The cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy for low risk localised prostate cancer.

PubMed

Lao, Chunhuan; Edlin, Richard; Rouse, Paul; Brown, Charis; Holmes, Michael; Gilling, Peter; Lawrenson, Ross

2017-08-08

Radical prostatectomy is the most common treatment for localised prostate cancer in New Zealand. Active surveillance was introduced to prevent overtreatment and reduce costs while preserving the option of radical prostatectomy. This study aims to evaluate the cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy. Markov models were constructed to estimate the life-time cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy for low risk localised prostate cancer patients aged 45-70 years, using national datasets in New Zealand and published studies including the SPCG-4 study. This study was from the perspective of the Ministry of Health in New Zealand. Radical prostatectomy is less costly than active surveillance in men aged 45-55 years with low risk localised prostate cancer, but more costly for men aged 60-70 years. Scenario analyses demonstrated significant uncertainty as to the most cost-effective option in all age groups because of the unavailability of good quality of life data for men under active surveillance. Uncertainties around the likelihood of having radical prostatectomy when managed with active surveillance also affect the cost-effectiveness of active surveillance against radical prostatectomy. Active surveillance is less likely to be cost-effective compared to radical prostatectomy for younger men diagnosed with low risk localised prostate cancer. The cost-effectiveness of active surveillance compared to radical prostatectomy is critically dependent on the 'trigger' for radical prostatectomy and the quality of life in men on active surveillance. Research on the latter would be beneficial.

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.

[Brachytherapy for Prostate Cancer: Potentials and Limitations of Social Health Insurance Data for Benefit Assessment].

PubMed

Horenkamp-Sonntag, D; Linder, R; Engel, S; Verheyen, F

2016-05-01

Due to the insufficient data base the Federal Joint Committee (G-BA) had in 2009 after 7 years of deliberation decided to initiate consultation regarding ambulatory brachytherapy for localised prostate cancer for 10 years from social health insurance (SHI) benefits. The aim is to gain more findings by means of comparative studies. Based on the non-availability of clinical primary data of a methodologically acceptable level, it was analysed to what extent secondary data of the SHI may be used in order to arrive at valid conclusions for benefit aspects. As base approx. 8 million insured of TK with their data of cost reimbursement between 2006 and 2011 were considered. In SHI secondary data no clinical information regarding tumour stage and other prognostic factors are available. Therefore, a novel method with therapy-specific multisectoral inclusion and exclusion criteria, respectively, was developed in order to differentiate between localised and advanced tumours of the prostate. Overall survival, relapse-free survival, event-free survival and side-effects associated to prostate cancer were analysed. Out of 87 822 insured persons with the diagnosis prostate cancer, 795 with PBT, 10 936 with RP and 1 925 with EBRT were investigated in detail. The 4-year event-free survival rate was 73% for RP, 77% for PBT and 71% for EBRT. Many prostate cancer-specific side effects appeared already before intervention. Side effects of the intestinal tract (23.8%) and sexual impairments (26.5%) were more frequent for EBRT than for RP (17.1%/14.8%) and PBT (16.4%/13.2%). By means of SHI secondary data and adequate operationalisation important findings regarding relevant aspects of prostate cancer in healthcare research can be generated. However, these hold methodological limitations and are not suited to draw valid conclusions for benefit assessment. Based solely on SHI routine data valid statements regarding comparative benefit assessment are limited. Limitations could be reduced by applying a record linkage with clinical data. Such primary data should include information on tumour stages as well as therapy assignment and observation of survival time. © Georg Thieme Verlag KG Stuttgart · New York.

Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis.

PubMed

Cooperberg, Matthew R; Ramakrishna, Naren R; Duff, Steven B; Hughes, Kathleen E; Sadownik, Sara; Smith, Joseph A; Tewari, Ashutosh K

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Multiple treatment alternatives exist for localised prostate cancer, with few high-quality studies directly comparing their comparative effectiveness and costs. The present study is the most comprehensive cost-effectiveness analysis to date for localised prostate cancer, conducted with a lifetime horizon and accounting for survival, health-related quality-of-life, and cost impact of secondary treatments and other downstream events, as well as primary treatment choices. The analysis found minor differences, generally slightly favouring surgical methods, in quality-adjusted life years across treatment options. However, radiation therapy (RT) was consistently more expensive than surgery, and some alternatives, e.g. intensity-modulated RT for low-risk disease, were dominated - that is, both more expensive and less effective than competing alternatives. To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model. A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis. Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6-10.5 for intermediate-risk patients and 7.8-9.3 for high-risk patients. There were no statistically significant differences among surgical methods, which tended to be more effective than RT methods, with the exception of combined external beam + brachytherapy for high-risk disease. RT methods were consistently more expensive than surgical methods; costs ranged from $19 901 (robot-assisted prostatectomy for low-risk disease) to $50 276 (combined RT for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions about strategies to improve efficiency of treatment selection for localised prostate cancer. © 2012 BJU International.

Efficacy and toxicity of external-beam radiation therapy for localised prostate cancer: a network meta-analysis

PubMed Central

Zhu, Z; Zhang, J; Liu, Y; Chen, M; Guo, P; Li, K

2014-01-01

Background: Many radiation regimens for treating prostate cancer have been used over the years, but which regimen is optimal for localised or locally advanced prostate cancer lacks consensus. We performed a network meta-analysis to identify the optimal radiation regimen. Methods: We systematically reviewed data from 27 randomised controlled trials and could group seven radiation regimens as follows: low- and high-dose radiation therapy (LDRT and HDRT), LDRT+ short- or long-term androgen deprivation therapy (LDRT+SADT and LDRT+LADT), HDRT+SADT, hypofractionated radiotherapy (HFRT), and HFRT+SADT. The main outcomes were overall mortality (OM), prostate-specific antigen (PSA) failure, cancer-specific mortality, and adverse events. Results: For the network meta-analysis of 27 trials, LDRT+LADT and LDRT+SADT were associated with decreased risk of OM as compared with LDRT alone as was LDRT+LADT compared with HDRT. Apart from HFRT, all other treatments were associated with decreased risk of PSA failure as compared with LDRT. HFRT+SADT was associated with decreased risk of cancer-specific mortality as compared with HFRT, LDRT+SADT, HDRT, and LDRT. Conclusions: HFRT+SADT therapy might be the most efficacious treatment but with worst toxicity for localised or locally advanced prostate cancer, and HDRT showed excellent efficacy but more adverse events. PMID:24736585

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial.

PubMed

Hackshaw-McGeagh, Lucy; Lane, J Athene; Persad, Raj; Gillatt, David; Holly, Jeff M P; Koupparis, Anthony; Rowe, Edward; Johnston, Lyndsey; Cloete, Jenny; Shiridzinomwa, Constance; Abrams, Paul; Penfold, Chris M; Bahl, Amit; Oxley, Jon; Perks, Claire M; Martin, Richard

2016-03-07

A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

Localised carcinoma of the prostate: a paradigm of uncertainty.

PubMed Central

Sandhu, S. S.; Kaisary, A. V.

1997-01-01

The incidence and prevalence of prostate cancer is increasing. A number of aetiological factors including age, race, family history and diet have been implicated. The majority of patients present with disease which is amenable only to palliation. Digital rectal examination, serum prostate-specific antigen and transrectal ultrasound can lead to a prostatic biopsy. Transrectal ultrasound, magnetic resonance imaging, bone scan and a chest X-ray are used for staging. The management of localised cancer is shrouded in uncertainty. Three options exist, watchful waiting, radiotherapy, and radical total prostatectomy. The published data are inadequate for a valid comparison of these, and none has been shown to offer an advantage. Surgery, and to a lesser degree radiotherapy, have a significant morbidity. It is hoped that through better understanding our management of this disease will improve. Images Figure 1 Figure 2 Figure 33 PMID:9519179

High-intensity focused ultrasound (HIFU) in prostate cancer: a single centre experience in patients with low, intermediate or high-risk of progression.

PubMed

Callea, Andrea; Piccinni, Roberto; Zizzi, Vito; Sblendorio, Domenico; Berardi, Bartolomeo; Tempesta, Antonio; Gala, Francesco Giuseppe; Traficante, Antonio

2010-12-01

High-intensity focused ultrasound (HIFU) is a minimally invasive treatment based on thermal ablation of tissues which are warmed up to 85 degrees C in the focal area. Clinical studies have shown such treatment modality to be safe and effective in the management of localised prostate cancer as well as of local recurrences after radical prostatectomy or radiotherapy. From May 2002 to June 2010, 171 patients with no previous treatment for prostate cancer, aged 44 to 86 years (mean 74.7) underwent 197 HIFU treatments; 22 patients needed a second treatment as the first was incomplete (4 patients) or because of recurrence (18 patients). The prognosis subgroups were defined as low-risk in 29 patients (clinical stage T1-T2a, PSA < or = 10 ng/mL and Gleason score lower than 7), intermediate-risk in 47 patients (clinical stage T2b or PSA 10 - 20 ng/mL or Gleason score of 7), and high-risk in 95 patients (clinical stage > or = T2c or PSA > 20 ng/mL or Gleason score higher than 7). At a mean follow-up of 67.9 months, biochemical success rate (PSA constantly < 0.5 ng/ml) was obtained in 84.2% of low and intermediate risk patients and in 43.1% of high risk patients; post-treatment biopsies (6 months after treatment) revealed no residual tumour in 93.4% of low or intermediate risk patients and in 63.1% of high risk patients. Radical prostatectomy remains the "gold standard" for localised prostate cancer. However, HIFU seems to be a promising alternative and less invasive treatment modality with an encouraging success rate, at least in the short-term, in patients with low and medium risk of progression, not candidates for radical surgery; in cancers with clinical stage > or = T2c, or PSA > 20 ng/mL, or Gleason score higher than 7 seems to get good results in about half of patients.

