If further studies of low-risk PCa are needed, they will need real-world conditions that an RCT can not provide. To obtain clinically relevant results, we need to rethink things: When planning the study, biometricians and clinicians must understand that the statistical methods used in RCTs are of limited use and they must select a method (e.g. propensity scores) appropriate for health care research.

Effect of Mahayavanala Roma Kshara and Dhanyaka Gokshura Ghrita in benign prostatic hyperplasia

PubMed Central

Vasava, Yogesh R.; Bhuyan, Chaturbhuja; Rajagopala, Manjusha; Gupta, S. K.; Dudhamal, T. S.

2010-01-01

Vatastheela is a disease of Mutravahasrotasa, one among the 12 types of Mutraghata disorders elaborated by Sushruta in his seminal work, the Sushruta Samhita. Vatastheela, as described in Ayurveda, closely resembles benign prostatic hyperplasia (BPH) of modern medicine in its signs and symptoms. It is a senile disorder and chiefly affects individuals above the age of 40 years. The symptoms are those of bladder outflow obstruction, with increased frequency of micturition, dribbling, hesitancy, and the features of chronic urinary retention. Surgical management has been accepted as the standard management but is associated with many disadvantages as well as complications, which may not be acceptable at this age. Conservative management with modern medicines is also not free from side effects. So, in this age-group, there is a need for much safer alternative method of management. In this regard, many works have been carried out and shown that the Ayurvedic approach, using natural medicines, is a far better approach. We carried out a comparative study of Mahayavanala Roma Kshara (MRK) and Dhanyaka Gokshura Ghrita (DGG), which are the compounds prescribed for Mutraghata in Ayurvedic literature. The patients were randomly selected from the OPD and IPD of IPGT and RA hospital, Jamnagar, Gujarat, and divided into two groups. In first group, one (500 mg) capsule of MRK was given twice a day with lukewarm water for 45 days; in second group, 10 gm of DGG was given orally twice a day with lukewarm water for 45 days. DGG showed significantly greater relief in the subjective parameters as per International Prostate Symptoms Score (IPSS) than MRK. However, reduction in the size of the prostate and in the volume of the post-void residual urine was found much better in the MRK group. PMID:22131735

Effect of Mahayavanala Roma Kshara and Dhanyaka Gokshura Ghrita in benign prostatic hyperplasia.

PubMed

Vasava, Yogesh R; Bhuyan, Chaturbhuja; Rajagopala, Manjusha; Gupta, S K; Dudhamal, T S

2010-07-01

Vatastheela is a disease of Mutravahasrotasa, one among the 12 types of Mutraghata disorders elaborated by Sushruta in his seminal work, the Sushruta Samhita. Vatastheela, as described in Ayurveda, closely resembles benign prostatic hyperplasia (BPH) of modern medicine in its signs and symptoms. It is a senile disorder and chiefly affects individuals above the age of 40 years. The symptoms are those of bladder outflow obstruction, with increased frequency of micturition, dribbling, hesitancy, and the features of chronic urinary retention. Surgical management has been accepted as the standard management but is associated with many disadvantages as well as complications, which may not be acceptable at this age. Conservative management with modern medicines is also not free from side effects. So, in this age-group, there is a need for much safer alternative method of management. In this regard, many works have been carried out and shown that the Ayurvedic approach, using natural medicines, is a far better approach. We carried out a comparative study of Mahayavanala Roma Kshara (MRK) and Dhanyaka Gokshura Ghrita (DGG), which are the compounds prescribed for Mutraghata in Ayurvedic literature. The patients were randomly selected from the OPD and IPD of IPGT and RA hospital, Jamnagar, Gujarat, and divided into two groups. In first group, one (500 mg) capsule of MRK was given twice a day with lukewarm water for 45 days; in second group, 10 gm of DGG was given orally twice a day with lukewarm water for 45 days. DGG showed significantly greater relief in the subjective parameters as per International Prostate Symptoms Score (IPSS) than MRK. However, reduction in the size of the prostate and in the volume of the post-void residual urine was found much better in the MRK group.

Estimating the harms and benefits of prostate cancer screening as used in common practice versus recommended good practice: A microsimulation screening analysis.

PubMed

Carlsson, Sigrid V; de Carvalho, Tiago M; Roobol, Monique J; Hugosson, Jonas; Auvinen, Anssi; Kwiatkowski, Maciej; Villers, Arnauld; Zappa, Marco; Nelen, Vera; Páez, Alvaro; Eastham, James A; Lilja, Hans; de Koning, Harry J; Vickers, Andrew J; Heijnsdijk, Eveline A M

2016-11-15

Prostate-specific antigen (PSA) screening and concomitant treatment can be implemented in several ways. The authors investigated how the net benefit of PSA screening varies between common practice versus "good practice." Microsimulation screening analysis (MISCAN) was used to evaluate the effect on quality-adjusted life-years (QALYs) if 4 recommendations were followed: limited screening in older men, selective biopsy in men with elevated PSA, active surveillance for low-risk tumors, and treatment preferentially delivered at high-volume centers. Outcomes were compared with a base model in which annual screening started at ages 55 to 69 years and were simulated using data from the European Randomized Study of Screening for Prostate Cancer. In terms of QALYs gained compared with no screening, for 1000 screened men who were followed over their lifetime, recommended good practice led to 73 life-years (LYs) and 74 QALYs gained compared with 73 LYs and 56 QALYs for the base model. In contrast, common practice led to 78 LYs gained but only 19 QALYs gained, for a greater than 75% relative reduction in QALYs gained from unadjusted LYs gained. The poor outcomes for common practice were influenced predominantly by the use of aggressive treatment for men with low-risk disease, and PSA testing in older men also strongly reduced potential QALY gains. Commonly used PSA screening and treatment practices are associated with little net benefit. Following a few straightforward clinical recommendations, particularly greater use of active surveillance for low-risk disease and reducing screening in older men, would lead to an almost 4-fold increase in the net benefit of prostate cancer screening. Cancer 2016;122:3386-3393. © 2016 American Cancer Society. © 2016 American Cancer Society.

Mechanism of Selenium Chemoprevention and Therapy in Prostate Cancer

DTIC Science & Technology

2010-11-01

06-1-0006 TITLE: Mechanism of Selenium Chemoprevention and Therapy in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Allen Gao...Introduction The goal of this application is to elucidate the importance of down regulation of AR signaling by multiple selenium compounds and...select the best leading selenium compound for prostate cancer chemoprevention and therapy. In this application, we will further study the mechanisms of

Enforced epithelial expression of IGF-1 causes hyperplastic prostate growth while negative selection is requisite for spontaneous metastogenesis

USDA-ARS?s Scientific Manuscript database

The insulin-like growth factor-1 (IGF-1) signaling axis is important for cell growth, differentiation, and survival, and increased serum IGF is a risk factor for prostate and other cancers. To study IGF-1 action on the prostate, we created transgenic (PB-Des) mice that specifically express human IGF...

Imaging Prostate Cancer Microenvironment by Collagen Hybridization

DTIC Science & Technology

2016-12-01

2: Evaluation of 18F-DCFPyL labelling and tracking of PSMA+ CAR T cells Title: PSMA Directed Imaging of Prostate Cancer Focus on Androgen Receptor ... receptors to treat cancer Title: Plasmid Selection and Characterisation Time Commitments: 1.20 calendar months Supporting Agency: Cancer Targeting...AWARD NUMBER: W81XWH-12-1-0556 TITLE: Imaging Prostate Cancer Microenvironment by Collagen Hybridization PRINCIPAL INVESTIGATOR: Martin

Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample.

PubMed

Berges, Richard; Gsur, Andrea; Feik, Elisabeth; Höfner, Klaus; Senge, Theodor; Pientka, Ludger; Baierl, Andreas; Michel, Martin C; Ponholzer, Anton; Madersbacher, Stephan

2011-04-01

The known importance of testosterone for the development of benign prostatic hyperplasia (BPH) prompted us to test the hypothesis whether polymorphisms of two genes (CYP19A1 and CYP3A4) involved in testosterone metabolism are associated with clinical BPH-parameters. A random sample of the population-based Herne lower urinary tract symptoms cohort was analysed. All these men underwent a detailed urological work-up. Two polymorphisms in the CYP19A1 gene [rs700518 in exon 4 (A57G); rs10046 at the 3'UTR(C268T)] and one in the 3'UTR of CYP3A4 [rs2740574 (A392G)] were determined by TaqMan assay from genomic DNA of peripheral blood. These polymorphisms were correlated to clinical and laboratory BPH-parameters. A total of 392 men (65.4 ± 7.0 years; 52-79 years) were analysed. Mean International Prostate Symptom Score (IPSS; 7.5), Q (max) (15.4 ml/s), prostate volume (31 ml) and prostate specific antigen (PSA) (1.8 ng/ml) indicated a typical elderly population. Both polymorphisms in the CYP19A1 gene were not correlated to age, IPSS, Q (max), prostate volume and post-void residual volume. Serum PSA was higher in men carrying the heterozygous rs10046 genotype (2.0 ± 0.1 ng/ml) than in those with the CC-genotype (1.7 ± 0.2 ng/ml, P = 0.012). Men carrying one a mutated allele of the CYP3A4 gene had smaller prostates (27.0 ± 2.0 vs. 32 ± 0.8 ml, P = 0.02) and lower PSA levels (1.6 ± 0.3 vs. 1.9 ± 0.1 ng/ml). The inconsistent associations observed herein and for other gene polymorphisms warrant further studies. In general, the data regarding the association of gene polymorphism to BPH-parameters suggest that this disease is caused by multiple rather than a single genetic variant. A rigorous patient selection based on anatomo-pathological and hormonal profile may possible reduce the number of confounders for future studies thus enabling a more detailed assessment of the association between genetic factors and BPH-parameters.

Anti-androgenic effects of S-40542, a novel non-steroidal selective androgen receptor modulator (SARM) for the treatment of benign prostatic hyperplasia.

PubMed

Nejishima, Hiroaki; Yamamoto, Noriko; Suzuki, Mika; Furuya, Kazuyuki; Nagata, Naoya; Yamada, Shizuo

2012-10-01

Selective androgen receptor modulators (SARMs) would provide alternative therapeutic agent for androgen-related diseases. We identified a tetrahydroquinoline (THQ) derivative, 1-(8-nitro-3a, 4, 5, 9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl) ethane-1, 2-diol (S-40542) as a novel SARM antagonist. Affinity for nuclear receptors of S-40542 was evaluated in receptor-binding studies. Androgen receptor (AR) transcriptional activity of S-40542 was investigated by luciferase reporter assay in DU145AR cells. Normal and benign prostatic hyperplasia (BPH) model rats were repeatedly treated with S-40542 and flutamide. The tissue weights of prostate and levator ani muscle as well as blood levels of testosterone and luteinizing hormone were measured. S-40542 bound to the AR with high affinity. S-40542 at relatively high concentrations increased the transcriptional activity. This agent also showed a concentration-dependent AR antagonistic action in the presence of 1 nM 5α-dihydrotestosterone. Repeated treatment with S-40542 and flutamide decreased dose-dependently the weights of the prostate to a similar extent. In contrast, the tissue weight-reducing effect by S-40542 treatment on the levator ani muscle was much weaker than that of flutamide. S-40542 had little effect on the blood level of testosterone and luteinizing hormone, whereas flutamide increased the level of both hormones. Furthermore, S-40542 decreased dose-dependently prostate weight of BPH rats. The current results indicate that S-40542 possesses the prostate-selective SARM activity, suggestive of clinical benefit against benign prostate hyperplasia. THQ compounds may be useful for the research of mode of action of SARMs and for the development of safe SARM antagonists. Copyright © 2012 Wiley Periodicals, Inc.

A general method for the definition of margin recipes depending on the treatment technique applied in helical tomotherapy prostate plans.

PubMed

Sevillano, David; Mínguez, Cristina; Sánchez, Alicia; Sánchez-Reyes, Alberto

2016-01-01

To obtain specific margin recipes that take into account the dosimetric characteristics of the treatment plans used in a single institution. We obtained dose-population histograms (DPHs) of 20 helical tomotherapy treatment plans for prostate cancer by simulating the effects of different systematic errors (Σ) and random errors (σ) on these plans. We obtained dosimetric margins and margin reductions due to random errors (random margins) by fitting the theoretical results of coverages for Gaussian distributions with coverages of the planned D99% obtained from the DPHs. The dosimetric margins obtained for helical tomotherapy prostate treatments were 3.3 mm, 3 mm, and 1 mm in the lateral (Lat), anterior-posterior (AP), and superior-inferior (SI) directions. Random margins showed parabolic dependencies, yielding expressions of 0.16σ(2), 0.13σ(2), and 0.15σ(2) for the Lat, AP, and SI directions, respectively. When focusing on values up to σ = 5 mm, random margins could be fitted considering Gaussian penumbras with standard deviations (σp) equal to 4.5 mm Lat, 6 mm AP, and 5.5 mm SI. Despite complex dose distributions in helical tomotherapy treatment plans, we were able to simplify the behaviour of our plans against treatment errors to single values of dosimetric and random margins for each direction. These margins allowed us to develop specific margin recipes for the respective treatment technique. The method is general and could be used for any treatment technique provided that DPHs can be obtained. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Modelling gene expression profiles related to prostate tumor progression using binary states

PubMed Central

2013-01-01

Background Cancer is a complex disease commonly characterized by the disrupted activity of several cancer-related genes such as oncogenes and tumor-suppressor genes. Previous studies suggest that the process of tumor progression to malignancy is dynamic and can be traced by changes in gene expression. Despite the enormous efforts made for differential expression detection and biomarker discovery, few methods have been designed to model the gene expression level to tumor stage during malignancy progression. Such models could help us understand the dynamics and simplify or reveal the complexity of tumor progression. Methods We have modeled an on-off state of gene activation per sample then per stage to select gene expression profiles associated to tumor progression. The selection is guided by statistical significance of profiles based on random permutated datasets. Results We show that our method identifies expected profiles corresponding to oncogenes and tumor suppressor genes in a prostate tumor progression dataset. Comparisons with other methods support our findings and indicate that a considerable proportion of significant profiles is not found by other statistical tests commonly used to detect differential expression between tumor stages nor found by other tailored methods. Ontology and pathway analysis concurred with these findings. Conclusions Results suggest that our methodology may be a valuable tool to study tumor malignancy progression, which might reveal novel cancer therapies. PMID:23721350

Efficacy of Cabazitaxel in Castration-resistant Prostate Cancer Is Independent of the Presence of AR-V7 in Circulating Tumor Cells.

PubMed

Onstenk, Wendy; Sieuwerts, Anieta M; Kraan, Jaco; Van, Mai; Nieuweboer, Annemieke J M; Mathijssen, Ron H J; Hamberg, Paul; Meulenbeld, Hielke J; De Laere, Bram; Dirix, Luc Y; van Soest, Robert J; Lolkema, Martijn P; Martens, John W M; van Weerden, Wytske M; Jenster, Guido W; Foekens, John A; de Wit, Ronald; Sleijfer, Stefan

2015-12-01

Androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) from patients with metastatic castration-resistant prostate cancer (mCRPC) was recently demonstrated to be associated with resistance to abiraterone and enzalutamide. Cabazitaxel might, however, remain effective in AR-V7-positive patients. To investigate the association between AR-V7 expression in CTCs and resistance to cabazitaxel. We selected patients with mCRPC from the multicenter, randomized, phase 2, randomized, open-label, multicenter study in mCRPC on the pharmacodynamic effects of budesonide on cabazitaxel (Jevtana) (CABARESC). Before the start of the first and third cabazitaxel cycle, CTCs were enumerated using the CellSearch System. In patients with ≥10 CTCs in 7.5 ml blood at baseline, the expression of AR-V7 was assessed by quantitative polymerase chain reaction. The primary end point was the association between the AR-V7 status and the CTC response rate (decrease to fewer than five CTCs in 7.5 ml blood during treatment). Secondary end points were the prostate-specific antigen (PSA) response rate (RR) and overall survival (OS). Analyses were performed using chi-square and log-rank tests. AR-V7 was detected in 16 of 29 patients (55%) with ≥10 CTCs and was more frequently found in abiraterone pretreated patients (5 of 5 [100%] treated vs 7 of 20 [35%] untreated; p=0.009). We found no differences in CTC and PSA RRs. The presence of AR-V7 in CTCs was not associated with progression-free survival (hazard ratio [HR]: 0.8; 95% confidence interval [CI], 0.4-1.8) or overall survival (HR 1.6; 95% CI, 0.6-4.4). The response to cabazitaxel seems to be independent of the AR-V7 status of CTCs from mCRPC patients. Consequently, cabazitaxel might be a valid treatment option for patients with AR-V7-positive CTCs. Tools are needed to select specific treatments for specific patients at specific times. The presence of the gene AR-V7 in CTCs has been associated with resistance to anti-androgen receptor treatments. We investigated whether this holds true for cabazitaxel, but we found cabazitaxel to be effective independent of the presence of AR-V7. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia.

PubMed

Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd; Ludwig, Nicole; Meese, Eckart

2015-01-01

Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients' sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.

Prostate Artery Embolization as a New Treatment for Benign Prostate Hyperplasia: Contemporary Status in 2016.

PubMed

Noor, Amir; Fischman, Aaron M

2016-07-01

The gold standard treatment for benign prostate hyperplasia (BPH) is transurethral resection of the prostate (TURP) or open prostatectomy (OP). Recently, there has been increased interest and research in less invasive alternative treatments with less morbidity including prostate artery embolization (PAE). Several studies have shown PAE to be an effective alternative to TURP to treat lower urinary tract symptoms (LUTS) associated with BPH with decreased morbidity. Specifically, PAE has been advantageous in selected patient populations such as those with prostates too large for TURP or unsuitable surgical candidates, showing a promising potential for the future care of patients with BPH. Further studies are being done to demonstrate the clinical applications and advantages of this therapy in reduction of LUTS.

European Randomized Study of Screening for Prostate Cancer Risk Calculator: External Validation, Variability, and Clinical Significance.

PubMed

Gómez-Gómez, Enrique; Carrasco-Valiente, Julia; Blanca-Pedregosa, Ana; Barco-Sánchez, Beatriz; Fernandez-Rueda, Jose Luis; Molina-Abril, Helena; Valero-Rosa, Jose; Font-Ugalde, Pilar; Requena-Tapia, Maria José

2017-04-01

To externally validate the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) and to evaluate its variability between 2 consecutive prostate-specific antigen (PSA) values. We prospectively catalogued 1021 consecutive patients before prostate biopsy for suspicion of prostate cancer (PCa). The risk of PCa and significant PCa (Gleason score ≥7) from 749 patients was calculated according to ERSPC-RC (digital rectal examination-based version 3 of 4) for 2 consecutive PSA tests per patient. The calculators' predictions were analyzed using calibration plots and the area under the receiver operating characteristic curve (area under the curve). Cohen kappa coefficient was used to compare the ability and variability. Of 749 patients, PCa was detected in 251 (33.5%) and significant PCa was detected in 133 (17.8%). Calibration plots showed an acceptable parallelism and similar discrimination ability for both PSA levels with an area under the curve of 0.69 for PCa and 0.74 for significant PCa. The ERSPC showed 226 (30.2%) unnecessary biopsies with the loss of 10 significant PCa. The variability of the RC was 16% for PCa and 20% for significant PCa, and a higher variability was associated with a reduced risk of significant PCa. We can conclude that the performance of the ERSPC-RC in the present cohort shows a high similitude between the 2 PSA levels; however, the RC variability value is associated with a decreased risk of significant PCa. The use of the ERSPC in our cohort detects a high number of unnecessary biopsies. Thus, the incorporation of ERSPC-RC could help the clinical decision to carry out a prostate biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

PTV margin definition in hypofractionated IGRT of localized prostate cancer using cone beam CT and orthogonal image pairs with fiducial markers.

PubMed

Oehler, Christoph; Lang, Stephanie; Dimmerling, Peter; Bolesch, Christian; Kloeck, Stephan; Tini, Alessandra; Glanzmann, Christoph; Najafi, Yousef; Studer, Gabriela; Zwahlen, Daniel R

2014-11-11

To evaluate PTV margins for hypofractionated IGRT of prostate comparing kV/kV imaging or CBCT. Between 2009 and 2012, 20 patients with low- (LR), intermediate- (IR) and high-risk (HR) prostate cancer were treated with VMAT in supine position with fiducial markers (FM), endorectal balloon (ERB) and full bladder. CBCT's and kV/kV imaging were performed before and additional CBCT's after treatment assessing intra-fraction motion. CTVP for 5 patients with LR and CTVPSV for 5 patients with IR/HR prostate cancer were contoured independently by 3 radiation oncologists using MRI. The van Hark formula (PTV margin =2.5Σ +0.7σ) was applied to calculate PTV margins of prostate/seminal vesicles (P/PSV) using CBCT or FM. 172 and 52 CBCTs before and after RT and 507 kV/kV images before RT were analysed. Differences between FM in CBCT or in planar kV image pairs were below 1 mm. Accounting for both random and systematic uncertainties anisotropic PTV margins were 5-8 mm for P (LR) and 6-11 mm for PSV (IR/HR). Random uncertainties like intra-fraction and inter-fraction (setup) uncertainties were of similar magnitude (0.9-1.4 mm). Largest uncertainty was introduced by CTV delineation (LR: 1-2 mm, IR/HR: 1.6-3.5 mm). Patient positioning using bone matching or ERB-matching resulted in larger PTV margins. For IGRT CBCT or kV/kV-image pairs with FM are interchangeable in respect of accuracy. Especially for hypofractionated RT, PTV margins can be kept in the range of 5 mm or below if stringent daily IGRT, ideally including prostate tracking, is applied. MR-based CTV delineation optimization is recommended.

Serial personal digital assistant data capture of health-related quality of life: A randomized controlled trial in a prostate cancer clinic

PubMed Central

Matthew, Andrew G; Currie, Kristen L; Irvine, Jane; Ritvo, Paul; Santa Mina, Daniel; Jamnicky, Leah; Nam, Robert; Trachtenberg, John

2007-01-01

Background In clinical and research practice linked to prostate cancer treatment, frequent monitoring of patient health-related quality of life (HRQOL) is essential. Practical and analytic limitations of paper questionnaire data capture may be overcome with the use of self-administered personal digital assistant (PDA) data collection. The objective of this study was to assess the reliability, validity, and feasibility of using PDA in place of paper versions of the International Prostate Symptom Score (IPSS), the Patient Oriented Prostate Cancer Utility Survey (PORPUS), and the International Index of Erectile Function-5 (IIEF-5) in a prostate cancer clinic setting. Methods 152 participants were randomly assigned to one of three conditions: 1) paper followed by PDA survey; 2) PDA followed by paper survey; or 3) PDA followed by PDA survey. Evaluation included an assessment of data quality (internal consistency, test-retest reliability, response correlation, completeness of data), and feasibility (participation rates, time to completion, preference and difficultly/ease of using PDA). Results Internal consistency was similar for both PDA and paper applications. Test-retest reliability was confirmed for PDA repeated administration. Data from paper and PDA questionnaires were strongly correlated. Lower missed item rates were found in PDA administration. 82.8% of participants preferred using the PDA or had no preference. Mean difficulty/ease ratings indicated that participants found the PDA easy to use. Age did not significantly correlate with preference or difficulty. Conclusion The results confirm the adaptability of the IPSS, IIEF-5, and the PORPUS to PDA administration. Similarly, the findings of this study support the feasibility of using PDA technology for HRQOL serial data capture in the prostate cancer patient population. PMID:17617906

Evaluation of Adherence to Quality Measures for Prostate Cancer Radiotherapy in the United States: Results from the Quality Research in Radiation Oncology (QRRO) Survey

PubMed Central

Zelefsky, Michael J.; Lee, W. Robert; Zietman, Anthony; Khalid, Najma; Crozier, Cheryl; Owen, Jean; Wilson, J. Frank

2012-01-01

Purpose To test the feasibility of using proposed quality indicators to assess radiotherapy quality in prostate cancer management based on a 2007 stratified random survey of treating academic and non-academic US institutions. Methods and Materials 414 patients with clinically localized prostate cancer treated with external beam radiotherapy (EBRT) or brachytherapy were selected from 45 institutions. Indicators used as specific measurable clinical performance measures to represent surrogates for quality of radiotherapy delivery included established measures, such as the use of prescription doses ≥75 Gy for intermediate- and high-risk EBRT patients and androgen-deprivation therapy (ADT) in conjunction with EBRT for patients with high-risk disease, and emerging measures, including daily target localization (image-guidance) to correct for organ motion for EBRT patients. Results 167 patients (47%) were treated with 6 MV photons, 31 (9%) were treated with 10 MV, 65 (18%) received 15 MV, and the remaining 90 (26%) 16–23 MV. For intermediate- plus high-risk patients (n=181), 78% were treated to ≥75 Gy. Among favorable-risk patients, 72% were treated to ≥75 Gy. Among high-risk EBRT patients, 60 (87%) were treated with ADT in conjunction with EBRT and 13% (n=9) with radiotherapy alone. Among low- and intermediate-risk patients, 10% and 42%, respectively, were treated with ADT plus EBRT. For 24% of EBRT patients (85/354), weekly electronic portal imaging was obtained as verification films without daily target localization and the remaining 76% were treated with daily localization of the target using various methods. Conclusions Adherence to defined quality indicators was observed in a majority of patients. ≈90% of high-risk patients are treated with ADT plus EBRT and ≈80% of intermediate- and high-risk patients receive prescription doses >=75 Gy, consistent with the published results of randomized trials. PMID:23471563

Evaluation of Adherence to Quality Measures for Prostate Cancer Radiotherapy in the United States: Results from the Quality Research in Radiation Oncology (QRRO) Survey.

PubMed

Zelefsky, Michael J; Lee, W Robert; Zietman, Anthony; Khalid, Najma; Crozier, Cheryl; Owen, Jean; Wilson, J Frank

2013-01-01

To test the feasibility of using proposed quality indicators to assess radiotherapy quality in prostate cancer management based on a 2007 stratified random survey of treating academic and non-academic US institutions. 414 patients with clinically localized prostate cancer treated with external beam radiotherapy (EBRT) or brachytherapy were selected from 45 institutions. Indicators used as specific measurable clinical performance measures to represent surrogates for quality of radiotherapy delivery included established measures, such as the use of prescription doses ≥75 Gy for intermediate- and high-risk EBRT patients and androgen-deprivation therapy (ADT) in conjunction with EBRT for patients with high-risk disease, and emerging measures, including daily target localization (image-guidance) to correct for organ motion for EBRT patients. 167 patients (47%) were treated with 6 MV photons, 31 (9%) were treated with 10 MV, 65 (18%) received 15 MV, and the remaining 90 (26%) 16-23 MV. For intermediate- plus high-risk patients (n=181), 78% were treated to ≥75 Gy. Among favorable-risk patients, 72% were treated to ≥75 Gy. Among high-risk EBRT patients, 60 (87%) were treated with ADT in conjunction with EBRT and 13% (n=9) with radiotherapy alone. Among low- and intermediate-risk patients, 10% and 42%, respectively, were treated with ADT plus EBRT. For 24% of EBRT patients (85/354), weekly electronic portal imaging was obtained as verification films without daily target localization and the remaining 76% were treated with daily localization of the target using various methods. Adherence to defined quality indicators was observed in a majority of patients. ≈90% of high-risk patients are treated with ADT plus EBRT and ≈80% of intermediate- and high-risk patients receive prescription doses >=75 Gy, consistent with the published results of randomized trials.

Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or After Docetaxel-Based Therapy: ELM-PC 5

PubMed Central

Fizazi, Karim; Jones, Robert; Oudard, Stephane; Efstathiou, Eleni; Saad, Fred; de Wit, Ronald; De Bono, Johann; Cruz, Felipe Melo; Fountzilas, George; Ulys, Albertas; Carcano, Flavio; Agarwal, Neeraj; Agus, David; Bellmunt, Joaquim; Petrylak, Daniel P.; Lee, Shih-Yuan; Webb, Iain J.; Tejura, Bindu; Borgstein, Niels; Dreicer, Robert

2015-01-01

Purpose Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. Patients and Methods In our study, 1,099 men were randomly assigned in a 2:1 schedule to receive orteronel 400 mg plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily, stratified by region (Europe, North America [NA], and non-Europe/NA) and Brief Pain Inventory–Short Form worst pain score. Primary end point was overall survival (OS). Key secondary end points (radiographic progression-free survival [rPFS], ≥ 50% decrease of prostate-specific antigen [PSA50], and pain response at 12 weeks) were to undergo statistical testing only if the primary end point analysis was significant. Results The study was unblinded after crossing a prespecified OS futility boundary. The median OS was 17.0 months versus 15.2 months with orteronel-prednisone versus placebo-prednisone (hazard ratio [HR], 0.886; 95% CI, 0.739 to 1.062; P = .190). Improved rPFS was observed with orteronel-prednisone (median, 8.3 v 5.7 months; HR, 0.760; 95% CI, 0.653 to 0.885; P < .001). Orteronel-prednisone showed advantages over placebo-prednisone in PSA50 rate (25% v 10%, P < .001) and time to PSA progression (median, 5.5 v 2.9 months, P < .001) but not pain response rate (12% v 9%; P = .128). Adverse events (all grades) were generally more frequent with orteronel-prednisone, including nausea (42% v 26%), vomiting (36% v 17%), fatigue (29% v 23%), and increased amylase (14% v 2%). Conclusion Our study did not meet the primary end point of OS. Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity. PMID:25624429

Rationale, conduct, and outcome using hypofractionated radiotherapy in prostate cancer

PubMed Central

Ritter, Mark

2008-01-01

Hypofractionated radiation therapy for prostate cancer has become of increasing interest with the recognition of a potential improvement in therapeutic ratio with treatments delivered in larger-sized fractions. In addition, the associated reduction in fraction number produces attractive cost and patient convenience advantages as well. A still limited but growing number of hypofractionation trials have reported acceptable short-term levels of toxicity and biochemical control, but most have insufficient follow-up to assure the long-term safety and efficacy of this approach. This situation will improve as many currently active trials mature, particularly several high value randomized trials. In contrast, extreme hypofractionation, with schedules delivering only on the order of 5 fractions, is truly in its infancy for prostate cancer, with extremely limited tolerance and efficacy information currently available. Several uncertainties in the radiobiology of hypofractionation mitigate for an organized, cautious investigational approach. The fractionation response (α/β ratio) of prostate cancers and, for that matter, late responding normal tissues, has yet to be rigorously defined. Additionally, the linear quadratic (LQ) model used in the design of hypofractionation schedules is subject to its own uncertainties, particularly with respect to the upper limit of fraction sizes for which it remains valid. Contemporary dose escalated radiation therapy is already highly effective, making it imperative that ongoing and future studies of hypofractionation be carried out in carefully designed, randomized clinical trials. Clinical validation permitting, the adaptation of hypofractionation as a standard of care could profoundly influence future management of localized prostate cancer. PMID:18725112

PROSTVAC® targeted immunotherapy candidate for prostate cancer.

PubMed

Shore, Neal D

2014-01-01

Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

Ultrasound detection of prostatic calculi as a parameter to predict the appearance of hematospermia after a prostate biopsy.

PubMed

Dell'Atti, Lucio

2017-01-01

We evaluated the correlation between prostate calculi and hematospermia in patients undergoing prostate biopsy, and its impact on sexual activity of patients. A single-center prospective randomized study of 212 patients referred for transrectal ultrasound-guided prostate biopsy (TRUSBx) was performed. All patients were divided into two groups: Group A (GA), 106 patients with moderate/marked presence of prostatic calculi visualized by TRUS; Group B (GB), 106 patients with absence/scarce of prostatic calcifications. Patients were handed questionnaires to obtain a validated data on the duration and impact of hematospermia on sexual activity. The anxiety scores were recorded using a visual analogue scale. No significant difference was noted between the two groups when comparing age, preoperative PSA level, prostate volume, and biopsy number, except for digital rectal examination (DRE) findings. Post-biopsy results of patients included in GA revealed that the complication of hematospermia was present in 65.1%, while in GB was present in 39.7% (p<0.001). On multivariate analysis for identifying significant preoperative predictors of hematospermia, which included variables of age, PSA, prostate volume, and prostate cancer were not shown to be significant predictors of hematospermia, except DRE and prostate calculi (p<0.001). The mean anxiety score was 3.7±2.8 in GA and 2.3±1.9 in GB, respectively (p<0.001). Prostatic calculi are an independent predictive factor of severe hematospermia after TRUSBx on the basis of multivariate analysis, but don't affect the positive rate of prostate cancer. Patients should be adequately counselled before TRUSBx to avoid undue anxiety and alterations in sexual activity. Copyright® by the International Brazilian Journal of Urology.

Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

PubMed

Albanes, Demetrius; Till, Cathee; Klein, Eric A; Goodman, Phyllis J; Mondul, Alison M; Weinstein, Stephanie J; Taylor, Philip R; Parnes, Howard L; Gaziano, J Michael; Song, Xiaoling; Fleshner, Neil E; Brown, Powel H; Meyskens, Frank L; Thompson, Ian M

2014-09-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose α-tocopherol. We, therefore, examined whether presupplementation plasma α-tocopherol or γ-tocopherol was associated with overall or high-grade prostate cancer. A stratified case-cohort sample that included 1,746 incident prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry from 2001 to 2004, and median follow-up was 5.5 years (range, 0-7.9 years). Incidence of prostate cancer as a function of plasma α-tocopherol, γ-tocopherol, and supplementation with α-tocopherol or selenomethionine was estimated by the hazard ratio (HR). Plasma γ-tocopherol was not associated with prostate cancer. Men with higher α-tocopherol concentrations seemed to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21; 95 % confidence interval (CI), 0.88-1.66; P-trend = 0.24; in the trial placebo arm, Q5 HR, 0.85; 95% CI, 0.44-1.62; P-trend = 0.66]. We found a strong positive plasma α-tocopherol association among men receiving the trial selenomethionine supplement [Q5 HR, 2.04; 95% CI, 1.29-3.22; P-trend = 0.005]. A positive plasma α-tocopherol-prostate cancer association also seemed limited to high-grade disease (Gleason grade, 7-10; overall Q5 HR, 1.59; 95% CI, 1.13-2.24; P-trend = 0.001; among men receiving selenomethionine, Q5 HR, 2.12; 95% CI, 1.32-3.40; P-trend = 0.0002). Our findings indicate that higher plasma α-tocopherol concentrations may interact with selenomethionine supplements to increase high-grade prostate cancer risk, suggesting a biologic interaction between α-tocopherol and selenium itself or selenomethionine. ©2014 American Association for Cancer Research.

Plasma Tocopherols and Risk of Prostate Cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

PubMed Central

Albanes, Demetrius; Till, Cathee; Klein, Eric A.; Goodman, Phyllis J.; Mondul, Alison M.; Weinstein, Stephanie J.; Taylor, Philip R.; Parnes, Howard L.; Gaziano, J. Michael; Song, Xiaoling; Fleshner, Neil E.; Brown, Powel H.; Meyskens, Frank L.; Thompson, Ian M.

2014-01-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose α-tocopherol. We therefore examined whether pre-supplementation plasma α-tocopherol or γ-tocopherol was associated with overall or high-grade prostate cancer. A stratified case-cohort sample that included 1,746 incident prostate cancer cases diagnosed through June, 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry in 2001–2004, and median follow-up was 5.5 years (range, 0 – 7.9 years). Incidence of prostate cancer as a function of plasma α-tocopherol, γ-tocopherol, and supplementation with α-tocopherol or selenomethionine was estimated by the hazard ratio (HR). Plasma γ-tocopherol was not associated with prostate cancer. Men with higher α-tocopherol concentrations appeared to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21 (95% confidence interval (CI), 0.88–1.66, P-trend=0.24; in the trial placebo arm, Q5 HR, 0.85, 95% CI, 0.44–1.62, P-trend=0.66]. We found a strong positive plasma α-tocopherol association among men receiving the trial selenomethionine supplement [Q5 HR, 2.04, 95% CI, 1.29–3.22; P-trend=0.005]. A positive plasma α-tocopherol-prostate cancer association also appeared limited to high-grade disease (Gleason grade 7––10, overall Q5 HR, 1.59, 95% CI, 1.13–2.24, P-trend=0.001; among men receiving selenomethionine, HR, 2.12, 95% CI, 1.32–3.40; P-trend=0.0002). Our findings indicate that higher plasma α-tocopherol concentrations may interact with selenomethionine supplements to increase high-grade prostate cancer risk, suggesting a biological interaction between α-tocopherol and selenium itself or selenomethionine. PMID:24961880

Prostatic Artery Embolization for Enlarged Prostates Due to Benign Prostatic Hyperplasia. How I Do It

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carnevale, Francisco C., E-mail: fcarnevale@uol.com.br; Antunes, Alberto A., E-mail: antunesuro@uol.com.br

2013-12-15

Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory. Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality ofmore » life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results.« less

Acupuncture for chronic prostatitis: A systematic review and meta-analysis protocol.

PubMed

Peng, Tianzhong; Cheng, Ying; Jin, Yuhao; Xu, Na; Guo, Taipin

2018-04-01

Chronic prostatitis (CP) is a prevalent genitourinary condition. Considering its safety profile, acupuncture can be an option treating CP symptoms. The aim of this review is to undertake a systematic review to estimate the effectiveness and safety of acupuncture on CP. We will search all randomized controlled trials for CP in August 2018 in the databases of MEDLINE, Cochrane Library, Web of Science, EMBASE, Springer, WHO International Clinical Trials Registry Platform (ICTRP), China National Knowledge Infrastructure (CNKI), Wan fang, Chinese Biomedical Literature Database (CBM), PsycInfo, Chinese Scientific Journal Database (VIP), and other available resources. Languages are limited as English and Chinese. Search terms used are will "acupuncture," and "chronic prostatitis," "non-bacterial prostatitis," "abacterial prostatitis." And duplicates will be screened. The primary outcomes consisted of improvement rate and pain relief evaluated by The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) index. Secondary outcomes include the recurrence rate and side effects, such as pneumothorax, discomforts, and infection. This study will demonstrate an evidence-based review of acupuncture for chronic prostatitis. The study will provide clear evidence to assess the effectiveness and side effects of acupuncture for chronic prostatitis. There is no requirement of ethical approval and it will be in print or disseminated by electronic copies. CRD42018088834.

[Ultrasonography of the prostate gland : From B‑image through multiparametric ultrasound to targeted biopsy].

PubMed

Steinkohl, F; Luger, A; Bektic, J; Aigner, F

2017-08-01

Prostate cancer is the most frequent cancer in men. The diagnosis is normally achieved by a systematic prostate biopsy; however, this is a randomized approach by which a substantial number of significant carcinomas go undetected. For this reason, in recent years imaging techniques have been continuously developed, which enable visualization and therefore targeted biopsies. The use of systematic biopsies is a standard procedure for the detection of prostate cancer. The quality of biopsies can be increased if the prostate is examined for the presence of suspected cancerous alterations during the biopsy. This can be carried out using multiparametric transrectral ultrasound. Multiparametric ultrasound within the framework of a targeted biopsy increases the detection rate of significant prostate carcinomas with a simultaneous decrease in detection of insignificant carcinomas; however, the diagnostic reliability and the evidence level of multiparametric transrectal ultrasound are not yet sufficiently high to be able to replace a systematic biopsy. In the hands of a well-trained examiner multiparametric transrectal ultrasound represents a good method for detection of prostate carcinomas. With the progression in technical developments of ultrasound technology, the detection rate will presumably be further increased.

Preventive effects of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

2007-12-01

Plant extracts are useful in the management of benign prostatic hyperplasia (BPH). This study investigates whether ACTICOA (Barry Callebaut France, Louviers, France) powder (AP), a cocoa polyphenolic extract, could prevent prostate hyperplasia induced by testosterone propionate (TP) in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one negative control group receiving subcutaneous injections of corn oil and treated with vehicle and three groups injected subcutaneously with TP and treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments were given orally and started 2 weeks before the induction of prostate hyperplasia. The influence of TP and AP on body weights and food and water consumption of rats was examined. On day 36, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumption, while AP at both doses tested reduced significantly these differences. TP significantly increased prostate size ratio (P < .001), and this induced increase was significantly inhibited in AP-treated rats in comparison with positive controls (P < .001) in a dose-dependent manner. We conclude that AP can prevent TP-induced prostate hyperplasia and therefore may be beneficial in the management of BPH.

Photoselective vaporization of the prostate with GreenLight 120-W laser versus transurethral resection of the prostate for benign prostatic hyperplasia: a systematic review with meta-analysis of randomized controlled trials.

PubMed

Zang, Ya-Chen; Deng, Xin-Xi; Yang, Dong-Rong; Xue, Bo-Xin; Xu, Li-Jun; Liu, Xiao-Long; Zhou, Yi-Bin; Shan, Yu-Xi

2016-02-01

The aim of this study is to assess the overall efficacy and safety of photoselective vaporization of the prostate (PVP) with GreenLight 120-W laser versus transurethral resection of the prostate (TURP) for treating patients of benign prostate hyperplasia (BPH) with lower urinary tract symptoms (LUTS). We performed a literature search of The Cochrane Library and the electronic databases, including Embase, Medline, and Web of Science. Manual searches were conducted of the conference proceedings, including European Association of Urology and American Urological Association (2007 to 2012). Outcomes reviewed included clinical baseline characteristics, perioperative data, complications, and postoperative functional results, such as postvoid residual (PVR), international prostate symptom score (IPSS), quality of life (QoL), and maximum flow rate (Qmax). Six randomized controlled trials (RCTs) were enrolled. Three hundred and forty-seven patients undergone 120-W PVP, and 350 patients were treated with TURP in the RCTs. There were no significant differences for clinical characteristics in these trials. In perioperative data, catheterization time and length of hospital stay were shorter in the PVP group. However, the operation time was shorter in the TURP group. Capsular perforation, blood transfusion, clot retention, and macroscopic hematuria were markedly less likely in PVP-treated subjects. The other complications between PVP and TURP did not demonstrate a statistic difference. There were no significant differences in QoL, PVR, IPSS, and Qmax in the 1, 3, 6, 12, and 24 months of postoperative follow-up. There was no significant difference at postoperation follow-up of functional outcomes including IPSS, PVR, Qmax, and QoL between the TURP-treated subjects and PVP-treated subjects. Owing to a shorter catheterization time, reduced hospital duration and less complication, PVP could be used as an alternative and a promising minimal invasive surgical procedure for the treatment of BPH.

Mortality results from a randomized prostate-cancer screening trial.

PubMed

Andriole, Gerald L; Crawford, E David; Grubb, Robert L; Buys, Saundra S; Chia, David; Church, Timothy R; Fouad, Mona N; Gelmann, Edward P; Kvale, Paul A; Reding, Douglas J; Weissfeld, Joel L; Yokochi, Lance A; O'Brien, Barbara; Clapp, Jonathan D; Rathmell, Joshua M; Riley, Thomas L; Hayes, Richard B; Kramer, Barnett S; Izmirlian, Grant; Miller, Anthony B; Pinsky, Paul F; Prorok, Philip C; Gohagan, John K; Berg, Christine D

2009-03-26

The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.) 2009 Massachusetts Medical Society

Analysis of Prostate Patient Setup and Tracking Data: Potential Intervention Strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su Zhong, E-mail: zsu@floridaproton.org; Zhang Lisha; Murphy, Martin

Purpose: To evaluate the setup, interfraction, and intrafraction organ motion error distributions and simulate intrafraction intervention strategies for prostate radiotherapy. Methods and Materials: A total of 17 patients underwent treatment setup and were monitored using the Calypso system during radiotherapy. On average, the prostate tracking measurements were performed for 8 min/fraction for 28 fractions for each patient. For both patient couch shift data and intrafraction organ motion data, the systematic and random errors were obtained from the patient population. The planning target volume margins were calculated using the van Herk formula. Two intervention strategies were simulated using the tracking data:more » the deviation threshold and period. The related planning target volume margins, time costs, and prostate position 'fluctuation' were presented. Results: The required treatment margin for the left-right, superoinferior, and anteroposterior axes was 8.4, 10.8, and 14.7 mm for skin mark-only setup and 1.3, 2.3, and 2.8 mm using the on-line setup correction, respectively. Prostate motion significantly correlated among the superoinferior and anteroposterior directions. Of the 17 patients, 14 had prostate motion within 5 mm of the initial setup position for {>=}91.6% of the total tracking time. The treatment margin decreased to 1.1, 1.8, and 2.3 mm with a 3-mm threshold correction and to 0.5, 1.0, and 1.5 mm with an every-2-min correction in the left-right, superoinferior, and anteroposterior directions, respectively. The periodic corrections significantly increase the treatment time and increased the number of instances when the setup correction was made during transient excursions. Conclusions: The residual systematic and random error due to intrafraction prostate motion is small after on-line setup correction. Threshold-based and time-based intervention strategies both reduced the planning target volume margins. The time-based strategies increased the treatment time and the in-fraction position fluctuation.« less

A randomized prospective study of laser ablation of the prostate versus transurethral resection of the prostate in men with benign prostatic hyperplasia.

PubMed

Shingleton, W B; Terrell, F; Renfroe, D L; Kolski, J M; Fowler, J E

1999-12-01

To compare the safety and efficacy of laser ablation of the prostate, one of the minimally invasive treatments available for men with benign prostatic hyperplasia, to transurethral resection of the prostate (TURP). A prospective randomized study of 100 men with benign prostatic hyperplasia, with 50 patients in each treatment arm, was conducted. All patients met the entry criteria: age older than 45 years, no history of carcinoma of the prostate, a peak flow rate less than 15 mL/s, medical therapy failure, and the ability to undergo regional or general anesthesia. All patients underwent a preoperative evaluation consisting of the American Urological Association (AUA) symptom score, uroflowmetry, pressure-flow study, transrectal ultrasound for prostate volume, and serum prostate-specific antigen determination. Patients underwent either TURP or laser ablation of the prostate using the potassium titanyl phosphate (KTP)/neodymium: yttrium-aluminum-garnet laser. Patients were seen for follow-up at 1, 3, 6, and 12 months. The mean age was 68.2 years (range 45 to 90) for the laser group and 67.4 years (range 54 to 82) for the TURP group. The mean AUA symptom score was 22 for the laser group and 21 for the TURP group. The mean peak uroflow rate was 7.6 +/- 3.4 mL/s for the laser group and 6.5 +/- 4.0 mL/s for the TURP group. At 12 months of follow-up, the mean AUA symptom score had decreased to 7 (-69.5%) for the laser group and to 3 (-80.9%) for the TURP group. The mean peak uroflow rate increased to 15.4 mL/s (+ 107.8%) for the laser group and to 16.7 mL/s (+ 150.7%) for the TURP cohort. Seventy-five percent of the laser group had a 50% or greater decrease in their individual AUA symptom score compared with 93% of the TURP group. Sixty-five percent of the laser cohort had a 50% or greater increase in their peak uroflow rate compared with 75% of the TURP cohort. Laser prostatectomy produced improvements in the peak flow rate and symptom score similar to those produced by TURP. The patients who underwent laser treatment required a longer period to reach maximum improvement, which probably reflects the lack of tissue debulking at the time of surgery. Further improvement in laser technology will be required to produce more immediate results.

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer.

PubMed

Beer, Tomasz M; Kwon, Eugene D; Drake, Charles G; Fizazi, Karim; Logothetis, Christopher; Gravis, Gwenaelle; Ganju, Vinod; Polikoff, Jonathan; Saad, Fred; Humanski, Piotr; Piulats, Josep M; Gonzalez Mella, Pablo; Ng, Siobhan S; Jaeger, Dirk; Parnis, Francis X; Franke, Fabio A; Puente, Javier; Carvajal, Roman; Sengeløv, Lisa; McHenry, M Brent; Varma, Arvind; van den Eertwegh, Alfonsus J; Gerritsen, Winald

2017-01-01

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viani, Gustavo Arruda, E-mail: gusviani@gmail.com; Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose

2012-08-01

Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trialsmore » showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.« less

The effect of fibrinogen concentrate on perioperative bleeding in transurethral resection of the prostate: a double-blind placebo-controlled and randomized study.

PubMed

Soleimani, M; Masoumi, N; Nooraei, N; Lashay, A; Safarinejad, M R

2017-02-01

Essentials Perioperative bleeding during prostate surgery is still a common morbidity. Anticoagulant and antiplatelet medications contribute to the risk of hemorrhage and prolonged hospital stay. Multiple pharmacological agents have been proposed, but none of them have been widely accepted. It is crucial to find a safe and effective modality to reduce hemorrhage. Background Hemorrhage during transurethral resection of the prostate (TUR-P) has always been a concern. Several studies have shown preoperative administration of fibrinogen concentrate to have promising results in reducing hemorrhage in cardiac surgery. Objectives To investigate the hemostatic effect of fibrinogen concentrate administration on reducing the amount of bleeding during TUR-P in patients with benign prostatic hyperplasia. Methods Sixty men with benign prostatic hyperplasia, who were chosen to undergo TUR-P, entered this prospective randomized double-blind placebo-controlled study. The participants were randomly assigned to two groups: treatment (n = 31) and placebo (n = 29). They received an infusion of 2 g of fibrinogen concentrate (treatment group) or normal saline (placebo group) before surgery. Data regarding the amount of bleeding, the operation and complications were recorded and analyzed. Results No difference was observed in bleeding between the fibrinogen and placebo groups during (521 mL versus 557 mL, respectively) and after (291 mL versus 341 mL, respectively) surgery. This lack of difference was also seen in operation time (43 min versus 42 min), irrigating fluid volume used during (17 L versus 19 L) and after (29 L versus 28 L) surgery, and resected adenoma volume (19 g versus 19 g). The mean blood pressure was also similar in both groups as a confounding factor for the amount of bleeding. Conclusion Preoperative administration of fibrinogen concentrate had no significant influence on intraoperative and postoperative bleeding in TUR-P surgery. © 2016 International Society on Thrombosis and Haemostasis.

Comparative effects of Yi Jin Jing versus Tai Chi exercise training on benign prostatic hyperplasia-related outcomes in older adults: study protocol for a randomized controlled trial.

PubMed

Liu, XiangYun; Huang, Guoyuan; Chen, Peijie; Li, Yong; Xiang, JiuLin; Chen, Ting; Wang, Ru

2016-07-16

Benign prostatic hyperplasia (BPH) and its associated lower urinary tract symptoms (LUTS) occur very commonly in older men. BPH and LUTS cause substantial physical and psychological impairment that could seriously affect the quality of late life and greatly cost the health-care systems. Current surgical and pharmacological therapies are expensive, may not effectively improve prostate function and health but cause adverse effects. There is an urgent need to find new and effective non-pharmacological preventions and treatments. Yi Jin Jing and Tai Chi are two common traditional Chinese mind-body exercises with different movements and techniques, but both emphasize regulating functional homeostasis and keeping whole body harmony. Yi Jin Jing and Tai Chi have not been studied much for potentially use in the treatment of BPH-related problems. The primary purpose of this protocol is to assess the effectiveness of Yi Jin Jing versus Tai Chi on the monographic and functional changes of prostate in older men. A prospective single-center randomized controlled trial will be conducted. A total of 150 old men (60-70 years old) will be recruited from the urban tertiary of Shanghai, China. Of these, 50 eligible participants will be randomly assigned to a control group and two intervention groups with either Yi Jin Jing or Tai Chi exercise training. They will undergo 30 minutes for each exercise for five times a week for 6 months. The primary outcomes are changes of signs and symptoms in BPH and lower urinary tract from baseline to post-intervention. The main secondary outcomes are exercise-induced effects on the circulating levels of estrogen and androgen. All the outcome measures will be assessed at baseline, immediately after the 6-month intervention, and at the 3-month post-intervention follow-up. This proposed study will be the first comparative randomized clinical trial to evaluate the effectiveness of Yi Jin Jing versus Tai Chi exercise on prostate health among older adults. The results will provide an evidence-based recommendation for Chinese older men on the use of Yi Jin Jing and Tai Chi training to promote prostatic function and health. Potential mechanisms for the regulatory effect of the two exercises elucidated by multiple outcomes are also explored. A clarification of the effects and mechanisms may provide information for the development of new strategies in the prevention and treatment of BPH-related conditions. ClinicalTrials.gov Identifier: ChiCTR-IOR-16007698 . This trial was registered on 4 January 2016.

The Missing Pieces in Reporting of Randomized Controlled Trials of External Beam Radiation Therapy Dose Escalation for Prostate Cancer.

PubMed

Zaorsky, Nicholas G; Egleston, Brian L; Horwitz, Eric M; Dicker, Adam P; Nguyen, Paul L; Showalter, Timothy N; Den, Robert B

2016-08-01

Randomized controlled trials (RCTs) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost-effectiveness of a treatment. For many patients, cancer is a chronic illness; RCTs evaluating treatments for indolent cancers must evolve to facilitate medical decision-making, as "concrete" patient outcomes (eg, survival) will likely be excellent independent of the intervention, and detecting a difference between trial arms may be impossible. In this commentary, we articulate 9 recommendations that we hope future clinical trialists and funding agencies (including those under the National Cancer Institute) will take into consideration when planning RCTs to help guide subsequent interpretation of results and clinical decision making, based on RCTs of external beam radiation therapy dose escalation for the most common indolent cancer in men, that is, prostate cancer. We recommend routinely reporting: (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics (eg, number of centers involved, type of facilities, yearly hospital volumes). We discuss how these factors independently affect patient outcomes and toxicities; future clinicians and governing organizations should consider this information to plan RCTs accordingly (to maximize patient accrual and total n), select appropriate endpoints (eg, toxicity, quality of life, sexual function), actively monitor RCTs, and report results so as to identify the optimal treatment among subpopulations.

HBCU Summer Undergraduate Training Program in Prostate Cancer Research

DTIC Science & Technology

2011-08-01

in Prostate Cancer Research INTRODUCTION: The goal of this award was to provide prostate cancer (CaP) research summer internships to the...Selection Process: USU/CPDR summer internship program announcements for 2008, 2009 and 2010 were made by Dr. Deepak Kumar (Partnering PI) at the...Department of Anatomy, Physiology and Genetics and Department of Microbiology and Immunology actively participated in training of UDC students under the

Ethnic minorities (African American and Hispanic) males prefer prostate cryoablation as aggressive treatment of localized prostate cancer.

PubMed

Kim, Fernando J; Werahera, Priya N; Sehrt, David E; Gustafson, Diedra; Silva, Rodrigo D; Molina, Wilson R

2014-06-01

Our safety net hospital offers minimally invasive, traditional open and perineal radical prostatectomies, as well as radiation therapy and medical oncological services when appropriate. Historically, only few African American and Hispanic patients elected surgical procedures due to unknown reasons. Interestingly, after initiation of the prostate cryoablation program (Whole Gland) in 2003 at Denver Health Medical Center (DHMC) we noticed a trend towards cryotherapy in these specific patient populations for the treatment of localized prostate cancer. We analyzed the profile of ethnic minority men evaluated for localized prostate cancer and evaluated the associated factors in the decision making for the treatment of localized prostate cancer. A retrospective review of 524 patients seen for prostate cancer from January 2003 to January 2012 in our safety net hospital was conducted. The treatment selected by the patient after oncologic consultation was then recorded. The health insurance status, demographic data, and personal statements of reasons for elected procedure were obtained. A multivariate logistic regression for associated factors influencing treatment decisions was then formed. Patients were categorized by using the D'Amico risk stratification criteria. The insurance status revealed that only 1% of African American patients had private health insurance versus 5% Hispanic and 26% of Caucasians. African American men were at higher D'Amico risk with more positive metastasis evaluation yet were less likely to undergo surgery and instead often elected for radiation therapy. Conversely, Hispanic and Caucasian men often elected cryoablation and radical prostatectomy for their treatment. Referrals for surgery were primarily Caucasian males with private health insurance. Most minority patients had indigent health coverage. Statistical analysis further revealed that age, marital status, indigent enrollment, D'Amico risk, and the option of cryoablation may influence patient's selection for surgical management of localized prostate cancer. Many factors influence treatment selection including race, age, marital status, enrollment in an indigent program, and a high D'Amico risk. The less invasive nature of cryoablation appeared to influence patients' opinion regarding surgery for the treatment of localized prostate cancer, especially in African American men.

A multiresolution prostate representation for automatic segmentation in magnetic resonance images.

PubMed

Alvarez, Charlens; Martínez, Fabio; Romero, Eduardo

2017-04-01

Accurate prostate delineation is necessary in radiotherapy processes for concentrating the dose onto the prostate and reducing side effects in neighboring organs. Currently, manual delineation is performed over magnetic resonance imaging (MRI) taking advantage of its high soft tissue contrast property. Nevertheless, as human intervention is a consuming task with high intra- and interobserver variability rates, (semi)-automatic organ delineation tools have emerged to cope with these challenges, reducing the time spent for these tasks. This work presents a multiresolution representation that defines a novel metric and allows to segment a new prostate by combining a set of most similar prostates in a dataset. The proposed method starts by selecting the set of most similar prostates with respect to a new one using the proposed multiresolution representation. This representation characterizes the prostate through a set of salient points, extracted from a region of interest (ROI) that encloses the organ and refined using structural information, allowing to capture main relevant features of the organ boundary. Afterward, the new prostate is automatically segmented by combining the nonrigidly registered expert delineations associated to the previous selected similar prostates using a weighted patch-based strategy. Finally, the prostate contour is smoothed based on morphological operations. The proposed approach was evaluated with respect to the expert manual segmentation under a leave-one-out scheme using two public datasets, obtaining averaged Dice coefficients of 82% ± 0.07 and 83% ± 0.06, and demonstrating a competitive performance with respect to atlas-based state-of-the-art methods. The proposed multiresolution representation provides a feature space that follows a local salient point criteria and a global rule of the spatial configuration among these points to find out the most similar prostates. This strategy suggests an easy adaptation in the clinical routine, as supporting tool for annotation. © 2017 American Association of Physicists in Medicine.

Prostate cancer: cryotherapy.

PubMed

Shinohara, Katsuto

2003-11-01

The incidence of prostate cancer has more than doubled in the last 10 years, and 220,900 new cases will be detected in 2003. This increase is due in large part to increased use of prostate-specific antigen (PSA)-based screening, transrectal ultrasonography, and random biopsy of the prostate. The treatment of prostate cancer, however, remains controversial, and no consensus has been established as to what constitutes appropriate treatment for any stage of disease, especially for localized cancers. Radical prostatectomy, radiation therapy, or watchful waiting all have their advocates, and the risks and benefits of these approaches are discussed frequently. Skepticism about conventional treatments has stimulated patients and physicians to search for alternatives that are effective and associated with limited morbidity. Technologic developments have rekindled interest in cryotherapy as a viable alternative to other, more conventional localized therapies. Given the relative paucity of alternatives for patients who experience biochemical progression after radiotherapy, cryosurgery also may prove to be a good alternative for those patients whose tumors appear to remain localized despite progression. In addition, it appears that cryosurgery will play an increased role in the future management of prostate cancer.

Identification of Prostate Cancer-Specific microDNAs

DTIC Science & Technology

2014-12-01

displacement amplification (MDA). 2 adopted multiple displacement amplification (MDA) with random primers for enriched circular DNA by rolling circle ... amplification (RCA) (Fig. 1) and then amplified DNA fragments were subject to deep sequencing. Sequence NO of Reads seq 1 184 seq 2 133 seq 3 2407 seq...prostate cancer cells through multiple displacement amplification .  Clone #7 is the top candidate which has been cloned in an expression vector and it

Prevention of Post-Radiotherapy Failure in Prostate Cancer by Vitamin D

DTIC Science & Technology

2006-03-01

in the fall of 2003, Dr. Vijayakumar consulted extensively with the statistician for the UCD Cancer Center, Dr. Laurel Beckett , to confirm and...phone (Surgical Oncology, UIC), Dr. William Hall (Radiation Oncology), and Phil Boerner (Writer, Radiation Oncology). As a result of this meeting...RG, Mehta RR, Hall WH, Boerner PS, Beckett LA, Vijayakumar S. Designing a randomized phase I/II prostate cancer chemoprevention trial using 1alpha

Radiation proctopathy in the treatment of prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garg, Amit K.; Mai Weiyan; McGary, John E.

2006-12-01

Purpose: To compile and review data on radiation proctopathy in the treatment of prostate cancer with respect to epidemiology, clinical manifestations, pathogenesis, risk factors, and treatment. Methods: Medical literature databases including PubMed and Medline were screened for pertinent reports, and critically analyzed for relevance in the scope of our purpose. Results: Rectal toxicity as a complication of radiotherapy has received attention over the past decade, especially with the advent of dose-escalation in prostate cancer treatment. A number of clinical criteria help to define acute and chronic radiation proctopathy, but lack of a unified grading scale makes comparing studies difficult. Amore » variety of risk factors, related to either radiation delivery or patient, are the subject of intense study. Also, a variety of treatment options, including medical therapy, endoscopic treatments, and surgery have shown varied results, but a lack of large randomized trials evaluating their efficacy prevents forming concrete recommendations. Conclusion: Radiation proctopathy should be an important consideration for the clinician in the treatment of prostate cancer especially with dose escalation. With further study of possible risk factors, the advent of a standardized grading scale, and more randomized trials to evaluate treatments, patients and physicians will be better armed to make appropriate management decisions.« less

Entertainment education for prostate cancer screening: a randomized trial among primary care patients with low health literacy.

PubMed

Volk, Robert J; Jibaja-Weiss, Maria L; Hawley, Sarah T; Kneuper, Suzanne; Spann, Stephen J; Miles, Brian J; Hyman, David J

2008-12-01

To evaluate an entertainment-based patient decision aid for prostate cancer screening among patients with low or high health literacy. Male primary care patients from two clinical sites, one characterized as serving patients with low health literacy (n=149) and the second as serving patients with high health literacy (n=301), were randomized to receive an entertainment-based decision aid for prostate cancer screening or an audiobooklet-control aid with the same learner content but without the entertainment features. Postintervention and 2-week follow-up assessments were conducted. Patients at the low-literacy site were more engaged with the entertainment-based aid than patients at the high-literacy site. Overall, knowledge improved for all patients. Among patients at the low-literacy site, the entertainment-based aid was associated with lower decisional conflict and greater self-advocacy (i.e., mastering and obtaining information about screening) when compared to patients given the audiobooklet. No differences between the aids were observed for patients at the high-literacy site. Entertainment education may be an effective strategy for promoting informed decision making about prostate cancer screening among patients with lower health literacy. As barriers to implementing computer-based patient decision support programs decrease, alternative models for delivering these programs should be explored.

Salvage prostatectomy in patients who have failed radiation therapy or cryotherapy as primary treatment for prostate cancer.

PubMed

Chen, Bert T; Wood, David P

2003-12-29

Asymptomatic prostate-specific antigen (PSA) recurrence after radiation therapy for prostate carcinoma poses a diagnostic and therapeutic dilemma for clinicians. Patients with locally recurrent disease can consider treatment options of salvage surgery, cryotherapy, watchful waiting, or androgen deprivation. Of these options, only salvage surgery has been shown to result in long-term disease-free survival for selected patients. However, salvage surgery is associated with significant morbidity, including urinary incontinence and rectal injuries. Ideally, salvage surgery outcomes can be optimized with careful patient selection according to clinical stage, serum PSA levels before radiation and surgery, the medical condition of the patient, and clear expectations of the physician and patient. Among patients with locally recurrent disease, those with localized prostate carcinoma amenable to radical prostatectomy before radiation or cryotherapy would be the most suitable candidates for salvage surgery.

Mortality results from the Göteborg Randomised Prostate Cancer Screening Trial

PubMed Central

Hugosson, Jonas; Carlsson, Sigrid; Aus, Gunnar; Bergdahl, Svante; Khatami, Ali; Lodding, Pär; Pihl, Carl-Gustaf; Stranne, Johan; Holmberg, Erik; Lilja, Hans

2013-01-01

Summary Background Prostate cancer is one of the leading causes of death from malignant disease among men in the Western world. One strategy to decrease the risk of dying from this disease is screening with Prostate-Specific Antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate. Methods In December 1994, 20 000 men born 1930 to 1944, randomly sampled from the Population Register, were computer randomised in a 1:1 ratio to a screening group invited for biennial PSA testing or to a control group not invited. In each arm, 48 men were excluded from analysis due to either death or emigration before randomization date or prevalent prostate cancer. The primary endpoint was prostate cancer specific mortality analyzed according to the intention-to-screen principle. Men in the screening group were invited up to the upper age limit (median 69, range 67–71 years) and only men with elevated PSA were offered additional tests such as digital rectal examination and prostate biopsies. The study is still ongoing inviting men who have not yet reached the upper age limit. This is the first planned report on cumulative prostate cancer incidence and mortality calculated up to Dec 31 2008. This study is registered [as an International Standard Randomised Controlled Trial], number [ISRCTN49127736]. Findings Among men randomised to screening 7578/9952 (76%) attended at least once (attendees). During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer resulting in a cumulative incidence of prostate cancer of 12.7% in the screening arm and 8.2% in the control arm (hazard ratio 1.64; 95% confidence interval [CI] 1.50–1.80; p<0.0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.40% (95% CI 0.17–0.64%), from 0.90% in the control group to 0.50% in the screening group. The incidence rate ratio for death from prostate cancer was 0.56 (95% CI 0.39–0.82; p=0.002) in the screening compared to the control group. The incidence rate ratio of attendees compared to the control group was 0.44 (95% CI 0.28–0.68; p=0.0002). Overall, 293 men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. Interpretation The benefit of prostate cancer screening compares favourably to other cancer screening programs and in this study prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over diagnosis is substantial and the number needed to treat is at least as high as in breast cancer screening. Funding The Swedish Cancer Society, the Swedish Research Council and the National Cancer Institute. PMID:20598634

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

PubMed

Kasivisvanathan, Veeru; Rannikko, Antti S; Borghi, Marcelo; Panebianco, Valeria; Mynderse, Lance A; Vaarala, Markku H; Briganti, Alberto; Budäus, Lars; Hellawell, Giles; Hindley, Richard G; Roobol, Monique J; Eggener, Scott; Ghei, Maneesh; Villers, Arnauld; Bladou, Franck; Villeirs, Geert M; Virdi, Jaspal; Boxler, Silvan; Robert, Grégoire; Singh, Paras B; Venderink, Wulphert; Hadaschik, Boris A; Ruffion, Alain; Hu, Jim C; Margolis, Daniel; Crouzet, Sébastien; Klotz, Laurence; Taneja, Samir S; Pinto, Peter; Gill, Inderbir; Allen, Clare; Giganti, Francesco; Freeman, Alex; Morris, Stephen; Punwani, Shonit; Williams, Norman R; Brew-Graves, Chris; Deeks, Jonathan; Takwoingi, Yemisi; Emberton, Mark; Moore, Caroline M

2018-05-10

Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .).

Enhancing Informed Choice to Undergo Health Screening: A Systematic Review

PubMed Central

Biesecker, Barbara Bowles; Schwartz, Marc D.; Marteau, Theresa M.

2012-01-01

Objective To assess the effectiveness of health screening interventions aimed at enhancing informed choice. Methods Studies were selected if (1) they were randomized controlled trials conducted between January 1, 2000, and March 30, 2010, (2) participants in one arm underwent a prescreening intervention aimed at improving informed choice, and (3) informed choice was the primary outcome. Results Eight studies that met the inclusion criteria involved screening for prostate, colorectal and breast cancer, and diabetes. Five of the 8 prescreening interventions led to greater informed choice. Conclusions With researchers mindful of the limited number of studies, findings were encouraging, but conclusions regarding the most effective ways of facilitating informed choice for screening are at best tentative. PMID:23985182

Improvement in Therapeutic Efficacy and Reduction in Cellular Toxicity: Introduction of a Novel Anti-PSMA-Conjugated Hybrid Antiandrogen Nanoparticle.

PubMed

Thangavel, Chellappagounder; Perepelyuk, Maryna; Boopathi, Ettickan; Liu, Yi; Polischak, Steven; Deshpande, Deepak A; Rafiq, Khadija; Dicker, Adam P; Knudsen, Karen E; Shoyele, Sunday A; Den, Robert B

2018-05-07

Second generation antiandrogens have improved overall survival for men with metastatic castrate resistant prostate cancer; however, the antiandrogens result in suppression of androgen receptor (AR) activity in all tissues resulting in dose limiting toxicity. We sought to overcome this limitation through encapsulation in a prostate specific membrane antigen (PSMA)-conjugated nanoparticle. We designed and characterized a novel nanoparticle containing an antiandrogen, enzalutamide. Selectivity and enhanced efficacy was achieved through coating the particle with PSMA. The PSMA-conjugated nanoparticle was internalized selectively in AR expressing prostate cancer cells. It did not elicit an inflammatory effect. The efficacy of enzalutamide was not compromised through insertion into the nanoparticle; in fact, lower systemic drug concentrations of enzalutamide resulted in comparable clinical activity. Normal muscle cells were not impacted by the PSMA-conjugated containing antiandrogen. This approach represents a novel strategy to increase the specificity and effectiveness of antiandrogen treatment for men with castrate resistant prostate cancer. The ability to deliver higher drug concentrations in prostate cancer cells may translate into improved clinical end points including overall survival.

Poster - 32: Atlas Selection for Automated Segmentation of Pelvic CT for Prostate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mallawi, Abrar; Farrell, TomTom; Diamond, Kevin-Ro

2016-08-15

Atlas based-segmentation has recently been evaluated for use in prostate radiotherapy. In a typical approach, the essential step is the selection of an atlas from a database that the best matches of the target image. This work proposes an atlas selection strategy and evaluate it impacts on final segmentation accuracy. Several anatomical parameters were measured to indicate the overall prostate and body shape, all of these measurements obtained on CT images. A brute force procedure was first performed for a training dataset of 20 patients using image registration to pair subject with similar contours; each subject was served as amore » target image to which all reaming 19 images were affinity registered. The overlap between the prostate and femoral heads was quantified for each pair using the Dice Similarity Coefficient (DSC). Finally, an atlas selection procedure was designed; relying on the computation of a similarity score defined as a weighted sum of differences between the target and atlas subject anatomical measurement. The algorithm ability to predict the most similar atlas was excellent, achieving mean DSCs of 0.78 ± 0.07 and 0.90 ± 0.02 for the CTV and either femoral head. The proposed atlas selection yielded 0.72 ± 0.11 and 0.87 ± 0.03 for CTV and either femoral head. The DSC obtained with the proposed selection method were slightly lower than the maximum established using brute force, but this does not include potential improvements expected with deformable registration. The proposed atlas selection method provides reasonable segmentation accuracy.« less

Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study.

PubMed

Jamnagerwalla, Juzar; Howard, Lauren E; Allott, Emma H; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freeman, Michael R; Freedland, Stephen J

2017-12-27

Epidemiologic evidence for a serum cholesterol-prostate cancer link is mixed. Prostate-specific antigen (PSA) is positively correlated with cholesterol, potentially increasing PSA-driven biopsy recommendations in men with high cholesterol, though biopsy compliance may be lower in men with comorbid conditions. These potential biases may affect PSA-driven biopsy rates and subsequent prostate cancer detection in men with high serum cholesterol. Our objective was to test the association between serum cholesterol and prostate cancer risk in men receiving PSA independent, study-mandated prostate biopsies. We conducted a post hoc analysis of data from 4974 non-statin users in REDUCE, a randomized trial in men with elevated PSA and a negative baseline biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies. Associations between baseline serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and prostate cancer risk, overall and by Gleason grade (<7 vs. ≥7), were examined using multivariable logistic regression. High total serum cholesterol was associated with an increased risk of high-grade prostate cancer diagnosis (OR per 10 mg/dL 1.05; 95% CI 1.00-1.09; p = 0.048), but cholesterol was unrelated to either overall or low-grade prostate cancer risk (p-values >0.185). There was no association between serum LDL and overall, low- or high-grade prostate cancer risk (p-values >0.137). In contrast, elevated serum HDL was associated with increased risk of both overall (OR per 10 mg/dL 1.08; 95% CI 1.01-1.16; p = 0.033) and high-grade prostate cancer (OR per 10 mg/dL 1.14; 95% CI 1.01-1.28; p = 0.034). In REDUCE, where all men received PSA independent, trial-mandated biopsies thus ensuring complete prostate cancer ascertainment, high total serum cholesterol and high HDL were associated with increased risk of high-grade prostate cancer, supporting a cholesterol-prostate cancer link.

Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

2007-12-01

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Plant extracts are frequently used to treat BPH rather than therapeutics that can cause severe side effects. ACTICOA() (Ba0rry Callebaut France, Louviers, France) powder (AP) is a cocoa polyphenolic extract, and we have shown in a previous study that oral treatment with AP prevented prostate hyperplasia. This study investigated whether AP could improve established prostate hyperplasia using the same testosterone propionate (TP)-induced prostate hyperplasia model in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one group injected with corn oil and orally treated with the vehicle (negative control) and three groups injected subcutaneously with TP and orally treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments started 1 week after the start of the induction of prostate hyperplasia and lasted for 2 weeks. The influence of TP and AP on body weights, food and water consumptions, plasma polyphenolic concentration, and serum dihydrotestoterone (DHT) level of rats was examined. At completion of the study, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumptions, while AP reduced significantly these differences in a dose-dependent manner. AP significantly reduced serum DHT level and prostate size ratio in comparison with positive controls also dose-dependently. In conclusion, AP orally administered was effective for reducing established prostate hyperplasia, especially at the dose of 48 mg/kg/day.

A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats.

PubMed

Allan, George; Sbriscia, Tifanie; Linton, Olivia; Lai, Muh-Tsann; Haynes-Johnson, Donna; Bhattacharjee, Sheela; Ng, Raymond; Sui, Zhihua; Lundeen, Scott

2008-06-01

Androgens are required for the maintenance of normal sexual activity in adulthood and for enhancing muscle growth and lean body mass in adolescents and adults. Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-37654032 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle with ED(50) 0.8 mg/kg, stimulating maximal growth at a dose of 3mg/kg. In contrast, it stimulated ventral prostate growth to 21% of its full size at 3mg/kg. At the same time, JNJ-37654032 reduced prostate weight in intact rats by 47% at 3mg/kg, while having no inhibitory effect on muscle. Using magnetic resonance imaging to monitor body composition, JNJ-37654032 restored about 20% of the lean body mass lost following orchidectomy in aged rats. JNJ-37654032 reduced follicle-stimulating hormone levels in orchidectomized rats and reduced testis size in intact rats. JNJ-37654032 is a potent prostate-sparing SARM with the potential for clinical benefit in muscle-wasting diseases.

PSMA-Targeted Theranostic Nanocarrier for Prostate Cancer

PubMed Central

Flores, Orielyz; Santra, Santimukul; Kaittanis, Charalambos; Bassiouni, Rania; Khaled, Amr S; Khaled, Annette R.; Grimm, Jan; Perez, J Manuel

2017-01-01

Herein, we report the use of a theranostic nanocarrier (Folate-HBPE(CT20p)) to deliver a therapeutic peptide to prostate cancer tumors that express PSMA (folate hydrolase 1). The therapeutic peptide (CT20p) targets and inhibits the chaperonin-containing TCP-1 (CCT) protein-folding complex, is selectively cytotoxic to cancer cells, and is non-toxic to normal tissue. With the delivery of CT20p to prostate cancer cells via PSMA, a dual level of cancer specificity is achieved: (1) selective targeting to PSMA-expressing prostate tumors, and (2) specific cytotoxicity to cancer cells with minimal toxicity to normal cells. The PSMA-targeting theranostic nanocarrier can image PSMA-expressing cells and tumors when a near infrared dye is used as cargo. Meanwhile, it can be used to treat PSMA-expressing tumors when a therapeutic, such as the CT20p peptide, is encapsulated within the nanocarrier. Even when these PSMA-targeting nanocarriers are taken up by macrophages, minimal cell death is observed in these cells, in contrast with doxorubicin-based therapeutics that result in significant macrophage death. Incubation of PSMA-expressing prostate cancer cells with the Folate-HBPE(CT20p) nanocarriers induces considerable changes in cell morphology, reduction in the levels of integrin β1, and lower cell adhesion, eventually resulting in cell death. These results are relevant as integrin β1 plays a key role in prostate cancer invasion and metastatic potential. In addition, the use of the developed PSMA-targeting nanocarrier facilitates the selective in vivo delivery of CT20p to PSMA-positive tumor, inducing significant reduction in tumor size. PMID:28744329

How Precisely Can Prostate Cancer Be Managed?