Overcoming difficulties with equipoise to enable recruitment to a randomised controlled trial of partial ablation versus radical prostatectomy for unilateral localised prostate cancer.

PubMed

Elliott, Daisy; Hamdy, Freddie C; Leslie, Tom A; Rosario, Derek; Dudderidge, Tim; Hindley, Richard; Emberton, Mark; Brewster, Simon; Sooriakumaran, Prasanna; Catto, James W F; Emara, Amr; Ahmed, Hashim; Whybrow, Paul; le Conte, Steffi; Donovan, Jenny L

2018-06-11

To describe how clinicians conceptualised equipoise in the PART (Partial prostate Ablation versus Radical prosTatectomy in intermediate risk, unilateral clinically localised prostate cancer) feasibility study and how this affected recruitment. PART included a QuinteT Recruitment Intervention (QRI) to optimise recruitment. Phase I aimed to understand recruitment, and included scrutinising recruitment data, interviewing the Trial Management Group and recruiters (n=13), and audio-recording recruitment consultations (n=64). Data were analysed using qualitative content and thematic analysis methods. In Phase II, strategies to improve recruitment were developed and delivered. Initially many recruiters found it difficult to maintain a position of equipoise and held preconceptions about which treatment was best for particular patients. They did not feel comfortable about approaching all eligible patients, and when the study was discussed, biases were conveyed through the use of terminology, poorly balanced information and direct treatment recommendations. Individual and group feedback led to presentations to patients becoming clearer and enabled recruiters to reconsider their sense of equipoise. Although the precise impact of the QRI alone cannot be determined, recruitment increased (from mean 1.4 (range=0-4) to 4.5 (range=0-12) patients per month) and the feasibility study reached its recruitment target. Although clinicians find it challenging to recruit participants to a trial comparing different contemporary treatments for prostate cancer, training and support can enable recruiters to become more comfortable with conveying equipoise and providing clearer information to patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

EphB4 localises to the nucleus of prostate cancer cells

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

Mertens-Walker, Inga, E-mail: inga.mertenswalker@qut.edu.au; Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD; Lisle, Jessica E.

2015-04-10

The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of bothmore » NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor. - Highlights: • The EphB4 protein can be found in the nucleus of prostate cancer cell lines. • EphB4 contains two functional nuclear localisation signals. • Chromatin immunoprecipitation has identified potential genome sequences to which EphB4 binds. • Lef1 is a confirmed target for EphB4-mediated gene regulation.« less

Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study.

PubMed

Thomsen, F B; Brasso, K; Berg, K D; Gerds, T A; Johansson, J-E; Angelsen, A; Tammela, T L J; Iversen, P

2016-03-01

The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting. Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml. We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values. NCT00672282. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Trends in stage-specific incidence of prostate cancer in Norway, 1980-2010: a population-based study.

PubMed

Møller, Mette H; Kristiansen, Ivar S; Beisland, Christian; Rørvik, Jarle; Støvring, Henrik

2016-10-01

To estimate changes in the stage distribution of prostate cancer during the time period where opportunistic prostate-specific antigen (PSA) testing was introduced. Cancer stage, age, and year of diagnosis were obtained for all men aged >50 years diagnosed with prostate cancer in Norway during the period 1980-2010. Three calendar-time periods (1980-1989, 1990-2000, and 2001-2010) and three age groups (50-65, 66-74, and ≥75 years) were defined. Birth cohorts were categorised into four intervals: ≤1915, 1916-1925, 1926-1940 and ≥1941. We used Poisson regressions to conduct both a time period and cohort-based analysis of trends in the incidence of localised, regional, and distant cancer for each combination of age groups and calendar-time periods or birth cohorts, respectively. Additionally, we explored the effect of cohorts on the stage-specific incidence graphically with a Poisson regression using 5-year age groups, and by estimating cumulative incidence rates for each birth cohort. The annual incidence of localised cancers among men aged 50-65 and 66-74 years rose from 41.4 and 255.2 per 100 000, respectively, before the introduction of PSA testing to 137.9 and 418.7 in 2001-2010 afterwards, corresponding to 3.3 [95% confidence interval (CI) 3.1-3.5] and 1.6 (95% CI 1.6-1.7) fold increases. The incidence of regional cancers increased by a factor seven among men aged <75 years. The incidence of distant cancers in men aged ≥75 years decreased by 29% (95% CI 25-33%). These findings were confirmed in the cohort-based approach. Opportunistic PSA testing substantially increased the incidence of localised and regional prostate cancers among men aged 50-74 years, which was not fully compensated by the 30% decrease in incidence of distant prostate cancers in older men. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

FOXA1 and SOX9 Expression in the Developing Urogenital Sinus of the Tammar Wallaby (Macropus eugenii).

PubMed

Gamat, Melissa; Chew, Keng Yih; Shaw, Geoffrey; Renfree, Marilyn B

2015-01-01

The mammalian prostate is a compact structure in humans but multi-lobed in mice. In humans and mice, FOXA1 and SOX9 play pivotal roles in prostate morphogenesis, but few other species have been examined. We examined FOXA1 and SOX9 in the marsupial tammar wallaby, Macropus eugenii, which has a segmented prostate more similar to human than to mouse. In males, prostatic budding in the urogenital epithelium (UGE) was initiated by day 24 postpartum (pp), but in the female the UGE remained smooth and had begun forming the marsupial vaginal structures. FOXA1 was upregulated in the male urogenital sinus (UGS) by day 51 pp, whilst in the female UGS FOXA1 remained basal. FOXA1 was localised in the UGE in both sexes between day 20 and 80 pp. SOX9 was upregulated in the male UGS at day 21-30 pp and remained high until day 51-60 pp. SOX9 protein was localised in the distal tips of prostatic buds which were highly proliferative. The persistent upregulation of the transcription factors SOX9 and FOXA1 after the initial peak and fall of androgen levels suggest that in the tammar, as in other mammals, these factors are required to sustain prostate differentiation, development and proliferation as androgen levels return to basal levels. © 2015 S. Karger AG, Basel.

Reduction in expression of the benign AR transcriptome is a hallmark of localised prostate cancer progression.

PubMed

Stuchbery, Ryan; Macintyre, Geoff; Cmero, Marek; Harewood, Laurence M; Peters, Justin S; Costello, Anthony J; Hovens, Christopher M; Corcoran, Niall M

2016-05-24

Despite the importance of androgen receptor (AR) signalling to prostate cancer development, little is known about how this signalling pathway changes with increasing grade and stage of the disease. To explore changes in the normal AR transcriptome in localised prostate cancer, and its relation to adverse pathological features and disease recurrence. Publically accessible human prostate cancer expression arrays as well as RNA sequencing data from the prostate TCGA. Tumour associated PSA and PSAD were calculated for a large cohort of men (n=1108) undergoing prostatectomy. We performed a meta-analysis of the expression of an androgen-regulated gene set across datasets using Oncomine. Differential expression of selected genes in the prostate TCGA database was probed using the edgeR Bioconductor package. Changes in tumour PSA density with stage and grade were assessed by Student's t-test, and its association with biochemical recurrence explored by Kaplan-Meier curves and Cox regression. Meta-analysis revealed a systematic decline in the expression of a previously identified benign prostate androgen-regulated gene set with increasing tumour grade, reaching significance in nine of 25 genes tested despite increasing AR expression. These results were confirmed in a large independent dataset from the TCGA. At the protein level, when serum PSA was corrected for tumour volume, significantly lower levels were observed with increasing tumour grade and stage, and predicted disease recurrence. Lower PSA secretion-per-tumour-volume is associated with increasing grade and stage of prostate cancer, has prognostic relevance, and reflects a systematic perturbation of androgen signalling.

Current state of prostate cancer treatment in Jamaica.

PubMed

Morrison, Belinda F; Aiken, William D; Mayhew, Richard

2014-01-01

Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide. Prostate cancer accounts for a large portion of the clinical practice for health-care practitioners in Jamaica. The Jamaica Urological Society is a professional body comprising 19 urologists in Jamaica who provide most of the care for men with prostate cancer in collaboration with medical oncologists, radiation oncologists, and a palliative care physician. The health-care system is structured in two tiers in Jamaica: public and private. The urologist-to-patient ratio is high, and this limits adequate urological care. Screening for prostate cancer is not a national policy in Jamaica. However, the Jamaica Urological Society and the Jamaica Cancer Society work synergistically to promote screening as well as to provide patient education for prostate cancer. Adequate treatment for localised prostate cancer is available in Jamaica in the forms of active surveillance, nerve-sparing radical retropubic prostatectomy, external beam radiation, and brachytherapy. However, there is a geographic maldistribution of centres that provide prostate cancer treatment, which leads to treatment delays. Also, there is difficulty in affording some treatment options in the private health-care sectors. Androgen deprivation therapy is available for treatment of locally advanced and metastatic prostate cancer and is subsidised through a programme called the National Health Fund. Second-line hormonal agents and chemotherapeutic agents are available but are costly to most of the population. The infrastructure for treatment of prostate cancer in Jamaica is good, but it requires additional technological advances as well as additional specialist services.