PubMed Central

2016-01-01

Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2-ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy. Oncotype DX, Prolaris, the biopsy-based Decipher prostate cancer test, and ProMark may improve predictive risk stratification in addition to the traditional Gleason score and tumor stage. Decipher and Prolaris may predict biochemical recurrence and metastasis after radical prostatectomy and possibly help identify patients who need adjuvant therapy. Androgen receptor splice variant 7 appears effective in guiding the selection of second hormonal manipulation with abiraterone or enzalutamide versus chemotherapy when treating metastatic castration-resistant prostate cancer. PMID:27915475

The roles of prostate-specific antigen (PSA) density, prostate volume, and their zone-adjusted derivatives in predicting prostate cancer in patients with PSA less than 20.0 ng/mL.

PubMed

Shen, P; Zhao, J; Sun, G; Chen, N; Zhang, X; Gui, H; Yang, Y; Liu, J; Shu, K; Wang, Z; Zeng, H

2017-05-01

The aim of this study was to develop nomograms for predicting prostate cancer and its zonal location using prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives. A total of 928 consecutive patients with prostate-specific antigen (PSA) less than 20.0 ng/mL, who underwent transrectal ultrasound-guided transperineal 12-core prostate biopsy at West China Hospital between 2011 and 2014, were retrospectively enrolled. The patients were randomly split into training cohort (70%, n = 650) and validation cohort (30%, n = 278). Predicting models and the associated nomograms were built using the training cohort, while the validations of the models were conducted using the validation cohort. Univariate and multivariate logistic regression was performed. Then, new nomograms were generated based on multivariate regression coefficients. The discrimination power and calibration of these nomograms were validated using the area under the ROC curve (AUC) and the calibration curve. The potential clinical effects of these models were also tested using decision curve analysis. In total, 285 (30.7%) patients were diagnosed with prostate cancer. Among them, 131 (14.1%) and 269 (29.0%) had transition zone prostate cancer and peripheral zone prostate cancer. Each of zone-adjusted derivatives-based nomogram had an AUC more than 0.75. All nomograms had higher calibration and much better net benefit than the scenarios in predicting patients with or without different zones prostate cancer. Prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives have important roles in detecting prostate cancer and its zonal location for patients with PSA 2.5-20.0 ng/mL. To the best of our knowledge, this is the first nomogram using these parameters to predict outcomes of 12-core prostate biopsy. These instruments can help clinicians to increase the accuracy of prostate cancer screening and to avoid unnecessary prostate biopsy. © 2017 American Society of Andrology and European Academy of Andrology.

Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4-month randomised trial in middle-aged men.

PubMed

Kjaer, Thomas Nordstrøm; Ornstrup, Marie Juul; Poulsen, Morten Møller; Jørgensen, Jens Otto Lunde; Hougaard, David Michael; Cohen, Arieh Sierra; Neghabat, Shadman; Richelsen, Bjørn; Pedersen, Steen Bønløkke

2015-09-01

Resveratrol is a naturally occurring polyphenol with purported inhibitory effects on prostate growth and cancer development. A number of studies have demonstrated that resveratrol reduces prostate growth in animal models and reduces prostate cell growth in vitro. Based on these pre-clinical findings, interest in resveratrol is increasing in relation to the management of benign prostate hyperplasia (BPH) and prostate cancer. So far, no human trials have evaluated the effects of resveratrol on circulating androgens, prostate size, or biochemical markers of prostate size. In a randomized placebo controlled clinical study using two doses of resveratrol (150 mg or 1,000 mg resveratrol daily) for 4 months, we evaluated the effects on prostate size, prostate specific antigen (PSA) and sex steroid hormones in 66 middle-aged men suffering from the metabolic syndrome(MetS). At baseline, prostate size and PSA were positively correlated (R = 0.34, P < 0.007) as was prostate size and age (R = 0.37, P < 0.003). Prostate size did not correlate with testosterone, free testosterone, dihydrotestosterone (DHT), or any other androgen precursor at baseline. The highest dose of resveratrol lowered the serum level of androstenedione 24% (P = 0.052), dehydroepiandrosterone (DHEA) 41% (P < 0.01), and dehydroepiandrosterone-sulphate (DHEAS) 50% (p<0.001), compared to the control group. However, prostate size and levels of PSA, testosterone, free testosterone and DHT remained unchanged. In this population of middle-aged men suffering from MetS, high dose resveratrol (1,000 mg daily) administration for 4 months significantly lowered serum levels of the androgen precursors androstenedione, DHEA and DHEAS, whereas prostate size and circulating levels of PSA, testosterone, free testosterone, and dihydrotestosterone were unaffected. The present study suggests that resveratrol does not affect prostate volume in healthy middle-aged men as measured by PSA levels and CT acquired prostate volumes. Consequently, we find no support for the use of resveratrol in the treatment of benign prostate hyperplasia. © 2015 Wiley Periodicals, Inc.

Randomized, Double-Blind, Placebo-Controlled Phase III Trial Comparing Docetaxel and Prednisone With or Without Bevacizumab in Men With Metastatic Castration-Resistant Prostate Cancer: CALGB 90401

PubMed Central

Kelly, William Kevin; Halabi, Susan; Carducci, Michael; George, Daniel; Mahoney, John F.; Stadler, Walter M.; Morris, Michael; Kantoff, Philip; Monk, J. Paul; Kaplan, Ellen; Vogelzang, Nicholas J.; Small, Eric J.

2012-01-01

Purpose A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status ≤ 2 and adequate bone marrow, hepatic, and renal function were randomly assigned to receive docetaxel 75 mg/m2 intravenously (IV) over 1 hour for 21 days plus prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV every 3 weeks (DP + B) or placebo. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), 50% decline in prostate-specific antigen, objective response (OR), and toxicity. Results In total, 1,050 patients were randomly assigned. The median OS for patients given DP + B was 22.6 months compared with 21.5 months for patients treated with DP (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log-rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P = .0013). Grade 3 or greater treatment-related toxicity was more common with DP + B (75.4% v 56.2%; P ≤ .001), as was the number of treatment-related deaths (4.0% v 1.2%; P = .005). Conclusion Despite an improvement in PFS and OR, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC and was associated with greater toxicity. PMID:22454414

Computation of restoration of ligand response in the random kinetics of a prostate cancer cell signaling pathway.

PubMed

Dana, Saswati; Nakakuki, Takashi; Hatakeyama, Mariko; Kimura, Shuhei; Raha, Soumyendu

2011-01-01

Mutation and/or dysfunction of signaling proteins in the mitogen activated protein kinase (MAPK) signal transduction pathway are frequently observed in various kinds of human cancer. Consistent with this fact, in the present study, we experimentally observe that the epidermal growth factor (EGF) induced activation profile of MAP kinase signaling is not straightforward dose-dependent in the PC3 prostate cancer cells. To find out what parameters and reactions in the pathway are involved in this departure from the normal dose-dependency, a model-based pathway analysis is performed. The pathway is mathematically modeled with 28 rate equations yielding those many ordinary differential equations (ODE) with kinetic rate constants that have been reported to take random values in the existing literature. This has led to us treating the ODE model of the pathways kinetics as a random differential equations (RDE) system in which the parameters are random variables. We show that our RDE model captures the uncertainty in the kinetic rate constants as seen in the behavior of the experimental data and more importantly, upon simulation, exhibits the abnormal EGF dose-dependency of the activation profile of MAP kinase signaling in PC3 prostate cancer cells. The most likely set of values of the kinetic rate constants obtained from fitting the RDE model into the experimental data is then used in a direct transcription based dynamic optimization method for computing the changes needed in these kinetic rate constant values for the restoration of the normal EGF dose response. The last computation identifies the parameters, i.e., the kinetic rate constants in the RDE model, that are the most sensitive to the change in the EGF dose response behavior in the PC3 prostate cancer cells. The reactions in which these most sensitive parameters participate emerge as candidate drug targets on the signaling pathway. 2011 Elsevier Ireland Ltd. All rights reserved.

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

PubMed

Faiella, Eliodoro; Santucci, Domiziana; Greco, Federico; Frauenfelder, Giulia; Giacobbe, Viola; Muto, Giovanni; Zobel, Bruno Beomonte; Grasso, Rosario Francesco

2018-02-01

To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis. 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test. There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml). mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

PubMed Central

Khankari, Nikhil K.; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei

2016-01-01

Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers. PMID:27598322

Shearwave Dispersion Ultrasonic Vibrometry (SDUV) for measuring prostate shear stiffness and viscosity – An in vitro pilot study

PubMed Central

Urban, M.W.; Fatemi, M.; Greenleaf, J.F.

2011-01-01

This paper reports shear stiffness and viscosity “virtual biopsy” measurements of three excised non-cancerous human prostates using shearwave dispersion ultrasound vibrometry (SDUV) in vitro. Improved methods for prostate guided-biopsy are required to effectively guide needle biopsy to the suspected site. In addition, tissue stiffness measurement helps identifying a suspected site to perform biopsy because stiffness has been shown to correlate with pathology. More importantly, early detection of prostate cancer may guide minimally-invasive therapy and eliminate insidious procedures. In this work, “virtual” biopsies were taken in multiple locations in three excised prostates. Then, SDUV shear elasticity and viscosity measurements have been performed at the selected “suspicious” locations within the prostates. SDUV measurements of prostate elasticity and viscosity are generally in agreement with preliminary values reported previously in the literature. It is however important to emphasize that the obtained viscoelastic parameters values are local, and not a mean value for the whole prostate. PMID:20595086

Tunable cytotoxic aptamer-drug conjugates for the treatment of prostate cancer.

PubMed

Powell Gray, Bethany; Kelly, Linsley; Ahrens, Douglas P; Barry, Ashley P; Kratschmer, Christina; Levy, Matthew; Sullenger, Bruce A

2018-05-01

Therapies that can eliminate both local and metastatic prostate tumor lesions while sparing normal organ tissue are desperately needed. With the goal of developing an improved drug-targeting strategy, we turned to a new class of targeted anticancer therapeutics: aptamers conjugated to highly toxic chemotherapeutics. Cell selection for aptamers with prostate cancer specificity yielded the E3 aptamer, which internalizes into prostate cancer cells without targeting normal prostate cells. Chemical conjugation of E3 to the drugs monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) yields a potent cytotoxic agent that efficiently kills prostate cancer cells in vitro but does not affect normal prostate epithelial cells. Importantly, the E3 aptamer targets tumors in vivo and treatment with the MMAF-E3 conjugate significantly inhibits prostate cancer growth in mice, demonstrating the in vivo utility of aptamer-drug conjugates. Additionally, we report the use of antidotes to block E3 aptamer-drug conjugate cytotoxicity, providing a safety switch in the unexpected event of normal cell killing in vivo.

Estrogen receptor beta in prostate cancer: friend or foe?

PubMed

Nelson, Adam W; Tilley, Wayne D; Neal, David E; Carroll, Jason S

2014-08-01

Prostate cancer is the commonest, non-cutaneous cancer in men. At present, there is no cure for the advanced, castration-resistant form of the disease. Estrogen has been shown to be important in prostate carcinogenesis, with evidence resulting from epidemiological, cancer cell line, human tissue and animal studies. The prostate expresses both estrogen receptor alpha (ERA) and estrogen receptor beta (ERB). Most evidence suggests that ERA mediates the harmful effects of estrogen in the prostate, whereas ERB is tumour suppressive, but trials of ERB-selective agents have not translated into improved clinical outcomes. The role of ERB in the prostate remains unclear and there is increasing evidence that isoforms of ERB may be oncogenic. Detailed study of ERB and ERB isoforms in the prostate is required to establish their cell-specific roles, in order to determine if therapies can be directed towards ERB-dependent pathways. In this review, we summarise evidence on the role of ERB in prostate cancer and highlight areas for future research. © 2014 Society for Endocrinology.

Cholesterol and Prostate Cancer

PubMed Central

Pelton, Kristine; Freeman, Michael R.; Solomon, Keith R.

2012-01-01

Summary Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations. PMID:22824430

Nutrition therapy with high intensity interval training to improve prostate cancer-related fatigue in men on androgen deprivation therapy: a study protocol.

PubMed

Baguley, Brenton J; Skinner, Tina L; Leveritt, Michael D; Wright, Olivia R L

2017-01-03

Cancer-related fatigue is one of the most prevalent, prolonged and distressing side effects of prostate cancer treatment with androgen deprivation therapy. Preliminary evidence suggests natural therapies such as nutrition therapy and structured exercise prescription can reduce symptoms of cancer-related fatigue. Men appear to change their habitual dietary patterns after prostate cancer diagnosis, yet prostate-specific dietary guidelines provide limited support for managing adverse side effects of treatment. The exercise literature has shown high intensity interval training can improve various aspects of health that are typically impaired with androgen deprivation therapy; however exercise at this intensity is yet to be conducted in men with prostate cancer. The purpose of this study is to examine the effects of nutrition therapy beyond the current healthy eating guidelines with high intensity interval training for managing cancer-related fatigue in men with prostate cancer treated with androgen deprivation therapy. This is a two-arm randomized control trial of 116 men with prostate cancer and survivors treated with androgen deprivation therapy. Participants will be randomized to either the intervention group i.e. nutrition therapy and high intensity interval training, or usual care. The intervention group will receive 20 weeks of individualized nutrition therapy from an Accredited Practising Dietitian, and high intensity interval training (from weeks 12-20 of the intervention) from an Accredited Exercise Physiologist. The usual care group will maintain their standard treatment regimen over the 20 weeks. Both groups will undertake primary and secondary outcome testing at baseline, week 8, 12, and 20; testing includes questionnaires of fatigue and quality of life, objective measures of body composition, muscular strength, cardiorespiratory fitness, biomarkers for disease progression, as well as dietary analysis. The primary outcomes for this trial are measures of fatigue and quality of life. This study is the first of its kind to determine the efficacy of nutrition therapy above the healthy eating guidelines and high intensity interval training for alleviating prostate-cancer related fatigue. If successful, nutrition therapy and high intensity interval training may be proposed as an effective therapy for managing cancer-related fatigue and improving quality of life in men during and after prostate cancer treatment. Australian New Zealand Clinical Trials Registry ACTRN12615000512527 . Trial registered on the 22/5/2015.

Aptamers and apple pies: a mini-review of PSMA aptamers and lessons from Donald S. Coffey

PubMed Central

Lupold, Shawn E

2018-01-01

This mini-review article is part of a special issue dedicated to Donald S. Coffey, a pioneer translational research scientist, exemplary mentor, and leader in urologic and urologic oncology research. This article first briefly reflects on life and scientific lessons from Don Coffey. It then reviews the development of two prostate cancer targeting RNA aptamers, xPSM-A9 and xPSM-A10, through in vitro selection for aptamers that bind to the extracellular domain of the Prostate Specific Membrane Antigen (PSMA). These 2’-fluorpyrimidine RNA aptamers selectively bind PSMA on the surface of prostate cancer cells, inhibit PSMA glutamate carboxypeptidase activity, and internalize into PSMA-expressing cancer cells. The truncation of both aptamers, through experimentation as well as logical design, has produced smaller isoforms including A10-3, A10-3.2, A9g and A9L. The larger aptamer isoforms xPSM-A9 and xPSM-A10 are limited to production by in vitro transcription and polyacrylamide gel purification, while smaller isoforms can be generated by chemically synthesis. A series of aptamer conjugates have been developed through chemical crosslinking, complementary annealing strategies, or a combination of both, for the targeting of experimental therapeutics to and into prostate cancer cells. The resulting aptamer conjugates, including nanoparticles and siRNA conjugates, selectively target PSMA-positive prostate cancer cells and xenograft tumors, and demonstrate potent cytotoxic and tumoricidal activity. These experimental therapeutic agents provide a platform for realizing and optimizing the potential of tumor-selective targeting and drug delivery. PMID:29666835

Influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer.

PubMed

López, Escarlata; Lazo, Antonio; Gutiérrez, Antonio; Arregui, Gregorio; Núñez, Isabel; Sacchetti, Antonio

2015-01-01

To evaluate the influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer patients. Precise information on the extension of prostate cancer is crucial for the choice of an appropriate therapeutic strategy. (11)C-choline positron emission tomography ((11)C-choline PET/CT) has two roles in radiation oncology (RT): (1) patient selection for treatment and (2) target volume selection and delineation. In conjunction with high-accuracy techniques, it might offer an opportunity of dose escalation and better tumour control while sparing healthy tissues. We carried out a retrospective study in order to analyse RT planning modification based on (11)C-choline PET/CT in 16 prostate cancer patients. Patients were treated with hypofractionated step-and-shoot Intensity Modulated Radiotherapy (IMRT), or Volumetric Modulated Arc Therapy (VMAT), and a daily cone-beam CT for Image Guided Radiation Therapy (IGRT). All patients underwent a (11)C-choline-PET/CT scan prior to radiotherapy. In 37.5% of cases, a re-delineation and new dose prescription occurred. Data show good preliminary clinical results in terms of biochemical control and toxicity. No gastrointestinal (GI)/genitourinary (GU) grade III toxicities were observed after a median follow-up of 9.5 months. In our experience, concerning the treatment of prostate cancer (PCa), (11)C-choline PET/CT may be helpful in radiotherapy planning, either for dose escalation or exclusion of selected sites.

Genomic Basis of Prostate Cancer Health Disparity Among African-American Men

DTIC Science & Technology

2013-07-01

amplification and deletion) in a limited repertoire of genes Is highly predictive of prostate cancer metastasis. This signature is present in primary...laboratory has demonstrated that the specific genes within metastatic prostate cancers have been altered by amplification (increase in the copy number...or deletion (decrease in the copy number) (3). These genes appeared to have been selected by the advantages that they conveyed to tumors, such as

Overcoming Drug Resistant Prostate Cancer with APE1/Ref-1 Blockade

DTIC Science & Technology

2015-10-01

cells avoid being killed by chemotherapy: Apurinic/apyrimidinic endonuclease/ redox -factor 1, or simply, Ref-1, for short. In this report, we...survivin signaling in human prostate cancer specimens. Genetic knockdown of APE1/Ref-1 disrupts prostate cancer cell growth and survival in cell culture...In addition, inhibition of the redox function selectively of Ref-1 results in cell growth inhibition, with this therapy preferentially inhibiting

Overcoming Drug Resistant Prostate Cancer with APE1/Ref 1 Blockade

DTIC Science & Technology

2015-10-01

cells avoid being killed by chemotherapy: Apurinic/apyrimidinic endonuclease/ redox -factor 1, or simply, Ref-1, for short. In this report, we...survivin signaling in human prostate cancer specimens. Genetic knockdown of APE1/Ref-1 disrupts prostate cancer cell growth and survival in cell culture...In addition, inhibition of the redox function selectively of Ref-1 results in cell growth inhibition, with this therapy preferentially inhibiting

[Treatment for locally advanced prostate cancer: value of surgery].

PubMed

Azuma, Haruhito; Katsuoka, Yoji

2006-06-01

Surgical therapy is not only a therapeutic method but also an important procedure to provide useful information in determining a postoperative treatment strategy. Compared with postoperative cancer staging based on specimens obtained during surgery, more than 30% of cancers were inaccurately staged preoperatively, even when a current advanced diagnostic imaging technique was used. Compared with postoperative histological 30-40% of cancer staging were inaccurately staged based on a preoperative biopsy. These misstaging cases pose a significantly important problem. Approximately 15% and 30% of clinical stage C prostate cancers have been rated as pT2 and pN(+), respectively. Patients with pT3 prostate cancer who underwent radical prostatectomy had 5-year and 10-year overall survival rates of 82% and 67%, respectively, which were comparable to those in patients with pT2 prostate cancer (82% and 67%, respectively). However, patients with prostate cancer rated as pT4 and pN(+) had very poor outcomes with 5-year overall survival rates of 42.4% and 32.6%, respectively. Therefore, even in patients with stage C prostate cancer, surgical therapy should be recommended if no infiltration of adjacent tissue has been noted and the operation is applicable; and an optimal postoperative therapeutic strategy should be selected based on the accurate pathological staging and histological grading using postoperative pathological specimens. Such approaches will prevent unnecessary hormone therapy in patients with pT2 prostate cancer and prevent missing optimal timing for radical cure, as well as allowing appropriate therapy to be selected for patients with pT4 and pN(+) prostate cancer, for whom prognosis may be poor.

Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers.

PubMed

Xu, Yi; Dalrymple, Susan L; Becker, Robyn E; Denmeade, Samuel R; Isaacs, John T

2006-07-01

Prostatic dihydrotestosterone (DHT) concentration is regulated by precursors from systemic circulation and prostatic enzymes of androgen metabolism, particularly 5alpha-reductases (i.e., SRD5A1 and SRD5A2). Therefore, the levels of expression SRD5A1 and SRD5A2 and the antiprostatic cancer growth response to finasteride, a selective SRD5A2 inhibitor, versus the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, were compared. Real-time PCR and enzymatic assays were used to determine the levels of SRD5A1 and SRD5A2 in normal versus malignant rat and human prostatic tissues. Rats bearing the Dunning R-3327H rat prostate cancer and nude mice bearing LNCaP or PC-3 human prostate cancer xenografts were used as model systems. Tissue levels of testosterone and DHT were determined using liquid chromatography-mass spectrometry. Prostate cancer cells express undetectable to low levels of SRD5A2 but elevated levels of SRD5A1 activity compared with nonmalignant prostatic tissue. Daily oral treatment of rats with the SRD5A2 selective inhibitor, finasteride, reduces prostate weight and DHT content but did not inhibit R-3327H rat prostate cancer growth or DHT content in intact (i.e., noncastrated) male rats. In contrast, daily oral treatment with even a low 1 mg/kg/d dose of the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, reduces both normal prostate and H tumor DHT content and weight in intact rats while elevating tissue testosterone. Daily oral treatment with finasteride significantly (P < 0.05) inhibits growth of LNCaP human prostate cancer xenografts in intact male nude mice, but this inhibition is not as great as that by equimolar oral dosing with dutasteride. This anticancer efficacy is not equivalent, however, to that produced by castration. Only combination of dutasteride and castration produces a greater tumor inhibition (P < 0.05) than castration monotherapy against androgen-responsive LNCaP cancers. In contrast, no response was induced by dutasteride in nude mice bearing androgen-independent PC-3 human prostatic cancer xenografts. These results document that testosterone is not as potent as DHT but does stimulate prostate cancer growth, thus combining castration with dutasteride enhances therapeutic efficacy.

The 24th Annual Prostate Cancer Foundation scientific retreat report.

PubMed

Miyahira, Andrea K; Soule, Howard R

2018-05-15

The 24th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 5-7, 2017, at the Omni Shoreham Hotel in Washington, DC. The PCF Scientific Retreat is a scientific conference that specifically focuses on cutting edge research deemed to have significant promise for accelerating advances in prostate cancer biology and treatment. Themes highlighted at this year's meeting included: (i) new understandings in prostate cancer biology and disease progression; (ii) new mechanisms and treatment targets in advanced prostate cancer; (iii) advances in precision medicine genomics, germline genetics, and selection of targeted therapies; (iv) PSMA-targeted agents for PET imaging and radionuclide therapy; (v) approaches for improving the efficacy of immunotherapy in prostate cancer; (vi) applications of 3D Genomics in prostate cancer research; and (vii) potential applications of artificial intelligence in prostate cancer. This article reviews the research presented at the PCF Scientific Retreat, in order to improve understanding of the current state of prostate cancer research, encourage discourse and exchange of novel ideas, and stimulate new basic, translational, and clinical research that will ultimately improve the lives of patients. © 2018 Wiley Periodicals, Inc.

Prostate Cancer Relevant Antigens and Enzymes for Targeted Drug Delivery

PubMed Central

Barve, Ashutosh; Jin, Wei; Cheng, Kun

2014-01-01

Chemotherapy is one of the most widely used approaches in combating advanced prostate cancer, but its therapeutic efficacy is usually insufficient due to lack of specificity and associated toxicity. Lack of targeted delivery to prostate cancer cells is also the primary obstacles in achieving feasible therapeutic effect of other promising agents including peptide, protein, and nucleic acid. Consequently, there remains a critical need for strategies to increase the selectivity of anti-prostate cancer agents. This review will focus on various prostate cancer-specific antigens and enzymes that could be exploited for prostate cancer targeted drug delivery. Among various targeting strategies, active targeting is the most advanced approach to specifically deliver drugs to their designated cancer cells. In this approach, drug carriers are modified with targeting ligands that can specifically bind to prostate cancer-specific antigens. Moreover, there are several specific enzymes in the tumor microenvironment of prostate cancer that can be exploited for stimulus-responsive drug delivery systems. These systems can specifically release the active drug in the tumor microenvironment of prostate cancer, leading to enhanced tumor penetration efficiency. PMID:24878184

Selective nanoparticle-directed photothermal ablation of the canine prostate

NASA Astrophysics Data System (ADS)

Schwartz, Jon A.; Price, Roger E.; Gill-Sharp, Kelly L.; Sang, Krystina L.; Khorchani, Jennifer D.; Payne, J. Donald; Goodwin, Bradford S.

2011-03-01

This study adapted AuroLase® Therapy, previously reported for the treatment of brain tumors, to the treatment of prostate disease by 1) using normal canine prostate in vivo, directly injected with a solution of nanoparticles as a proxy for prostate tumor and, 2) developing an appropriate laser dosimetry for prostate which is which is subablative in native prostate while simultaneously producing photothermal coagulation in prostate tissue containing therapeutic nanoshells. Healthy, mixed-breed hound dogs were given surgical laparotomies during which nanoshells were injected directly into one or both prostate hemispheres. Laser energy was delivered percutaneously to the parenchyma of the prostate along 1-5 longitudinal tracts via a liquid-cooled optical fiber catheter terminated with a 1-cm isotropic diffuser after which the incision was closed and sutured using standard surgical techniques. The photothermal lesions were permitted to resolve for up to 8 days, after which each animal was euthanized, necropsied, and the prostate taken for histopathological analysis. We developed a laser dosimetry which is sub- to marginally ablative in native prostate and simultaneously ablative of prostate tissue containing nanoshells which would indicate a viable means of treating tumors of the prostate which are known from other studies to accumulate nanoshells. Secondly, we determined that multiple laser treatments of nanoshell-containing prostate tissue could be accomplished while sparing the urethra and prostate capsule thermal damage. Finally, we determined that the extent of damage zone radii correlate positively with nanoshell concentration, and negatively to the length of time between nanoshell injection and laser treatment.

Impact of resistance training on body composition and metabolic syndrome variables during androgen deprivation therapy for prostate cancer: a pilot randomized controlled trial.

PubMed

Dawson, Jacqueline K; Dorff, Tanya B; Todd Schroeder, E; Lane, Christianne J; Gross, Mitchell E; Dieli-Conwright, Christina M

2018-04-03

Prostate cancer patients on androgen deprivation therapy (ADT) experience adverse effects such as lean mass loss, known as sarcopenia, fat gain, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance training can increase lean mass, reduce body fat, and improve physical function and quality of life, but no exercise interventions in prostate cancer patients on ADT have concomitantly improved body composition and MetS. This pilot trial investigated 12 weeks of resistance training on body composition and MetS changes in prostate cancer patients on ADT. An exploratory aim examined if a combined approach of training and protein supplementation would elicit greater changes in body composition. Prostate cancer patients on ADT were randomized to resistance training and protein supplementation (TRAINPRO), resistance training (TRAIN), protein supplementation (PRO), or control stretching (STRETCH). Exercise groups (EXE = TRAINPRO, TRAIN) performed supervised exercise 3 days per week for 12 weeks, while non-exercise groups (NoEXE = PRO, STRETCH) performed a home-based stretching program. TRAINPRO and PRO received 50 g⋅day - 1 of whey protein. The primary outcome was change in lean mass assessed through dual energy x-ray absorptiometry. Secondary outcomes examined changes in sarcopenia, assessed through appendicular skeletal mass (ASM) index (kg/m 2 ), body fat %, strength, physical function, quality of life, MetS score and the MetS components of waist circumference, blood pressure, glucose, high-density lipoprotein-cholesterol, and triglyceride levels. A total of 37 participants were randomized; 32 participated in the intervention (EXE n = 13; NoEXE n = 19). At baseline, 43.8% of participants were sarcopenic and 40.6% met the criteria for MetS. Post-intervention, EXE significantly improved lean mass (d = 0.9), sarcopenia prevalence (d = 0.8), body fat % (d = 1.1), strength (d = 0.8-3.0), and prostate cancer-specific quality of life (d = 0.9) compared to NoEXE (p < 0.05). No significant differences were observed between groups for physical function or MetS-related variables except waist circumference (d = 0.8). A 12-week resistance training intervention effectively improved sarcopenia, body fat %, strength and quality of life in hypogonadal prostate cancer patients, but did not change MetS or physical function. PRO did not offer additional benefit in improving body composition. ClinicalTrials.gov: NCT01909440 . Registered 24 July 2013.

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanchard, Pierre, E-mail: pierre.blanchard@gustaveroussy.fr; University of Paris-Sud, Cancer Campus, Villejuif; Faivre, Laura

Purpose: The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Methods and Materials: Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was leftmore » to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). Results: A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. Conclusions: This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients.« less

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

PubMed

Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

2011-02-01

To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

Feasibility study using a Ni-Ti stent and electronic portal imaging to localize the prostate during radiotherapy.

PubMed

Carl, Jesper; Lund, Bente; Larsen, Erik Hoejkjaer; Nielsen, Jane

2006-02-01

A new method for localization of the prostate during external beam radiotherapy is presented. The method is based on insertion of a thermo-expandable Ni-Ti stent. The stent is originally developed for treatment of bladder outlet obstruction caused by benign hyperplasia. The radiological properties of the stent are used for precise prostate localization during treatment using electronic portal images. Patients referred for intended curative radiotherapy and having a length of their prostatic urethra in the range from 25 to 65 mm were included. Pairs of isocentric orthogonal portal images were used to determine the 3D position at eight different treatment sessions for each patient. Fourteen patients were enrolled in the study. The data obtained demonstrated that the stent position was representative of the prostate location. The stent may also improve delineation of the prostate GTV, and prevent obstruction of bladder outlet during treatment. Precision in localization of the stent was less than 1 mm. Random errors in stent position were left-right 1.6 mm, cranial-caudal 2.2 mm and anterior-posterior 3.2 mm. In four of 14 patients a dislocation of the stent to the bladder occurred. Dislocation only occurred in patients with length of prostatic urethra less than 40 mm. A new method for radiological high precision localization of the prostate during radiotherapy is presented. The method is based on insertion of a standard Ni-Ti thermo-expandable stent, designed for treatment of benign prostate hyperplasia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawton, Colleen A.F., E-mail: clawton@mcw.edu; Lin, Xiaolei; Hanks, Gerald E.

Purpose: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Methods and Materials: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelinmore » 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Results: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non–prostate cancer) did not differ (5% relative reduction, P=.48). Conclusions: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.« less

Inhibitory Ah Receptor-Androgen Receptor Crosstalk in Prostate Cancer

DTIC Science & Technology

2005-02-01

Balk,S.P. Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res. 59:2511-2515, 1999. 5. Ris...expression, 24-hydroxylase activity, and inhibition of growth hydrocarbon receptor modulators ( SARMs ) for treatment of breast by lca,25-dihydroxyvitamin D3...Safe, A. McDougal, M.S. Gupta, K. Ramamoorthy, Selective Ah [20] D.M. Peehl, R.J. Skowronski, G.K. Leung, S.T. Wong, T.A. Stamey, receptor modulators

Differential receptor dependencies: expression and significance of muscarinic M1 receptors in the biology of prostate cancer.

PubMed

Mannan Baig, Abdul; Khan, Naveed A; Effendi, Vardah; Rana, Zohaib; Ahmad, H R; Abbas, Farhat

2017-01-01

Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown its growth-promoting role in prostate cancer. Additional studies report the proliferative effect of the cholinergic agonist carbachol on prostate cancer by its agonistic action on CHRM3. This study shows that the type 1 acetylcholine muscarinic receptor (CHRM1) contributes toward the proliferation and growth of prostate cancer. We used growth and cytotoxic assays, the prostate cancer microarray database and CHRM downstream pathways' homology of CHRM subtypes to uncover multiple signals leading to the growth of prostate cancer. Growth assays showed that pilocarpine stimulates the proliferation of prostate cancer. Moreover, it shows that carbachol exerts an additional agonistic action on nicotinic cholinergic receptor of prostate cancer cells that can be blocked by tubocurarine. With the use of selective CHRM1 antagonists such as pirenzepine and dicyclomine, a considerable inhibition of proliferation of prostate cancer cell lines was observed in dose ranging from 15-60 µg/ml of dicyclomine. The microarray database of prostate cancer shows a dominant expression of CHRM1 in prostate cancer compared with other cholinergic subtypes. The bioinformatics of prostate cancer and CHRM pathways show that the downstream signalling include PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells. Our study suggests that antagonism of CHRM1 may be a potential therapeutic target against prostate cancer.

Smooth muscle cell-specific knockout of androgen receptor: a new model for prostatic disease.

PubMed

Welsh, Michelle; Moffat, Lindsey; McNeilly, Alan; Brownstein, David; Saunders, Philippa T K; Sharpe, Richard M; Smith, Lee B

2011-09-01

Androgen-driven stromal-epithelial interactions play a key role in normal prostate development and function as well as in the progression of common prostatic diseases such as benign prostatic hyperplasia and prostate cancer. However, exactly how, and via which cell type, androgens mediate their effects in the adult prostate remains unclear. This study investigated the role for smooth muscle (SM) androgen signaling in normal adult prostate homeostasis and function using mice in which androgen receptor was selectively ablated from prostatic SM cells. In adulthood the knockout (KO) mice displayed a 44% reduction in prostate weight and exhibited histological abnormalities such as hyperplasia, inflammation, fibrosis, and reduced expression of epithelial, SM, and stem cell identify markers (e.g. p63 reduced by 27% and Pten by 31%). These changes emerged beyond puberty and were not explained by changes in serum hormones. Furthermore, in response to exogenous estradiol, adult KO mice displayed an 8.5-fold greater increase in prostate weight than controls and developed urinary retention. KO mice also demonstrated a reduced response to castration compared with controls. Together these results demonstrate that prostate SM cells are vital in mediating androgen-driven stromal-epithelial interactions in adult mouse prostates, determining cell identity and function and limiting hormone-dependent epithelial cell proliferation. This novel mouse model provides new insight into the possible role for SM androgen action in prostate disease.

Expression and Genetic Variation in Neuroendocrine Signaling Pathways in Lethal and Nonlethal Prostate Cancer among Men Diagnosed with Localized Disease.

PubMed

Lu, Donghao; Carlsson, Jessica; Penney, Kathryn L; Davidsson, Sabina; Andersson, Swen-Olof; Mucci, Lorelei A; Valdimarsdóttir, Unnur; Andrén, Ove; Fang, Fang; Fall, Katja

2017-12-01

Background: Recent data suggest that neuroendocrine signaling pathways may play a role in the progression of prostate cancer, particularly for early-stage disease. We aimed to explore whether expression of selected genes in the adrenergic, serotoninergic, glucocorticoid, and dopaminergic pathways differs in prostate tumor tissue from men with lethal disease compared with men with nonlethal disease. Methods: On the basis of the Swedish Watchful Waiting Cohort, we included 511 men diagnosed with incidental prostate cancer through transurethral resection of the prostate during 1977-1998 with follow-up up to 30 years. For those with tumor tissue ( N = 262), we measured mRNA expression of 223 selected genes included in neuroendocrine pathways. Using DNA from normal prostate tissue ( N = 396), we genotyped 36 SNPs from 14 receptor genes. Lethal prostate cancer was the primary outcome in analyses with pathway gene expression and genetic variants. Results: Differential expression of genes in the serotoninergic pathway was associated with risk of lethal prostate cancer ( P = 0.007); similar but weaker associations were noted for the adrenergic ( P = 0.014) and glucocorticoid ( P = 0.020) pathways. Variants of the HTR2A (rs2296972; P = 0.002) and NR3CI (rs33388; P = 0.035) genes (within the serotoninergic and glucocorticoid pathways) were associated with lethal cancer in overdominant models. These genetic variants were correlated with expression of several genes in corresponding pathways ( P < 0.05). Conclusions: Our findings lend support to hypothesis that the neuroendocrine pathways, particularly serotoninergic pathway, are associated with lethal outcome in the natural course of localized prostate cancer. Impact: This study provides evidence of the role of neuroendocrine pathways in prostate cancer progression that may have clinical utility. Cancer Epidemiol Biomarkers Prev; 26(12); 1781-7. ©2017 AACR . ©2017 American Association for Cancer Research.

A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma.

PubMed

Windsor, Phyllis M; Nicol, Kathleen F; Potter, Joan

2004-08-01

Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental. Aerobic walking improves physical functioning and has been an intervention for chemotherapy-related fatigue. A prospective, randomized, controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma. Sixty-six men were randomized before they received radical radiotherapy for localized prostate carcinoma, with 33 men randomized to an exercise group and 33 men randomized to a control group. Outcome measures were fatigue and distance walked in a modified shuttle test before and after radiotherapy. There were no significant between group differences noted with regard to fatigue scores at baseline (P = 0.55) or after 4 weeks of radiotherapy (P = 0.18). Men in the control group had significant increases in fatigue scores from baseline to the end of radiotherapy (P = 0.013), with no significant increases observed in the exercise group (P = 0.203). A nonsignificant reduction (2.4%) in shuttle test distance at the end of radiotherapy was observed in the control group; however, in the exercise group, there was a significant increase (13.2%) in distance walked (P = 0.0003). Men who followed advice to rest and take things easy if they became fatigued demonstrated a slight deterioration in physical functioning and a significant increase in fatigue at the end of radiotherapy. Home-based, moderate-intensity walking produced a significant improvement in physical functioning with no significant increase in fatigue. Improved physical functioning may be necessary to combat radiation fatigue.

Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.

PubMed

Wen, Simeng; Chang, Hong-Chiang; Tian, Jing; Shang, Zhiqun; Niu, Yuanjie; Chang, Chawnshang

2015-02-01

The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers

PubMed Central

Abderrahman, Balkees; Curpan, Ramona F; Hawsawi, Yousef M; Fan, Ping; Jordan, V Craig

2018-01-01

Prostate and breast cancer are the two cancers with the highest incidence in men and women, respectively. Here, we focus on the known biology of acquired resistance to antihormone therapy of prostate and breast cancer and compare laboratory and clinical similarities in the evolution of the disease. Laboratory studies and clinical observations in prostate and breast cancer demonstrate that cell selection pathways occur during acquired resistance to antihormonal therapy. Following sex steroid deprivation, both prostate and breast cancer models show an initial increased acquired sensitivity to the growth potential of sex steroids. Subsequently, prostate and breast cancer cells either become dependent upon the antihormone treatment or grow spontaneously in the absence of hormones. Paradoxically, the physiologic sex steroids now kill a proportion of selected, but vulnerable, resistant tumor cells. The sex steroid receptor complex triggers apoptosis. We draw parallels between acquired resistance in prostate and breast cancer to sex steroid deprivation. Clinical observations and patient trials confirm the veracity of the laboratory studies. We consider therapeutic strategies to increase response rates in clinical trials of metastatic disease that can subsequently be applied as a preemptive salvage adjuvant therapy. The goal of future advances is to enhance response rates and deploy a safe strategy earlier in the treatment plan to save lives. The introduction of a simple evidence-based enhanced adjuvant therapy as a global healthcare strategy has the potential to control recurrence, reduce hospitalization, reduce healthcare costs and maintain a healthier population that contributes to society. PMID:29162647

Systemic GLIPR1-ΔTM protein as a novel therapeutic approach for prostate cancer.

PubMed

Karantanos, Theodoros; Tanimoto, Ryuta; Edamura, Kohei; Hirayama, Takahiro; Yang, Guang; Golstov, Alexei A; Wang, Jianxiang; Kurosaka, Shinji; Park, Sanghee; Thompson, Timothy C

2014-04-15

GLIPR1 is a p53 target gene known to be downregulated in prostate cancer, and increased endogenous GLIPR1 expression has been associated with increased production of reactive oxygen species, increased apoptosis, decreased c-Myc protein levels and increased cell cycle arrest. Recently, we found that upregulation of GLIPR1 in prostate cancer cells increases mitotic catastrophe through interaction with heat shock cognate protein 70 (Hsc70) and downregulation of Aurora kinase A and TPX2. In this study, we evaluated the mechanisms of recombinant GLIPR1 protein (glioma pathogenesis-related protein 1-transmembrane domain deleted [GLIPR1-ΔTM]) uptake by prostate cancer cells and the efficacy of systemic GLIPR1-ΔTM administration in a prostate cancer xenograft mouse model. GLIPR1-ΔTM was selectively internalized by prostate cancer cells, leading to increased apoptosis through reactive oxygen species production and to decreased c-Myc protein levels. Interestingly, GLIPR1-ΔTM was internalized through clathrin-mediated endocytosis in association with Hsc70. Systemic administration of GLIPR1-ΔTM significantly inhibited VCaP xenograft growth. GLIPR1-ΔTM showed no evidence of toxicity following elimination from mouse models 8 hr after injection. Our results demonstrate that GLIPR1-ΔTM is selectively endocytosed by prostate cancer cells, leading to increased reactive oxygen species production and apoptosis, and that systemic GLIPR1-ΔTM significantly inhibits growth of VCaP xenografts without substantial toxicity. © 2013 UICC.

Exercise effects on adipokines and the IGF axis in men with prostate cancer treated with androgen deprivation: A randomized study

PubMed Central

Mina, Daniel Santa; Connor, Michael K.; Alibhai, Shabbir M.H.; Toren, Paul; Guglietti, Crissa; Matthew, Andrew G.; Trachtenberg, John; Ritvo, Paul

2013-01-01

Background Androgen deprivation therapy (ADT) has significant deleterious effects on body composition that may be accompanied by unfavourable changes in adipokine levels. While exercise has been shown to improve a number of side effects associated with ADT for prostate cancer, no studies have assessed the effect of exercise on adiponectin and leptin levels, which have been shown to alter the mitogenic environment. Methods: Twenty-six men with prostate cancer treated with ADT were randomized to home-based aerobic exercise training or resistance exercise training for 24 weeks. Adiponectin, leptin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3) were analyzed by ELISA (enzyme-linked immunosorbent assay), in addition to physical activity volume, peak aerobic capacity, and anthropometric measurements, at baseline, 3 months and 6 months. Results: Resistance exercise significantly reduced IGF-1 after 3 months (p = 0.019); however, this change was not maintained at 6 months. At 6 months, IGFBP-3 was significantly increased compared to baseline for the resistance training group (p = 0.044). In an exploratory analysis of all exercisers, favourable changes in body composition and aerobic fitness were correlated with favourable levels of leptin, and favourable leptin:adiponectin and IGF-1:IGFBP-3 ratios at 3 and 6 months. Conclusions: Home-based exercise is correlated with positive changes in adipokine levels and the IGF-axis that may be related to healthy changes in physical fitness and body composition. While the improvements of adipokine markers appear to be more apparent with resistance training compared to aerobic exercise, these findings must be considered cautiously and require replication from larger randomized controlled trials to clarify the role of exercise on adipokines and IGF-axis proteins for men with prostate cancer. PMID:24282459

Feasibility, acceptability and preliminary psychological benefits of mindfulness meditation training in a sample of men diagnosed with prostate cancer on active surveillance: results from a randomized controlled pilot trial.

PubMed

Victorson, David; Hankin, Vered; Burns, James; Weiland, Rebecca; Maletich, Carly; Sufrin, Nathaniel; Schuette, Stephanie; Gutierrez, Bruriah; Brendler, Charles

2017-08-01

In a pilot randomized controlled trial, examine the feasibility and preliminary efficacy of an 8-week, mindfulness training program (Mindfulness Based Stress Reduction) in a sample of men on active surveillance on important psychological outcomes including prostate cancer anxiety, uncertainty intolerance and posttraumatic growth. Men were randomized to either mindfulness (n = 24) or an attention control arm (n = 19) and completed self-reported measures of prostate cancer anxiety, uncertainty intolerance, global quality of life, mindfulness and posttraumatic growth at baseline, 8 weeks, 6 months and 12 months. Participants in the mindfulness arm demonstrated significant decreases in prostate cancer anxiety and uncertainty intolerance, and significant increases in mindfulness, global mental health and posttraumatic growth. Participants in the control condition also demonstrated significant increases in mindfulness over time. Longitudinal increases in posttraumatic growth were significantly larger in the mindfulness arm than they were in the control arm. While mindfulness training was found to be generally feasible and acceptable among participants who enrolled in the 8-week intervention as determined by completion rates and open-ended survey responses, the response rate between initial enrollment and the total number of men approached was lower than desired (47%). While larger sample sizes are necessary to examine the efficacy of mindfulness training on important psychological outcomes, in this pilot study posttraumatic growth was shown to significantly increase over time for men in the treatment group. Mindfulness training has the potential to help men cope more effectively with some of the stressors and uncertainties associated with active surveillance. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Long-term supplementation of decaffeinated green tea extract does not modify body weight or abdominal obesity in a randomized trial of men at high risk for prostate cancer

PubMed Central

Kumar, Nagi B.; Patel, Roshni; Pow-Sang, Julio; Spiess, Philippe E.; Salup, Raoul; Williams, Christopher R.; Schell, Michael J.

2017-01-01

Background Evidence continues to demonstrate the role of obesity in prostate carcinogenesis and prognosis, underscoring the need to identify and continue to evaluate the effective interventions to reduce obesity in populations at high risk. The aim of the study was to determine the effect of daily consumption of decaffeinated green tea catechins (GTC) formulation (Polyphenon E® (PolyE)) for 1 year on biomarkers of obesity in men who are at high risk for prostate cancer. Materials and Methods A randomized, double-blinded trial was conducted targeting 97 men diagnosed with HGPIN or ASAP. Subjects were randomized to receive GTC (PolyE) (n = 49) or placebo (n = 48) for 1 year. Anthropometric data were collected at baseline, 6 and 12 months and data analyzed to observe change in weight, body mass index (indicator of obesity) and waist: hip ratio (indicator of abdominal obesity). Results Decaffeinated GTC containing 400 mgs of the bioactive catechin, EGCG administered for 1 year to men diagnosed with ASAP and HGPIN appears to be bioavailable, well tolerated but not effective in reducing biomarkers of obesity including body weight, body mass index and waist: hip ratio. Conclusions The results of our trial demonstrates that men who are obese and at high risk for prostate cancer should resort to effective weight management strategies to reduce obesity and not resort to ineffective measures such as taking supplements of green tea to reduce biomarkers of obesity. Changes in body mass index and abdominal obesity seen in other studies were potentially due to caffeine and not GTC. PMID:29228755

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial.

PubMed

Kyriakopoulos, Christos E; Chen, Yu-Hui; Carducci, Michael A; Liu, Glenn; Jarrard, David F; Hahn, Noah M; Shevrin, Daniel H; Dreicer, Robert; Hussain, Maha; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R; Vogelzang, Nicholas J; Picus, Joel; Cooney, Matthew M; Garcia, Jorge A; DiPaola, Robert S; Sweeney, Christopher J

2018-04-10

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m 2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

A urinary biomarker-based risk score correlates with multiparametric MRI for prostate cancer detection.

PubMed

Hendriks, Rianne J; van der Leest, Marloes M G; Dijkstra, Siebren; Barentsz, Jelle O; Van Criekinge, Wim; Hulsbergen-van de Kaa, Christina A; Schalken, Jack A; Mulders, Peter F A; van Oort, Inge M

2017-10-01

Prostate cancer (PCa) diagnostics would greatly benefit from more accurate, non-invasive techniques for the detection of clinically significant disease, leading to a reduction of over-diagnosis and over-treatment. The aim of this study was to determine the association between a novel urinary biomarker-based risk score (SelectMDx), multiparametric MRI (mpMRI) outcomes, and biopsy results for PCa detection. This retrospective observational study used data from the validation study of the SelectMDx score, in which urine was collected after digital rectal examination from men undergoing prostate biopsies. A subset of these patients also underwent a mpMRI scan of the prostate. The indications for performing mpMRI were based on persistent clinical suspicion of PCa or local staging after PCa was found upon biopsy. All mpMRI images were centrally reviewed in 2016 by an experienced radiologist blinded for the urine test results and biopsy outcome. The PI-RADS version 2 was used. In total, 172 patients were included for analysis. Hundred (58%) patients had PCa detected upon prostate biopsy, of which 52 (52%) had high-grade disease correlated with a significantly higher SelectMDx score (P < 0.01). The median SelectMDx score was significantly higher in patients with a suspicious significant lesion on mpMRI compared to no suspicion of significant PCa (P < 0.01). For the prediction of mpMRI outcome, the area-under-the-curve of SelectMDx was 0.83 compared to 0.66 for PSA and 0.65 for PCA3. There was a positive association between SelectMDx score and the final PI-RADS grade. There was a statistically significant difference in SelectMDx score between PI-RADS 3 and 4 (P < 0.01) and between PI-RADS 4 and 5 (P < 0.01). The novel urinary biomarker-based SelectMDx score is a promising tool in PCa detection. This study showed promising results regarding the correlation between the SelectMDx score and mpMRI outcomes, outperforming PCA3. Our results suggest that this risk score could guide clinicians in identifying patients at risk for significant PCa and selecting patients for further radiological diagnostics to reduce unnecessary procedures. © 2017 Wiley Periodicals, Inc.

The Utility of PET/CT in the Planning of External Radiation Therapy for Prostate Cancer.

PubMed

Calais, Jeremie; Cao, Minsong; Nickols, Nicholas G

2018-04-01

Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising level of prostate-specific antigen after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, the irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and the salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of PET into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. 18 F-FDG PET/CT is now routinely used in radiation planning for several cancer types. However, 18 F-FDG PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include 18 F-sodium fluoride, 11 C-acetate, 11 C- or 18 F-choline, 18 F-fluciclovine, and 68 Ga- or 18 F-labeled ligands that bind prostate-specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific but have not yet received Food and Drug Administration New Drug Application approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT-aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of 18 F-fluciclovine PET/CT for planning of salvage radiotherapy with clinical endpoints are under way. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Effects of pumpkin seed oil and saw palmetto oil in Korean men with symptomatic benign prostatic hyperplasia.

PubMed

Hong, Heeok; Kim, Chun-Soo; Maeng, Sungho

2009-01-01

This study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia. For this purpose, a randomized, double-blind, placebo-controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8. Subjects received either sweet potato starch (group A, placebo, 320 mg/day), pumpkin seed oil (group B, 320 mg/day), saw palmetto oil (group C, 320 mg/day) or pumpkin seed oil plus saw palmetto oil (group D, each 320 mg/day). International prostate symptom score, quality of life, serum prostate specific antigen, prostate volume and maximal urinary flow rate were measured. In groups B, C and D, the international prostate symptom score were reduced by 3 months. Quality of life score was improved after 6 months in group D, while those of groups B and C were improved after 3 months, compared to the baseline value. Serum prostate specific antigen was reduced only in group D after 3 months, but no difference was observed in prostate volume in all treatment groups. Maximal urinary flow rate were gradually improved in groups B and C, with statistical significance after 6 months in group B and after 12 months in group C. None of the parameters were significantly improved by combined treatment with pumpkin seed oil and saw palmetto oil. From these results, it is suggested that administrations of pumpkin seed oil and saw palmetto oil are clinically safe and may be effective as complementary and alternative medicine treatments for benign prostatic hyperplasia.

Effects of pumpkin seed oil and saw palmetto oil in Korean men with symptomatic benign prostatic hyperplasia

PubMed Central

Hong, Heeok; Kim, Chun-Soo

2009-01-01

This study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia. For this purpose, a randomized, double-blind, placebo-controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8. Subjects received either sweet potato starch (group A, placebo, 320 mg/day), pumpkin seed oil (group B, 320 mg/day), saw palmetto oil (group C, 320 mg/day) or pumpkin seed oil plus saw palmetto oil (group D, each 320 mg/day). International prostate symptom score, quality of life, serum prostate specific antigen, prostate volume and maximal urinary flow rate were measured. In groups B, C and D, the international prostate symptom score were reduced by 3 months. Quality of life score was improved after 6 months in group D, while those of groups B and C were improved after 3 months, compared to the baseline value. Serum prostate specific antigen was reduced only in group D after 3 months, but no difference was observed in prostate volume in all treatment groups. Maximal urinary flow rate were gradually improved in groups B and C, with statistical significance after 6 months in group B and after 12 months in group C. None of the parameters were significantly improved by combined treatment with pumpkin seed oil and saw palmetto oil. From these results, it is suggested that administrations of pumpkin seed oil and saw palmetto oil are clinically safe and may be effective as complementary and alternative medicine treatments for benign prostatic hyperplasia. PMID:20098586

A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.

PubMed

Petimar, Joshua; Wilson, Kathryn M; Wu, Kana; Wang, Molin; Albanes, Demetrius; van den Brandt, Piet A; Cook, Michael B; Giles, Graham G; Giovannucci, Edward L; Goodman, Gary E; Goodman, Phyllis J; Håkansson, Niclas; Helzlsouer, Kathy; Key, Timothy J; Kolonel, Laurence N; Liao, Linda M; Männistö, Satu; McCullough, Marjorie L; Milne, Roger L; Neuhouser, Marian L; Park, Yikyung; Platz, Elizabeth A; Riboli, Elio; Sawada, Norie; Schenk, Jeannette M; Tsugane, Shoichiro; Verhage, Bas; Wang, Ying; Wilkens, Lynne R; Wolk, Alicja; Ziegler, Regina G; Smith-Warner, Stephanie A

2017-08-01

Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear. Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model. Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index. Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer. Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR . ©2017 American Association for Cancer Research.

Androgen Deprivation Accelerates the Prostatic Urethra Wound Healing After Thulium Laser Resection of the Prostate by Promoting Re-Epithelialization and Regulating the Macrophage Polarization.

PubMed

Wang, Xing-Jie; Zhuo, Jian; Luo, Guang-Heng; Zhu, Yi-Ping; Yu, Dian-Jun; Zhao, Rui-Zhe; Jiang, Chen-Yi; Shi, Yun-Feng; Li, Hao; Chen, Lei; Hao, Kui-Yuan; Han, Xia; Zhao, Sheng; Bei, Xiao-Yu; Jing, Yi-Feng; Xia, Shu-Jie

2017-05-01

Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Deep Learning Role in Early Diagnosis of Prostate Cancer

PubMed Central

Reda, Islam; Khalil, Ashraf; Elmogy, Mohammed; Abou El-Fetouh, Ahmed; Shalaby, Ahmed; Abou El-Ghar, Mohamed; Elmaghraby, Adel; Ghazal, Mohammed; El-Baz, Ayman

2018-01-01

The objective of this work is to develop a computer-aided diagnostic system for early diagnosis of prostate cancer. The presented system integrates both clinical biomarkers (prostate-specific antigen) and extracted features from diffusion-weighted magnetic resonance imaging collected at multiple b values. The presented system performs 3 major processing steps. First, prostate delineation using a hybrid approach that combines a level-set model with nonnegative matrix factorization. Second, estimation and normalization of diffusion parameters, which are the apparent diffusion coefficients of the delineated prostate volumes at different b values followed by refinement of those apparent diffusion coefficients using a generalized Gaussian Markov random field model. Then, construction of the cumulative distribution functions of the processed apparent diffusion coefficients at multiple b values. In parallel, a K-nearest neighbor classifier is employed to transform the prostate-specific antigen results into diagnostic probabilities. Finally, those prostate-specific antigen–based probabilities are integrated with the initial diagnostic probabilities obtained using stacked nonnegativity constraint sparse autoencoders that employ apparent diffusion coefficient–cumulative distribution functions for better diagnostic accuracy. Experiments conducted on 18 diffusion-weighted magnetic resonance imaging data sets achieved 94.4% diagnosis accuracy (sensitivity = 88.9% and specificity = 100%), which indicate the promising results of the presented computer-aided diagnostic system. PMID:29804518

Defining Aggressive Prostate Cancer Using a 12-Gene Model1

PubMed Central

Riva, Alberto; Kim, Robert; Varambally, Sooryanarayana; He, Le; Kutok, Jeff; Aster, Jonathan C; Tang, Jeffery; Kuefer, Rainer; Hofer, Matthias D; Febbo, Phillip G; Chinnaiyan, Arul M; Rubin, Mark A

2006-01-01

Abstract The critical clinical question in prostate cancer research is: How do we develop means of distinguishing aggressive disease from indolent disease? Using a combination of proteomic and expression array data, we identified a set of 36 genes with concordant dysregulation of protein products that could be evaluated in situ by quantitative immunohistochemistry. Another five prostate cancer biomarkers were included using linear discriminant analysis, we determined that the optimal model used to predict prostate cancer progression consisted of 12 proteins. Using a separate patient population, transcriptional levels of the 12 genes encoding for these proteins predicted prostate-specific antigen failure in 79 men following surgery for clinically localized prostate cancer (P = .0015). This study demonstrates that cross-platform models can lead to predictive models with the possible advantage of being more robust through this selection process. PMID:16533427

Discovery of Novel Gene Elements Associated with Prostate Cancer Progression

DTIC Science & Technology

2014-12-01

consent under an Institutional Review Board (IRB) approved protocol at the University of Michigan [SPORE in Prostate Cancer (Tissue/Serum/Urine) Bank IRB...1994-0481]. For the Weill Cornell Medical College patient samples, prostate tissues were collected as part of an IRB- approved protocol at Weill...PCAT-1 or nontargeting short hairpin RNA (shRNA) lentiviral constructs for 48 hours. GFPþ cells were drug -selected using 1 mg/mL puromycin. PCAT-1

Novel Biomarker Discovery for Diagnostic and Therapeutic Strategies in Prostate Cancer

DTIC Science & Technology

2015-06-01

PURPOSE: to identify high affinity aptamers that distinguish between prostate cancers that are likely to remain organ- confined and those with potential to...metastasize. SCOPE: This was a pilot project to generate RNA aptamers that selectively react with a prostate cancer cell line that remains confined... Aptamer -Facilitated Biomarker Discovery (AptaBiD) technology. TASKS AND PROGRESS: (1) Non-metastatic LNCaP-Pro-5 cells, metastasis-prone LNCaP-LN3

HBCU Summer Undergraduate Training Program in Prostate Cancer: A Partnership Between USU-CPDR and UDC

DTIC Science & Technology

2015-10-02

conferences. 3 BODY Task 1: Selection Process: USU-CPDR summer internship program announcements for 2015 were made at the UDC through...AD_________________ Award Number: W81XWH-14-2-0142 TITLE: HBCU Summer Undergraduate Training Program in Prostate Cancer: A Partnership Between...DATES COVERED (From - To) 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE: HBCU Summer Undergraduate Training Program in Prostate Cancer: A Partnership

Glyphosate Vedotin for Treatment of Bone Metastatic Castration-Resistant Prostate Cancer

DTIC Science & Technology

2015-07-01

eventual death. However, there is no effective treatment available for bone metastatic CRPC. In this project, we propose to create a new drug and test...its selective anti-cancer effects in the cultured prostate cancer cell lines (Specific Aim 1) and in the bone tumor animal models that mimic human...prostate cancer patients. However, there is no effective treatment available for bone metastatic CRPC. The existing FDA-approved therapies only extend

Commentary on "the E3 ubiquitin ligase Siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity." Qi J, Tripathi M, Mishra R, Sahgal N, Fazli L, Ettinger S, Placzek WJ, Claps G, Chung LW, Bowtell D, Gleave M, Bhowmick N, Ronai ZA, Signal Transduction Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.: Cancer Cell 2013;23(6):332-46.

PubMed

Olumi, Aria F

2014-02-01

Understanding the mechanism underlying the regulation of the androgen receptor (AR), a central player in the development of castration-resistant prostate cancer (CRPC), holds promise for overcoming the challenge of treating CRPC. We demonstrate that the ubiquitin ligase Siah2 targets a select pool of NCOR1-bound, transcriptionally-inactive AR for ubiquitin-dependent degradation, thereby promoting expression of select AR target genes implicated in lipid metabolism, cell motility, and proliferation. Siah2 is required for prostate cancer cell growth under androgen-deprivation conditions in vitro and in vivo, and Siah2 inhibition promotes prostate cancer regression upon castration. Notably, Siah2 expression is markedly increased in human CRPCs. Collectively, we find that selective regulation of AR transcriptional activity by the ubiquitin ligase Siah2 is important for CRPC development. Copyright © 2014 Elsevier Inc. All rights reserved.

Prostate cancer stem cells: from theory to practice.

PubMed

Adamowicz, Jan; Pakravan, Katayoon; Bakhshinejad, Babak; Drewa, Tomasz; Babashah, Sadegh

2017-04-01

None of the generally accepted theories on prostate cancer development can fully explain many distinguishing features of the disease, such as intratumoral heterogeneity, metastatic growth, drug resistance and tumor relapse. Prostate stem cells are a heterogeneous and small subpopulation of self-renewing cells which can actively proliferate in response to changes in the androgen level and give rise to all the cell lineages that build the prostate epithelium. According to the cancer stem cell hypothesis, prostate cancer could be a stem cell disease. Prostate cancer stem cells, which represent only a minimal percentage of the tumor mass, are characterized by a markedly increased clonogenicity and therapeutic resistance. These tumor-initiating cells reside in dynamic niches distributed within the prostate but at a higher concentration in proximal regions of the prostatic ducts. Several markers have been used to identify prostate cancer stem cells. Nevertheless, a definitive profile has not yet been established owing to specificity issues. As cancer stem cells play determining roles in the birth and burst of prostate malignancy, strategies that selectively target them have gained huge clinical attention. Unraveling the mechanisms underlying the physiological functions of cancer stem cells and gaining fundamental insights into their putative involvement in the pathogenesis of prostate tumors provide novel opportunities for the development of efficient and sophisticated therapeutic strategies in the future.

Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

PubMed

Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

2016-01-01

In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Population-Based Study of Cardiovascular Mortality Among Patients With Prostate Cancer Treated With Radical External Beam Radiation Therapy With and Without Adjuvant Androgen Deprivation Therapy at the British Columbia Cancer Agency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Julian; Vaid, Moninder; Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca

2011-07-01

Purpose: There are conflicting studies of the impact of androgen deprivation therapy (ADT) on cardiovascular (CV) mortality among prostate cancer patients receiving curative intent external beam radiation therapy (EBRT). We assessed the impact of ADT on CV mortality in patients treated in British Columbia. Methods and Materials: Provincial pharmacy and radiotherapy databases were linked to the provincial cancer registry, and defined a cohort of patients treated with curative intent EBRT between 1998 and 2005. We determined the duration of ADT and the cumulative incidence of CV death. We compared death from CV disease with and without ADT, and by durationmore » of ADT using competing risk analysis and Fine and Gray multivariant analysis. A total of 600 randomly selected patients were reviewed to determine baseline CV disease, CV risk factors, and Charlson Index. Results: Of 5,948 prostate cancer patients treated with radical intent EBRT, of whom 1,933 were treated without ADT, 674 received ADT for {<=}6 months and 3,341 received > 6 months of ADT. The cumulative CV mortality at 7 years was 2.6% (95% confidence interval [CI] 1.9-3.5%), 2.1% (95% CI = 1.2-3.5%), and 1.4 (95% CI = 1.0-2.0%) for patients with no ADT, {<=}6 months of ADT, and >6 months of ADT, respectively (Gray's p = 0.002). Baseline CV disease and risk factors were more prevalent in the no-ADT group compared with the >6-month ADT group. Conclusions: This study demonstrated a lower CV mortality rate among patients treated with longer durations of ADT than those treated without ADT. These differences likely relate to selection of patients for ADT rather than effect of ADT itself.« less

Texture analysis of tissues in Gleason grading of prostate cancer

NASA Astrophysics Data System (ADS)

Alexandratou, Eleni; Yova, Dido; Gorpas, Dimitris; Maragos, Petros; Agrogiannis, George; Kavantzas, Nikolaos

2008-02-01

Prostate cancer is a common malignancy among maturing men and the second leading cause of cancer death in USA. Histopathological grading of prostate cancer is based on tissue structural abnormalities. Gleason grading system is the gold standard and is based on the organization features of prostatic glands. Although Gleason score has contributed on cancer prognosis and on treatment planning, its accuracy is about 58%, with this percentage to be lower in GG2, GG3 and GG5 grading. On the other hand it is strongly affected by "inter- and intra observer variations", making the whole process very subjective. Therefore, there is need for the development of grading tools based on imaging and computer vision techniques for a more accurate prostate cancer prognosis. The aim of this paper is the development of a novel method for objective grading of biopsy specimen in order to support histopathological prognosis of the tumor. This new method is based on texture analysis techniques, and particularly on Gray Level Co-occurrence Matrix (GLCM) that estimates image properties related to second order statistics. Histopathological images of prostate cancer, from Gleason grade2 to Gleason grade 5, were acquired and subjected to image texture analysis. Thirteen texture characteristics were calculated from this matrix as they were proposed by Haralick. Using stepwise variable selection, a subset of four characteristics were selected and used for the description and classification of each image field. The selected characteristics profile was used for grading the specimen with the multiparameter statistical method of multiple logistic discrimination analysis. The subset of these characteristics provided 87% correct grading of the specimens. The addition of any of the remaining characteristics did not improve significantly the diagnostic ability of the method. This study demonstrated that texture analysis techniques could provide valuable grading decision support to the pathologists, concerning prostate cancer prognosis.

A Prospective Study of Chronic Inflammation in Benign Prostate Tissue and Risk of Prostate Cancer: Linked PCPT and SELECT Cohorts

PubMed Central

Platz, Elizabeth A.; Kulac, Ibrahim; Barber, John R.; Drake, Charles G.; Joshu, Corinne E.; Nelson, William G.; Lucia, M. Scott; Klein, Eric A.; Lippman, Scott M.; Parnes, Howard L.; Thompson, Ian M.; Goodman, Phyllis J.; Tangen, Catherine M.; De Marzo, Angelo M.

2017-01-01

Background We leveraged two trials to test the hypothesis of an inflammation-prostate cancer link prospectively in men without indication for biopsy. Methods Prostate Cancer Prevention Trial (PCPT) participants who had an end-of-study biopsy performed per protocol that was negative for cancer and who subsequently enrolled in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were eligible. We selected all 100 cases and sampled 200 frequency-matched controls and used PCPT end-of-study biopsies as “baseline”. Five men with PSA >4 ng/mL at end-of-study biopsy were excluded. Tissue was located for 92 cases and 193 controls. We visually assessed inflammation in benign tissue. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression adjusting for age and race. Results Mean time between biopsy and diagnosis was 5.9 years. In men previously in the PCPT placebo arm, 78.1% of cases (N=41) and 68.2% of controls (N=85) had at least one baseline biopsy core (~5 evaluated per man) with inflammation. The odds of prostate cancer (N=41 cases) appeared to increase with increasing mean percentage of tissue area with inflammation, a trend that was statistically significant for Gleason sum <4+3 disease (N=31 cases; versus 0%, >0–<1.8% OR=1.70, 1.8%–<5.0% OR=2.39, ≥5% OR=3.31, p-trend=0.047). In men previously in the finasteride arm, prevalence of inflammation did not differ between cases (76.5%; N=51) and controls (75.0%; N=108). Conclusions Benign tissue inflammation was positively associated with prostate cancer. Impact This first prospective study of men without biopsy indication supports the hypothesis that inflammation influences prostate cancer development. PMID:28754796

Imaging Prostate Cancer With Prostate-Specific Membrane Antigen PET/CT and PET/MRI: Current and Future Applications.

PubMed

Hope, Thomas A; Afshar-Oromieh, Ali; Eiber, Matthias; Emmett, Louise; Fendler, Wolfgang P; Lawhn-Heath, Courtney; Rowe, Steven P

2018-06-27

The purpose of this article is to describe the large number of radiotracers being evaluated for prostate-specific membrane antigen (PSMA) PET, which is becoming a central tool in the staging of prostate cancer. PSMA PET is a highly promising modality for the staging of prostate cancer because of its higher detection rate compared with that of conventional imaging. Both PET/CT and PET/MRI offer benefits with PSMA radiotracers, and PSMA PET findings frequently lead to changes in management. It is imperative that subsequent treatment changes be evaluated to show improved outcomes. PSMA PET also has potential applications, including patient selection for PSMA-based radioligand therapy and evaluation of treatment response.

Watchful waiting and factors predictive of secondary treatment of localized prostate cancer.

PubMed

Wu, Hongyan; Sun, Leon; Moul, Judd W; Wu, Hong Yu; McLeod, David G; Amling, Christopher; Lance, Raymond; Kusuda, Leo; Donahue, Timothy; Foley, John; Chung, Andrew; Sexton, Wade; Soderdahl, Douglas

2004-03-01

Watchful waiting remains an important treatment option for some patients with localized prostate cancer. We defined the demographic, clinical and outcome features of men selecting watchful waiting as an initial treatment strategy, and determined factors predictive of eventual progression to secondary treatment. Of 8390 patients diagnosed with prostate cancer from 1990 to 2001 in the Department of Defense Center for Prostate Disease Research Database, 1158 patients chose watchful waiting as initial treatment. The demographic and clinical differences between patients on watchful waiting and those choosing other initial treatments were compared using the chi-square test. Secondary treatment-free survival according to various prognostic factors was plotted using the Kaplan-Meier method and differences were tested using the log rank test. A multivariate Cox proportional hazards regression analysis was performed to determine which factors were independent predictors of secondary treatment. Compared to other patients, those selecting watchful waiting were older, had lower prostate specific antigen (PSA) at diagnosis, and were more likely to have lower stage (cT1) and lower grade (Gleason sum 7 or less) cancers. Age, PSA and clinical stage were all significant and independent predictors of secondary treatment. The relative risk of secondary treatment can be expressed as EXP (-0.034 x age at diagnosis + 0.284 x LOG (diagnostic PSA) + 0.271 x clinical stage T2 + 0.264 x clinical stage T3). Men who elect watchful waiting as initial management for prostate cancer are older with lower Gleason sums and serum PSA. In these men, age at diagnosis, serum PSA and clinical stage are the most significant predictors of requiring or selecting secondary treatment.

Plant extracts: sense or nonsense?

PubMed

Madersbacher, Stephan; Berger, Ingrid; Ponholzer, Anton; Marszalek, Martin

2008-01-01

To assess the current role of plant extracts in the medical management of lower urinary tract symptoms due to benign prostatic enlargement/benign prostatic obstruction. In 2006, two clinical trials meeting the WHO benign prostatic hyperplasia consensus conference criteria (randomized against placebo/standard therapy, study duration 12 months) were published. One trial compared a saw palmetto extract with placebo. This industry-independent trial published in the New England Journal of Medicine was negative, that is, this saw palmetto extract had no effect on symptoms, Qmax and postvoid residual volume. In another trial, a saw palmetto/urtica combination was compared with tamsulosin. After 12 months, the improvement of symptoms was identical in both study arms. No detailed data were presented, however, on Qmax, postvoid residual or prostate volume. The biological mechanisms of plant extracts in vivo are still unknown and the numerous metaanalyses cannot supplement high-quality prospective trials. Further prospective studies according to WHO benign prostatic hyperplasia standards are required to reliably determine the role of plant extracts in contemporary lower urinary tract symptoms management and to be able to answer the question in the title: 'plant extracts: sense or nonsense?' Plant extracts are currently not recommended by the American and European Association of Urology benign prostatic hyperplasia guidelines.

Design of FRESH START: A Randomized Trial of Exercise and Diet among Cancer Survivors.

ERIC Educational Resources Information Center

Demark-Wahnefried, Wendy; Clipp, Elizabeth C.; McBride, Colleen; Lobach, David F.; Lipkus, Isaac; Peterson, Bercedis; Snyder, Denise Clutter; Sloane, Richard; Arbanas, Jennifer; Kraus, William E.

2003-01-01

Fresh Start is a randomized, controlled trial that will test whether personally tailored, distance-medicine-based programs will increase exercise and fruit and vegetable consumption and decrease fat intake among individuals recently diagnosed with breast or prostate cancer. People from hospital cancer registries and oncologic practices will…

Behavioral stress accelerates prostate cancer development in mice

PubMed Central

Hassan, Sazzad; Karpova, Yelena; Baiz, Daniele; Yancey, Dana; Pullikuth, Ashok; Flores, Anabel; Register, Thomas; Cline, J. Mark; D’Agostino, Ralph; Danial, Nika; Datta, Sandeep Robert; Kulik, George

2013-01-01

Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress–prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor involution both in phosphatase and tensin homolog–deficient (PTEN-deficient) prostate cancer xenografts treated with PI3K inhibitor and in prostate tumors of mice with prostate-restricted expression of c-MYC (Hi-Myc mice) subjected to androgen ablation therapy with bicalutamide. Additionally, stress accelerated prostate cancer development in Hi-Myc mice. The effects of stress were prevented by treatment with the selective β2-adrenergic receptor (ADRB2) antagonist ICI118,551 or by inducible expression of PKA inhibitor (PKI) or of BCL2-associated death promoter (BAD) with a mutated PKA phosphorylation site (BADS112A) in xenograft tumors. Effects of stress were also blocked in Hi-Myc mice expressing phosphorylation-deficient BAD (BAD3SA). These results demonstrate interactions between prostate tumors and the psychosocial environment mediated by activation of an adrenaline/ADRB2/PKA/BAD antiapoptotic signaling pathway. Our findings could be used to identify prostate cancer patients who could benefit from stress reduction or from pharmacological inhibition of stress-induced signaling. PMID:23348742

Entertainment Education for Prostate Cancer Screening: A Randomized Trial among Primary Care Patients with Low Health Literacy

PubMed Central

Volk, Robert J.; Jibaja-Weiss, Maria L.; Hawley, Sarah T.; Kneuper, Suzanne; Spann, Stephen J.; Miles, Brian J.; Hyman, David J.

2008-01-01

Objective To evaluate an entertainment-based patient decision aid for prostate cancer screening among patients with low or high health literacy. Methods Male primary care patients from two clinical sites, one characterized as serving patients with low health literacy (n=149) and the second as serving patients with high health literacy (n=301), were randomized to receive an entertainment-based decision aid for prostate cancer screening or an audiobooklet-control aid with the same learner content but without the entertainment features. Postintervention and 2-week follow-up assessments were conducted. Results Patients at the low-literacy site were more engaged with the entertainment-based aid than patients at the high-literacy site. Overall, knowledge improved for all patients. Among patients at the low-literacy site, the entertainment-based aid was associated with lower decisional conflict and greater self-advocacy (i.e., mastering and obtaining information about screening) when compared to patients given the audiobooklet. No differences between the aids were observed for patients at the high-literacy site. Conclusions Entertainment education may be an effective strategy for promoting informed decision making about prostate cancer screening among patients with lower health literacy. Practice Implications As barriers to implementing computer-based patient decision support programs decrease, alternative models for delivering these programs should be explored. PMID:18760888

Is effective a prior multiparametric magnetic resonance scan in patients candidates to prostate biopsy? CAT Study.

PubMed

Ramos Rodríguez, J R; Molinero Pérez, M; Herrera Imbroda, B; Domínguez Pinos, M D

2016-01-01

We carried out a critically appraised topic (CAT)-type study to determine whether the relevant scientific evidence supports the recommendation of doing a multiparametric magnetic resonance imaging study of the prostate in all patients who are candidates for prostate biopsy with the aim of improving the detection of clinically significant prostate cancer and stratifying patients to receive active surveillance or treatment. After a formal literature search and an analysis of the two most relevant articles it found, we reached the conclusion that, despite promising results that point to the potential usefulness of this approach, there is still not enough clear scientific evidence to endorse it categorically. Before this approach can be endorsed, we need evidence from well-designed prospective randomized trials using widely agreed upon criteria and including large numbers of patients at multiple centers. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Monoamine Oxidase Deficiency Causes Prostate Atrophy and Reduces Prostate Progenitor Cell Activity.