Modelling second malignancy risks from low dose rate and high dose rate brachytherapy as monotherapy for localised prostate cancer.

PubMed

Murray, Louise; Mason, Joshua; Henry, Ann M; Hoskin, Peter; Siebert, Frank-Andre; Venselaar, Jack; Bownes, Peter

2016-08-01

To estimate the risks of radiation-induced rectal and bladder cancers following low dose rate (LDR) and high dose rate (HDR) brachytherapy as monotherapy for localised prostate cancer and compare to external beam radiotherapy techniques. LDR and HDR brachytherapy monotherapy plans were generated for three prostate CT datasets. Second cancer risks were assessed using Schneider's concept of organ equivalent dose. LDR risks were assessed according to a mechanistic model and a bell-shaped model. HDR risks were assessed according to a bell-shaped model. Relative risks and excess absolute risks were estimated and compared to external beam techniques. Excess absolute risks of second rectal or bladder cancer were low for both LDR (irrespective of the model used for calculation) and HDR techniques. Average excess absolute risks of rectal cancer for LDR brachytherapy according to the mechanistic model were 0.71 per 10,000 person-years (PY) and 0.84 per 10,000 PY respectively, and according to the bell-shaped model, were 0.47 and 0.78 per 10,000 PY respectively. For HDR, the average excess absolute risks for second rectal and bladder cancers were 0.74 and 1.62 per 10,000 PY respectively. The absolute differences between techniques were very low and clinically irrelevant. Compared to external beam prostate radiotherapy techniques, LDR and HDR brachytherapy resulted in the lowest risks of second rectal and bladder cancer. This study shows both LDR and HDR brachytherapy monotherapy result in low estimated risks of radiation-induced rectal and bladder cancer. LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer. In absolute terms these differences between techniques were very small. Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

MARCKS promotes invasion and is associated with biochemical recurrence in prostate cancer

PubMed Central

Dorris, Emma; O'Neill, Amanda; Hanrahan, Karen; Treacy, Ann; Watson, R. William

2017-01-01

Background Overtreatment of low-grade prostate cancer is a recognised problem for clinicians and patients. However, under-treatment runs the risk of missing the opportunity for cure in those who could benefit. Identification of new biomarkers of disease progression, including metastases, is required to better stratify and appropriately treat these patients. The ability to predict if prostate cancer will recur is an important clinical question that would impact treatment options for patients. Studies in other cancers have associated MARCKS with metastasis. Methods Tissue microarrays of local prostatectomy samples from a cohort of biochemical recurrent and non-biochemical recurrent tumours were assayed for MARCKS protein expression. Prostate cancer cell lines were transfected with siRNA targeting MARCKS or a control and functional endpoints of migration, invasion, proliferation, viability and apoptosis were measured. Actin was visualised by fluorescent microscopy and evidence of a cadherin switch and activation of the AKT pathway were assayed. Results MARCKS was upregulated in biochemical recurrent patients compared to non-biochemical recurrent. Knockdown of MARCKS reduced migration and invasion of prostate cancer cells, reduced MMP9 mRNA expression, as well as decreasing cell spreading and increased cell:cell adhesion in prostate cancer cell colonies. Knockdown of MARCKS had no effect on proliferation, viability or apoptosis of the prostate cancer cells. Conclusions In conclusion, MARCKS promotes migration and invasion and is associated with biochemical recurrence in localised prostate cancer tumours. The mechanisms by which this occurs have yet to be fully elucidated but lack of a cadherin switch indicates it is not via epithelial-to-mesenchymal transition. Actin rearrangement indicates that MARCKS promotes invasion through regulating the architecture of the cell. PMID:29069765

Biomarkers in the Detection of Prostate Cancer in African Americans

DTIC Science & Technology

2012-09-01

176:1534–1542 19. Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL (2005) Fas ligand- positive membranous vesicles isolated from...Larregina AT, Shufesky WJ, Sullivan MMLG, Sullivan DBS, Papworth GD, ZahorchakAF, LogarAJ, Wang Z, Watkins SC, Falo, LD Jr, ThomsonAW (2004... Seth , Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence af- ter surgery for localised prostate cancer, British Journal of Cancer 97(12

Developing a novel therapeutic strategy targeting Kallikrein-4 to inhibit prostate cancer growth and metastasis

DTIC Science & Technology

Kallikrein-related peptidase 4 (KLK4) is a rational therapeutic target for prostate cancer (PCa) as it is up-regulated in both localised and bone ...in PCa homing to bone . We therefore hypothesize that blockade of KLK4 activity will inhibit PCa growth and prevent metastasis to secondary sites like... bone . This project aims to develop a novel therapeutic strategy targeting KLK4 specifically in PCa. KLK4 siRNA is incorporated into a novel polymeric

Genome-wide analysis of AR binding and comparison with transcript expression in primary human fetal prostate fibroblasts and cancer associated fibroblasts.

PubMed

Nash, Claire; Boufaied, Nadia; Mills, Ian G; Franco, Omar E; Hayward, Simon W; Thomson, Axel A

2017-05-05

The androgen receptor (AR) is a transcription factor, and key regulator of prostate development and cancer, which has discrete functions in stromal versus epithelial cells. AR expressed in mesenchyme is necessary and sufficient for prostate development while loss of stromal AR is predictive of prostate cancer progression. Many studies have characterized genome-wide binding of AR in prostate tumour cells but none have used primary mesenchyme or stroma. We applied ChIPseq to identify genomic AR binding sites in primary human fetal prostate fibroblasts and patient derived cancer associated fibroblasts, as well as the WPMY1 cell line overexpressing AR. We identified AR binding sites that were specific to fetal prostate fibroblasts (7534), cancer fibroblasts (629), WPMY1-AR (2561) as well as those common among all (783). Primary fibroblasts had a distinct AR binding profile versus prostate cancer cell lines and tissue, and showed a localisation to gene promoter binding sites 1 kb upstream of the transcriptional start site, as well as non-classical AR binding sequence motifs. We used RNAseq to define transcribed genes associated with AR binding sites and derived cistromes for embryonic and cancer fibroblasts as well as a cistrome common to both. These were compared to several in vivo ChIPseq and transcript expression datasets; which identified subsets of AR targets that were expressed in vivo and regulated by androgens. This analysis enabled us to deconvolute stromal AR targets active in stroma within tumour samples. Taken together, our data suggest that the AR shows significantly different genomic binding site locations in primary prostate fibroblasts compared to that observed in tumour cells. Validation of our AR binding site data with transcript expression in vitro and in vivo suggests that the AR target genes we have identified in primary fibroblasts may contribute to clinically significant and biologically important AR-regulated changes in prostate tissue. Copyright © 2017. Published by Elsevier B.V.

The psychosocial impact of prostate cancer on patients and their partners.

PubMed

Couper, Jeremy W; Bloch, Sidney; Love, Anthony; Duchesne, Gillian; Macvean, Michelle; Kissane, David W

2006-10-16

To assess the psychosocial impact of the diagnosis of either localised or metastatic prostate cancer (PCA) on patients and their female partners. Observational, prospective study at Time 1 and 6 months later at Time 2 of two groups of couples facing PCA. Time 1 was when patients were first diagnosed with histologically confirmed localised (potentially curable) PCA or metastatic (incurable) PCA. Depression and anxiety disorders according to the Diagnostic and statistical manual of mental disorders 4th edition (DSM-IV); psychological distress; marital satisfaction. At Time 1, partners had rates of DSM-IV major depression and generalised anxiety disorder twice those of women in the Australian community, and considerably higher than the patients' rates. At Time 2, psychological distress in partners had lessened but that in patients had increased. On the other hand, at Time 2, partners' marital satisfaction had deteriorated. To be fully effective, interventions aimed at reducing the psychosocial morbidity of PCA must involve both patient and partner, rather than the patient alone.

Laparoscopic and robotic-assisted versus open radical prostatectomy for the treatment of localised prostate cancer.