PubMed

Yin, Lijuan; Li, Jingjing; Liao, Chun-Peng; Jason Wu, Boyang

2018-04-10

Monoamine oxidases (MAOs) degrade a number of biogenic and dietary amines, including monoamine neurotransmitters, and play an essential role in many biological processes. Neurotransmitters and related neural events have been shown to participate in the development, differentiation, and maintenance of diverse tissues and organs by regulating the specialized cellular function and morphological structures of innervated organs such as the prostate. Here we show that mice lacking both MAO isoforms, MAOA and MAOB, exhibit smaller prostate mass and develop epithelial atrophy in the ventral and dorsolateral prostates. The cellular composition of prostate epithelium showed reduced CK5 + or p63 + basal cells, accompanied by lower Sca-1 expression in p63 + basal cells, but intact differentiated CK8 + luminal cells in MAOA/B-deficient mouse prostates. MAOA/B ablation also decreased epithelial cell proliferation without affecting cell apoptosis in mouse prostates. Using a human prostate epithelial cell line, we found that stable knockdown of MAOA and MAOB impaired the capacity of prostate stem cells to form spheres, coinciding with a reduced CD133 + /CD44 + /CD24 - stem cell population and less expression of CK5 and select stem cell markers, including ALDH1A1, TROP2, and CD166. Alternative pharmacological inhibition of MAOs also repressed prostate cell stemness. In addition, we found elevated expression of MAOA and MAOB in epithelial and/or stromal components of human prostate hyperplasia samples compared with normal prostate tissues. Taken together, our findings reveal critical roles for MAOs in the regulation of prostate basal progenitor cells and prostate maintenance. Stem Cells 2018. © AlphaMed Press 2018.

The Role of the Urologist in Treating Patients with Hormone-Refractory Prostate Cancer

PubMed Central

Crawford, E. David

2003-01-01

Objectives: To ascertain what percentage of urologists’ oncology practice is dedicated to the care of prostate cancer patients and to determine urologists’ attitudes towards the treatment of patients with metastatic and hormone-refractory prostate cancer (HRPC). An additional objective is to determine urologists’ interest in administering various types of chemotherapy in HRPC patients. Materials and Methods: The American Urological Association (AUA) directory of practicing urologists was obtained, and 3000 randomly selected members of the AUA, as well as the complete list of 168 Society of Urologic Oncology (SUO) members, were chosen for the mailing of a 16-item questionnaire. The urologists were asked about how many of their patients have prostate cancer, how many have metastatic disease, and how many have HRPC and are currently receiving intravenous (IV) chemotherapy. In addition, the urologists were queried regarding their level of interest in learning about chemotherapy options as well as learning how to administer chemotherapy. Results: A total of 654 survey questionnaires were completed and returned for tabulation, resulting in a 21% effective response rate. Sixty-four percent of the responding urologists’ cancer patients had prostate cancer, 21% had metastatic disease, and 19% had HRPC; only 4% of the urologists currently administer IV chemotherapy themselves. When asked to describe their interest in learning how to deliver and be reimbursed for IV chemotherapy, 26% expressed an extremely low level of interest, 23% a low level of interest, 31% a high level of interest, and 17% an extremely high level of interest. The results of other questions are presented and correlated with the number of years the urologists have been in practice and other demographic data. Conclusions: The management of prostate cancer comprises a major portion of urologists’ practices. Almost one half (48%) of the urologists in this survey were interested in administering and being reimbursed for IV chemotherapy. Several chemotherapy regimens have been shown to improve quality of life in patients with HRPC, yet only about 30% of these patients were referred for chemotherapy. If more urologists were able to deliver these drugs, then the number of patients referred for chemotherapy would likely increase, as would accrual to important clinical trials in HRPC. The results of this survey suggest that methods to implement the training and reimbursement of urologists in the use of chemotherapy regimens should be investigated. PMID:16986047

DUPA conjugation of a cytotoxic indenoisoquinoline topoisomerase I inhibitor for selective prostate cancer cell targeting.

PubMed

Roy, Jyoti; Nguyen, Trung Xuan; Kanduluru, Ananda Kumar; Venkatesh, Chelvam; Lv, Wei; Reddy, P V Narasimha; Low, Philip S; Cushman, Mark

2015-04-09

Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate cancer cells while being present at low or undetectable levels in normal cells. This difference provides an opportunity to selectively deliver cytotoxic drugs to prostate cancer cells while sparing normal cells that lack PSMA, thus improving potencies and reducing toxicities. PSMA has high affinity for 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA) (Ki = 8 nM). After binding to a DUPA-drug conjugate, PSMA internalizes, unloads the conjugate, and returns to the surface. In the present studies, an indenoisoquinoline topoisomerase I inhibitor was conjugated to DUPA via a peptide linker and a drug-release segment that facilitates intracellular cleavage to liberate the drug cargo. The DUPA-indenoisoquinoline conjugate exhibited an IC50 in the low nanomolar range in 22RV1 cell cultures and induced a complete cessation of tumor growth with no toxicity, as determined by loss of body weight and death of treated mice.

Trichomonas vaginalis infection and risk of advanced prostate cancer.

PubMed

Shui, Irene M; Kolb, Suzanne; Hanson, Christi; Sutcliffe, Siobhan; Rider, Jennifer R; Stanford, Janet L

2016-05-01

The epidemiologic evidence for an association of Trichomonas vaginalis (Tv) with overall prostate cancer is mixed, but some studies suggest Tv may increase risk of more aggressive disease. The aim of this study was to assess whether Tv serostatus is associated with advanced or fatal prostate cancer. A total of 146 men with advanced (metastatic or fatal) prostate cancer and 181 age-matched controls were selected from two prior population-based, case-control studies. Tv serostatus was determined with the same laboratory methods used in previous epidemiologic studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression to compare Tv serostatus in prostate cancer cases and controls adjusted for potential confounders. The seroprevalence of Tv in controls was 23%. Tv serostatus was not associated with an increased risk of metastatic or fatal prostate cancer (ORs < 1). Our study does not support an increased risk of advanced or fatal prostate cancer in men seropositive for Tv. © 2016 Wiley Periodicals, Inc.

LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.

PubMed

Fiano, Valentina; Zugna, Daniela; Grasso, Chiara; Trevisan, Morena; Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna; Merletti, Franco; Richiardi, Lorenzo

2017-01-02

Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.

Evolution of a CDC Public Health Research Agenda for Low-Risk Prostate Cancer

PubMed Central

Hall, Ingrid J.; Smith, Judith Lee

2016-01-01

Men with prostate cancer face difficult choices when selecting a therapy for localized prostate cancer. Comparative data from controlled studies are lacking and clinical opinions diverge about the benefits and harms of treatment options. Consequently, there is limited guidance for patients regarding the impact of treatment decisions on quality of life. There are opportunities for public health to intervene at several decision-making points. Information on typical quality of life outcomes associated with specific prostate cancer treatments could help patients select treatment options. From 2003 to present, the Division of Cancer Prevention and Control at CDC has supported projects to explore patient information-seeking behavior post-diagnosis, caregiver and provider involvement in treatment decision making, and patient quality of life following prostate cancer treatment. CDC's work also includes research that explores barriers and facilitators to the presentation of active surveillance as a viable treatment option and promotes equal access to information for men and their caregivers. This article provides an overview of the literature and considerations that initiated establishing a prospective public health research agenda around treatment decision making. Insights gathered from CDC-supported studies are poised to enhance understanding of the process of shared decision making and the influence of patient, caregiver, and provider preferences on the selection of treatment choices. These findings provide guidance about attributes that maximize patient experiences in survivorship, including optimal quality of life and patient and caregiver satisfaction with information, treatment decisions, and subsequent care. PMID:26590643

Development of an MRI-Guided Intra-Prostatic Needle Placement System

DTIC Science & Technology

2011-07-01

and intra-operative imaging using techniques such as those described by Haker , et al. [18]. Target points for the needle insertion are selected... Haker , S., Fichtinger, G., Tem- pany, C.: Transperineal prostate biopsy under magnetic resonance image guid- ance: A needle placement accuracy study 26...clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 42(3), 507–515 (1998) 9. DiMaio, S.P., Pieper, S., Chinzei, K., Hata, N., Haker , S.J

Lifestyle and dietary factors in the prevention of lethal prostate cancer

PubMed Central

Wilson, Kathryn M; Giovannucci, Edward L; Mucci, Lorelei A

2012-01-01

The prevention of lethal prostate cancer is a critical public health challenge that would improve health and reduce suffering from this disease. In this review, we discuss the evidence surrounding specific lifestyle and dietary factors in the prevention of lethal prostate cancer. We present a summary of evidence for the following selected behavioral risk factors: obesity and weight change, physical activity, smoking, antioxidant intake, vitamin D and calcium, and coffee intake. PMID:22504869

Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy.

PubMed

Nejadmoghaddam, Mohammad-Reza; Zarnani, Amir-Hassan; Ghahremanzadeh, Ramin; Ghods, Roya; Mahmoudian, Jafar; Yousefi, Maryam; Nazari, Mahboobeh; Ghahremani, Mohammad Hossein; Abolhasani, Maryam; Anissian, Ali; Mahmoudi, Morteza; Dinarvand, Rassoul

2017-10-17

Our recent findings strongly support the idea of PLAC1 being as a potential immunotherapeutic target in prostate cancer (PCa). Here, we have generated and evaluated an anti-placenta-specific1 (PLAC1)-based antibody drug conjugate (ADC) for targeted immunotherapy of PCa. Prostate cancer cells express considerable levels of PLAC1. The Anti-PLAC1 clone, 2H12C12, showed high reactivity with recombinant PLAC1 and selectivity recognized PLAC1 in prostate cancer cells but not in LS180 cells, the negative control. PLAC1 binding induced rapid internalization of the antibody within a few minutes which reached to about 50% after 15 min and almost completed within an hour. After SN38 conjugation to antibody, a drug-antibody ratio (DAR) of about 5.5 was achieved without apparent negative effect on antibody affinity to cell surface antigen. The ADC retained intrinsic antibody activity and showed enhanced and selective cytotoxicity with an IC50 of 62 nM which was about 15-fold lower compared to free drug. Anti-PLAC1-ADC induced apoptosis in human primary prostate cancer cells and prostate cell lines. No apparent cytotoxic effect was observed in in vivo animal safety experiments. Our newly developed anti-PLAC1-based ADCs might pave the way for a reliable, efficient, and novel immunotherapeutic modality for patients with PCa.

Fostering Informed Decisions: Impact of a Decision Aid Among Men Registered to Undergo Mass Screening for Prostate Cancer in a Randomized Controlled Trial

PubMed Central

Williams, Randi M.; Davis, Kimberly M.; Luta, George; Edmond, Sara N.; Dorfman, Caroline S.; Schwartz, Marc D.; Lynch, John; Ahaghotu, Chiledum; Taylor, Kathryn L.

2013-01-01

Objective Screening asymptomatic men for prostate cancer is controversial and informed decision making is recommended. Within two prostate cancer screening programs, we evaluated the impact of a print-based decision aid (DA) on decision-making outcomes. Methods Men (N=543) were 54.9 (SD=8.1) years old and 61% were African-American. The 2 (booklet type: DA vs. usual care (UC)) × 2 (delivery mode: Home vs. Clinic) randomized controlled trial assessed decisional and screening outcomes at baseline, two-months, and 13-months. Results Intention-to-treat linear regression analyses using generalized estimating equations revealed that DA participants reported improved knowledge relative to UC (B=.41, p<.05). For decisional conflict, per-protocol analyses revealed a group by time interaction (B = −.69, p<.05), indicating that DA participants were less likely to report decisional conflict at two-months compared to UC participants (OR=.49, 95% CI: .26–.91, p<.05). Conclusion This is the first randomized trial to evaluate a DA in the context of free mass screening, a challenging setting in which to make an informed decision. The DA was highly utilized by participants, improved knowledge and reduced decisional conflict. Practice implications These results are valuable in understanding ways to improve the decisions of men who seek screening and can be easily implemented within many settings. PMID:23357414

Androgen-deprivation therapy plus chemotherapy in metastatic hormone-sensitive prostate cancer. A systematic review and meta-analysis of randomized clinical trials.

PubMed

Ramos-Esquivel, Allan; Fernández, Cristina; Zeledón, Zenén

2016-08-01

To assess the efficacy and toxicity of androgen-deprivation therapy (ADT) plus chemotherapy in patients with hormone-sensitive metastatic prostate cancer. Randomized clinical trials were identified after systematic searching of databases and conference proceedings. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes-overall survival (OS), biochemical progression-free survival (PFS), and clinical PFS, according to the inverse-variance method. Heterogeneity was measured using the Q and I(2) statistics. A narrative review was done to explore the major adverse drug reactions reported for each trial. After systematic searching, we included 6 trials (n = 2,675) in this meta-analysis. Estramustine-based chemotherapy plus ADT was not associated with improved OS (HR = 0.64; 95% CI: 0.22-1.89; P = 0.42). In contrast, docetaxel plus ADT was associated with improved OS (HR = 0.75; 95% CI: 0.61-0.91; P = 0.004) and clinical PFS (HR = 0.64; 95% CI: 0.57-0.72; P<0.00001). There was no significant heterogeneity detected among trials. Regarding adverse drug reactions grade 3 or higher, neutropenia was the most frequent side effect reported in a range from 12% to 32%. The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS in hormone-sensitive metastatic prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of pumpkin seed in men with lower urinary tract symptoms due to benign prostatic hyperplasia in the one-year, randomized, placebo-controlled GRANU study.

PubMed

Vahlensieck, Winfried; Theurer, Christoph; Pfitzer, Edith; Patz, Brigitte; Banik, Norbert; Engelmann, Udo

2015-01-01

The German Research Activities on Natural Urologicals (GRANU) study was a randomized, partially blinded, placebo-controlled, parallel-group trial that investigated the efficacy of pumpkin seed in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS). A total of 1,431 men (50-80 years) with BPH/LUTS were randomly assigned to either pumpkin seed (5 g b.i.d.), capsules with pumpkin seed extract (500 mg b.i.d.) or matching placebo. The primary response criterion was a decrease in International Prostate Symptom Score (IPSS) of ≥5 points from baseline after 12 months. Secondary outcome measures included IPSS-related quality of life, IPSS single items and diary-recorded nocturia. After 12 months, the response rate (intention-to-treat/last-observation-carried-forward approach) did not differ between pumpkin seed extract and placebo. In the case of pumpkin seed (responders: 58.5%), the difference compared with placebo (responders: 47.3%) was descriptively significant. The study products were well tolerated. Overall, in men with BPH, 12 months of treatment with pumpkin seed led to a clinically relevant reduction in IPSS compared with placebo. In order to fully justify a recommendation for the use of pumpkin seed to treat moderate LUTS, these findings need to be substantiated in a confirmatory study or systematic review. 2014 S. Karger AG, Basel

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia.

PubMed

Cha, Joo Young; Wee, Jungwon; Jung, Jooyoung; Jang, Yongwoo; Lee, Byeongjun; Hong, Gyu-Sang; Chang, Beom Chul; Choi, Yoon-La; Shin, Young Kee; Min, Hye-Young; Lee, Ho-Young; Na, Tae-Young; Lee, Mi-Ock; Oh, Uhtaek

2015-08-04

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca(2+)-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH.

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia

PubMed Central

Cha, Joo Young; Wee, Jungwon; Jung, Jooyoung; Jang, Yongwoo; Lee, Byeongjun; Hong, Gyu-Sang; Chang, Beom Chul; Choi, Yoon-La; Shin, Young Kee; Min, Hye-Young; Lee, Ho-Young; Na, Tae-Young; Lee, Mi-Ock; Oh, Uhtaek

2015-01-01

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca2+-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH. PMID:26153424

Interstitial laser prostatectomy

NASA Astrophysics Data System (ADS)

Johnson, Douglas E.; Cromeens, Douglas M.; Price, Roger E.

1994-05-01

Interstitial laser coagulation of the canine prostate using the Sharplan interstitial thermal therapy fiber (Model 25432) was performed in 9 adult dogs and the subsequent gross and histopathologic changes occurring in the prostate were studied at intervals ranging from 1 hour to 5 weeks. A large well-demarcated area of acute coagulative necrosis developed around each fiber tract which in turn was surrounded by a prominent narrow zone of marked tissue disruption and an outer zone of hemorrhage. Liquefaction developed within the coagulative areas within 24 hours and by 4 days, each prostatic lobe contained an irregular cavity which became lined by normal-appearing transitional epithelium and that by 5 weeks, communicated with the prostatic urethra. These changes, similar to those reported following transurethral visual laser ablation of the prostate, suggest that interstitial laser thermal therapy may provide an alternative means for treating selected patients suffering from prostatic enlargement.

Study of NGEP expression in androgen sensitive prostate cancer cells: A potential target for immunotherapy

PubMed Central

Mohsenzadegan, Monireh; Tajik, Nader; Madjd, Zahra; Shekarabi, Mehdi; Farajollahi, Mohammad M

2015-01-01

Background: Prostate cancer is one of the leading causes of cancer deaths among men. New gene expressed in prostate (NGEP), is a prostate-specific gene expressed only in normal prostate and prostate cancer tissue. Because of its selective expression in prostate cancer cell surface, NGEP is a potential immunotherapeutic target. To target the NGEP in prostate cancer, it is essential to investigate its expression in prostate cancer cells. Methods: In the present study, we investigated NGEP expression in LNCaP and DU145 cells by real time and RT-PCR, flow cytometric and immunocytochemical analyses. Results: Real time and RT-PCR analyses of NGEP expression showed that NGEP was expressed in the LNCaP cells but not in DU145 cells. The detection of NGEP protein by flow cytometric and immunocytochemistry analyses indicated that NGEP protein was weakly expressed only in LNCaP cell membrane. Conclusion: Our results demonstrate that LNCaP cell line is more suitable than DU145 for NGEP expression studies; however, its low-level expression is a limiting issue. NGEP expression may be increased by androgen supplementation of LNCaP cell culture medium. PMID:26000254

Biomarkers identified for prostate cancer patients through genome-scale screening.

PubMed

Wang, Lei-Yun; Cui, Jia-Jia; Zhu, Tao; Shao, Wei-Hua; Zhao, Yi; Wang, Sai; Zhang, Yu-Peng; Wu, Ji-Chu; Zhang, Le

2017-11-03

Prostate cancer is a threat to men and usually occurs in aged males. Though prostate specific antigen level and Gleason score are utilized for evaluation of the prostate cancer in clinic, the biomarkers for this malignancy have not been widely recognized. Furthermore, the outcome varies across individuals receiving comparable treatment regimens and the underlying mechanism is still unclear. We supposed that genetic feature may be responsible for, at least in part, this process and conducted a two-cohort study to compare the genetic difference in tumorous and normal tissues of prostate cancer patients. The Gene Expression Omnibus dataset were used and a total of 41 genes were found significantly differently expressed in tumor tissues as compared with normal prostate tissues. Four genes (SPOCK3, SPON1, PTN and TGFB3) were selected for further evaluation after Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and clinical association analysis. MIR1908 was also found decreased expression level in prostate cancer whose target genes were found expressing in both prostate tumor and normal tissues. These results indicated that these potential biomarkers deserve attention in prostate cancer patients and the underlying mechanism should be further investigated.

IMRT: Improvement in treatment planning efficiency using NTCP calculation independent of the dose-volume-histogram

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grigorov, Grigor N.; Chow, James C.L.; Grigorov, Lenko

2006-05-15

The normal tissue complication probability (NTCP) is a predictor of radiobiological effect for organs at risk (OAR). The calculation of the NTCP is based on the dose-volume-histogram (DVH) which is generated by the treatment planning system after calculation of the 3D dose distribution. Including the NTCP in the objective function for intensity modulated radiation therapy (IMRT) plan optimization would make the planning more effective in reducing the postradiation effects. However, doing so would lengthen the total planning time. The purpose of this work is to establish a method for NTCP determination, independent of a DVH calculation, as a quality assurancemore » check and also as a mean of improving the treatment planning efficiency. In the study, the CTs of ten randomly selected prostate patients were used. IMRT optimization was performed with a PINNACLE3 V 6.2b planning system, using planning target volume (PTV) with margins in the range of 2 to 10 mm. The DVH control points of the PTV and OAR were adapted from the prescriptions of Radiation Therapy Oncology Group protocol P-0126 for an escalated prescribed dose of 82 Gy. This paper presents a new model for the determination of the rectal NTCP ({sub R}NTCP). The method uses a special function, named GVN (from Gy, Volume, NTCP), which describes the {sub R}NTCP if 1 cm{sup 3} of the volume of intersection of the PTV and rectum (R{sub int}) is irradiated uniformly by a dose of 1 Gy. The function was 'geometrically' normalized using a prostate-prostate ratio (PPR) of the patients' prostates. A correction of the {sub R}NTCP for different prescribed doses, ranging from 70 to 82 Gy, was employed in our model. The argument of the normalized function is the R{sub int}, and parameters are the prescribed dose, prostate volume, PTV margin, and PPR. The {sub R}NTCPs of another group of patients were calculated by the new method and the resulting difference was <{+-}5% in comparison to the NTCP calculated by the PINNACLE3 software where Kutcher's dose-response model for NTCP calculation is adopted.« less

SU-F-T-272: Patient Specific Quality Assurance of Prostate VMAT Plans with Portal Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darko, J; Osei, E; University of Waterloo, Waterloo, ON

Purpose: To evaluate the effectiveness of using the Portal Dosimetry (PD) method for patient specific quality assurance of prostate VMAT plans. Methods: As per institutional protocol all VMAT plans were measured using the Varian Portal Dosimetry (PD) method. A gamma evaluation criterion of 3%-3mm with a minimum area gamma pass rate (gamma <1) of 95% is used clinically for all plans. We retrospectively evaluated the portal dosimetry results for 170 prostate patients treated with VMAT technique. Three sets of criterions were adopted for re-evaluating the measurements; 3%-3mm, 2%-2mm and 1%-1mm. For all criterions two areas, Field+1cm and MLC-CIAO were analysed.Tomore » ascertain the effectiveness of the portal dosimetry technique in determining the delivery accuracy of prostate VMAT plans, 10 patients previously measured with portal dosimetry, were randomly selected and their measurements repeated using the ArcCHECK method. The same criterion used in the analysis of PD was used for the ArcCHECK measurements. Results: All patient plans reviewed met the institutional criteria for Area Gamma pass rate. Overall, the gamma pass rate (gamma <1) decreases for 3%-3mm, 2%-2mm and 1%-1mm criterion. For each criterion the pass rate was significantly reduced when the MLC-CIAO was used instead of FIELD+1cm. There was noticeable change in sensitivity for MLC-CIAO with 2%-2mm criteria and much more significant reduction at 1%-1mm. Comparable results were obtained for the ArcCHECK measurements. Although differences were observed between the clockwise verses the counter clockwise plans in both the PD and ArcCHECK measurements, this was not deemed to be statistically significant. Conclusion: This work demonstrates that Portal Dosimetry technique can be effectively used for quality assurance of VMAT plans. Results obtained show similar sensitivity compared to ArcCheck. To reveal certain delivery inaccuracies, the use of a combination of criterions may provide an effective way in improving the overall sensitivity of PD. Funding provided in part by the Prostate Ride for Dad, Kitchener-Waterloo, Canada.« less

Impact of Clinical History on Maximum PI-RADS Version 2 Score: A Six-Reader 120-Case Sham History Retrospective Evaluation.

PubMed

Shankar, Prasad R; Kaza, Ravi K; Al-Hawary, Mahmoud M; Masch, William R; Curci, Nicole E; Mendiratta-Lala, Mishal; Sakala, Michelle D; Johnson, Timothy D; Davenport, Matthew S

2018-04-17

Purpose To assess the impact of clinical history on the maximum Prostate Imaging Recording and Data System (PI-RADS) version 2 (v2) score assigned to multiparametric magnetic resonance (MR) imaging of the prostate. Materials and Methods This retrospective cohort study included 120 consecutively selected multiparametric prostate MR imaging studies performed between November 1, 2016, and December 31, 2016. Sham clinical data in four domains (digital rectal examination, prostate-specific antigen level, plan for biopsy, prior prostate cancer history) were randomly assigned to each case by using a balanced orthogonal design. Six fellowship-trained abdominal radiologists independently reviewed the sham data, actual patient age, and each examination while they were blinded to interreader scoring, true clinical data, and histologic findings. Readers were told the constant sham histories were true, believed the study to be primarily investigating interrater agreement, and were asked to assign a maximum PI-RADS v2 score to each case. Linear regression was performed to assess the association between clinical variables and maximum PI-RADS v2 score designation. Intraclass correlation coefficients (ICCs) were obtained to compare interreader scoring. Results Clinical information had no significant effect on maximum PI-RADS v2 scoring for any of the six readers (P = .09-.99, 42 reader-variable pairs). Distributions of maximum PI-RADS v2 scores in the research context were similar to the distribution of the scores assigned clinically and had fair-to-excellent pairwise interrater agreement (ICC range: 0.53-0.76). Overall interrater agreement was good (ICC: 0.64; 95% confidence interval: 0.57, 0.71). Conclusion Clinical history does not appear to be a substantial bias in maximum PI-RADS v2 score assignment. This is potentially important for clinical nomograms that plan to incorporate PI-RADS v2 score and clinical data into their algorithms (ie, PI-RADS v2 scoring is not confounded by clinical data). © RSNA, 2018 Online supplemental material is available for this article.

Prostate cancer localization with multispectral MRI using cost-sensitive support vector machines and conditional random fields.

PubMed

Artan, Yusuf; Haider, Masoom A; Langer, Deanna L; van der Kwast, Theodorus H; Evans, Andrew J; Yang, Yongyi; Wernick, Miles N; Trachtenberg, John; Yetik, Imam Samil

2010-09-01

Prostate cancer is a leading cause of cancer death for men in the United States. Fortunately, the survival rate for early diagnosed patients is relatively high. Therefore, in vivo imaging plays an important role for the detection and treatment of the disease. Accurate prostate cancer localization with noninvasive imaging can be used to guide biopsy, radiotherapy, and surgery as well as to monitor disease progression. Magnetic resonance imaging (MRI) performed with an endorectal coil provides higher prostate cancer localization accuracy, when compared to transrectal ultrasound (TRUS). However, in general, a single type of MRI is not sufficient for reliable tumor localization. As an alternative, multispectral MRI, i.e., the use of multiple MRI-derived datasets, has emerged as a promising noninvasive imaging technique for the localization of prostate cancer; however almost all studies are with human readers. There is a significant inter and intraobserver variability for human readers, and it is substantially difficult for humans to analyze the large dataset of multispectral MRI. To solve these problems, this study presents an automated localization method using cost-sensitive support vector machines (SVMs) and shows that this method results in improved localization accuracy than classical SVM. Additionally, we develop a new segmentation method by combining conditional random fields (CRF) with a cost-sensitive framework and show that our method further improves cost-sensitive SVM results by incorporating spatial information. We test SVM, cost-sensitive SVM, and the proposed cost-sensitive CRF on multispectral MRI datasets acquired from 21 biopsy-confirmed cancer patients. Our results show that multispectral MRI helps to increase the accuracy of prostate cancer localization when compared to single MR images; and that using advanced methods such as cost-sensitive SVM as well as the proposed cost-sensitive CRF can boost the performance significantly when compared to SVM.

Higher-Than-Conventional Radiation Doses in Localized Prostate Cancer Treatment: A Meta-analysis of Randomized, Controlled Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viani, Gustavo Arruda; Stefano, Eduardo Jose; Afonso, Sergio Luis

2009-08-01

Purpose: To determine in a meta-analysis whether the outcomes in men with localized prostate cancer treated with high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT), by quantifying the effect of the total dose of radiotherapy on biochemical control (BC). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing HDRT with CDRT for localized prostate cancer. To evaluate the dose-response relationship, we conducted a meta-regression analysis of BC ratios by means of weighted linear regression. Results:more » Seven RCTs with a total patient population of 2812 were identified that met the study criteria. Pooled results from these RCTs showed a significant reduction in the incidence of biochemical failure in those patients with prostate cancer treated with HDRT (p < 0.0001). However, there was no difference in the mortality rate (p = 0.38) and specific prostate cancer mortality rates (p = 0.45) between the groups receiving HDRT and CDRT. However, there were more cases of late Grade >2 gastrointestinal toxicity after HDRT than after CDRT. In the subgroup analysis, patients classified as being at low (p = 0.007), intermediate (p < 0.0001), and high risk (p < 0.0001) of biochemical failure all showed a benefit from HDRT. The meta-regression analysis also detected a linear correlation between the total dose of radiotherapy and biochemical failure (BC = -67.3 + [1.8 x radiotherapy total dose in Gy]; p = 0.04). Conclusions: Our meta-analysis showed that HDRT is superior to CDRT in preventing biochemical failure in low-, intermediate-, and high-risk prostate cancer patients, suggesting that this should be offered as a treatment for all patients, regardless of their risk status.« less

Residual Seminal Vesicle Displacement in Marker-Based Image-Guided Radiotherapy for Prostate Cancer and the Impact on Margin Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smitsmans, Monique H.P.; Bois, Josien de; Sonke, Jan-Jakob

Purpose: The objectives of this study were to quantify residual interfraction displacement of seminal vesicles (SV) and investigate the efficacy of rotation correction on SV displacement in marker-based prostate image-guided radiotherapy (IGRT). We also determined the effect of marker registration on the measured SV displacement and its impact on margin design. Methods and Materials: SV displacement was determined relative to marker registration by using 296 cone beam computed tomography scans of 13 prostate cancer patients with implanted markers. SV were individually registered in the transverse plane, based on gray-value information. The target registration error (TRE) for the SV due tomore » marker registration inaccuracies was estimated. Correlations between prostate gland rotations and SV displacement and between individual SV displacements were determined. Results: The SV registration success rate was 99%. Displacement amounts of both SVs were comparable. Systematic and random residual SV displacements were 1.6 mm and 2.0 mm in the left-right direction, respectively, and 2.8 mm and 3.1 mm in the anteroposterior (AP) direction, respectively. Rotation correction did not reduce residual SV displacement. Prostate gland rotation around the left-right axis correlated with SV AP displacement (R{sup 2} = 42%); a correlation existed between both SVs for AP displacement (R{sup 2} = 62%); considerable correlation existed between random errors of SV displacement and TRE (R{sup 2} = 34%). Conclusions: Considerable residual SV displacement exists in marker-based IGRT. Rotation correction barely reduced SV displacement, rather, a larger SV displacement was shown relative to the prostate gland that was not captured by the marker position. Marker registration error partly explains SV displacement when correcting for rotations. Correcting for rotations, therefore, is not advisable when SV are part of the target volume. Margin design for SVs should take these uncertainties into account.« less

Effects of a Group-Mediated Exercise and Dietary Intervention in the Treatment of Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: Results From the IDEA-P Trial.

PubMed

Focht, Brian C; Lucas, Alexander R; Grainger, Elizabeth; Simpson, Christina; Fairman, Ciaran M; Thomas-Ahner, Jennifer M; Buell, Jackie; Monk, J Paul; Mortazavi, Amir; Clinton, Steven K

2018-04-19

Although androgen-deprivation therapy (ADT) is the foundation of treatment for prostate cancer, the physiological impacts of ADT result in functional decline and enhanced risk of chronic disease and metabolic syndrome. The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is a single-blind, randomized, pilot trial comparing the effects of a group-mediated, cognitive-behavioral (GMCB) exercise and dietary intervention (EX+D) with those of a standard-of-care (SC) control during the treatment of prostate cancer patients undergoing ADT. A total of 32 prostate cancer patients (M age = 66.28, SD = 7.79) undergoing ADT were randomly assigned to the 12-week EX+D intervention (n = 16) or control (n = 16). The primary outcome in IDEA-P was change in mobility performance with secondary outcomes including body composition and muscular strength. Blinded assessment of outcomes were obtained at baseline and at 2- and 3-month follow-ups. Favorable adherence and retention rates were observed, and no serious intervention-related adverse events were documented. Intent-to-treat ANCOVA controlling for baseline value and ADT duration demonstrated that EX+D resulted in significantly greater improvements in mobility performance (p < .02), muscular strength (p < .01), body fat percentage (p < .05), and fat mass (p < .03) at 3-month follow-up, relative to control. Findings from the IDEA-P trial suggest that a GMCB-based EX+D intervention resulted in significant, clinically meaningful improvements in mobility performance, muscular strength, and body composition, relative to controls. Collectively, these results suggest that the EX+D was a safe and well-tolerated intervention for prostate cancer patients on ADT. The utility of implementing this approach in the treatment of prostate cancer patients on ADT should be evaluated in future large-scale efficacy trials. NCT02050906.

Entacapone and prostate cancer in Parkinson's disease patients: A large Veterans Affairs healthcare system study.

PubMed

Major, Jacqueline M; Dong, Diane; Cunningham, Francesca; By, Kunthel; Hur, Kwan; Shih, David C; Jiang, Rong; Podskalny, Gerald D; Wei, XiangMing; Pinheiro, Simone; Bird, Steven T; Keeton, Stephine; Graham, David J

2018-05-05

An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S. ambulatory setting. To investigate whether entacapone is associated with prostate cancer and to assess whether the associations are correlated with advanced disease at the time of cancer diagnosis. Using data from the Department of Veterans Affairs healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014. Patients were followed on-treatment for occurrence of prostate cancer, identified via linkage to the VA cancer registry. Mean follow-up time was 3.1 and 4.0 years in the entacapone and control cohort, respectively. There were 17,666 subjects meeting study criteria (mean age, 74 (SD 8.6) years); the entacapone-treated group comprised 5,257 subjects. Twenty-three prostate cancer cases occurred in the entacapone cohort and ninety-seven in the control cohort. The overall incidence of prostate cancer was 1.8 per 1,000 person-years of risk. There was no difference in risk of prostate cancer between the cohorts for increased duration of entacapone intake (adjusted HR: 1.08; 95% confidence interval: 0.46-2.51 for cumulative exposure of ≥2 years). Time since starting drug therapy and cumulative dose (mg) also do not suggest a difference in prostate cancer risk between cohorts. Prolonged therapy with entacapone was not associated with increased prostate cancer incidence; however, findings suggest a higher severity of prostate cancer. Published by Elsevier Ltd.

Elevated phospholipase D activity in androgen-insensitive prostate cancer cells promotes both survival and metastatic phenotypes.

PubMed

Utter, Matthew; Chakraborty, Sohag; Goren, Limor; Feuser, Lucas; Zhu, Yuan-Shan; Foster, David A

2018-06-01

Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking activation of the androgen receptor by androgens. Androgen deprivation therapy can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study we provide evidence that androgen-insensitive prostate cancer cells have elevated PLD activity relative to the androgen-sensitive prostate cancer cells. PLD activity has been linked with promoting survival in many human cancer cell lines; and consistent with the previous studies, suppression of PLD activity in the prostate cancer cells resulted in apoptotic cell death. Of significance, suppressing the elevated PLD activity in androgen resistant prostate cancer lines also blocked the ability of these cells to migrate and invade Matrigel™. Since survival signals are generally an early event in tumorigenesis, the apparent coupling of survival and metastatic phenotypes implies that metastasis is an earlier event in malignant prostate cancer than generally thought. This finding has implications for screening strategies designed to identify prostate cancers before dissemination. Copyright © 2018 Elsevier B.V. All rights reserved.

Micrornas in prostate cancer: an overview.

PubMed

Vanacore, Daniela; Boccellino, Mariarosaria; Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Di Franco, Rossella; Romano, Francesco Jacopo; Montanari, Micaela; La Mantia, Elvira; Piscitelli, Raffaele; Nocerino, Flavia; Cappuccio, Francesca; Grimaldi, Giovanni; Izzo, Alessandro; Castaldo, Luigi; Pepe, Maria Filomena; Malzone, Maria Gabriella; Iovane, Gelsomina; Ametrano, Gianluca; Stiuso, Paola; Quagliuolo, Lucio; Barberio, Daniela; Perdonà, Sisto; Muto, Paolo; Montella, Maurizio; Maiolino, Piera; Veneziani, Bianca Maria; Botti, Gerardo; Caraglia, Michele; Facchini, Gaetano

2017-07-25

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.

Distinguishing prostate cancer from benign confounders via a cascaded classifier on multi-parametric MRI

NASA Astrophysics Data System (ADS)

Litjens, G. J. S.; Elliott, R.; Shih, N.; Feldman, M.; Barentsz, J. O.; Hulsbergen-van de Kaa, C. A.; Kovacs, I.; Huisman, H. J.; Madabhushi, A.

2014-03-01

Learning how to separate benign confounders from prostate cancer is important because the imaging characteristics of these confounders are poorly understood. Furthermore, the typical representations of the MRI parameters might not be enough to allow discrimination. The diagnostic uncertainty this causes leads to a lower diagnostic accuracy. In this paper a new cascaded classifier is introduced to separate prostate cancer and benign confounders on MRI in conjunction with specific computer-extracted features to distinguish each of the benign classes (benign prostatic hyperplasia (BPH), inflammation, atrophy or prostatic intra-epithelial neoplasia (PIN). In this study we tried to (1) calculate different mathematical representations of the MRI parameters which more clearly express subtle differences between different classes, (2) learn which of the MRI image features will allow to distinguish specific benign confounders from prostate cancer, and (2) find the combination of computer-extracted MRI features to best discriminate cancer from the confounding classes using a cascaded classifier. One of the most important requirements for identifying MRI signatures for adenocarcinoma, BPH, atrophy, inflammation, and PIN is accurate mapping of the location and spatial extent of the confounder and cancer categories from ex vivo histopathology to MRI. Towards this end we employed an annotated prostatectomy data set of 31 patients, all of whom underwent a multi-parametric 3 Tesla MRI prior to radical prostatectomy. The prostatectomy slides were carefully co-registered to the corresponding MRI slices using an elastic registration technique. We extracted texture features from the T2-weighted imaging, pharmacokinetic features from the dynamic contrast enhanced imaging and diffusion features from the diffusion-weighted imaging for each of the confounder classes and prostate cancer. These features were selected because they form the mainstay of clinical diagnosis. Relevant features for each of the classes were selected using maximum relevance minimum redundancy feature selection, allowing us to perform classifier independent feature selection. The selected features were then incorporated in a cascading classifier, which can focus on easier sub-tasks at each stage, leaving the more difficult classification tasks for later stages. Results show that distinct features are relevant for each of the benign classes, for example the fraction of extra-vascular, extra-cellular space in a voxel is a clear discriminator for inflammation. Furthermore, the cascaded classifier outperforms both multi-class and one-shot classifiers in overall accuracy for discriminating confounders from cancer: 0.76 versus 0.71 and 0.62.

Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients.

PubMed

Logozzi, Mariantonia; Angelini, Daniela F; Iessi, Elisabetta; Mizzoni, Davide; Di Raimo, Rossella; Federici, Cristina; Lugini, Luana; Borsellino, Giovanna; Gentilucci, Alessandro; Pierella, Federico; Marzio, Vittorio; Sciarra, Alessandro; Battistini, Luca; Fais, Stefano

2017-09-10

Prostate specific antigen (PSA) test is the most common, clinically validated test for the diagnosis of prostate cancer (PCa). While neoplastic lesions of the prostate may cause aberrant levels of PSA in the blood, the quantitation of free or complexed PSA poorly discriminates cancer patients from those developing benign lesions, often leading to invasive and unnecessary surgical procedures. Microenvironmental acidity increases exosome release by cancer cells. In this study we evaluated whether acidity, a critical phenotype of malignancy, could influence exosome release and increase the PSA expression in nanovesicles released by PCa cells. To this aim, we exploited Nanoparticle Tracking Analysis (NTA), an immunocapture-based ELISA, and nanoscale flow-cytometry. The results show that microenvironmental acidity induces an increased release of nanovesicles expressing both PSA and the exosome marker CD81. In order to verify whether the changes induced by the local selective pressure of extracellular acidity may correspond to a clinical pathway we used the same approach to evaluate the levels of PSA-expressing exosomes in the plasma of PCa patients and controls, including subjects with benign prostatic hypertrophy (BPH). The results show that only PCa patients have high levels of nanovesicles expressing both CD81 and PSA. This study shows that tumor acidity exerts a selective pressure leading to the release of extracellular vesicles that express both PSA and exosome markers. A comparable scenario was shown in the plasma of prostate cancer patients as compared to both BPH and healthy controls. These results suggest that microenvironmental acidity may represent a key factor which determines qualitatively and quantitatively the release of extracellular vesicles by malignant tumors, including prostate cancer. This condition leads to the spill-over of nanovesicles into the peripheral blood of prostate cancer patients, where the levels of tumor biomarkers expressed by exosomes, such as PSA-exosomes, may represent a novel, non-invasive clinical tool for the screening and early diagnosis of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Deregulation of an imprinted gene network in prostate cancer

PubMed Central

Ribarska, Teodora; Goering, Wolfgang; Droop, Johanna; Bastian, Klaus-Marius; Ingenwerth, Marc; Schulz, Wolfgang A

2014-01-01

Multiple epigenetic alterations contribute to prostate cancer progression by deregulating gene expression. Epigenetic mechanisms, especially differential DNA methylation at imprinting control regions (termed DMRs), normally ensure the exclusive expression of imprinted genes from one specific parental allele. We therefore wondered to which extent imprinted genes become deregulated in prostate cancer and, if so, whether deregulation is due to altered DNA methylation at DMRs. Therefore, we selected presumptive deregulated imprinted genes from a previously conducted in silico analysis and from the literature and analyzed their expression in prostate cancer tissues by qRT-PCR. We found significantly diminished expression of PLAGL1/ZAC1, MEG3, NDN, CDKN1C, IGF2, and H19, while LIT1 was significantly overexpressed. The PPP1R9A gene, which is imprinted in selected tissues only, was strongly overexpressed, but was expressed biallelically in benign and cancerous prostatic tissues. Expression of many of these genes was strongly correlated, suggesting co-regulation, as in an imprinted gene network (IGN) reported in mice. Deregulation of the network genes also correlated with EZH2 and HOXC6 overexpression. Pyrosequencing analysis of all relevant DMRs revealed generally stable DNA methylation between benign and cancerous prostatic tissues, but frequent hypo- and hyper-methylation was observed at the H19 DMR in both benign and cancerous tissues. Re-expression of the ZAC1 transcription factor induced H19, CDKN1C and IGF2, supporting its function as a nodal regulator of the IGN. Our results indicate that a group of imprinted genes are coordinately deregulated in prostate cancers, independently of DNA methylation changes. PMID:24513574

Deregulation of an imprinted gene network in prostate cancer.

PubMed

Ribarska, Teodora; Goering, Wolfgang; Droop, Johanna; Bastian, Klaus-Marius; Ingenwerth, Marc; Schulz, Wolfgang A

2014-05-01

Multiple epigenetic alterations contribute to prostate cancer progression by deregulating gene expression. Epigenetic mechanisms, especially differential DNA methylation at imprinting control regions (termed DMRs), normally ensure the exclusive expression of imprinted genes from one specific parental allele. We therefore wondered to which extent imprinted genes become deregulated in prostate cancer and, if so, whether deregulation is due to altered DNA methylation at DMRs. Therefore, we selected presumptive deregulated imprinted genes from a previously conducted in silico analysis and from the literature and analyzed their expression in prostate cancer tissues by qRT-PCR. We found significantly diminished expression of PLAGL1/ZAC1, MEG3, NDN, CDKN1C, IGF2, and H19, while LIT1 was significantly overexpressed. The PPP1R9A gene, which is imprinted in selected tissues only, was strongly overexpressed, but was expressed biallelically in benign and cancerous prostatic tissues. Expression of many of these genes was strongly correlated, suggesting co-regulation, as in an imprinted gene network (IGN) reported in mice. Deregulation of the network genes also correlated with EZH2 and HOXC6 overexpression. Pyrosequencing analysis of all relevant DMRs revealed generally stable DNA methylation between benign and cancerous prostatic tissues, but frequent hypo- and hyper-methylation was observed at the H19 DMR in both benign and cancerous tissues. Re-expression of the ZAC1 transcription factor induced H19, CDKN1C and IGF2, supporting its function as a nodal regulator of the IGN. Our results indicate that a group of imprinted genes are coordinately deregulated in prostate cancers, independently of DNA methylation changes.

Management of high risk metastatic prostate cancer: the case for novel therapies.

PubMed

Brand, Timothy C; Tolcher, Anthony W

2006-12-01

We reviewed the results of preliminary studies of select novel agents for metastatic prostate cancer and discuss the potential benefit of these agents for earlier stage disease, eg biochemically recurrent prostate cancer with high risk features. Available data on select investigational immunotherapies as well as endothelin-A receptor antagonists and survivin inhibitors were obtained and reviewed through PubMed searches, conference proceedings and unpublished proprietary information, when available. A large number of promising agents are in varying stages of development. Phase III results have been reported for the endothelin-A receptor antagonist atrasentan. Several immunotherapies are currently in phase II/III trials, namely the GM-CSF transduced tumor cell vaccine GVAX, the prostatic acid phosphatase loaded dendritic cell vaccine Provenge and the prostate specific antigen expressing poxvirus vaccine PROSTVAC-VF. Another immunotherapy, the prostate specific membrane antigen immunoconjugate MLN2704 (Millennium Pharmaceuticals, Cambridge, Massachusetts), is in phase I/II study. The first clinical inhibitors of survivin are in early phase I studies. Several of these agents, including atrasentan, have shown statistically significant but modest effects in the advanced disease setting in which they have been studied. Clinical trial design with these novel therapies presents particular challenges since most of these agents may induce disease stabilization rather than disease regression. There is a risk of false-negative results and failure to recognize a potentially efficacious agent if these cytostatic agents are studied only in men with advanced, heavily pretreated disease in whom life expectancy is measured in months. We advocate the early referral and enrollment of men with high risk prostate cancer in clinical trials.

Vitamins, Metabolomics and Prostate Cancer

PubMed Central

Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

2016-01-01

Purpose How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms by which vitamins influence prostate cancer risk. Methods Prostate cancer risk data related to vitamins E, A, and D and metabolomics profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Results Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomics profiling of fasting serum collected 1-20 years prior to clinical diagnoses found lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with risk of aggressive disease. Conclusions Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study. PMID:27339624

Screening for prostate cancer: estimating the magnitude of overdetection

PubMed Central

McGregor, M; Hanley, J A; Boivin, J F; McLean, R G

1998-01-01

BACKGROUND: No randomized controlled trial of prostate cancer screening has been reported and none is likely to be completed in the near future. In the absence of direct evidence, the decision to screen must therefore be based on estimates of benefits and risks. The main risk of screening is overdetection--the detection of cancer that, if left untreated, would not cause death. In this study the authors estimate the level of overdetection that might result from annual screening of men aged 50-70. METHODS: The annual rate of lethal screen-detectable cancer (detectable cancer that would prove fatal before age 85 if left untreated) was calculated from the observed prostate cancer mortality rate in Quebec; the annual rate of all cases of screen-detectable prostate cancer was calculated from 2 recent screening studies. RESULTS: The annual rate of lethal screen-detectable prostate cancer was estimated to be 1.3 per 1000 men. The annual rate of all cases of screen-detectable prostate cancer was estimated to be 8.0 per 1000 men. The estimated case-fatality rate among men up to 85 years of age was 16% (1.3/8.0) (sensitivity analysis 13% to 22%). INTERPRETATION: Of every 100 men with screen-detected prostate cancer, only 16 on average (13 to 22) could have their lives extended by surgery, since the prostate cancer would not cause death before age 85 in the remaining 84 (78 to 87). PMID:9861205

Vitamins, metabolomics, and prostate cancer.

PubMed

Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

2017-06-01

How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease. Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

Automatic Gleason grading of prostate cancer using SLIM and machine learning

NASA Astrophysics Data System (ADS)

Nguyen, Tan H.; Sridharan, Shamira; Marcias, Virgilia; Balla, Andre K.; Do, Minh N.; Popescu, Gabriel

2016-03-01

In this paper, we present an updated automatic diagnostic procedure for prostate cancer using quantitative phase imaging (QPI). In a recent report [1], we demonstrated the use of Random Forest for image segmentation on prostate cores imaged using QPI. Based on these label maps, we developed an algorithm to discriminate between regions with Gleason grade 3 and 4 prostate cancer in prostatectomy tissue. The Area-Under-Curve (AUC) of 0.79 for the Receiver Operating Curve (ROC) can be obtained for Gleason grade 4 detection in a binary classification between Grade 3 and Grade 4. Our dataset includes 280 benign cases and 141 malignant cases. We show that textural features in phase maps have strong diagnostic values since they can be used in combination with the label map to detect presence or absence of basal cells, which is a strong indicator for prostate carcinoma. A support vector machine (SVM) classifier trained on this new feature vector can classify cancer/non-cancer with an error rate of 0.23 and an AUC value of 0.83.

Rapid Selection of Mesenchymal Stem and Progenitor Cells in Primary Prostate Stromal Cultures

PubMed Central

Brennen, W. Nathaniel; Kisteman, L. Nelleke; Isaacs, John T.

2016-01-01

BACKGROUND Carcinoma-associated fibroblasts (CAFs) are a dominant component of the tumor microenvironment with pro-tumorigenic properties. Despite this knowledge, their physiologic origins remain poorly understood. Mesenchymal stem cells (MSCs) can be recruited from the bone marrow to areas of tissue damage and inflammation, including prostate cancer. MSCs can generate and have many overlapping properties with CAFs in preclinical models. METHODS Multiparameter flow cytometry and multipotent differentiation assays used to define MSCs in primary prostate stromal cultures derived from young (>25 yrs) organ donors and prostate cancer patients compared with bone marrow-derived stromal cultures. Population doubling times, population doublings, cell size, and differentiation potential determined under multiple culture conditions, including normoxia, hypoxia, and a variety of media. TGF-β measured by ELISA. RESULTS MSCs and stromal progenitors are not only present in normal and malignant prostate tissue, but are quickly selected for in primary stromal cultures derived from these tissues; becoming the dominant population within just a few passages. Growth potential inversely associated with TGF-β concentrations. All conditions generated populations with an average cell diameter >15 μm. All cultures tested had the ability to undergo osteogenic and chondrogenic differentiation, but unlike bone marrow-derived MSCs, primary stromal cultures derived from normal prostate tissue lack adipogenic differentiation potential. In contrast, a subset of stromal cultures derived from prostate cancer patients retain the ability to differentiate into adipocytes; a property that is significantly suppressed under hypoxic conditions in both bone marrow- and prostate-derived MSCs. CONCLUSIONS Primary prostate stromal cultures are highly enriched in cells with an MSC or stromal progenitor phenotype. The use of primary cultures such as these to study CAFs raises interesting implications when considering their overlapping properties. The lack of adipogenesis in stromal cultures derived from normal prostates suggests they have a lineage-restricted progenitor phenotype. The retention of adipogenic differentiation in cultures from a subset of prostate cancer patients suggests the active recruitment of less committed progenitors or MSCs from the bone marrow as a function of disease progression. This recruitment can potentially be exploited for prognostic purposes or a cell-based platform for the systemic delivery of cytotoxic agents to sites of prostate cancer. PMID:26732992

Rapid selection of mesenchymal stem and progenitor cells in primary prostate stromal cultures.

PubMed

Brennen, W Nathaniel; Kisteman, L Nelleke; Isaacs, John T

2016-05-01

Carcinoma-associated fibroblasts (CAFs) are a dominant component of the tumor microenvironment with pro-tumorigenic properties. Despite this knowledge, their physiologic origins remain poorly understood. Mesenchymal stem cells (MSCs) can be recruited from the bone marrow to areas of tissue damage and inflammation, including prostate cancer. MSCs can generate and have many overlapping properties with CAFs in preclinical models. Multiparameter flow cytometry and multipotent differentiation assays used to define MSCs in primary prostate stromal cultures derived from young (<25 yrs) organ donors and prostate cancer patients compared with bone marrow-derived stromal cultures. Population doubling times, population doublings, cell size, and differentiation potential determined under multiple culture conditions, including normoxia, hypoxia, and a variety of media. TGF-β measured by ELISA. MSCs and stromal progenitors are not only present in normal and malignant prostate tissue, but are quickly selected for in primary stromal cultures derived from these tissues; becoming the dominant population within just a few passages. Growth potential inversely associated with TGF-β concentrations. All conditions generated populations with an average cell diameter >15 µm. All cultures tested had the ability to undergo osteogenic and chondrogenic differentiation, but unlike bone marrow-derived MSCs, primary stromal cultures derived from normal prostate tissue lack adipogenic differentiation potential. In contrast, a subset of stromal cultures derived from prostate cancer patients retain the ability to differentiate into adipocytes; a property that is significantly suppressed under hypoxic conditions in both bone marrow- and prostate-derived MSCs. Primary prostate stromal cultures are highly enriched in cells with an MSC or stromal progenitor phenotype. The use of primary cultures such as these to study CAFs raises interesting implications when considering their overlapping properties. The lack of adipogenesis in stromal cultures derived from normal prostates suggests they have a lineage-restricted progenitor phenotype. The retention of adipogenic differentiation in cultures from a subset of prostate cancer patients suggests the active recruitment of less committed progenitors or MSCs from the bone marrow as a function of disease progression. This recruitment can potentially be exploited for prognostic purposes or a cell-based platform for the systemic delivery of cytotoxic agents to sites of prostate cancer. © 2016 Wiley Periodicals, Inc.

Denosumab treatment of prostate cancer with bone metastases and increased urine N-telopeptide levels after therapy with intravenous bisphosphonates: results of a randomized phase II trial.

PubMed

Fizazi, Karim; Bosserman, Linda; Gao, Guozhi; Skacel, Tomas; Markus, Richard

2009-08-01

Patients with bone metastases have high rates of RANKL driven bone resorption and an increased risk of skeletal morbidity. Osteoclast mediated bone resorption can be assessed by measuring urine N-telopeptide and can be inhibited by denosumab, a fully human antibody against RANKL. Eligible patients (111) had bone metastases from prostate cancer, other solid tumors or multiple myeloma, 1 or more bone lesions and urine N-telopeptide greater than 50 nM bone collagen equivalents per mM creatinine (urine N-telopeptide greater than 50) despite the use of intravenous bisphosphonates. Patients were stratified by cancer type and screening urine N-telopeptide, and randomized to continue intravenous bisphosphonates every 4 weeks or receive 180 mg subcutaneous denosumab every 4 weeks or 180 mg every 12 weeks. The primary end point was the proportion of patients with urine N-telopeptide less than 50 at week 13. We report the efficacy results for the subset of patients with prostate cancer. Patients with prostate cancer represented 45% (50 of 111) of the study population. At week 13, 22 of 32 (69%) patients in the denosumab arms had urine N-telopeptide less than 50 vs 3 of 16 (19%) in the intravenous bisphosphonates cohort. At week 25, 22 of 32 (69%) denosumab treated patients continued to have urine N-telopeptide less than 50 vs 5 of 16 (31%) treated with intravenous bisphosphonates. Grade 4, asymptomatic, reversible hypophosphatemia, possibly related to denosumab, was reported in 1 patient. In patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates.

An online psychological intervention can improve the sexual satisfaction of men following treatment for localized prostate cancer: outcomes of a Randomised Controlled Trial evaluating My Road Ahead.

PubMed

Wootten, Addie C; Meyer, Denny; Abbott, Jo-Anne M; Chisholm, Katherine; Austin, David W; Klein, Britt; McCabe, Marita; Murphy, Declan G; Costello, Anthony J

2017-07-01

Prostate cancer treatment often results in significant psycho-sexual challenges for men following treatment; however, many men report difficulty in accessing appropriate care. A randomized controlled trial was undertaken to assess the efficacy of a 10-week self-guided online psychological intervention called My Road Ahead (MRA) for men with localized prostate cancer in improving sexual satisfaction. Participants were randomized to 1 of 3 conditions MRA alone or MRA plus online forum, or forum access alone. Pre, post, and follow-up assessments of overall sexual satisfaction were conducted. Mixed models and structural equation modeling were used to analyze the data. One hundred forty-two men (mean age 61 y; SD = 7) participated. The majority of participants had undergone radical prostatectomy (88%) and all men had received treatment for localized prostate cancer. Significant differences were obtained for the 3 groups (P = .026) and a significant improvement in total sexual satisfaction was observed only for participants who were allocated to MRA + forum with a large effect size (P = .004, partial η 2  = 0.256). Structural equation modeling indicated that increases in sexual function, masculine self-esteem, and sexual confidence contributed significantly to overall sexual satisfaction for the MRA + forum plus forum condition. This study is the first, to our knowledge, that has evaluated a self-guided online psychological intervention tailored to the specific needs of men with prostate cancer. The findings indicate the potential for MRA to deliver support that men may not otherwise receive and also highlight the importance of psychological intervention to facilitate improved sexual outcomes. Copyright © 2016 John Wiley & Sons, Ltd.

Fermented whey-based product improves the quality of life of males with moderate lower urinary tract symptoms: A randomized double-blind study.

PubMed

Ausmees, Kristo; Ehrlich-Peets, Kersti; Vallas, Mirjam; Veskioja, Andre; Rammul, Kadi; Rehema, Aune; Zilmer, Mihkel; Songisepp, Epp; Kullisaar, Tiiu

2018-01-01

The purpose of this research was to evaluate the effect of a specific fermented whey product on lower urinary tract symptoms, main prostate related indices and oxidative stress/inflammatory markers in urine and seminal plasma in men with moderate dysuric symptoms. An additional purpose was to clarify associations between different parameters with special emphasis on pain. This was a prospective randomized double-blind 4-weeks study on men with moderate lower urinary tract symptoms who underwent the evaluation for quality of life at the baseline and at the end of the study. The symptoms were characterized by International Prostate Symptom Score (I-PSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-PSI), the maximum urinary flow and the main prostate-related indices. In order to obtain more comprehensive information about the effects of fermented whey product on systemic oxidative stress marker 8-EPI and seminal plasma inflammatory markers (interleukin-6 and interleukin-8) were also measured. After 4 weeks consumption of fermented whey product there was a statistically significant decrease of prostate-specific antigen level in serum and systemic stress marker 8-EPI in urine compared to control group. Maximum urinary flow and NIH-PSI all studied scores and sub-scores had also significant improvement. In addition, seminal plasma interleukin-8 level substantially decreased. The consumption of special fermented whey product improved urinary function, reduced lower urinary tract symptoms, systemic oxidative stress marker and seminal plasma inflammatory status. Thus it contributed to an improvement of the quality of life in men with moderate lower urinary tract symptoms.

Pharmacokinetics and pharmacodynamics of LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2-f]quinolin-7(6H)-one], an orally available nonsteroidal-selective androgen receptor modulator.

PubMed

Vajda, Eric G; López, Francisco J; Rix, Peter; Hill, Robert; Chen, Yanling; Lee, Kyoung-Jin; O'Brien, Z; Chang, William Y; Meglasson, Martin D; Lee, Yong-Hee

2009-02-01

Selective androgen receptor modulators (SARMs) are a new class of molecules in development to treat a variety of diseases. SARMs maintain the beneficial effects of androgens, including increased muscle mass and bone density, while having reduced activity on unwanted side effects. The mechanisms responsible for the tissue-selective activity of SARMs are not fully understood, and the pharmacokinetic (PK)/pharmacodynamic (PD) relationships are poorly described. Tissue-specific compound distribution potentially could be a mechanism responsible for apparent tissue selectivity. We examined the PK/PD relationship of a novel SARM, LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo[3,2-f]quinolin-7(6H)-one], in a castrated rat model of androgen deficiency. LGD-3303 has potent activity on levator ani muscle but is a partial agonist on the preputial gland and ventral prostate. LGD-3303 never stimulated ventral prostate above intact levels despite increasing plasma concentrations of compound. Tissue-selective activity was maintained when LGD-3303 was dosed orally or by continuous infusion, two routes of administration with markedly different time versus exposure profiles. Despite the greater muscle activity relative to prostate activity, local tissue concentrations of LGD-3303 were higher in the prostate than in the levator ani muscle. LGD-3303 has SARM properties that are independent of its pharmacokinetic profile, suggesting that the principle mechanism for tissue-selective activity is the result of altered molecular interactions at the level of the androgen receptor.

Fish Oil Supplementation and Fatty Acid Synthase Expression in the Prostate: A Randomized Controlled Trial

DTIC Science & Technology

2008-03-01

green tea catechin, epigallocatechin -3- gallate ( EGCG ), is the fatty acid synthase (FAS) pathway. FAS, a lipogenic multienzyme that catalyzes the final...severity. Both EGCG and ω-3 FA have been shown in vitro and in vivo to inhibit this overexpression of FAS. Plan: The primary objective or our...proposal is to elucidate in men at high risk for prostate cancer, a potential biologic mechanism whereby EGCG , alone or in combination with ω-3 FA

HBCU Summer Undergraduate Training Program in Prostate Cancer: A Partnership Between USU-CPDR and UDC

DTIC Science & Technology

2016-10-01

Award Number: W81XWH-14-2-0142 TITLE: HBCU Summer Undergraduate Training Program in Prostate Cancer : A Partnership Between USU-CPDR and UDC... Cancer : A Partnership Between USU-CPDR and UDC 5a. CONTRACT NUMBER: 5b. GRANT NUMBER: W81XWH-14-2-0142 5c. PROGRAM ELEMENT NUMBER: 6. AUTHOR(S...second year of the award (2016), 4 meritorious students were selected under HBCU Summer Undergraduate Training Program in Prostate Cancer by USU-CPDR

Online updating of context-aware landmark detectors for prostate localization in daily treatment CT images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Xiubin; Gao, Yaozong; Shen, Dinggang, E-mail: dgshen@med.unc.edu

2015-05-15

Purpose: In image guided radiation therapy, it is crucial to fast and accurately localize the prostate in the daily treatment images. To this end, the authors propose an online update scheme for landmark-guided prostate segmentation, which can fully exploit valuable patient-specific information contained in the previous treatment images and can achieve improved performance in landmark detection and prostate segmentation. Methods: To localize the prostate in the daily treatment images, the authors first automatically detect six anatomical landmarks on the prostate boundary by adopting a context-aware landmark detection method. Specifically, in this method, a two-layer regression forest is trained as amore » detector for each target landmark. Once all the newly detected landmarks from new treatment images are reviewed or adjusted (if necessary) by clinicians, they are further included into the training pool as new patient-specific information to update all the two-layer regression forests for the next treatment day. As more and more treatment images of the current patient are acquired, the two-layer regression forests can be continually updated by incorporating the patient-specific information into the training procedure. After all target landmarks are detected, a multiatlas random sample consensus (multiatlas RANSAC) method is used to segment the entire prostate by fusing multiple previously segmented prostates of the current patient after they are aligned to the current treatment image. Subsequently, the segmented prostate of the current treatment image is again reviewed (or even adjusted if needed) by clinicians before including it as a new shape example into the prostate shape dataset for helping localize the entire prostate in the next treatment image. Results: The experimental results on 330 images of 24 patients show the effectiveness of the authors’ proposed online update scheme in improving the accuracies of both landmark detection and prostate segmentation. Besides, compared to the other state-of-the-art prostate segmentation methods, the authors’ method achieves the best performance. Conclusions: By appropriate use of valuable patient-specific information contained in the previous treatment images, the authors’ proposed online update scheme can obtain satisfactory results for both landmark detection and prostate segmentation.« less

Zinc Intake and Risk of Prostate Cancer: Case-Control Study and Meta-Analysis.

PubMed

Mahmoud, Abeer M; Al-Alem, Umaima; Dabbous, Firas; Ali, Mohamed M; Batai, Ken; Shah, Ebony; Kittles, Rick A

2016-01-01

Zinc is an essential dietary element that has been implicated in the pathogenesis of prostate cancer, a cancer that disproportionately affects men of African descent. Studies assessing the association of zinc intake and prostate cancer have yielded inconsistent results. Furthermore, very little is known about the relationship between zinc intake and prostate cancer among African Americans. We examined the association between self-reported zinc intake and prostate cancer in a hospital-based case-control study of African Americans. We then compared our results with previous studies by performing a meta-analysis to summarize the evidence regarding the association between zinc and prostate cancer. Newly diagnosed African American men with histologically confirmed prostate cancer (n = 127) and controls (n = 81) were recruited from an urban academic urology clinic in Washington, DC. Controls had higher zinc intake, with a mean of 14 mg/day versus 11 mg/day for cases. We observed a non-significant, non-linear increase in prostate cancer when comparing tertiles of zinc intake (OR <6.5 vs 6.5-12.5mg/day 1.8, 95% CI: 0.6,5.6; OR <6.5 vs >12.5mg/day 1.3, 95% CI: 0.2,6.5). The pooled estimate from 17 studies (including 3 cohorts, 2 nested case-control, 11 case-control studies, and 1 randomized clinical trial, with a total of 111,199 participants and 11,689 cases of prostate cancer) was 1.07hi vs lo 95% CI: 0.98-1.16. Using a dose-response meta-analysis, we observed a non-linear trend in the relationship between zinc intake and prostate cancer (p for nonlinearity = 0.0022). This is the first study to examine the relationship between zinc intake in black men and risk of prostate cancer and systematically evaluate available epidemiologic evidence about the magnitude of the relationship between zinc intake and prostate cancer. Despite of the lower intake of zinc by prostate cancer patients, our meta-analysis indicated that there is no evidence for an association between zinc intake and prostate cancer.

[Influence of Kudou Shencha decotion on INF-gamma, ICAM-1, MCP-1 levels of prostate tissue homogenate in immunity prostatitis model rats].

PubMed

Xia, Li-Ying; Liu, Wei-Jia; Li, Ming-Xi; Ge, Wen-Jin; Gao, Xue-Min; Zhang, Jian-Jun

2014-05-01

To investigate the influence of Kudou Shencha decotion on INF-y, ICAM-1, MCP-1 levels of prostate tissue homogenate in immunity prostatitis model rats. Forty Wistar male rats were divided into 5 groups randomly: Kudou Shencha decotion group with high dosage and low dosage, Qianleitai group, the model control group and normal group. The rat model of chronic nonbacterial prostatitis was established by multiple hypodermical injection of the suspension of prostatic protein purification with Freund's completed adjuvant. The level of intercellular adhesion molecule (ICAM-1), interferon gamma (INF-gamma) and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme linked immunosorbent assay (ELISA). The content of ICAM-1 and MCP-1 in the model group was higher than that of the normal group (P < 0.05), the content of ICAM-1 was obviously decreased in Kudou Shencha decotion group with high dosage (P <0.05), the contents of MCP-1 were all obviously decreased in Kudou Shencha decotion groups and Qianlietai group. Compared with the model group, the contents of INF-gamma in all treatment groups were decreased insignificantly. Kudou Shencha decotion has the action of lowering the level of ICAM-1 and MCP-1, which may be one of the mechanisms of Kudou Shencha decotion in the therapy of chronic prostatitis.

The histological and histometrical effects of Urtica dioica extract on rat's prostate hyperplasia.

PubMed

Moradi, Hamid Reza; Erfani Majd, Naeem; Esmaeilzadeh, Saleh; Fatemi Tabatabaei, Sayed Reza

2015-01-01

Benign prostatic hyperplasia (BPH) is a common disease in human that gradual overgrowth of the prostate gland leads to impinge on the urethra with impairment in urinary function. Numerous plants improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with BPH. In this study, 25 healthy adult male Wistar rats were divided randomly in five groups: G1 (Control group) received ordinary feed without any treatment, G2 received 10 mg kg(-1) testosterone subcutaneously, G3 received 50 mg kg(-1) nettle root extract orally, G4 received 50 mg kg(-1) nettle root extract orally and 10 mg kg(-1) testosterone, G5 received 10 mg kg(-1) almond oil (Almond oil was used as testosterone solvent) subcutaneously. After six weeks, volume and weight of each lobe were measured and samples were taken. The 5 to 6 µm thickness sections were made using paraffin embedding method and stained by hematoxylin and eosin and periodic acid-Schiff. The results showed that prostate volume and ratio of prostate to body weight were increased significantly in the testosterone. Histological and histometrical results showed that dorsal and lateral type 1 and 2 lobes were not changed significantly but the ventral and anterior lobes have changed significantly. Over all, the nettle root could prevent from some of prostatic hyperplasia effects, so that percentage of folded alveoli in ventral lobe reduced insignificantly.

Saw palmetto for benign prostatic hyperplasia.

PubMed

Bent, Stephen; Kane, Christopher; Shinohara, Katsuto; Neuhaus, John; Hudes, Esther S; Goldberg, Harley; Avins, Andrew L

2006-02-09

Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration. In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects. There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups. In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.). Copyright 2006 Massachusetts Medical Society.

Prostate cancer testing: behaviour, motivation and attitudes among Western Australian men.

PubMed

Slevin, T J; Donnelly, N; Clarkson, J P; English, D R; Ward, J E

1999-08-16

To estimate the proportion of Western Australian men aged 40-80 years who had been tested for prostate cancer, their experiences of screening and perception of its benefit. Cross-sectional survey (random telephone survey) of Western Australian men conducted in February 1998. 400 men aged 40-80 years from 670 eligible households (60% response rate from contactable households with eligible men). Proportion of respondents tested for prostate cancer (by prostate-specific antigen [PSA] test or digital rectal examination); reasons for having been tested; information provided by the doctor before testing; reasons given for and beliefs about the benefits of testing. Of 391 asymptomatic men, 220 (56%) recalled having been tested for prostate cancer and 167 (43%) had had a PSA test. Of those tested, 86% had their first test in the previous five years. The two most common reasons for testing were media publicity and general practitioner recommendation. Thirty-eight per cent of men tested during the previous five years reported that the doctor did not discuss the "pros and cons" of the test; 39% reported a discussion of less than five minutes' duration; 17% were given printed information before undergoing the test for the first time. Half were "very convinced" of the benefits of testing for prostate cancer. Men are being tested for prostate cancer with minimal pretest counselling or written information.

A review and meta-analysis of prospective studies of red and processed meat intake and prostate cancer

PubMed Central

2010-01-01

Over the past decade, several large epidemiologic investigations of meat intake and prostate cancer have been published. Therefore, a meta-analysis of prospective studies was conducted to estimate potential associations between red or processed meat intake and prostate cancer. Fifteen studies of red meat and 11 studies of processed meat were included in the analyses. High vs. low intake and dose-response analyses were conducted using random effects models to generate summary relative risk estimates (SRRE). No association between high vs. low red meat consumption (SRRE = 1.00, 95% CI: 0.96-1.05) or each 100 g increment of red meat (SRRE = 1.00, 95% CI: 0.95-1.05) and total prostate cancer was observed. Similarly, no association with red meat was observed for advanced prostate cancer (SRRE = 1.01, 95% CI: 0.94-1.09). A weakly elevated summary association between processed meat and total prostate cancer was found (SRRE = 1.05, 95% CI: 0.99-1.12), although heterogeneity was present, the association was attenuated in a sub-group analysis of studies that adjusted for multiple potential confounding factors, and publication bias likely affected the summary effect. In conclusion, the results of this meta-analysis are not supportive of an independent positive association between red or processed meat intake and prostate cancer. PMID:21044319

Changes in and Impact of the Death Review Process in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

PubMed

Miller, Anthony B; Feld, Ronald; Fontana, Robert; Gohagan, John K; Jatoi, Ismail; Lawrence, Walter; Miller, Amy; ProroK, Philip C; Rajput, Ashwani; Sherman, Morris; Welch, Gilbert; Wright, Patrick; Yurgalevitch, Susan; Albertsen, Peter

2015-01-01

Death review was conducted for the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial to avoid the biases associated with causes of death entered on death certificates. An algorithm selected deaths for review. Records on diagnosis and terminal illness were perused in the coordinating center and by the chair of the death review committee (DRC). Identifying information and randomization arm was removed. Three reviewers independently determined the cause of death. Disagreement was resolved at a meeting of the DRC. This process was subsequently simplified. The cause of death was determined by one DRC member and compared to the death certificate. With agreement the case was finalized. When discordant, the records were sent to a second DRC member. If the reviewers agreed, the case was finalized. If not, a third member reviewed. If two of the three reviewers agreed, the case was sent back to the discordant reviewer. If the reviewer remained discordant the case was resolved by a conference call. Of the 4728 death reviews that were completed, the DRC confirmed the death certificate underlying cause for over 90%. Between 5% and 13% of the certified deaths were regarded as indirect causes of death, associated with the treatment of the ascertained cancer; differential for prostate cancer, 11% in the intervention arm and 6% in the control. Without review, between 1% and 6% of the deaths that occurred would not have been assigned to the relevant PLCO cancer. The DRC completed 76% of those requiring review before the process ceased.

Withanolides from Aeroponically Grown Physalis peruviana and Their Selective Cytotoxicity to Prostate Cancer and Renal Carcinoma Cells.

PubMed

Xu, Ya-Ming; Wijeratne, E M Kithsiri; Babyak, Ashley L; Marks, Hanna R; Brooks, Alan D; Tewary, Poonam; Xuan, Li-Jiang; Wang, Wen-Qiong; Sayers, Thomas J; Gunatilaka, A A Leslie

2017-07-28

Investigation of aeroponically grown Physalis peruviana resulted in the isolation of 11 new withanolides, including perulactones I-L (1-4), 17-deoxy-23β-hydroxywithanolide E (5), 23β-hydroxywithanolide E (6), 4-deoxyphyperunolide A (7), 7β-hydroxywithanolide F (8), 7β-hydroxy-17-epi-withanolide K (9), 24,25-dihydro-23β,28-dihydroxywithanolide G (10), and 24,25-dihydrowithanolide E (11), together with 14 known withanolides (12-25). The structures of 1-11 were elucidated by the analysis of their spectroscopic data, and 12-25 were identified by comparison of their spectroscopic data with those reported. All withanolides were evaluated for their cytotoxic activity against a panel of tumor cell lines including LNCaP (androgen-sensitive human prostate adenocarcinoma), 22Rv1 (androgen-resistant human prostate adenocarcinoma), ACHN (human renal adenocarcinoma), M14 (human melanoma), SK-MEL-28 (human melanoma), and normal human foreskin fibroblast cells. Of these, the 17β-hydroxywithanolides (17-BHWs) 6, 8, 9, 11-13, 15, and 19-22 showed selective cytotoxic activity against the two prostate cancer cell lines LNCaP and 22Rv1, whereas 13 and 20 exhibited selective toxicity for the ACHN renal carcinoma cell line. These cytotoxicity data provide additional structure-activity relationship information for the 17-BHWs.

A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE).

PubMed

Radwan, Noura; Phillips, Ryan; Ross, Ashley; Rowe, Steven P; Gorin, Michael A; Antonarakis, Emmanuel S; Deville, Curtiland; Greco, Stephen; Denmeade, Samuel; Paller, Channing; Song, Daniel Y; Diehn, Maximilian; Wang, Hao; Carducci, Michael; Pienta, Kenneth J; Pomper, Martin G; DeWeese, Theodore L; Dicker, Adam; Eisenberger, Mario; Tran, Phuoc T

2017-06-29

We describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy (ADT)-free survival (ADT-FS). Further fundamental analysis of the oligometastatic state with be achieved through correlation with investigational 18 F-DCFPyL PET/CT imaging and measurement of circulating tumor cells, circulating tumor DNA, and circulating T-cell receptor repertoires, facilitating an unprecedented opportunity to characterize, in isolation, the effects of SABR on the dynamics of and immunologic response to oligometastatic disease. Patients will be randomized 2:1 to SABR or observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. Progression after 6 months will be compared using Fisher's exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival (PFS), ADT free survival (ADT-FS), time to locoregional progression (TTLP) and time to distant progression (TTDP) will be calculated based on an intention-to-treat. Local control will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Withdrawal from the study prior to 6 months will be counted as progression. Adverse events will be summarized by type and grade. Quality of life pre- and post- SABR will be measured by Brief Pain Inventory. The ORIOLE trial is the first randomized, non-blinded Phase II interventional study in the North America evaluating the safety and efficacy of SABR in oligometastatic hormone-sensitive prostate cancer. Leading-edge laboratory and imaging correlates will provide unique insight into the effects of SABR on the oligometastatic state. ClinicalTrials.gov Identifier: NCT02680587. URL of Registry: https://clinicaltrials.gov/show/NCT02680587 Date of Registration: 02/08/2016. Date of First Participant Enrollment: 05/23/2016.

Bispecific small molecule-antibody conjugate targeting prostate cancer.

PubMed

Kim, Chan Hyuk; Axup, Jun Y; Lawson, Brian R; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V; Schultz, Peter G

2013-10-29

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.

A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R-3327G and anabolic activity on skeletal muscle mass & function in castrated mice.

PubMed

Chisamore, Michael J; Gentile, Michael A; Dillon, Gregory Michael; Baran, Matthew; Gambone, Carlo; Riley, Sean; Schmidt, Azriel; Flores, Osvaldo; Wilkinson, Hilary; Alves, Stephen E

2016-10-01

The androgen receptor (AR) is a member of the nuclear hormone receptor super family of transcription factors. Androgens play an essential role in the development, growth, and maintenance of male sex organs, as well as the musculoskeletal and central nervous systems. Yet with advancing age, androgens can drive the onset of prostate cancer, the second leading cause of cancer death in males within the United States. Androgen deprivation therapy (ADT) by pharmacologic and/or surgical castration induces apoptosis of prostate cells and subsequent shrinkage of the prostate and prostate tumors. However, ADT is associated with significant musculoskeletal and behavioral adverse effects. The unique pharmacological activity of selective androgen receptor modulator (SARM) MK-4541 recently has been reported as an AR antagonist with 5α-reductase inhibitor function. The molecule inhibits proliferation and induces apoptosis in AR positive, androgen dependent prostate cancer cells. Importantly, MK-4541 inhibited androgen-dependent prostate growth in male rats yet maintained lean body mass and bone formation following ovariectomy in female rats. In the present study, we evaluated the effects of SARM MK-4541 in the androgen-dependent Dunning R3327-G prostate carcinoma xenograft mouse model as well as on skeletal muscle mass and function, and AR-regulated behavior in mice. MK-4541 significantly inhibited the growth of R3327-G prostate tumors, exhibited anti-androgen effects on the seminal vesicles, reduced plasma testosterone concentrations in intact males, and inhibited Ki67 expression. MK-4541 treated xenografts appeared similar to xenografts in castrated mice. Importantly, we demonstrate that MK-4541 exhibited anabolic activity in androgen deficient conditions, increasing lean body mass and muscle function in adult castrated mice. Moreover, MK-4541 treatment restored general activity levels in castrated mice. Thus, MK-4541 exhibits an optimum profile as an adjuvant therapy to ADT which may provide potent anti-androgenic activity at the prostate yet protective activity on skeletal muscle and behavior in patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

The changing practice of transurethral resection of the prostate.

PubMed

Young, M J; Elmussareh, M; Morrison, T; Wilson, J R

2018-04-01

Introduction Transurethral resection of the prostate (TURP) is considered the gold standard surgical treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia. The number of TURPs performed has declined significantly over the last three decades owing to pharmaceutical therapy. TURP data from a single institution for the years 1990, 2000 and 2010 were compared to assess the difference in performance. Methods A retrospective analysis was undertaken of all patients who underwent TURP between January and December 2010. These findings were compared with historical data for the years 1990 and 2000: 100 sets of case notes were selected randomly from each of these years. Results The number of TURPs performed fell from 326 in 1990 to 113 in 2010. The mean age of patients increased from 70.6 years to 74.0 years. There was also a significant increase in the mean ASA grade from 1.9 to 2.3. The most common indication for TURP shifted from LUTS to acute urinary retention. No significant change in operating time was observed. The mean resection weight remained constant (22.95g in 1990, 22.55g in 2000, 20.76g in 2010). A reduction in transfusion rates was observed but there were higher rates of secondary haematuria and bladder neck stenosis. There was an increase from 2% to 11.5% of patients with long-term failure to void following TURP. Conclusions The number of TURPs performed continues to decline, which could lead to potential training issues. Urinary retention is still by far the most common indication. However, there has been a significant rise in the percentage of men presenting for TURP with high pressure chronic retention. The number of patients with bladder dysfunction who either have persistent storage LUTS or eventually require long-term catheterisation or intermittent self-catheterisation has increased markedly, which raises the question of what the long-term real life impact of medical therapy is on men with LUTS secondary to benign prostatic hyperplasia who eventually require surgery.

WE-DE-201-04: Cross Validation of Knowledge-Based Treatment Planning for Prostate LDR Brachytherapy Using Principle Component Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roper, J; Ghavidel, B; Godette, K

Purpose: To validate a knowledge-based algorithm for prostate LDR brachytherapy treatment planning. Methods: A dataset of 100 cases was compiled from an active prostate seed implant service. Cases were randomized into 10 subsets. For each subset, the 90 remaining library cases were registered to a common reference frame and then characterized on a point by point basis using principle component analysis (PCA). Each test case was converted to PCA vectors using the same process and compared with each library case using a Mahalanobis distance to evaluate similarity. Rank order PCA scores were used to select the best-matched library case. Themore » seed arrangement was extracted from the best-matched case and used as a starting point for planning the test case. Any subsequent modifications were recorded that required input from a treatment planner to achieve V100>95%, V150<60%, V200<20%. To simulate operating-room planning constraints, seed activity was held constant, and the seed count could not increase. Results: The computational time required to register test-case contours and evaluate PCA similarity across the library was 10s. Preliminary analysis of 2 subsets shows that 9 of 20 test cases did not require any seed modifications to obtain an acceptable plan. Five test cases required fewer than 10 seed modifications or a grid shift. Another 5 test cases required approximately 20 seed modifications. An acceptable plan was not achieved for 1 outlier, which was substantially larger than its best match. Modifications took between 5s and 6min. Conclusion: A knowledge-based treatment planning algorithm for prostate LDR brachytherapy is being cross validated using 100 prior cases. Preliminary results suggest that for this size library, acceptable plans can be achieved without planner input in about half of the cases while varying amounts of planner input are needed in remaining cases. Computational time and planning time are compatible with clinical practice.« less

A comprehensive comparison of IMRT and VMAT plan quality for prostate cancer treatment

PubMed Central

QUAN, ENZHUO M.; LI, XIAOQIANG; LI, YUPENG; WANG, XIAOCHUN; KUDCHADKER, RAJAT J.; JOHNSON, JENNIFER L.; KUBAN, DEBORAH A.; LEE, ANDREW K.; ZHANG, XIAODONG

2013-01-01

Purpose We performed a comprehensive comparative study of the plan quality between volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for the treatment of prostate cancer. Methods and Materials Eleven patients with prostate cancer treated at our institution were randomly selected for this study. For each patient, a VMAT plan and a series of IMRT plans using an increasing number of beams (8, 12, 16, 20, and 24 beams) were examined. All plans were generated using our in-house-developed automatic inverse planning (AIP) algorithm. An existing 8-beam clinical IMRT plan, which was used to treat the patient, was used as the reference plan. For each patient, all AIP-generated plans were optimized to achieve the same level of planning target volume (PTV) coverage as the reference plan. Plan quality was evaluated by measuring mean dose to and dose-volume statistics of the organs-at-risk, especially the rectum, from each type of plan. Results For the same PTV coverage, the AIP-generated VMAT plans had significantly better plan quality in terms of rectum sparing than the 8-beam clinical and AIP-generated IMRT plans (p < 0.0001). However, the differences between the IMRT and VMAT plans in all the dosimetric indices decreased as the number of beams used in IMRT increased. IMRT plan quality was similar or superior to that of VMAT when the number of beams in IMRT was increased to a certain number, which ranged from 12 to 24 for the set of patients studied. The superior VMAT plan quality resulted in approximately 30% more monitor units than the 8-beam IMRT plans, but the delivery time was still less than 3 minutes. Conclusions Considering the superior plan quality as well as the delivery efficiency of VMAT compared with that of IMRT, VMAT may be the preferred modality for treating prostate cancer. PMID:22704703

Coffee, Caffeine, and Health Outcomes: An Umbrella Review.

PubMed

Grosso, Giuseppe; Godos, Justyna; Galvano, Fabio; Giovannucci, Edward L

2017-08-21

To evaluate the associations between coffee and caffeine consumption and various health outcomes, we performed an umbrella review of the evidence from meta-analyses of observational studies and randomized controlled trials (RCTs). Of the 59 unique outcomes examined in the selected 112 meta-analyses of observational studies, coffee was associated with a probable decreased risk of breast, colorectal, colon, endometrial, and prostate cancers; cardiovascular disease and mortality; Parkinson's disease; and type-2 diabetes. Of the 14 unique outcomes examined in the 20 selected meta-analyses of observational studies, caffeine was associated with a probable decreased risk of Parkinson's disease and type-2 diabetes and an increased risk of pregnancy loss. Of the 12 unique acute outcomes examined in the selected 9 meta-analyses of RCTs, coffee was associated with a rise in serum lipids, but this result was affected by significant heterogeneity, and caffeine was associated with a rise in blood pressure. Given the spectrum of conditions studied and the robustness of many of the results, these findings indicate that coffee can be part of a healthful diet.

Cell growth inhibition and apoptotic effects of a specific anti-RTFscFv antibody on prostate cancer, but not glioblastoma, cells

PubMed Central

Nejatollahi, Foroogh; Bayat, Payam; Moazen, Bahareh

2017-01-01

Background: Single chain antibody (scFv) has shown interesting results in cancer immunotargeting approaches, due to its advantages over monoclonal antibodies. Regeneration and tolerance factor (RTF) is one of the most important regulators of extracellular and intracellular pH in eukaryotic cells. In this study, the inhibitory effects of a specific anti-RTF scFv were investigated and compared between three types of prostate cancer and two types of glioblastoma cells.  Methods: A phage antibody display library of scFv was used to select specific scFvs against RTF using panning process. The reactivity of a selected scFv was assessed by phage ELISA. The anti-proliferative and apoptotic effects of the antibody on prostate cancer (PC-3, Du-145 and LNCaP) and glioblastoma (U-87 MG and A-172) cell lines were investigated by MTT and Annexin V/PI assays.  Results: A specific scFv with frequency 35% was selected against RTF epitope. This significantly inhibited the proliferation of the prostate cells after 24 h. The percentages of cell viability (using 1000 scFv/cell) were 52, 61 and 73% for PC-3, Du-145 and LNCaP cells, respectively, compared to untreated cells. The antibody (1000 scFv/cell) induced apoptosis at 50, 40 and 25% in PC-3, Du-145 and LNCaP cells, respectively. No growth inhibition and apoptotic induction was detected for U-87 and A172 glioblastoma cells.  Conclusions: Anti-RTFscFv significantly reduced the proliferation of the prostate cancer cells. The inhibition of cell growth and apoptotic induction effects in PC-3 cells were greater than Du-145 and LNCaP cells. This might be due to higher expression of RTF antigen in PC-3 cells and/or better accessibility of RTF to scFv antibody. The resistance of glioblastoma cells to anti-RTF scFv offers the existence of mechanism(s) that abrogate the inhibitory effect(s) of the antibody to RTF. The results suggest that the selected anti-RTF scFv antibody could be an effective new alternative for prostate cancer immunotherapy. PMID:28491282

Hypofractionation for Prostate Cancer

PubMed Central

Ritter, Mark; Forman, Jeffrey; Kupelian, Patrick; Lawton, Colleen; Petereit, Daniel

2011-01-01

Hypofractionation for prostate cancer was originally carried out in the pursuit of efficiency and convenience, but has now attracted greatly renewed interest based upon a hypothesis that prostate cancers have a higher sensitivity to fraction size, reflected in a low α/β ratio, then do late responding organs at risk such as the rectum or bladder. Tumor control and acceptable toxicity outcomes from several hypofractionation or brachytherapy analyses do in fact support an α/β ratio for prostate cancer that is low, perhaps even lower that that for the normal organs that ordinarily constrain the delivery of radiation therapy. However, many of these studies lack sufficient patient numbers and follow-up, are clouded by dose inhomogeneity issues in the case of brachytherapy, or delivered effective doses that were too low by contemporary standards. Thus, the clinical efficacy of the approach has yet to be fully validated. However, a number of newer prospective trials, some randomized, are underway or have reached accrual await sufficient follow-up for analysis. These studies, which cover a wide range of doses per fraction, should ultimately be capable of validating the utility of prostate hypofractionation and the models that predict its effects. With hypofractionation’s significant potential for therapeutic gain, cost savings and improved patient convenience, the future management of localized prostate cancer could be profoundly altered in the process. PMID:19197165

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein].

PubMed

Ahmadzadehfar, H; Albers, P; Bockisch, A; Boegemann, M; Böhme, C; Burchert, W; Dietlein, M; Drzezga, A; Fabry, U; Feldmann, G; Heidenreich, A; Heinzel, A; Herrmann, K; Heyll, A; Höhling, C; Kreuzer, C; Laufer, D; Mengel, R; Mottaghy, F M; Müller, H-W; Müller, S C; Ost, E; Rahbar, K; Reifenhäuser, W; Schäfers, M; Schlenkhoff, C; Schmidt, M; Schmidt-Wolf, I; Wildenhain, C; Zimmer, B; Essler, M

2018-06-01

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

Evaluating the efficiency of a combination of Pygeum africanum and stinging nettle (Urtica dioica) extracts in treating benign prostatic hyperplasia (BPH): double-blind, randomized, placebo controlled trial.

PubMed

Melo, Ezer A; Bertero, Eduardo B; Rios, Luiz A S; Mattos, Demerval

2002-01-01

In spite of its historical use, published data about phytotherapic products is characterized by the absence of well conducted studies, leading to conflictive and indefinite results about efficiency and safety of theses drugs. In that sense, we have analyzed the results of a combination of Pygeum africanum and stinging nettle (Urtica dioica) extracts in patients with benign prostatic hyperplasia (BPH), based in a double-blind, randomized, placebo-controlled protocol. We have selected, according to inclusion and exclusion criteria, only patients with >or=50 years, presenting urinary symptoms assessed by the International Prostatic Symptoms Score (IPSS), with minimum score of 12, and Quality of Life (QoL) index of at least 3 points, rectal examination consistent with BPH, and maximum urinary flow rate (Q(max)) between 5 and 15 mL/s. Phytotherapic and placebo groups were formed by 27 and 22 patients, respectively. The major variables analyzed during the study were IPSS variation, Q(max), and side effects. Reduction of >or=30% and >or=50% in IPSS were the parameters used to define a clinically significant response (CSR). We have also analyzed >or=30% and >or=50% Q(max) increases. After six months of treatment we did not observe significant differences in clinical improvement potential between the phytotherapic combination and placebo groups. Percent IPSS drop of 21.6% in the phytotherapic group was similar to 19.7% obtained in the placebo group (p=0.928). Neither we observed any difference (p=0.530) for QoL improvement between phytotherapic (9.26%) and placebo (5.98%) groups. The alterations of Q(max) followed the trend line observed in clinical data, with no significant difference (p=0.463) in Q(max) increasing percent between phytotherapic (17.2%) and placebo (13.3%) groups. The CSR evaluation of clinical and urodynamic data was also similar between the groups. The combination of 25mg Pygeum africanum and 300mg stinging nettle extracts produced clinical and urodynamic effects similar to placebo in a group of HBP patients.

SU-D-204-06: Integration of Machine Learning and Bioinformatics Methods to Analyze Genome-Wide Association Study Data for Rectal Bleeding and Erectile Dysfunction Following Radiotherapy in Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oh, J; Deasy, J; Kerns, S

Purpose: We investigated whether integration of machine learning and bioinformatics techniques on genome-wide association study (GWAS) data can improve the performance of predictive models in predicting the risk of developing radiation-induced late rectal bleeding and erectile dysfunction in prostate cancer patients. Methods: We analyzed a GWAS dataset generated from 385 prostate cancer patients treated with radiotherapy. Using genotype information from these patients, we designed a machine learning-based predictive model of late radiation-induced toxicities: rectal bleeding and erectile dysfunction. The model building process was performed using 2/3 of samples (training) and the predictive model was tested with 1/3 of samples (validation).more » To identify important single nucleotide polymorphisms (SNPs), we computed the SNP importance score, resulting from our random forest regression model. We performed gene ontology (GO) enrichment analysis for nearby genes of the important SNPs. Results: After univariate analysis on the training dataset, we filtered out many SNPs with p>0.001, resulting in 749 and 367 SNPs that were used in the model building process for rectal bleeding and erectile dysfunction, respectively. On the validation dataset, our random forest regression model achieved the area under the curve (AUC)=0.70 and 0.62 for rectal bleeding and erectile dysfunction, respectively. We performed GO enrichment analysis for the top 25%, 50%, 75%, and 100% SNPs out of the select SNPs in the univariate analysis. When we used the top 50% SNPs, more plausible biological processes were obtained for both toxicities. An additional test with the top 50% SNPs improved predictive power with AUC=0.71 and 0.65 for rectal bleeding and erectile dysfunction. A better performance was achieved with AUC=0.67 when age and androgen deprivation therapy were added to the model for erectile dysfunction. Conclusion: Our approach that combines machine learning and bioinformatics techniques enabled designing better models and identifying more plausible biological processes associated with the outcomes.« less

Discovery of peptide drug carrier candidates for targeted multi-drug delivery into prostate cancer cells.

PubMed

Bashari, O; Redko, B; Cohen, A; Luboshits, G; Gellerman, G; Firer, M A

2017-11-01

Metastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells. Phage from a libraries displaying 7mer peptides were exposed to PC-3 cells and only internalized phage were recovered. The ability of these phage to internalize into other prostate cancer cells (LNCaP, DU-145) was validated. The displayed peptides of selected phage clones were synthesized and their specificity for target cells was validated in vitro and in vivo. One peptide (P12) which specifically targeted PC-3 tumors in vivo was incorporated into mono-drug (Chlorambucil, Combretastatin or Camptothecin) and dual-drug (Chlorambucil/Combretastatin or Chlorambucil/Camptothecin) PDCs and the cytotoxic efficacy of these conjugates for target cells was tested. Conjugation of P12 into dual-drug PDCs allowed discovery of new drug combinations with synergistic effects. The use of strict selection criteria can lead to discovery of novel peptides for use as drug carriers for TDD. PDCs represent an effective alternative to current modes of free drug chemotherapy for prostate cancer. Copyright © 2017. Published by Elsevier B.V.

Benzoxazinone-containing 3,5-dimethylisoxazole derivatives as BET bromodomain inhibitors for treatment of castration-resistant prostate cancer.

PubMed

Xue, Xiaoqian; Zhang, Yan; Wang, Chao; Zhang, Maofeng; Xiang, Qiuping; Wang, Junjian; Wang, Anhui; Li, Chenchang; Zhang, Cheng; Zou, Lingjiao; Wang, Rui; Wu, Shuang; Lu, Yongzhi; Chen, Hongwu; Ding, Ke; Li, Guohui; Xu, Yong

2018-04-21

The bromodomain and extra-terminal proteins (BET) have emerged as promising therapeutic targets for the treatment of castration-resistant prostate cancer (CRPC). We report the design, synthesis and evaluation of a new series of benzoxazinone-containing 3,5-dimethylisoxazole derivatives as selective BET inhibitors. One of the new compounds, (R)-12 (Y02234), binds to BRD4(1) with a K d value of 110 nM and blocks bromodomain and acetyl lysine interactions with an IC 50 value of 100 nM. It also exhibits selectivity for BET over non-BET bromodomain proteins and demonstrates reasonable anti-proliferation and colony formation inhibition effect in prostate cancer cell lines such as 22Rv1 and C4-2B. The BRD4 inhibitor (R)-12 also significantly suppresses the expression of ERG, Myc and AR target gene PSA at the mRNA level in prostate cancer cells. Treatment with (R)-12 significantly suppresses the tumor growth of prostate cancer (TGI = 70%) in a 22Rv1-derived xenograft model. These data suggest that compound (R)-12 is a promising lead compound for the development of a new class of therapeutics for the treatment of CRPC. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Are we selecting the right patients for treatment of localized prostate cancer? Results of an actuarial analysis.

PubMed

Koch, M O; Miller, D A; Butler, R; Lebos, L; Collings, D; Smith, J A

1998-02-01

To determine our accuracy in selecting patients with at least a 10-year life expectancy for aggressive treatment of localized prostate cancer. The medical records of 261 consecutive patients who underwent radical retropubic prostatectomy were submitted to the actuarial division of American General Life and Accident Insurance Company (AGLA) for estimation of life expectancy, excluding the diagnosis of prostate cancer. Survival curves were generated from predicted individual survivals. In patients with less than a 10-year life expectancy, AGLA provided us with the basis for assigning suboptimal survival rates. The mean life expectancy for the group was 15.2 years. Two hundred ten men (80%) were projected to have a life expectancy of more than 10 years, including 27 of 55 (49%) and 4 of 8 (50%) men who were older than or equal to 70 and 75 years of age, respectively. Coronary artery disease and diabetes mellitus were the most common coexisting medical conditions that adversely affected risk as single disease entities. Although clinicians do not estimate life expectancy with the scientific exactitude of an actuary, the ability to assess the patient in person and assimilate pertinent medical information in a less rigid format yields similar results. Selection of men for definitive treatment of localized prostate cancer should be based on the inherent aggressiveness of the disease and the health of the individual and should not be limited by specific age cutoffs. Populations of men undergoing radical prostatectomy are younger and healthier than those in reported series of watchful waiting for prostate cancer.

Prostate Cancer Detection and Diagnosis: The Role of MR and its Comparison to other Diagnostic Modalities – A Radiologist's Perspective

PubMed Central

Penzkofer, Tobias; Tempany-Afdhal, Clare M.

2013-01-01

It is now universally recognized that many prostate cancers are over-diagnosed and over-treated. The European Randomized Study of Screening for Prostate Cancer (ERSPC) from 2009 evidenced that, to save one man from death of prostate cancer, over 1,400 men had to be screened, and 48 had to undergo treatment. Detection of prostate cancer is traditionally based upon digital rectal examination (DRE) and measuring serum prostate specific antigen (PSA), followed by ultrasound guided biopsy. The primary role of imaging for the detection and diagnosis of prostate cancer has been transrectal ultrasound (TRUS) guidance during biopsy. MRI has traditionally been used primarily for staging disease in men with biopsy proven cancer. It is has a well-established role in detecting T3 disease, planning radiation therapy, especially 3D conformal or intensity modulated external beam radiation therapy (IMRT), and planning and guiding interstitial seed implant or brachytherapy. New advances have now established prostate MRI can accurately characterize focal lesions within the gland, an ability that has led to new opportunities for improved cancer detection and guidance for biopsy. There are two new approaches to prostate biopsy are under investigation both use pre-biopsy MRI to define potential targets for sampling and then the biopsy is performed either with direct real-time MR guidance (in-bore) or MR fusion/registration with TRUS images (out-of-bore). In-bore or out-of-bore MRI-guided prostate biopsies have the advantage of using the MR target definition for accurate localization and sampling of targets or suspicious lesions. The out-of-bore method uses combined MRI/TRUS with fusion software that provided target localization and increases the sampling accuracy for TRUS-guided biopsies by integrating prostate MRI information with TRUS. Newer parameters for each imaging modality such as sonoelastography or shear wave elastography (SWE), contrast enhanced US (CEUS) and MRI-elastography, show promise to further enrich data sets. PMID:24000133

Transurethral Resection of the Prostate (TURP) Versus Original and PErFecTED Prostate Artery Embolization (PAE) Due to Benign Prostatic Hyperplasia (BPH): Preliminary Results of a Single Center, Prospective, Urodynamic-Controlled Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carnevale, Francisco C., E-mail: fcarnevale@uol.com.br; Iscaife, Alexandre, E-mail: iscaifeboni@yahoo.com.br; Yoshinaga, Eduardo M., E-mail: dumuracca@ig.com.br

PurposeTo compare clinical and urodynamic results of transurethral resection of the prostate (TURP) to original and PErFecTED prostate artery embolization (PAE) methods for benign prostatic hyperplasia.MethodsWe prospectively randomized 30 patients to receive TURP or original PAE (oPAE) and compared them to a cohort of patients treated by PErFecTED PAE, with a minimum of 1-year follow-up. Patients were assessed for urodynamic parameters, prostate volume, international prostate symptom score (IPSS), and quality of life (QoL).ResultsAll groups were comparable for all pre-treatment parameters except bladder contractility and peak urine flow rate (Q{sub max}), both of which were significantly better in the TURP group,more » and IIEF score, which was significantly higher among PErFecTED PAE patients than TURP patients. All groups experienced significant improvement in IPSS, QoL, prostate volume, and Q{sub max}. TURP and PErFecTED PAE both resulted in significantly lower IPSS than oPAE but were not significantly different from one another. TURP resulted in significantly higher Q{sub max} and significantly smaller prostate volume than either original or PErFecTED PAE but required spinal anesthesia and hospitalization. Two patients in the oPAE group with hypocontractile bladders experienced recurrence of symptoms and were treated with TURP. In the TURP group, urinary incontinence occurred in 4/15 patients (26.7 %), rupture of the prostatic capsule in 1/15 (6.7 %), retrograde ejaculation in all patients (100 %), and one patient was readmitted for temporary bladder irrigation due to hematuria.ConclusionsTURP and PAE are both safe and effective treatments. TURP and PErFecTED PAE yield similar symptom improvement, but TURP is associated with both better urodynamic results and more adverse events.« less

LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality

PubMed Central

Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna

2017-01-01

ABSTRACT Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982–1988 and 1993–1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95–2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03–21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression. PMID:27892790

Automatic segmentation of the prostate on CT images using deep learning and multi-atlas fusion

NASA Astrophysics Data System (ADS)

Ma, Ling; Guo, Rongrong; Zhang, Guoyi; Tade, Funmilayo; Schuster, David M.; Nieh, Peter; Master, Viraj; Fei, Baowei

2017-02-01

Automatic segmentation of the prostate on CT images has many applications in prostate cancer diagnosis and therapy. However, prostate CT image segmentation is challenging because of the low contrast of soft tissue on CT images. In this paper, we propose an automatic segmentation method by combining a deep learning method and multi-atlas refinement. First, instead of segmenting the whole image, we extract the region of interesting (ROI) to delete irrelevant regions. Then, we use the convolutional neural networks (CNN) to learn the deep features for distinguishing the prostate pixels from the non-prostate pixels in order to obtain the preliminary segmentation results. CNN can automatically learn the deep features adapting to the data, which are different from some handcrafted features. Finally, we select some similar atlases to refine the initial segmentation results. The proposed method has been evaluated on a dataset of 92 prostate CT images. Experimental results show that our method achieved a Dice similarity coefficient of 86.80% as compared to the manual segmentation. The deep learning based method can provide a useful tool for automatic segmentation of the prostate on CT images and thus can have a variety of clinical applications.

Depletion kinetics of circulating prostate cancer cells studied by in vivo flow cytometer

NASA Astrophysics Data System (ADS)

Liu, Guangda; Guo, Jin; Li, Yan; Chen, Yun; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

2010-11-01

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal nearinfrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

Studying circulating prostate cancer cells by in-vivo flow cytometer

NASA Astrophysics Data System (ADS)

Guo, Jin; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

2012-03-01

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. We have measured the depletion kinetics of cancer cells with different metastatic potential. Interestingly, more invasive PC-3 prostate cancer cells are depleted faster from the circulation than LNCaP cells.

Studying depletion kinetics of circulating prostate cancer cells by in vivo flow cytometer

NASA Astrophysics Data System (ADS)

Liu, Guangda; Gu, Zhengqin; Guo, Jin; Li, Yan; Chen, Yun; Chen, Tong; Wang, Cheng; Wei, Xunbin

2011-03-01

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

Abiraterone acetate in the treatment of prostate cancer.

PubMed

Thakur, Abhimanyu; Roy, Aishwarya; Ghosh, Arijit; Chhabra, Mohit; Banerjee, Sugato

2018-05-01

Among all cancer-related death, prostate cancer accounts for the second prominent reason for cancer-associated death in men. Despite the castration mediated reduction in testosterone synthesis, adrenal glands, as well as tissues of prostate cancer, continue to produce androgens, which ultimately lead to the growth of prostate cancer. This phase is referred as metastatic castration-resistant prostate cancer, which throws an obstacle to treatment. Androgen antagonists, in addition to deprivation of hormone, is being used for reducing the level of prostate-specific antigen but has not successfully come in front as a choice for prolonging the life of patients suffering from prostate cancer. In this prevailing scenario, abiraterone acetate (AA) has proved to be a boon for patients suffering from prostate cancer. AA selectively inhibits the actions of enzymes C17, 20-lyase and 17α-hydroxylase on cytochrome P450 (CYP) 17 when administered orally. The signaling of androgen receptor, being important for primary to metastatic phases of prostate cancer, CYP17 is essential for the synthesis of androgen. Herein, the in-detail pharmacological profile of AA, including androgen signaling, mechanism of action of AA, mechanism of AA resistance, pharmacokinetics, latest clinical findings, predictive markers, optimal treatment sequence, toxicity, and food interaction profiles have been reviewed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Screening spectroscopy of prostate cancer

NASA Astrophysics Data System (ADS)

Yermolenko, S. B.; Voloshynskyy, D. I.; Fedoruk, O. S.

2015-11-01

The aim of the study was to establish objective parameters of the field of laser and incoherent radiation of different spectral ranges (UV, visible, IR) as a non-invasive optical method of interaction with different samples of biological tissues and fluids of patients to determine the state of prostate cancer and choosing the best personal treatment. The objects of study were selected venous blood plasma of patient with prostate cancer, histological sections of rat prostate gland in the postoperative period. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5-25 microns) dry residue of plasma by spectral diagnostic technique of thin histological sections of biological tissues.

Micrornas in prostate cancer: an overview

PubMed Central

Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Di Franco, Rossella; Romano, Francesco Jacopo; Montanari, Micaela; La Mantia, Elvira; Piscitelli, Raffaele; Nocerino, Flavia; Cappuccio, Francesca; Grimaldi, Giovanni; Izzo, Alessandro; Castaldo, Luigi; Pepe, Maria Filomena; Malzone, Maria Gabriella; Iovane, Gelsomina; Ametrano, Gianluca; Stiuso, Paola; Quagliuolo, Lucio; Barberio, Daniela; Perdonà, Sisto; Muto, Paolo; Montella, Maurizio; Maiolino, Piera; Veneziani, Bianca Maria; Botti, Gerardo; Caraglia, Michele; Facchini, Gaetano

2017-01-01

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis. PMID:28445135

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention

PubMed Central

Kumar, Nagi B.; Pow-Sang, Julio; Egan, Kathleen M.; Spiess, Philippe E.; Dickinson, Shohreh; Salup, Raoul; Helal, Mohamed; McLarty, Jerry; Williams, Christopher R.; Schreiber, Fred; Parnes, Howard L.; Sebti, Said; Kazi, Aslam; Kang, Loveleen; Quinn, Gwen; Smith, Tiffany; Yue, Binglin; Diaz, Karen; Chornokur, Ganna; Crocker, Theresa; Schell, Michael J.

2015-01-01

Preclinical, epidemiological and prior clinical trial data suggest that green tea catechins (GTCs) may reduce prostate cancer (PCa) risk. We conducted a placebo-controlled, randomized clinical trial of Polyphenon E® (PolyE), a proprietary mixture of GTCs, containing 400 mg (–)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). The primary study endpoint was a comparison of the cumulative one-year PCa rates on the two study arms. No differences in the number of PCa cases were observed: 5/49 (PolyE) versus 9/48 (placebo), P=0.25. A secondary endpoint comparing the cumulative rate of PCa plus ASAP among men with HGPIN without ASAP at baseline, revealed a decrease in this composite endpoint: 3/26 (PolyE) versus 10/25 (placebo), P<0.024. This finding was driven by a decrease in ASAP diagnoses on the Poly E (0/26) compared to the placebo arm (5/25). A decrease in serum prostate specific antigen (PSA) was observed on the PolyE arm [−0.87 ng/ml (95%CI: −1.66, −0.09)]. Adverse events related to the study agent did not significantly differ between the two study groups. Daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of PCa in men with baseline HGPIN or ASAP. PMID:25873370

[Multicentre randomized trial comparing triptorelin medical castration versus surgical castration in the treatment of locally advanced or metastatic prostate cancer].

PubMed

Botto, Henry; Rouprêt, Morgan; Mathieu, François; Richard, François

2007-04-01

To report the results of a trial comparing the efficacy of triptorelin and surgical castration in the treatment of locally advanced or metastatic prostate cancer. 80 patients with previously untreated locally advanced or metastatic prostate cancer prostate cancer were included in a one-year multicentre, randomized, prospective, open-label therapeutic trial. Patients either received a monthly injection of triptorelin (group 1; n = 40), or were treated by pulpectomy (group 2; n = 40). Patients were reviewed every 3 months, then every 6 months. The mean age of the patients was 71.22 +/- 8.25 years. At 1 month, 38 patients were castrated (plasma testosterone < 0.5 mg/ml) in the pulpectomy group versus 35 in the triptorelin group. The mean follow-up was 38.8 +/- 26 months in the triptorelin group and 36.3 +/- 25 months in the pulpectomy group. On multivariate analysis, age, impaired performance status and PAP level (> 3.2 ng/ml) were predictive factors of a poor outcome. The median survival was 37.5 +/- 9 months in the triptorelin group and 33 +/- 3 months in the pulpectomy group. At 3 years, no significant difference in specific survival was observed between the 2 groups. At 8 years of follow-up, 63 patients had died. This study demonstrates an equivalent specific survival between patients treated by triptorelin or surgical castration. Castration is rapidly obtained with triptorelin (< 2 months) and is maintained over time throughout the duration of treatment.

Transcriptome instability as a molecular pan-cancer characteristic of carcinomas.

PubMed

Sveen, Anita; Johannessen, Bjarne; Teixeira, Manuel R; Lothe, Ragnhild A; Skotheim, Rolf I

2014-08-10

We have previously proposed transcriptome instability as a genome-wide, pre-mRNA splicing-related characteristic of colorectal cancer. Here, we explore the hypothesis of transcriptome instability being a general characteristic of cancer. Exon-level microarray expression data from ten cancer datasets were analyzed, including breast cancer, cervical cancer, colorectal cancer, gastric cancer, lung cancer, neuroblastoma, and prostate cancer (555 samples), as well as paired normal tissue samples from the colon, lung, prostate, and stomach (93 samples). Based on alternative splicing scores across the genomes, we calculated sample-wise relative amounts of aberrant exon skipping and inclusion. Strong and non-random (P < 0.001) correlations between these estimates and the expression levels of splicing factor genes (n = 280) were found in most cancer types analyzed (breast-, cervical-, colorectal-, lung- and prostate cancer). This suggests a biological explanation for the splicing variation. Surprisingly, these associations prevailed in pan-cancer analyses. This is in contrast to the tissue and cancer specific patterns observed in comparisons across healthy tissue samples from the colon, lung, prostate, and stomach, and between paired cancer-normal samples from the same four tissue types. Based on exon-level expression profiling and computational analyses of alternative splicing, we propose transcriptome instability as a molecular pan-cancer characteristic. The affected cancers show strong and non-random associations between low expression levels of splicing factor genes, and high amounts of aberrant exon skipping and inclusion, and vice versa, on a genome-wide scale.

[Transurethral resection of bladder tumors and prostate enlargement in physiological saline solution (TURIS). A prospective study].

PubMed

Rose, A; Suttor, S; Goebell, P J; Rossi, R; Rübben, H

2007-09-01

Transurethral resection in a conductive irrigant medium is a new procedure in the surgical therapy of bladder tumors and prostate enlargement. In this prospective randomized trial we compared conventional TUR with TUR in saline regarding safety and efficiency. Between November 2004 and February 2005 a total number of 128 patients were included in this study. After randomization 58 patients were treated by conventional TUR and 70 patients by TURIS (Olympus, SurgMasterSystem). We evaluated resection time, weight of resected tissue, complications, blood loss, changes in serum sodium, and duration of catheterization. Among the tested procedures no statistically significant difference could be observed concerning blood loss, change of serum sodium, and complications. The mean weight of resected tissue of the prostate per time was 0.9 g/min with the TUR procedure and 0.8 g/min with the TURIS procedure. Severe complications like TUR syndrome or perforation of the bladder were not observed at all. In the TURIS group time until catheter removal was longer but also the mean weight of resected tissue of the prostate was higher in the TURIS group (42 g) than in the conventional TUR group (31 g). Transurethral resection in a conductive irrigant medium (TURIS) can be considered as a safe and effective surgical procedure in the treatment of BPH and superficial urothelial carcinoma. Moreover the risk of TUR syndrome and perforation of the bladder due to nerve stimulation is reduced.

Hypofractionated radiation therapy for prostate cancer: biologic and technical considerations

PubMed Central

Sanfilippo, Nicholas J; Cooper, Benjamin T

2014-01-01

The optimal radiation schedule for the curative treatment of prostate cancer is not known. The dose-response of tumors and normal tissues to fractionated irradiation can be described according to a parameter called the alpha-beta ratio (α/β). In the past several years numerous reports have been published that suggest that the alpha-beta ratio for prostate cancer may be quite low; between 1 and 3. If this hypothesis is true, then a radiation therapy schedule that employs less frequent and larger fractions, termed hypofractionation, may be more efficacious. Multiple randomized trials have been conducted comparing moderate (less than 5 Gy/day) hypofractionated radiation therapy and standard radiation therapy in men with prostate cancer. In the majority of these studies the moderate hypofractionated arm had equivalent efficacy with a similar or improved side effect profile. One area to use caution may be in patients with compromised (IPSS > 12) urinary function at baseline due to an increase in urinary toxicity observed in patients treated with hypofractionated radiation in one study. Extreme hypofractionation (greater than or equal to 5 Gy/day), is currently being compared in a randomized trial. Early prospectively collected data from multiple institutions demonstrates efficacy and toxicity that compares favorably with historical controls. The cost savings from hypofractionation could be profound on a national level and only increases the necessity of testing hypofractionated treatment schedules. Long term data and future trials will help radiation oncologists determine the ideal fractionation scheme based on cost, efficacy, and toxicity. PMID:25606574

[The local anesthesia for the prostatic biopsies echo-guided: forward-looking randomized study comparing two methods].