PubMed

Ilic, Dragan; Evans, Sue M; Allan, Christie Ann; Jung, Jae Hung; Murphy, Declan; Frydenberg, Mark

2017-09-12

Prostate cancer is commonly diagnosed in men worldwide. Surgery, in the form of radical prostatectomy, is one of the main forms of treatment for men with localised prostate cancer. Prostatectomy has traditionally been performed as open surgery, typically via a retropubic approach. The advent of laparoscopic approaches, including robotic-assisted, provides a minimally invasive alternative to open radical prostatectomy (ORP). To assess the effects of laparoscopic radical prostatectomy or robotic-assisted radical prostatectomy compared to open radical prostatectomy in men with localised prostate cancer. We performed a comprehensive search using multiple databases (CENTRAL, MEDLINE, EMBASE) and abstract proceedings with no restrictions on the language of publication or publication status, up until 9 June 2017. We also searched bibliographies of included studies and conference proceedings. We included all randomised controlled trials (RCTs) with a direct comparison of laparoscopic radical prostatectomy (LRP) and robotic-assisted radical prostatectomy (RARP) to ORP, including pseudo-RCTs. Two review authors independently classified studies and abstracted data. The primary outcomes were prostate cancer-specific survival, urinary quality of life and sexual quality of life. Secondary outcomes were biochemical recurrence-free survival, overall survival, overall surgical complications, serious postoperative surgical complications, postoperative pain, hospital stay and blood transfusions. We performed statistical analyses using a random-effects model and assessed the quality of the evidence according to GRADE. We included two unique studies with 446 randomised participants with clinically localised prostate cancer. The mean age, prostate volume, and prostate-specific antigen (PSA) of the participants were 61.3 years, 49.78 mL, and 7.09 ng/mL, respectively. Primary outcomes We found no study that addressed the outcome of prostate cancer-specific survival. Based on data from one trial, RARP likely results in little to no difference in urinary quality of life (MD -1.30, 95% CI -4.65 to 2.05) and sexual quality of life (MD 3.90, 95% CI -1.84 to 9.64). We rated the quality of evidence as moderate for both quality of life outcomes, downgrading for study limitations. Secondary outcomes We found no study that addressed the outcomes of biochemical recurrence-free survival or overall survival.Based on one trial, RARP may result in little to no difference in overall surgical complications (RR 0.41, 95% CI 0.16 to 1.04) or serious postoperative complications (RR 0.16, 95% CI 0.02 to 1.32). We rated the quality of evidence as low for both surgical complications, downgrading for study limitations and imprecision.Based on two studies, LRP or RARP may result in a small, possibly unimportant improvement in postoperative pain at one day (MD -1.05, 95% CI -1.42 to -0.68 ) and up to one week (MD -0.78, 95% CI -1.40 to -0.17). We rated the quality of evidence for both time-points as low, downgrading for study limitations and imprecision. Based on one study, RARP likely results in little to no difference in postoperative pain at 12 weeks (MD 0.01, 95% CI -0.32 to 0.34). We rated the quality of evidence as moderate, downgrading for study limitations.Based on one study, RARP likely reduces the length of hospital stay (MD -1.72, 95% CI -2.19 to -1.25). We rated the quality of evidence as moderate, downgrading for study limitations.Based on two study, LRP or RARP may reduce the frequency of blood transfusions (RR 0.24, 95% CI 0.12 to 0.46). Assuming a baseline risk for a blood transfusion to be 8.9%, LRP or RARP would result in 68 fewer blood transfusions per 1000 men (95% CI 78 fewer to 48 fewer). We rated the quality of evidence as low, downgrading for study limitations and indirectness.We were unable to perform any of the prespecified secondary analyses based on the available evidence. All available outcome data were short-term and we were unable to account for surgeon volume or experience. There is no high-quality evidence to inform the comparative effectiveness of LRP or RARP compared to ORP for oncological outcomes. Urinary and sexual quality of life-related outcomes appear similar.Overall and serious postoperative complication rates appear similar. The difference in postoperative pain may be minimal. Men undergoing LRP or RARP may have a shorter hospital stay and receive fewer blood transfusions. All available outcome data were short-term, and this study was unable to account for surgeon volume or experience.

The cost-utility of open prostatectomy compared with active surveillance in early localised prostate cancer

PubMed Central

2014-01-01

Background There is an on-going debate about whether to perform surgery on early stage localised prostate cancer and risk the common long term side effects such as urinary incontinence and erectile dysfunction. Alternatively these patients could be closely monitored and treated only in case of disease progression (active surveillance). The aim of this paper is to develop a decision-analytic model comparing the cost-utility of active surveillance (AS) and radical prostatectomy (PE) for a cohort of 65 year old men with newly diagnosed low risk prostate cancer. Methods A Markov model comparing PE and AS over a lifetime horizon was programmed in TreeAge from a German societal perspective. Comparative disease specific mortality was obtained from the Scandinavian Prostate Cancer Group trial. Direct costs were identified via national treatment guidelines and expert interviews covering in-patient, out-patient, medication, aids and remedies as well as out of pocket payments. Utility values were used as factor weights for age specific quality of life values of the German population. Uncertainty was assessed deterministically and probabilistically. Results With quality adjustment, AS was the dominant strategy compared with initial treatment. In the base case, it was associated with an additional 0.04 quality adjusted life years (7.60 QALYs vs. 7.56 QALYs) and a cost reduction of €6,883 per patient (2011 prices). Considering only life-years gained, PE was more effective with an incremental cost-effectiveness ratio of €96,420/life year gained. Sensitivity analysis showed that the probability of developing metastases under AS and utility weights under AS are a major sources of uncertainty. A Monte Carlo simulation revealed that AS was more likely to be cost-effective even under very high willingness to pay thresholds. Conclusion AS is likely to be a cost-saving treatment strategy for some patients with early stage localised prostate cancer. However, cost-effectiveness is dependent on patients’ valuation of health states. Better predictability of tumour progression and modified reimbursement practice would support widespread use of AS in the context of the German health care system. More research is necessary in order to reliably quantify the health benefits compared with initial treatment and account for patient preferences. PMID:24721557

Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy.

PubMed

Peters, Max; van der Voort van Zyp, Jochem R N; Moerland, Marinus A; Hoekstra, Carel J; van de Pol, Sandrine; Westendorp, Hendrik; Maenhout, Metha; Kattevilder, Rob; Verkooijen, Helena M; van Rossum, Peter S N; Ahmed, Hashim U; Shah, Taimur T; Emberton, Mark; van Vulpen, Marco

2016-04-01

Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to develop a multivariable, internally validated prognostic model for survival after whole-gland salvage I-125-brachytherapy. Whole-gland salvage I-125-brachytherapy patients treated in the Netherlands from 1993-2010 were included. Eligible patients had a transrectal ultrasound-guided biopsy-confirmed localised recurrence after biochemical failure (clinical judgement, ASTRO or Phoenix-definition). Recurrences were assessed clinically and with CT and/or MRI. Metastases were excluded using CT/MRI and technetium-99m scintigraphy. Multivariable Cox-regression was used to assess the predictive value of clinical characteristics in relation to PCa-specific and overall mortality. PCa-specific mortality was defined as patients dying with distant metastases present. Missing data were handled using multiple imputation (20 imputed sets). Internal validation was performed and the C-statistic calculated. Calibration plots were created to visually assess the goodness-of-fit of the final model. Optimism-corrected survival proportions were calculated. All analyses were performed according to the TRIPOD statement. Median total follow-up was 78months (range 5-139). A total of 62 patients were treated, of which 28 (45%) died from PCa after mean (±SD) 82 (±36) months. Overall, 36 patients (58%) patients died after mean 84 (±40) months. PSA doubling time (PSADT) remained a predictive factor for both types of mortality (PCa-specific and overall): corrected hazard ratio's (HR's) 0.92 (95% CI: 0.86-0.98, p=0.02) and 0.94 (95% CI: 0.90-0.99, p=0.01), respectively (C-statistics 0.71 and 0.69, respectively). Calibration was accurate up to 96month follow-up. Over 80% of patients can survive 8years if PSADT>24months (PCaSS) and >33months (OS). Only approximately 50% survival is achieved with a PSADT of 12months. A PSADT of respectively >24months and >33months can result in >80% probability of PCa- specific and overall survival 8years after whole-gland salvage I-125-brachytherapy. Survival should be weighed against toxicity from a salvage procedure. Larger series and external validation are necessary. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An Evaluation of Hemi-Ablation Therapy Using High-Intensity Focused Ultrasound in the Treatment of Localized Adenocarcinoma of the Prostate

NASA Astrophysics Data System (ADS)

Ahmed, Hashim Uddin; Freeman, Alex; Allen, Clare; Kirkham, Alex; Illing, Rowland; Emberton, Mark

2007-05-01

The current choice for men with localised prostate cancer lies between active surveillance and radical therapy. The best evidence for the difference between these two extremes of care is 5% in terms of cancer-related absolute mortality at 8 years. It is generally accepted that this small difference will decrease for men diagnosed in the PSA-era. Therein lays a dilemma for men. If they choose active surveillance they accept anxiety of living with a cancer diagnosis and risk of under-treatment in the long term. On the other hand, radical therapy carries significant toxicity (incontinence, impotence, rectal problems) because it treats the whole gland and damages surrounding structures in up to half of men. With increasing PSA screening practices men are diagnosed younger with lower risk disease — early stage, lower Gleason grade and lower volume of cancer. Many have unifocal or unilateral disease. We propose a new concept whereby only the tumour focus and a margin of normal tissue is treated. With emerging techniques that can accurately localise tumour in the gland and technology that can treat to within millimetre accuracy, focal therapy of prostate cancer is now possible. By treating focally, the psychological burden of active surveillance is avoided. Equally, it is proposed that toxicity will decrease whilst at the same time retaining effective cancer control.