PubMed

Moudouni, S M; Zahraoui, M R; Adarmouch, L; Lakmichi, M A; Bentani, N; Jarir, R; Dahami, Z; Amine, M; Sarf, I

2014-02-01

The realization of the prostatic biopsies is a painful act. The objective of our work was to compare the analgesic efficiency of the injection of the lidocaine at the level of periprostatics laterals and apical areas compared with the use of gel of lidocaine intrarectal associated with the taking of oral tramadol. Between November 2007 and December 2009, 60 patients admitted in the service of urology of the university hospital Mohammed VI of Marrakesh for prostatic biopsies were randomized in two groups. The group 1 (30 patients) received two tablets from tramadol 50mg with 10 mL of gel of lidocaine 2% intrarectal while 30 patients of the group 2 received 10 mL from lidocaine 2% injected at the level of periprostatics laterals and apicales. The pain was estimated by a visual analog scale (AVS) at the introduction of the probe of echography (AVS 1), at the time of the biopsy (AVS 2) and 20 minutes later (AVS 3). There was no significant difference between both groups concerning AVS 1 means. The average score of the pain was significantly lower in the group 2 for the AVS 2 and AVS 3. The periprostatics anesthesia assured a better control of the pain at the time of the prostatic biopsy and 20 minutes later, without increase of the complications. We recommend it to decrease the pain and the discomfort related to this technique. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Fried food and prostate cancer risk: systematic review and meta-analysis.

PubMed

Lippi, Giuseppe; Mattiuzzi, Camilla

2015-01-01

We performed systematic review and meta-analysis of published studies that investigated the potential association between fried food consumption and prostate cancer risk. Four case-control studies were finally selected for this systematic literature review, totaling 2579 cancer patients and 2277 matched controls. In two of these studies, the larger intake of fried food was associated with a 1.3- to 2.3-fold increased risk of prostate cancer, no significant association was found in another, whereas an inverse relationship was observed in the remaining. The meta-analysis of published data showed that larger intake of fried food was associated with a 35% (95% CI 17-57%) increased risk of prostate cancer. The results of this systematic literature review support the notion that larger intake of fried foods may have a role in increasing the risk of prostate cancer.

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

PubMed

Forno, Irene; Ferrero, Stefano; Russo, Maria Veronica; Gazzano, Giacomo; Giangiobbe, Sara; Montanari, Emanuele; Del Nero, Alberto; Rocco, Bernardo; Albo, Giancarlo; Languino, Lucia R; Altieri, Dario C; Vaira, Valentina; Bosari, Silvano

2015-01-01

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

Investigating the possible causal role of coffee consumption with prostate cancer risk and progression using Mendelian randomization analysis

PubMed Central

Martin, Richard M.; Geybels, Milan S.; Stanford, Janet L.; Shui, Irene; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay‐Tee; Blot, William; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Donovan, Jenny; Munafò, Marcus R.

2016-01-01

Coffee consumption has been shown in some studies to be associated with lower risk of prostate cancer. However, it is unclear if this association is causal or due to confounding or reverse causality. We conducted a Mendelian randomisation analysis to investigate the causal effects of coffee consumption on prostate cancer risk and progression. We used two genetic variants robustly associated with caffeine intake (rs4410790 and rs2472297) as proxies for coffee consumption in a sample of 46,687 men of European ancestry from 25 studies in the PRACTICAL consortium. Associations between genetic variants and prostate cancer case status, stage and grade were assessed by logistic regression and with all‐cause and prostate cancer‐specific mortality using Cox proportional hazards regression. There was no clear evidence that a genetic risk score combining rs4410790 and rs2472297 was associated with prostate cancer risk (OR per additional coffee increasing allele: 1.01, 95% CI: 0.98,1.03) or having high‐grade compared to low‐grade disease (OR: 1.01, 95% CI: 0.97,1.04). There was some evidence that the genetic risk score was associated with higher odds of having nonlocalised compared to localised stage disease (OR: 1.03, 95% CI: 1.01, 1.06). Amongst men with prostate cancer, there was no clear association between the genetic risk score and all‐cause mortality (HR: 1.00, 95% CI: 0.97,1.04) or prostate cancer‐specific mortality (HR: 1.03, 95% CI: 0.98,1.08). These results, which should have less bias from confounding than observational estimates, are not consistent with a substantial effect of coffee consumption on reducing prostate cancer incidence or progression. PMID:27741566

Prostate-specific antigen screening and mortality from prostate cancer.

PubMed

Marcella, Stephen W; Rhoads, George G; Carson, Jeffrey L; Merlino, Frances; Wilcox, Homer

2008-03-01

There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55-79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2-29.2% of cases and 21.8-26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality.

Prostate-Specific Antigen Screening and Mortality from Prostate Cancer

PubMed Central

Rhoads, George G.; Carson, Jeffrey L.; Merlino, Frances; Wilcox, Homer

2008-01-01

Background There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. Objective The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. Design, setting, and participants This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55–79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Results Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2–29.2% of cases and 21.8–26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. Conclusions PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality. PMID:18172740

Perinatal and childhood factors and risk of prostate cancer in adulthood: MCC-Spain case-control study.

PubMed

Lope, Virginia; García-Esquinas, Esther; Ruiz-Dominguez, José Manuel; LLorca, Javier; Jiménez-Moleón, José Juan; Ruiz-Cerdá, José L; Alguacil, Juan; Tardón, Adonina; Dierssen-Sotos, Trinidad; Tabernero, Ángel; Mengual, Lourdes; Kogevinas, Manolis; Aragonés, Nuria; Castaño-Vinyals, Gemma; Pollán, Marina; Pérez-Gómez, Beatriz

2016-08-01

In utero and early-life exposures are suspected to modulate the risk of prostate cancer. This study examines the influence of certain perinatal and childhood-related factors on prostate cancer risk overall and by Gleason score at biopsy. MCC-Spain is a multicase-control study where 1088 histologically-confirmed incident prostate cancer cases (aged 42-85years) and 1345 population-based controls (aged 38-85years), frequency matched by age and province of recruitment, were recruited in 7 Spanish provinces. Self-reported perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with prostate cancer risk, globally and according to Gleason score at biopsy, was evaluated using logistic and multinomial regression mixed models, adjusting for age, family history of prostate cancer, educational level and body mass index one year before the interview, and including the province as a random effect term. Most perinatal factors were not related to prostate cancer risk, with the exception of middle-high socioeconomic level at birth (OR for high grade tumors=1.36; 95%CI=1.09-1.68). Regarding puberty, risk rose by 6% for each year of delayed onset (OR=1.06; 95%CI=1.01-1.10; p trend=0.016), with a clear excess of risk in men who reached puberty after age 15 (OR:1.35; 95%CI=1.08-1.68). A borderline significant positive association with prepubertal height was also observed (p trend=0.094). Some exposures experienced in utero and during adolescence, when the prostate is still maturing, might be relevant for prostate cancer risk in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial.

PubMed

Wagenlehner, Florian M E; van Till, J W Olivier; Houbiers, Jos G A; Martina, Reynaldo V; Cerneus, Dirk P; Melis, Joost H J M; Majek, Antoni; Vjaters, Egils; Urban, Michael; Ramonas, Henrikas; Shoskes, Daniel A; Nickel, J Curtis

2017-05-01

To examine the effect of a peripherally active fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on safety and efficacy outcomes in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Inhibition of FAAH is hypothesized to reduce the excitability of urinary tract afferents including nociceptors. In this adaptive, randomized, double-blind, placebo-controlled study, adult male patients with moderate to severe CP/CPPS were treated for 12 weeks with an oral dose of ASP3652 (25, 75, 150, or 300 mg twice daily, or 300 mg once daily), or placebo. A Bayesian model was used for adaptive prospective modeling of randomization, study continuation decisions, and analysis of the efficacy variables. The study was stopped for futility at preplanned interim analysis when 239 patients were randomized (226 were included in the intention-to-treat set): the 25 mg group showed the largest reduction of the primary end point National Institutes of Health Chronic Prostatitis Symptom Index total score (7.0 points), but the placebo group showed a mean reduction of 7.3 points (difference: 0.3 [95% confidence interval: -1.9, 2.6]). Micturition outcomes improved compared with placebo in all ASP3652 groups; for example, in the 300 mg twice daily group, voiding frequency decreased by -1.10 (95% CI: -2.0, -0.2) voids/24 hours vs placebo. Safety outcomes were comparable across the treatment groups. ASP3652 was generally safe and well-tolerated. It did not show efficacy on pain symptoms in patients with CP/CPPS. However, the results indicate that FAAH inhibition may attenuate lower urinary tract symptoms. Dedicated studies in patients with lower urinary tract dysfunction are needed to confirm this. Copyright © 2017 Elsevier Inc. All rights reserved.

African-American Men with Gleason Score 3+3=6 Prostate Cancer Produce Less Prostate Specific Antigen than Caucasian Men: A Potential Impact on Active Surveillance.

PubMed

Kryvenko, Oleksandr N; Balise, Raymond; Soodana Prakash, Nachiketh; Epstein, Jonathan I

2016-02-01

We assess the difference in prostate specific antigen production between African-American and Caucasian men with Gleason score 3+3=6 prostate cancer. We measured tumor volume in 414 consecutive radical prostatectomies from men with National Comprehensive Cancer Network(®) low risk prostate cancer (348 Caucasian, 66 African-American) who had Gleason score 3+3=6 disease at radical prostatectomy. We then compared clinical presentation, pathological findings, prostate specific antigen, prostate specific antigen density and prostate specific antigen mass (an absolute amount of prostate specific antigen in patient's circulation) between African-American and Caucasian men. The t-test and Wilcoxon rank sum were used for comparison of means. African-American and Caucasian men had similar clinical findings based on age, body mass index and prostate specific antigen. There were no statistically significant differences between the dominant tumor nodule volume and total tumor volume (mean 0.712 vs 0.665 cm(3), p=0.695) between African-American and Caucasian men. Prostates were heavier in African-American men (mean 55.4 vs 46.3 gm, p <0.03). Despite the significantly greater weight of benign prostate tissue contributing to prostate specific antigen in African-American men, prostate specific antigen mass was not different from that of Caucasian men (mean 0.55 vs 0.558 μg, p=0.95). Prostate specific antigen density was significantly less in African-American men due to larger prostates (mean 0.09 vs 0.105, p <0.02). African-American men with Gleason score 3+3=6 prostate cancer produce less prostate specific antigen than Caucasian men. African-American and Caucasian men had equal serum prostate specific antigen and prostate specific antigen mass despite significantly larger prostates in African-American men with all other parameters, particularly total tumor volume, being the same. This finding has practical implications in T1c cases diagnosed with prostate cancer due to prostate specific antigen screening. Lowering the prostate specific antigen density threshold in African-American men may account for this disparity, particularly in selecting patients for active surveillance programs. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Janmejai K.; Department of Urology, University Hospitals of Cleveland, Cleveland, OH 44106; Gupta, Sanjay

2006-07-28

One of the requisite of cancer chemopreventive agent is elimination of damaged or malignant cells through cell cycle inhibition or induction of apoptosis without affecting normal cells. In this study, employing normal human prostate epithelial cells (PrEC), virally transformed normal human prostate epithelial cells (PZ-HPV-7), and human prostate cancer cells (LNCaP, DU145, and PC-3), we evaluated the growth-inhibitory and apoptotic effects of tocotrienol-rich fraction (TRF) extracted from palm oil. TRF treatment to PrEC and PZ-HPV-7 resulted in almost identical growth-inhibitory responses of low magnitude. In sharp contrast, TRF treatment resulted in significant decreases in cell viability and colony formation inmore » all three prostate cancer cell lines. The IC{sub 5} values after 24 h TRF treatment in LNCaP, PC-3, and DU145 cells were in the order 16.5, 17.5, and 22.0 {mu}g/ml. TRF treatment resulted in significant apoptosis in all the cell lines as evident from (i) DNA fragmentation (ii) fluorescence microscopy, and (iii) cell death detection ELISA, whereas the PrEC and PZ-HPV-7 cells did not undergo apoptosis, but showed modestly decreased cell viability only at a high dose of 80 {mu}g/ml. In cell cycle analysis, TRF (10-40 {mu}g/ml) resulted in a dose-dependent G0/G1 phase arrest and sub G1 accumulation in all three cancer cell lines but not in PZ-HPV-7 cells. These results suggest that the palm oil derivative TRF is capable of selectively inhibiting cellular proliferation and accelerating apoptotic events in prostate cancer cells. TRF offers significant promise as a chemopreventive and/or therapeutic agent against prostate cancer.« less

MR PROSTATE SEGMENTATION VIA DISTRIBUTED DISCRIMINATIVE DICTIONARY (DDD) LEARNING.

PubMed

Guo, Yanrong; Zhan, Yiqiang; Gao, Yaozong; Jiang, Jianguo; Shen, Dinggang

2013-01-01

Segmenting prostate from MR images is important yet challenging. Due to non-Gaussian distribution of prostate appearances in MR images, the popular active appearance model (AAM) has its limited performance. Although the newly developed sparse dictionary learning method[1, 2] can model the image appearance in a non-parametric fashion, the learned dictionaries still lack the discriminative power between prostate and non-prostate tissues, which is critical for accurate prostate segmentation. In this paper, we propose to integrate deformable model with a novel learning scheme, namely the Distributed Discriminative Dictionary ( DDD ) learning, which can capture image appearance in a non-parametric and discriminative fashion. In particular, three strategies are designed to boost the tissue discriminative power of DDD. First , minimum Redundancy Maximum Relevance (mRMR) feature selection is performed to constrain the dictionary learning in a discriminative feature space. Second , linear discriminant analysis (LDA) is employed to assemble residuals from different dictionaries for optimal separation between prostate and non-prostate tissues. Third , instead of learning the global dictionaries, we learn a set of local dictionaries for the local regions (each with small appearance variations) along prostate boundary, thus achieving better tissue differentiation locally. In the application stage, DDDs will provide the appearance cues to robustly drive the deformable model onto the prostate boundary. Experiments on 50 MR prostate images show that our method can yield a Dice Ratio of 88% compared to the manual segmentations, and have 7% improvement over the conventional AAM.

Bone Metastasis in Prostate Cancer: Recurring Mitochondrial DNA Mutation Reveals Selective Pressure Exerted by the Bone Microenvironment

PubMed Central

Arnold, Rebecca S.; Fedewa, Stacey A.; Goodman, Michael; Osunkoya, Adeboye O.; Kissick, Haydn T.; Morrissey, Colm; True, Lawrence D.; Petros, John A.

2015-01-01

Background Cancer progression and metastasis occurs such that cells with acquired mutations enhancing growth and survival (or inhibiting cell death) increase in number, a concept that has been recognized as analogous to Darwinian evolution of species since Peter C. Nowell’s description in 1976. Selective forces include those intrinsic to the host (including metastatic site) as well as those resulting from anti-cancer therapies. By examining the mutational status of multiple tumor sites within an individual patient some insight may be gained into those genetic variants that enhance site-specific metastasis. By comparing these data across multiple individuals, recurrent patterns may identify alterations that are fundamental to successful site-specific metastasis. Methods We sequenced the mitochondrial genome in 10 prostate cancer patients with bone metastases enrolled in a rapid autopsy program. Patients had late stage disease and received androgen ablation and frequently other systemic therapies. For each of 9 patients, 4 separate tissues were sequenced: the primary prostate cancer, a soft tissue metastasis, a bone metastasis and an uninvolved normal tissue that served as the non-cancerous control. An additional (10th) patient had no primary prostate available for sequencing but had both metastatic sites (and control DNA) sequenced. We then examined the number and location of somatically acquired mitochondrial DNA (mtDNA) mutations in the primary and two metastatic sites in each individual patient. Finally, we compared patients with each other to determine any common patterns of somatic mutation. Results Somatic mutations were significantly more numerous in bone compared to either the primary tumor or soft tissue metastases. A missense mutation at nucleotide position (np) 10398 (A10398G; Thr114Ala) in the respiratory complex I gene ND3 was the most common (7 of 10 patients) and was detected only in bone. Other notable somatic mutations that occurred in more than one patient include a tRNA Arg mutation at np 10436 and a tRNA Thr mutation at np 15928. The tRNA Arg mutation was restricted to bone metastases and occurred in three of 10 patients (30%). Somatic mutation at 15928 was not restricted to bone and also occurred in three patients. Conclusions Mitochondrial genomic variation was greater in metastatic sites than the primary tumor and bone metastases had statistically significantly greater numbers of somatic mutations than either the primary or the soft tissue metastases. The genome was not mutated randomly. At least one mutational “hot-spot” was identified at the individual base level (nucleotide position 10398 in bone metastases) indicating a pervasive selective pressure for bone metastatic cells that had acquired the 10398 mtDNA mutation. Two additional recurrent mutations (tRNA Arg and tRNA Thr) support the concept of bone site-specific “survival of the fittest” as revealed by variation in the mitochondrial genome and selective pressure exerted by the metastatic site. PMID:25952970

Bone metastasis in prostate cancer: Recurring mitochondrial DNA mutation reveals selective pressure exerted by the bone microenvironment.

PubMed

Arnold, Rebecca S; Fedewa, Stacey A; Goodman, Michael; Osunkoya, Adeboye O; Kissick, Haydn T; Morrissey, Colm; True, Lawrence D; Petros, John A

2015-09-01

Cancer progression and metastasis occur such that cells with acquired mutations enhancing growth and survival (or inhibiting cell death) increase in number, a concept that has been recognized as analogous to Darwinian evolution of species since Peter C. Nowell's description in 1976. Selective forces include those intrinsic to the host (including metastatic site) as well as those resulting from anti-cancer therapies. By examining the mutational status of multiple tumor sites within an individual patient some insight may be gained into those genetic variants that enhance site-specific metastasis. By comparing these data across multiple individuals, recurrent patterns may identify alterations that are fundamental to successful site-specific metastasis. We sequenced the mitochondrial genome in 10 prostate cancer patients with bone metastases enrolled in a rapid autopsy program. Patients had late stage disease and received androgen ablation and frequently other systemic therapies. For each of 9 patients, 4 separate tissues were sequenced: the primary prostate cancer, a soft tissue metastasis, a bone metastasis and an uninvolved normal tissue that served as the non-cancerous control. An additional (10th) patient had no primary prostate available for sequencing but had both metastatic sites (and control DNA) sequenced. We then examined the number and location of somatically acquired mitochondrial DNA (mtDNA) mutations in the primary tumor and two metastatic sites in each individual patient. Finally, we compared patients with each other to determine any common patterns of somatic mutation. Somatic mutations were significantly more numerous in the bone compared to either the primary tumor or soft tissue metastases. A missense mutation at nucleotide position (n.p.) 10398 (A10398G; Thr114Ala) in the respiratory complex I gene ND3 was the most common (7 of 10 patients) and was detected only in the bone. Other notable somatic mutations that occurred in more than one patient include a tRNA Arg mutation at n.p. 10436 and a tRNA Thr mutation at n.p. 15928. The tRNA Arg mutation was restricted to bone metastases and occurred in three of 10 patients (30%). Somatic mutation at 15928 was not restricted to the bone and also occurred in three patients. Mitochondrial genomic variation was greater in metastatic sites than in the primary tumor and bone metastases had statistically significantly greater numbers of somatic mutations than either the primary or the soft tissue metastases. The genome was not mutated randomly. At least one mutational "hot-spot" was identified at the individual base level (nucleotide position 10398 in bone metastases) indicating a pervasive selective pressure for bone metastatic cells that had acquired the 10398 mtDNA mutation. Two additional recurrent mutations (tRNA Arg and tRNA Thr) support the concept of bone site-specific "survival of the fittest" as revealed by variation in the mitochondrial genome and selective pressure exerted by the metastatic site. Published by Elsevier Inc.

Trends in PET Scan Usage for Imaging of Patients Diagnosed With Nonmetastatic Urologic Cancer.

PubMed

Adejoro, Oluwakayode; Alishahi, Amin; Soubra, Ayman; Konety, Badrinath

2016-02-01

The precise utility of positron emission tomography (PET) scanning for urologic cancers is not well defined. We examined the trends of usage in a population-based data set. PET scans were performed in 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with renal cell carcinoma. This selective usage might be driven by reimbursement constraints or identification of appropriate medical indications. Positron emission tomography (PET) scanning is increasingly being used for imaging a variety of cancers, including urologic cancers. The precise utility of PET scanning for bladder cancer, prostate cancer, and renal cell carcinoma (RCC) is not yet well known. We examined the trends in PET scan usage for 3 cancers using a large population-based data set. We analyzed all individuals identified with a diagnosis of nonmetastatic bladder cancer, prostate cancer, and RCC from the Surveillance, Epidemiology, and End Results-Medicare data set for 2004 to 2009 with follow-up data available to 2010. Logistic regression analysis and χ(2) and trend tests were performed to determine the predictors of performing PET scanning. Separate models were run for each of the cancer diagnoses. All analyses were performed using SAS, version 9.3, and P < .05 was considered significant. We identified 20,865, 70,414, and 7007 patients with a diagnosis of bladder cancer, prostate cancer, and RCC, respectively, from 2004 to 2009. PET scans had been performed for 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with RCC. On regression analysis, a more recent year of diagnosis, younger age, and high stage or grade were predictors of PET scan usage for patients with bladder cancer and RCC. A higher Gleason score and higher D'Amico risk group predicted imaging with prostate cancer. The usage of PET scanning for bladder cancer, prostate cancer, and RCC is increasing but still very selective. The selective use might be driven by a combination of reimbursement constraints and careful identification of the appropriate medical indication. Copyright © 2016 Elsevier Inc. All rights reserved.

What Is New with Sexual Side Effects After Transurethral Male Lower Urinary Tract Symptom Surgery?

PubMed

Rieken, Malte; Antunes-Lopes, Tiago; Geavlete, Bogdan; Marcelissen, Tom

2018-01-01

Transurethral resection of the prostate as well as laser prostatectomy (by either holmium laser enucleation of the prostate or Greenlight laser vaporization) is associated with risks of sexual dysfunction such as antegrade ejaculation and occasionally erectile dysfunction. While ejaculation-sparing variations of these techniques show promising results, larger multicenter studies are needed to confirm promising data. Prostatic urethral lift maintains erectile and ejaculatory function at 5-yr follow-up. The same is true for the 3-yr data on the Rezum system. Recently, Aquablation has shown promising results; however, these 6-mo data need to be confirmed during longer follow-up. An individualized, shared decision-making process based on clinical parameters and patient preference is warranted to select the ideal treatment option for each patient. Sexual dysfunction such as loss of ejaculation and, less frequently, erectile dysfunction can occur after transurethral prostate surgery. Ejaculation-sparing modifications as well as minimally invasive alternatives show promising results. An individualized approach is warranted to select the ideal technique for each patient. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Decisional conflict in economically disadvantaged men with newly diagnosed prostate cancer: Results from a shared decision-making trial

PubMed Central

Kaplan, Alan L.; Crespi, Catherine M.; Saucedo, Josemanuel D.; Connor, Sarah E.; Litwin, Mark S.; Saigal, Christopher S.

2015-01-01

BACKGROUND Decisional conflict is a source of anxiety and stress for men diagnosed with prostate cancer given uncertainty surrounding myriad treatment options. Few data exist to help clinicians identify which patients are at risk for decisional conflict. The purpose of this study was to examine factors associated with decisional conflict in economically disadvantaged men diagnosed with prostate cancer before any treatment choices were made. METHODS A total of 70 men were surveyed at a Veterans Administration clinic with newly diagnosed localized prostate cancer enrolled in a randomized trial testing a novel shared decision-making tool. Baseline demographic, clinical, and functional data were collected. Independent variables included age, race, education, comorbidity, relationship status, urinary/sexual dysfunction, and prostate cancer knowledge. Tested outcomes were Decisional Conflict Scale, Uncertainty Subscale, and Perceived Effectiveness Subscale. Multiple linear regression modeling was used to identify factors associated with decisional conflict. RESULTS Mean age was 63 years, 49% were African American, and 70% reported an income less than $30,000. Poor prostate cancer knowledge was associated with increased decisional conflict and higher uncertainty (P < .001 and P = 0.001, respectively). Poor knowledge was also associated with lower perceived effectiveness (P = 0.003) whereas being in a relationship was associated with higher decisional conflict (P = 0.03). CONCLUSIONS Decreased patient knowledge about prostate cancer is associated with increased decisional conflict and lower perceived effective decision-making. Interventions to increase comprehension of prostate cancer and its treatments may reduce decisional conflict. Further work is needed to better characterize this relationship and identify effective targeted interventions. PMID:24816472

Pulsed electromagnetic field with or without exercise therapy in the treatment of benign prostatic hyperplasia

PubMed Central

Elgohary, Hany M; Tantawy, Sayed A

2017-01-01

[Purpose] To investigate the effect of pulsed electromagnetic field with or without exercise therapy in the treatment of benign prostatic hyperplasia. [Subjects and Methods] Sixty male patients aged 55–65 years with benign prostatic hyperplasia were invited to participate in this study. Patients were randomly assigned to Group A (n=20; patients who received pulsed electromagnetic field in addition to pelvic floor and aerobic exercises), Group B (n=20; patients who received pulsed electromagnetic field), and Group C (n=20; patients who received placebo electromagnetic field). The assessments included post-void residual urine, urine flow rate, prostate specific antigen, white blood cells count, and International Prostate Symptom Score were weighed, before and after a 4-week intervention. [Results] There were significant differences in Group A and B in all parameters. Group C showed non-significant differences in all measured variables except for International Prostate Symptom Score. Among groups, all parameters showed highly significant differences in favor of Group A. There were non-significant differences between Group A and B and significant difference between Groups A and C and between Groups B and C. [Conclusion] The present study demonstrated that electromagnetic field had a significant impact on the treatment of benign prostatic hyperplasia. Accordingly, electromagnetic field can be utilized alone or in combination with other physiotherapy modalities. Moreover, clinicians should have the capacity to perceive the advantages accomplished using extra treatment alternatives. Electromagnetic field is a safe, noninvasive method and can be used for the treatment of benign prostatic hyperplasia. PMID:28878453

Method for selective thermal ablation

NASA Technical Reports Server (NTRS)

Ngo, Phong (Inventor); Arndt, G. Dickey (Inventor); Raffoul, George W. (Inventor); Carl, James (Inventor)

2003-01-01

A method, simulation, and apparatus are provided that are highly suitable for treatment of benign prostatic hyperplasia (BPH). A catheter is disclosed that includes a small diameter disk loaded monopole antenna surrounded by fusion material having a high heat of fusion and a melting point preferably at or near body temperature. Microwaves from the antenna heat prostatic tissue to promote necrosing of the prostatic tissue that relieves the pressure of the prostatic tissue against the urethra as the body reabsorbs the necrosed or dead tissue. The fusion material keeps the urethra cool by means of the heat of fusion of the fusion material. This prevents damage to the urethra while the prostatic tissue is necrosed. A computer simulation is provided that can be used to predict the resulting temperature profile produced in the prostatic tissue. By changing the various control features of the catheter and method of applying microwave energy a temperature profile can be predicted and produced that is similar to the temperature profile desired for the particular patient.

Method for Selective Thermal Ablation

NASA Technical Reports Server (NTRS)

Arndt, G. Dickey (Inventor); Carl, James (Inventor); Ngo, Phong (Inventor); Raffoul, George W. (Inventor)

2003-01-01

A method, simulation, and apparatus are provided that are highly suitable for treatment of benign prostatic hyperplasia (BPH). A catheter is disclosed that includes a small diameter disk loaded monopole antenna surrounded by fusion material having a high heat of fusion and a melting point preferably at or near body temperature. Microwaves from the antenna heat prostatic tissue to promote necrosing of the prostatic tissue that relieves the pressure of the prostatic tissue against the urethra as the body reabsorbs the necrosed or dead tissue. The fusion material keeps the urethra cool by means of the heat of fusion of the fusion material. This prevents damage to the urethra while the prostatic tissue is necrosed. A computer simulation is provided that can be used to predict the resulting temperature profile produced in the prostatic tissue. By changing the various control features of the catheter and method of applying microwave energy a temperature profile can be predicted and produced that is similar to the temperature profile desired for the particular patient.

Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

PubMed

Choo, Richard; Klotz, Laurence; Deboer, Gerrit; Danjoux, Cyril; Morton, Gerard C

2004-08-01

To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: < 2 years, 26 patients; 2-5 years, 65; 5-10 years, 42; 10-20 years, 26; 20-50 years, 16; >50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

Contemporary results of focal therapy for prostate cancer using cryotherapy.

PubMed

Chalasani, V; Williams, A K; Chin, J

2010-09-01

With the increasing diagnosis of prostate cancer, there have been concerns expressed regarding the potential over-treatment that may ensue following the diagnosis of localized prostate cancer. Minimally invasive treatments such as cryotherapy have been used successfully to treat the entire gland, however complications such as incontinence and erectile dysfunction can still occur. Focal cryotherapy is a modification of the standard cryotherapy technique, aiming to only treat the portion of the prostate gland which has the cancer of clinical significance. The potential advantage of this is the minimization of complications; however the remainder of the prostate is still viable and so can develop cancer subsequently. There have been several published studies demonstrating promising efficacy with a low morbidity rate using focal cryotherapy to treat prostate cancer, however further follow up is required before definitive conclusions can be reached. The appropriate selection of patients and subsequent follow up are areas needing further research and the development of improved imaging modalities.

Molecular profiles of finasteride effects on prostate carcinogenesis.

PubMed

Li, Jin; Kim, Jeri

2009-06-01

Our inability to distinguish between low-grade prostate cancers that pose no threat and those that can kill compels newly diagnosed early prostate cancer patients to make decisions that may negatively affect their lives needlessly for years afterward. To reliably stratify patients into different risk categories and apply appropriate treatment, we need a better molecular understanding of prostate cancer progression. Androgen ablation therapy and 5-alpha reductase inhibitors reduce dihydrotestosterone levels and increase apoptosis. Because of the differing biological potentials of tumor cells, however, these treatments may, in some cases, worsen outcome by selecting for or inducing adaptation of stronger androgen receptor signaling pathways. Reduced dihydrotestosterone also may be associated with altered survival pathways. Complicating treatment effects further, molecular adaptation may be accelerated by interactions between epithelial and stromal cells. The hypothesis that early prostate cancer cells with differing biological potential may respond differently to finasteride treatment is worth testing. Ongoing studies using a systems biology approach in a preoperative prostate cancer setting are testing this hypothesis toward developing more-rational clinical interventions.

A Randomized Controlled Trial for the Effectiveness of Progressive Muscle Relaxation and Guided Imagery as Anxiety Reducing Interventions in Breast and Prostate Cancer Patients Undergoing Chemotherapy

PubMed Central

Charalambous, Andreas; Giannakopoulou, Margarita; Bozas, Evangelos; Paikousis, Lefkios

2015-01-01

Objective. To test the effectiveness of guided imagery (GI) and progressive muscle relaxation (PMR) as stress reducing interventions in patients with prostate and breast cancer who undergo chemotherapy. Methods. Patients were randomly assigned to either the control group or the intervention group (PMR and GI). Patients were observed for a total duration of 3 weeks and assessed with the SAS and BECK-II questionnaires for anxiety and depression, respectively, in addiotion to two biological markers (saliva cortisol and saliva amylase) (trial registration number: NCT01275872). Results. 256 patients were registered and 236 were randomly assigned. In total 104 were randomised to the control group and 104 to the intervention group. Intervention's mean anxiety score and depression score changes were significantly different compared to the control's (b = −29.4, p < 0.001; b = −29.4, p < 0.001, resp.). Intervention group's cortisol levels before the intervention (0.30 ± 0.25) gradually decreased up to week 3 (0.16 ± 0.18), whilst the control group's cortisol levels before the intervention (0.21 ± 0.22) gradually increased up to week 3 (0.44 ± 0.35). The same interaction appears for the Amylase levels (p < 0.001). Conclusions. The findings showed that patients with prostate and breast cancer undergoing chemotherapy treatment can benefit from PMR and GI sessions to reduce their anxiety and depression. PMID:26347018

Mindfulness-Based Cognitive Therapy in Advanced Prostate Cancer: A Randomized Controlled Trial.

PubMed

Chambers, Suzanne K; Occhipinti, Stefano; Foley, Elizabeth; Clutton, Samantha; Legg, Melissa; Berry, Martin; Stockler, Martin R; Frydenberg, Mark; Gardiner, Robert A; Lepore, Stephen J; Davis, Ian D; Smith, David P

2017-01-20

Purpose Advanced prostate cancer (PC) is associated with substantial psychosocial morbidity. We sought to determine whether mindfulness-based cognitive therapy (MBCT) reduces distress in men with advanced PC. Methods Men with advanced PC (proven metastatic and/or castration-resistant biochemical progression) were randomly assigned to an 8-week, group-based MBCT intervention delivered by telephone (n = 94) or to minimally enhanced usual care (n = 95). Primary intervention outcomes were psychological distress, cancer-specific distress, and prostate-specific antigen anxiety. Mindfulness skills were assessed as potential mediators of effect. Participants were assessed at baseline and were followed up at 3, 6, and 9 months. Main statistical analyses were conducted on the basis of intention to treat. Results Fourteen MBCT groups were conducted in the intervention arm. Facilitator adherence ratings were high (> 93%). Using random-effects mixed-regression models, intention-to-treat analyses indicated no significant changes in intervention outcomes or in engagement with mindfulness for men in MBCT compared with those receiving minimally enhanced usual care. Per-protocol analyses also found no differences between arms in outcomes or engagement, with the exception of the mindfulness skill of observing, which increased over time for men in MBCT compared with usual care ( P = .032). Conclusion MBCT in this format was not more effective than minimally enhanced usual care in reducing distress in men with advanced PC. Future intervention research for these men should consider approaches that map more closely to masculinity.

Offline multiple adaptive planning strategy for concurrent irradiation of the prostate and pelvic lymph nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Peng; Xia, Ping, E-mail: xiap@ccf.org; Pouliot, Jean

2014-02-15

Purpose: Concurrent irradiation of the prostate and pelvic lymph nodes (PLNs) can be challenging due to the independent motion of the two target volumes. To address this challenge, the authors have proposed a strategy referred to as Multiple Adaptive Planning (MAP). To minimize the number of MAP plans, the authors’ previous work only considered the prostate motion in one major direction. After analyzing the pattern of the prostate motion, the authors investigated a practical number of intensity-modulated radiotherapy (IMRT) plans needed to accommodate the prostate motion in two major directions simultaneously. Methods: Six patients, who received concurrent irradiation of themore » prostate and PLNs, were selected for this study. Nine MAP-IMRT plans were created for each patient with nine prostate contours that represented the prostate at nine locations with respect to the PLNs, including the original prostate contour and eight contours shifted either 5 mm in a single anterior-posterior (A-P), or superior-inferior (S-I) direction, or 5 mm in both A-P and S-I directions simultaneously. From archived megavoltage cone beam CT (MV-CBCT) and a dual imaging registration, 17 MV-CBCTs from 33 available MV-CBCT from these patients showed large prostate displacements (>3 mm in any direction) with respect to the pelvic bones. For each of these 17 fractions, one of nine MAP-IMRT plans was retrospectively selected and applied to the MV-CBCT for dose calculation. For comparison, a simulated isocenter-shifting plan and a reoptimized plan were also created for each of these 17 fractions. The doses to 95% (D95) of the prostate and PLNs, and the doses to 5% (D5) of the rectum and bladder were calculated and analyzed. Results: For the prostate, D95 > 97% of the prescription dose was observed in 16, 16, and 17 of 17 fractions for the MAP, isocenter-shifted, and reoptimized plans, respectively. For PLNs, D95 > 97% of the prescription doses was observed in 10, 3, and 17 of 17 fractions for the three types of verification plans, respectively. The D5 (mean ± SD) of the rectum was 45.78 ± 5.75, 45.44 ± 4.64, and 44.64 ± 2.71 Gy, and the D5 (mean ± SD) of the bladder was 45.18 ± 2.70, 46.91 ± 3.04, and 45.67 ± 3.61 Gy for three types of verification plans, respectively. Conclusions: The MAP strategy with nine IMRT plans to accommodate the prostate motions in two major directions achieved good dose coverage to the prostate and PLNs. The MAP approach can be immediately used in clinical practice without requiring extra hardware and software.« less

Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor

PubMed Central

Guo, W; Liu, R; Bhardwaj, G; Yang, J C; Changou, C; Ma, A-H; Mazloom, A; Chintapalli, S; Xiao, K; Xiao, W; Kumaresan, P; Sanchez, E; Yeh, C-T; Evans, C P; Patterson, R; Lam, K S; Kung, H-J

2014-01-01

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a ‘wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model. PMID:25188519

Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor.

PubMed

Guo, W; Liu, R; Bhardwaj, G; Yang, J C; Changou, C; Ma, A-H; Mazloom, A; Chintapalli, S; Xiao, K; Xiao, W; Kumaresan, P; Sanchez, E; Yeh, C-T; Evans, C P; Patterson, R; Lam, K S; Kung, H-J

2014-09-04

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model.

New Paradigms for Advanced Prostate Cancer

PubMed Central

Petrylak, Daniel P

2007-01-01

In men with metastatic hormone-refractory prostate cancer, androgen blockade produces dramatic and rapid declines in prostate-specific antigen (PSA), bone pain, and urinary tract obstruction. Nevertheless, there have been limited options with at best palliative results for patients who progress despite a castrate testosterone level. This paradigm changed in 2004 with the publication of 2 randomized clinical trials that demonstrated a 20% to 24% survival benefit for docetaxel-based therapy when compared to mitoxantrone and prednisone, data that supported US Food and Drug Administration approval of docetaxel-based therapy for the treatment of metastatic hormone-refractory prostate cancer. This article reviews the preliminary data and the timing and sequencing implications of ongoing clinical trials. Studies are evaluating the combination of docetaxel with agents that target bone, tumor vasculature, and the vitamin D receptor as well as second-line agents, such as satraplatin. The role of immune therapy is also evolving, and further studies will define the optimal timing of chemotherapy with immune therapy. PMID:17554403