Pros and Cons of Focal Therapy for Localised Prostate Cancer

PubMed Central

Mearini, Luigi; Porena, Massimo

2011-01-01

In prostate cancer, an interesting and intriguing option to overcome the risks of whole-gland treatment is focal therapy, with the aim of eradicating known cancer foci and reducing collateral damages to the structures essential for maintaining normal urinary and sexual function. Ablation of all known lesions would favorably alter the natural history of the cancer without impacting health-related quality of life and allows for safe retreatment with repeated focal therapy or whole-gland approaches if necessary. Our objective is to reassess the possibilities and criticisms of such procedure: the rationale for focal therapy and the enthusiasm come from the success of conservative approaches in treating other malignancies and in the high incidence of overtreatment introduced by prostate cancer screening programs. One of the challenges in applying such an approach to the treatment of prostate cancer is the multifocal nature of the disease and current difficulties in accurate tumor mapmaking. PMID:22110990

Brachytherapy for Prostate Cancer: A Systematic Review

PubMed Central

Koukourakis, Georgios; Kelekis, Nikolaos; Armonis, Vassilios; Kouloulias, Vassilios

2009-01-01

Low-dose rate brachytherapy has become a mainstream treatment option for men diagnosed with prostate cancer because of excellent long-term treatment outcomes in low-, intermediate-, and high-risk patients. To a great extend due to patient lead advocacy for minimally invasive treatment options, high-quality prostate implants have become widely available in the US, Europe, and Japan. High-dose-rate (HDR) afterloading brachytherapy in the management of localised prostate cancer has practical, physical, and biological advantages over low-dose-rate seed brachytherapy. There are no free live sources used, no risk of source loss, and since the implant is a temporary procedure following discharge no issues with regard to radioprotection use of existing facilities exist. Patients with localized prostate cancer may benefit from high-dose-rate brachytherapy, which may be used alone in certain circumstances or in combination with external-beam radiotherapy in other settings. The purpose of this paper is to present the essentials of brachytherapies techniques along with the most important studies that support their effectiveness in the treatment of prostate cancer. PMID:19730753

Increased risk of suicide in New South Wales men with prostate cancer: Analysis of linked population-wide data.

PubMed

Smith, David P; Calopedos, Ross; Bang, Albert; Yu, Xue Qin; Egger, Sam; Chambers, Suzanne; O'Connell, Dianne L

2018-01-01

An elevated risk of suicide after a diagnosis of prostate cancer has been reported previously in the USA and Sweden. We aimed to identify whether prostate cancer survivors resident in New South Wales Australia are at higher risk of suicide and if so, who is most at risk. Data were obtained from the New South Wales (NSW) Cancer Registry for all men diagnosed with prostate cancer in NSW during 1997 to 2007. These were linked by the Centre for Health Record Linkage (CHeReL) to Australian Bureau of Statistics Mortality Data to the end of 2007 to determine vital status and cause of death. We compared the number of suicides observed for prostate cancer survivors with the expected number of suicides based on age- and calendar year- specific rates for the NSW male population using standardised mortality ratios (SMRs). Suicide rate ratios (RR) by disease and patients' characteristics were estimated using multivariable negative binomial regression to determine the most at risk groups. During the study period 51,924 NSW men were diagnosed with prostate cancer. Forty nine of these men were subsequently recorded as committing suicide up to 10 years after diagnosis with an SMR of 1.70 (95% CI:1.26-2.25). Twenty six (53%) of these suicides occurred within 12 months after diagnosis. Risk diminished over time since diagnosis (RR in 1-2 years after diagnosis = 0.29, 95% CI: 0.12-0.71, 2-4 years RR = 0.30, 95% CI: 0.14-0.16 and 4+ years RR = 0.26, 95% CI: 0.11-0.60 compared with <1 year since diagnosis). Men with non-localised disease had a higher risk of suicide compared to men with localised disease (RR = 2.68, 95% CI: 1.15-6.23). Men living outside major cities had lower risk of suicide compared to those resident in major cities (rate ratio = 0.42, 95% CI: 0.20-0.87). Single, divorced, widowed or separated men were more likely to commit suicide than married men (RR = 4.18, 95% CI: 2.36-7.42). Risk of suicide is higher for NSW men diagnosed with prostate cancer than the general age matched male population. Vulnerable or lonely men and those with pre-existing depression or suicidal ideation who are diagnosed with prostate cancer should be offered additional psychological support.

Evolving adoptive cellular therapies in urological malignancies.

PubMed

Wong, Yien Ning Sophia; Joshi, Kroopa; Pule, Martin; Peggs, Karl S; Swanton, Charles; Quezada, Sergio A; Linch, Mark

2017-06-01

Immunotherapies have long been used to treat urological cancers but rarely lead to cure. In the past 5 years, success of immune checkpoint inhibition has led to a resurgence of enthusiasm for immunotherapy in the treatment of solid tumours. Increased understanding of tumour immune biology, technological advancements of gene transfer and cell culture, and improved clinical infrastructures for routine delivery of cell products, has made cell-based immunotherapeutics a real prospect for cancer therapy. These scientific and clinical activities, attempting to exploit the innate and adaptive immune systems for therapeutic gain, are well exemplified by the urological malignancies of renal, bladder, prostate, and penile cancer, a group of anatomically localised diseases, each with a distinct biology and different immunotherapeutic challenges. In this Review, we present the results of clinical studies investigating autologous cellular therapies in urological malignancies. Specifically, we discuss the rationale for upcoming studies, and how novel therapies and adoptive cell combinations can be used for personalised cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cohort profile: the TrueNTH Global Registry - an international registry to monitor and improve localised prostate cancer health outcomes.

PubMed

Evans, Sue M; Millar, Jeremy L; Moore, Caroline M; Lewis, John D; Huland, Hartwig; Sampurno, Fanny; Connor, Sarah E; Villanti, Paul; Litwin, Mark S

2017-11-28

Globally, prostate cancer treatment and outcomes for men vary according to where they live, their race and the care they receive. The TrueNTH Global Registry project was established as an international registry monitoring care provided to men with localised prostate cancer (CaP). Sites with existing CaP databases in Movember fundraising countries were invited to participate in the international registry. In total, 25 Local Data Centres (LDCs) representing 113 participating sites across 13 countries have nominated to contribute to the project. It will collect a dataset based on the International Consortium for Health Outcome Measures (ICHOM) standardised dataset for localised CaP. A governance strategy has been developed to oversee registry operation, including transmission of reversibly anonymised data. LDCs are represented on the Project Steering Committee, reporting to an Executive Committee. A Project Coordination Centre and Data Coordination Centre (DCC) have been established. A project was undertaken to compare existing datasets, understand capacity at project commencement (baseline) to collect the ICHOM dataset and assist in determining the final data dictionary. 21/25 LDCs provided data dictionaries for review. Some ICHOM data fields were well collected (diagnosis, treatment start dates) and others poorly collected (complications, comorbidities). 17/94 (18%) ICHOM data fields were relegated to non-mandatory fields due to poor capture by most existing registries. Participating sites will transmit data through a web interface biannually to the DCC. Recruitment to the TrueNTH Global Registry-PCOR project will commence in late 2017 with sites progressively contributing reversibly anonymised data following ethical review in local regions. Researchers will have capacity to source deidentified data after the establishment phase. Quality indicators are to be established through a modified Delphi approach in later 2017, and it is anticipated that reports on performance against quality indicators will be provided to LDCs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ligand-independent activation of EphA2 by arachidonic acid induces metastasis-like behaviour in prostate cancer cells

PubMed Central

Tawadros, T; Brown, M D; Hart, C A; Clarke, N W

2012-01-01

Background: High intake of omega-6 polyunsaturated fatty acids (PUFA) has been associated with clinical progression in prostate cancer (CaP). This study investigates the signalling mechanism by which the omega-6 PUFA arachidonic acid (AA) induces prostatic cellular migration to bone marrow stroma. Methods: Western blot analysis of the PC-3, PC3-GFP, DU 145 and LNCaP cells or their lipid raft (LR) components post AA stimulation was conducted in association with assays for adhesion and invasion through the bone marrow endothelial monolayers. Results: Arachidonic acid increased transendothelial migration of PC3-GFP cells (adhesion 37%±0.08, P=0.0124; transmigration 270%±0.145, P=0.0008). Akt, Src and focal adhesion kinase (FAK) pathways were induced by AA and integrally involved in transendothelial migration. LR were critical in AA uptake and induced Akt activity. Ephrin receptor A2 (EphA2), localised in LR, is expressed in DU 145 and PC-3 cells. Arachidonic acid induced a rapid increase of EphA2 Akt-dependent/ligand-independent activation, while knockdown of the EphrinA1 ligand decreased AA induced transendothelial migration, with an associated decrease in Src and FAK activity. Arachidonic acid activated Akt in EphA2− LNCaP cells but failed to induce BMEC transendothelial invasion. Conclusion: Arachidonic acid induced stimulation of EphA2 in vitro is associated fundamentally with CaP epithelial migration across the endothelial barrier. PMID:23037715

RNA splicing and splicing regulator changes in prostate cancer pathology.

PubMed

Munkley, Jennifer; Livermore, Karen; Rajan, Prabhakar; Elliott, David J

2017-09-01

Changes in mRNA splice patterns have been associated with key pathological mechanisms in prostate cancer progression. The androgen receptor (abbreviated AR) transcription factor is a major driver of prostate cancer pathology and activated by androgen steroid hormones. Selection of alternative promoters by the activated AR can critically alter gene function by switching mRNA isoform production, including creating a pro-oncogenic isoform of the normally tumour suppressor gene TSC2. A number of androgen-regulated genes generate alternatively spliced mRNA isoforms, including a prostate-specific splice isoform of ST6GALNAC1 mRNA. ST6GALNAC1 encodes a sialyltransferase that catalyses the synthesis of the cancer-associated sTn antigen important for cell mobility. Genetic rearrangements occurring early in prostate cancer development place ERG oncogene expression under the control of the androgen-regulated TMPRSS2 promoter to hijack cell behaviour. This TMPRSS2-ERG fusion gene shows different patterns of alternative splicing in invasive versus localised prostate cancer. Alternative AR mRNA isoforms play a key role in the generation of prostate cancer drug resistance, by providing a mechanism through which prostate cancer cells can grow in limited serum androgen concentrations. A number of splicing regulator proteins change expression patterns in prostate cancer and may help drive key stages of disease progression. Up-regulation of SRRM4 establishes neuronal splicing patterns in neuroendocrine prostate cancer. The splicing regulators Sam68 and Tra2β increase expression in prostate cancer. The SR protein kinase SRPK1 that modulates the activity of SR proteins is up-regulated in prostate cancer and has already given encouraging results as a potential therapeutic target in mouse models.

Cost-effectiveness analysis of intensity-modulated radiation therapy with normal and hypofractionated schemes for the treatment of localised prostate cancer.

PubMed

Zemplényi, A T; Kaló, Z; Kovács, G; Farkas, R; Beöthe, T; Bányai, D; Sebestyén, Z; Endrei, D; Boncz, I; Mangel, L

2018-01-01

The aim of our analysis was to compare the cost-effectiveness of high-dose intensity-modulated radiation therapy (IMRT) and hypofractionated intensity-modulated radiation therapy (HF-IMRT) versus conventional dose three-dimensional radiation therapy (3DCRT) for the treatment of localised prostate cancer. A Markov model was constructed to calculate the incremental quality-adjusted life years and costs. Transition probabilities, adverse events and utilities were derived from relevant systematic reviews. Microcosting in a large university hospital was applied to calculate cost vectors. The expected mean lifetime cost of patients undergoing 3DCRT, IMRT and HF-IMRT were 7,160 euros, 6,831 euros and 6,019 euros respectively. The expected quality-adjusted life years (QALYs) were 5.753 for 3DCRT, 5.956 for IMRT and 5.957 for HF-IMRT. Compared to 3DCRT, both IMRT and HF-IMRT resulted in more health gains at a lower cost. It can be concluded that high-dose IMRT is not only cost-effective compared to the conventional dose 3DCRT but, when used with a hypofractionation scheme, it has great cost-saving potential for the public payer and may improve access to radiation therapy for patients. © 2016 John Wiley & Sons Ltd.

Histopathological changes associated with high intensity focused ultrasound (HIFU) treatment for localised adenocarcinoma of the prostate

PubMed Central

Van Leenders, G J L H; Beerlage, H; Ruijter, E; de la Rosette, J J M C H; van de Kaa, C A

2000-01-01

Aims—Investigation of the histopathological changes in prostatectomy specimens of patients with prostate cancer after high intensity focused ultrasound (HIFU) and identification of immunohistochemical markers for tissue damage after HIFU treatment. Methods—Nine patients diagnosed with adenocarcinoma of the prostate underwent unilateral HIFU treatment seven to 12 days before radical prostatectomy. The prostatectomy specimens were analysed histologically. Immunohistochemical staining and electron microscopy were performed to characterise more subtle phenotypic changes. Results—All prostatectomy specimens revealed well circumscribed HIFU lesions at the dorsal side of the prostate lobe treated. Most epithelial glands in the centre of the HIFU lesions revealed signs of necrosis. Glands without apparently necrotic features were also situated in the HIFU lesions, raising the question of whether lethal destruction had occurred. This epithelium reacted with antibodies to pancytokeratin, prostate specific antigen (PSA), and Ki67, but did not express cytokeratin 8, which is indicative of severe cellular damage. Ultrastructural examination revealed disintegration of cellular membranes and cytoplasmic organelles consistent with cell necrosis. HIFU treatment was incomplete at the ventral, lateral, and dorsal sides of the prostate lobe treated. Conclusions—HIFU treatment induces a spectrum of morphological changes ranging from apparent light microscopic necrosis to more subtle ultrastructural cell damage. All HIFU lesions are marked by loss of cytokeratin 8. HIFU does not affect the whole area treated, leaving vital tissue at the ventral, lateral, and dorsal sides of the prostate. Key Words: prostate cancer • high intensity focused ultrasound treatment PMID:10889823

Magnetic resonance imaging-directed transperineal limited-mapping prostatic biopsies to diagnose prostate cancer: a Scottish experience.

PubMed

Mukherjee, Ankur; Morton, Simon; Fraser, Sioban; Salmond, Jonathan; Baxter, Grant; Leung, Hing Y

2014-11-01

Transperineal prostatic biopsy is firmly established as an important tool in the diagnosis of prostate cancer. The benefit of additional imaging (magnetic resonance imaging) to target biopsy remains to be fully addressed. Using a cohort of consecutive patients undergoing transperineal template mapping biopsies, we studied positive biopsies in the context of magnetic resonance imaging findings and examined the accuracy of magnetic resonance imaging in predicting the location of transperineal template mapping biopsies-detected prostate cancer. Forty-four patients (mean age: 65 years, range 53-78) underwent transperineal template mapping biopsies. Thirty-four patients had 1-2 and 10 patients had ≥3 previous transrectal ultrasound scan-guided biopsies. The mean prostate-specific antigen was 15 ng/mL (range 2.5-79 ng/mL). High-grade prostatic intraepithelial neoplasia was found in 12 (27%) patients and prostate cancer with Gleason <7, 7 and >7 in 13, 10 and 8 patients, respectively. Suspicious lesions on magnetic resonance imaging scans were scored from 1 to 5. In 28 patients, magnetic resonance imaging detected lesions with score ≥3. Magnetic resonance imaging correctly localised transperineal template mapping biopsies-detected prostate cancer in a hemi-gland approach, particularly in a right to left manner (79% positive prediction rate), but not in a quadrant approach (33% positive prediction rate). Our findings support the notion of magnetic resonance imaging-based selection of patients for transperineal template mapping biopsies and that lesions revealed by magnetic resonance imaging are likely useful for targeted biopsies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Development of Indicators to Assess Quality of Care for Prostate Cancer.

PubMed

Nag, Nupur; Millar, Jeremy; Davis, Ian D; Costello, Shaun; Duthie, James B; Mark, Stephen; Delprado, Warick; Smith, David; Pryor, David; Galvin, David; Sullivan, Frank; Murphy, Áine C; Roder, David; Elsaleh, Hany; Currow, David; White, Craig; Skala, Marketa; Moretti, Kim L; Walker, Tony; De Ieso, Paolo; Brooks, Andrew; Heathcote, Peter; Frydenberg, Mark; Thavaseelan, Jeffery; Evans, Sue M

2016-02-20

The development, monitoring, and reporting of indicator measures that describe standard of care provide the gold standard for assessing quality of care and patient outcomes. Although indicator measures have been reported, little evidence of their use in measuring and benchmarking performance is available. A standard set, defining numerator, denominator, and risk adjustments, will enable global benchmarking of quality of care. To develop a set of indicators to enable assessment and reporting of quality of care for men with localised prostate cancer (PCa). Candidate indicators were identified from the literature. An international panel was invited to participate in a modified Delphi process. Teleconferences were held before and after each voting round to provide instruction and to review results. Panellists were asked to rate each proposed indicator on a Likert scale of 1-9 in a two-round iterative process. Calculations required to report on the endorsed indicators were evaluated and modified to reflect the data capture of the Prostate Cancer Outcomes Registry-Australia and New Zealand (PCOR-ANZ). A total of 97 candidate indicators were identified, of which 12 were endorsed. The set includes indicators covering pre-, intra-, and post-treatment of PCa care, within the limits of the data captured by PCOR-ANZ. The 12 endorsed quality measures enable international benchmarking on the quality of care of men with localised PCa. Reporting on these indicators enhances safety and efficacy of treatment, reduces variation in care, and can improve patient outcomes. PCa has the highest incidence of all cancers in men. Early diagnosis and relatively high survival rates mean issues of quality of care and best possible health outcomes for patients are important. This paper identifies 12 important measurable quality indicators in PCa care. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Cognitive existential couple therapy (CECT) in men and partners facing localised prostate cancer: a randomised controlled trial.

PubMed

Couper, Jeremy; Collins, Anna; Bloch, Sidney; Street, Annette; Duchesne, Gillian; Jones, Tessa; Olver, James; Love, Anthony

2015-04-01

To assess the efficacy of cognitive existential couple therapy (CECT) for relationship function, coping, cancer distress and mental health in men with localised prostate cancer and in their partners. A randomised controlled trial was conducted with 62 couples randomly assigned to the six-session CECT programme or care as usual. The couple's relationship function (primary outcome), and coping, cancer distress and mental health (secondary outcomes) were evaluated at T0 (baseline), T1 (after treatment) and T2 (9 months from T0). A repeated-measures analysis of covariance model, which incorporated T0 measurements as a covariate, was used to compare treatment groups at T1 and T2. After CECT, patients reported significantly greater use of adaptive coping (P = 0.03) and problem-focused coping (P = 0.01). These gains were maintained at follow-up, while relationship cohesion had improved (P = 0.03), as had relationship function for younger patients (P = 0.01). Younger partners reported less cancer-specific distress (P = 0.008), avoidance (P = 0.04), intrusive thought (P = 0.006), and hyperarousal (P = 0.01). Gains were maintained at follow-up, while relationship cohesion (P = 0.007), conflict resolution (P = 0.01) and relational function (P = 0.009) all improved. CECT resulted in improved coping for patients and lower cancer-distress for partners. Maintained over time this manifests as improved relationship function. CECT was acceptable to couples, alleviated long-term relationship decline, and is therefore suitable as a preventative mental health intervention for couples facing prostate cancer. Given resourcing demands, we recommend dissemination of CECT be targeted at younger couples, as CECT was more acceptable to the younger group, and they derived greater benefit from it. © 2015 The Authors. BJU International © 2015 BJU International.

Safety and Efficacy of Robot-assisted Radical Prostatectomy in a Low-volume Center: A 6-year Single-surgeon Experience.

PubMed

DI Pierro, Giovanni Battista; Grande, Pietro; Mordasini, Livio; Danuser, Hansjörg; Mattei, Agostino

2016-08-01

To analyze safety and efficacy of robot-assisted radical prostatectomy (RARP) in a low-volume centre. From 2008 to 2015, 400 consecutive patients undergoing RARP were prospectively enrolled. Complications were classified according to the Modified Clavien System. Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen (PSA) values ≥0.2 ng/ml. Functional outcomess were assessed using validated, self-administered questionnaires. Median patient age was 64.5 years. Mean standard deviation (SD) preoperative PSA level was 11.3 (11.7) ng/ml. Median interquartile range (IQR) follow-up was 36 (12-48) months. Overall complication rate was 27.7% (minor complications rate 16.2%). Overall 1-, 3- and 6-year BCR-free survival rates were 85.7%, 77.5% and 53.9%, respectively; these rates were 94.1%, 86.2% and 70.1% in pT2 diseases. At follow-up, 98.4% of patients were fully continent (median (IQR) time to continence was 2 (1-3) months) and 68.2% were potent (median (IQR) time to potency of 3 (3-4) months). RARP appears to be a valuable option for treating clinically localised prostate cancer also in a low-volume institution. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Importance of agonists in alpha-adrenoceptor classification and localisation of alpha1-adrenoceptors in human prostate.

PubMed

McGrath, J C; Naghadeh, M A; Pediani, J D; Mackenzie, J F; Daly, C J

1999-01-01

alpha-Adrenoceptor blocker drugs are commonly used in the clinical (non-surgical) treatment of BPH. alpha1-adrenoceptors were originally sub-divided using agonists but, subsequently, were sub-divided using only antagonists in ligand-ligand interactions, which did not require agonists at all. Ultimately, proof that adrenoceptors are functional receptors for the natural ligands, noradrenaline and adrenaline, requires that agonists be used. The earlier excitement engendered by finding varying agonist potency series in different tissues has not been revisited to place it in the context of current concepts of alpha1-adrenoceptor subtypes. This review will consider the advantages and limitations of different agonists for the study of alpha1-adrenoceptor subtypes including 'extreme' examples where the archetypal alpha1-adrenoceptor agonist phenylephrine activates alpha2-adrenoceptors and others where UK14304, often the alpha2-adrenoceptor agonist of choice, activates alpha1-adrenoceptors. New work will also be presented showing the interaction between agonists and the fluorescent alpha1-adrenoceptor antagonist QAPB. This introduces the novel point of view of studying the displacement of antagonists by agonists. Possible errors in antagonist classification arising from complexity in the actions of agonists and the recently developed method of fluorescent ligand binding on isolated living human prostatic smooth muscle cells will be discussed.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

PubMed

Turner, E L; Metcalfe, C; Donovan, J L; Noble, S; Sterne, J A C; Lane, J A; Avery, K N; Down, L; Walsh, E; Davis, M; Ben-Shlomo, Y; Oliver, S E; Evans, S; Brindle, P; Williams, N J; Hughes, L J; Hill, E M; Davies, C; Ng, S Y; Neal, D E; Hamdy, F C; Martin, R M

2014-06-10

Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

[Quantification of prostate movements during radiotherapy].

PubMed

Artignan, X; Rastkhah, M; Balosso, J; Fourneret, P; Gilliot, O; Bolla, M

2006-11-01

Decrease treatment uncertainties is one of the most important challenge in radiation oncology. Numerous techniques are available to quantify prostate motion and visualise prostate location day after day before each irradiation: CT-scan, cone-beam-CT-Scan, ultrason, prostatic markers... The knowledge of prostate motion is necessary to define the minimal margin around the target volume needed to avoid mispositioning during treatment session. Different kind of prostate movement have been studied and are reported in the present work: namely, those having a large amplitude extending through out the whole treatment period on one hand; and those with a shorter amplitude happening during treatment session one the other hand. The long lasting movement are mostly anterior-posterior (3 mm standard deviation), secondary in cranial-caudal (1-2 mm standard deviation) and lateral directions (0.5-1 mm standard deviation). They are mostly due to the rectal state of filling and mildly due to bladder filling or inferior limbs position. On the other hand, the shorter movement that occurs during the treatment session is mostly variation of position around a steady point represented by the apex. Ones again, the rectal filling state is the principle cause. This way, during the 20 minutes of a treatment session, including the positioning of the patient, a movement of less than 3 mm could be expected when the rectum is empty. Ideally, real time imaging tools should allow an accurate localisation of the prostate and the adaptation of the dosimetry before each treatment session in a time envelope not exceeding 20 minutes.

Can a peri-rectal hydrogel spaceOAR programme for prostate cancer intensity-modulated radiotherapy be successfully implemented in a regional setting?

PubMed

Te Velde, Bridget L; Westhuyzen, Justin; Awad, Nader; Wood, Maree; Shakespeare, Thomas P

2017-08-01

The aim of this study was to investigate whether the implementation of a hydrogel spacer (SpaceOAR) programme for patients treated with 81 Gy prostate intensity-modulated radiotherapy (IMRT) in a regional setting can reduce rectal doses and toxicity. In this retrospective study, 125 patients with localised prostate cancer treated between April 2014 (programme commencement) and June 2015 were compared: 65 with SpaceOAR (inserted by five different urologists) and 60 patients treated over the same time period without SpaceOAR. Patients were treated with 81 Gy in 45Fx of IMRT over 9 weeks. Planning aims included restricting rectal doses to V40 Gy < 35%, V65 Gy < 17%, V75 Gy < 10%. Acute toxicity was assessed weekly during radiotherapy and at 12 weeks. Rectal volume parameters were all significantly lower in the SpaceOAR group, with an associated reduction in acute diarrhoea (13.8% vs 31.7%). There were no significant differences in the very low rates of acute and late faecal incontinence or proctitis, however, there was a trend towards increased haemorrhoid rate in the SpaceOAR group (11.7% vs 3.1%, P = 0.09). A SpaceOAR programme in a regional setting with urologists performing low volumes of insertions (<1 per month on average) is of clinical benefit, and was associated with significantly lower radiation doses to the rectum and lower rates of acute diarrhoea. © 2017 The Royal Australian and New Zealand College of Radiologists.

Patterns of care for brachytherapy in Europe: updated results for Spain.

PubMed

Guedea, Ferran; López-Torrecilla, José; Londres, Bradley; Ventura, Montse; Bilbao, Pedro; Borràs, Josep M

2012-01-01

The aim of this follow-up pattern of care study was to evaluate current clinical practices, staffing and equipment, and to compare these results to a study performed 5 years previously. This descriptive, pattern of care study was carried out via an online questionnaire. The survey was sent to a total of 95 cancer care centres in Spain. Seventy-three centres (76.8%) responded to the survey. More than half (57.5%) of responding centres offered brachytherapy (BT). A mean of 120 patients/centre were treated by BT in 2007. The most common localisations were the endometrium (29.6% of cases), prostate (29.6%), cervix uteri (14.6%), breast (12.6%), head and neck (3.6%) and vagina (2.5%). Other sites accounted for less than 2% of cases each. Most centres that offered BT (33/40 = 82.5%) were equipped with a dedicated BT operating room. The most commonly reported dosimetric method was CT dosimetry (31 of 40 centres = 77.5%), followed by plain film (30/40 = 75%), ultrasound (26/40 = 65%), MRI (8/40 = 20%), in vivo (7/40 = 17.5%) and PET-CT (5/40 = 12.5%) dosimetry. The three most common treatment sites (gynaecological, breast and prostate) remain unchanged from 2002, with prostate treatments showing large increase. Advanced dosimetric techniques (MRI, PET-CT and CT-dosimetry) continue to gain adherents. Some centres treat small numbers of patients, a finding that deserves more attention in terms of cost and quality of care. Although BT remains strong in Spain, it could be further strengthened by making modern dosimetric techniques and treatments more widely available.

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

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

PubMed

Rybicki, B A; Kryvenko, O N; Wang, Y; Jankowski, M; Trudeau, S; Chitale, D A; Gupta, N S; Rundle, A; Tang, D

2016-06-01

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing-suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer

PubMed Central

Rybicki, BA; Kryvenko, ON; Wang, Y; Jankowski, M; Trudeau, S; Chitale, DA; Gupta, NS; Rundle, A; Tang, D

2016-01-01

BACKGROUND Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. METHODS Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I–III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). RESULTS Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR) = 0.47; 95% confidence interval (CI) = 0.27–0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR = 3.56; 95% CI = 1.15–10.99). Moreover, PSA velocity (P = 0.008) and frequency of PSA testing (P = 0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR = 2.97; 95% CI = 1.40–6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR = 1.91; 95% CI = 1.09–3.35). CONCLUSIONS In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing—suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection. PMID:26620738

Profile of NF-κBp(65/NFκBp50) among prostate specific antigen sera levels in prostatic pathologies.

PubMed

Bouraoui, Y; Ben Jemaa, A; Rodriguez, G; Ben Rais, N; Fraile, B; Paniagua, R; Sellemi, S; Royuela, M; Oueslati, R

2012-10-01

The aim of this work was to characterise the immunoexpression of NF-κB (p50/p65) in human prostatic pathologies and to study its profiles of activation among sera prostate specific antigen antigen (PSA) according the three groups: 0-4ng/mL, 4-20ng/mL and >20ng/mL. Twenty-four men with benign prostate hyperplasia (BPH); 19 men with prostate cancer (PC) and five men with normal prostates (NP). Immunohistochemical and western blot analysis was performed. Serum levels of PSA were assayed by immulite autoanalyser. In BPH and PC samples, immunoexpressions were observed for NF-κBp65 and NF-κBp50; while in NP samples, only were detected NF-κBp50. PC samples showed immunoreactions to NF-κBp65 and NF-κBp50 more intense (respectively 24.18±0.67 and 28.23±2.01) than that observed in BPH samples (respectively18.46±2.04 and 18.66±1.59) with special localisation in the nucleus. Different profiles of NF-κBp65 immunoexpressions were observed and BPH patients with sera PSA levels between 0-4ng/mL presented a significant weak percentage compared to BPH patients with sera PSA levels between 4-20ng/mL and >20ng/mL. No immunoreactions to NF-κBp65 were observed in PC patients with sera PSA levels between 4-20ng/mL. The sensibility of both NF-κB and PSA to inflammation allowed confirming the relationship between these two molecules and its involvement in prostatic diseases progression (inflammatory and neoplasic). Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Prostatic needle biopsies following primary high intensity focused ultrasound (HIFU) therapy for prostatic adenocarcinoma: histopathological features in tumour and non-tumour tissue.

PubMed

Ryan, Paul; Finelli, Antonio; Lawrentschuk, Nathan; Fleshner, Neil; Sweet, Joan; Cheung, Carol; van der Kwast, Theodorus; Evans, Andrew

2012-08-01

High intensity focused ultrasound (HIFU) is currently offered as primary treatment for patients with clinically localised prostate cancer. Data on histopathological features of post-treatment biopsies are limited. Pretreatment biopsies were identified in 45 men (age range 41-85) who received primary HIFU therapy. Post-HIFU biopsies were performed in 30 of these patients (67%) at mean 14.1 months (95% CI 11.7 to 16.5) follow-up, 22 due to rising PSA and eight as part of routine follow-up. Biopsies were examined for presence, distribution and extent of adenocarcinoma, Gleason scores, use of standard immunohistochemistry and ablative tissue changes were attributable to HIFU. In post-HIFU biopsies performed for biochemical failure, 17/22 (77%) contained adenocarcinoma; 4/22 (18%) had higher post-HIFU Gleason score; 3/22 (14%) had newly recognised bilateral involvement; and 4/22 (18%) had higher percentage tissue involvement compared with pre-HIFU biopsies. Of cases without rising post-HIFU PSA, 2/8 (25%) routine follow-up biopsies contained adenocarcinoma. Stromal fibrosis was the commonest finding in non-tumour post-HIFU biopsy tissue (17/30, 57%) with coagulative necrosis occurring in fewer cases (4/30, 13%) and over a shorter follow-up interval than cases showing fibrosis (8.5 (0.2-16.8) vs 15.3 (11.5-19.1) months). Treatment effects in tumour cells precluding the assignment of Gleason scores or use of immunohistochemistry in post-HIFU biopsies were not identified. Post-HIFU biopsies are positive in more than 75% of patients with elevated or rising PSA. Stromal fibrosis is common but the tissue effects of this modality do not appear to impair pathologists' ability to detect and grade adenocarcinoma in follow-up biopsies.

Wellbeing during Active Surveillance for localised prostate cancer: a systematic review of psychological morbidity and quality of life.

PubMed

Carter, Gregory; Clover, Kerrie; Britton, Ben; Mitchell, Alex J; White, Martin; McLeod, Nicholas; Denham, Jim; Lambert, Sylvie D

2015-01-01

Active Surveillance (AS) is recommended for the treatment of localised prostate cancer; however this option may be under-used, at least in part because of expectations of psychological adverse events in those offered or accepting AS. (1) Determine the impact on psychological wellbeing when treated with AS (non-comparative studies). (2) Compare AS with active treatments for the impact on psychological wellbeing (comparative studies). We used the PRISMA guidelines and searched Medline, PsychInfo, EMBASE, CINHAL, Web of Science, Cochrane Library and Scopus for articles published January 2000-2014. Eligible studies reported original quantitative data on any measures of psychological wellbeing. We identified 34 eligible articles (n=12,497 individuals); 24 observational, eight RCTs, and two other interventional studies. Studies came from North America (16), Europe (14) Australia (3) and North America/Europe (1). A minority (5/34) were rated as high quality. Most (26/34) used validated instruments, whilst a substantial minority (14/34) used watchful waiting or no active treatment rather than Active Surveillance. There was modest evidence of no adverse impact on psychological wellbeing associated with Active Surveillance; and no differences in psychological wellbeing compared to active treatments. Patients can be informed that Active Surveillance involves no greater threat to their psychological wellbeing as part of the informed consent process, and clinicians need not limit access to Active Surveillance based on an expectation of adverse impacts on psychological wellbeing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigating the possible causal role of coffee consumption with prostate cancer risk and progression using Mendelian randomization analysis.

PubMed

Taylor, Amy E; 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

2017-01-15

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. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Heat shock protein 27 is a potential indicator for response to YangZheng XiaoJi and chemotherapy agents in cancer cells.

PubMed

Owen, Sioned; Zhao, Huishan; Dart, Alwyn; Wang, Yamei; Ruge, Fiona; Gao, Yong; Wei, Cong; Wu, Yiling; Jiang, Wen G

2016-11-01

Heat shock protein 27 (HSP27) is a member of the heat shock protein family which has been linked to tumour progression and, most interestingly, to chemotherapy resistance in cancer patients. The present study examined the potential interplay between HSP27 and YangZheng XiaoJi, a traditional Chinese medicine used in cancer treatment. A range of cell lines from different tumour types including pancreatic, lung, gastric, colorectal, breast, prostate and ovarian cancer (both wild-type and resistant) were used. Levels and activation of HSP27 and its potential associated signalling pathways were evaluated by protein array and western blotting. Knockdown of HSP27 in cancer cells was achieved using siRNA. Localisation and co-localisation of HSP27 and other proteins were carried out by immunofluorescence. Cell growth and migration were evaluated in their response to a range of chemotherapeutic agents. The present study first identified, by way of protein array, that YangZheng XiaoJi was able to inhibit the phosphorylation of HSP27 protein in cancer cells. We further demonstrated that HSP27, which is co-localised with caspase-9, can be blocked from localising in focal adhesions and co-localising with caspase-9 by YangZheng XiaoJi. The study also demonstrated that YangZheng XiaoJi was able to sensitise cancer cells including those cells that were resistant to chemotherapy, to chemotherapeutic agents. Finally, knocking down HSP27 markedly reduced the migration of cancer cells and increased the sensitivity of cancer cells to the inhibitory effect on cellular migration by YangZheng XiaoJi. YangZheng XiaoJi can act as an agent in first sensitising cancer cells to chemotherapy and secondly to overcome, to some degree, chemoresistance when used in an appropriate fashion in patients who have active HSP27.

The effect of aerobic exercise on treatment-related acute toxicity in men receiving radical external beam radiotherapy for localised prostate cancer.

PubMed

Kapur, G; Windsor, P M; McCowan, C

2010-09-01

We retrospectively analysed acute radiation toxicity data for patients who had participated in a randomised controlled study in our centre in order to assess the impact of aerobic exercise on acute rectal and bladder morbidity during treatment. Data from 65 of 66 patients were analysed: 33 allocated into a control group (standard advice) and 33 into an exercise group (aerobic walking for 30 min at least three times per week) during 4 weeks of external beam radiotherapy; one patient in the exercise group withdrew after randomisation before starting radiotherapy. There was a trend towards less severe acute rectal toxicity in the exercise group with a statistically significant difference in mean toxicity scores over the 4 weeks of radiotherapy (P=0.004), with no significant difference in bladder toxicity scores between the two groups (P=0.123). The lack of an association for severity of bladder toxicity could be attributed to the confounding effect of lower urinary tract symptoms from their prostate cancer. Keeping active and being asked to adhere to a well-defined exercise schedule appears to reduce the severity of rectal toxicity during radiotherapy to the prostate.

A randomised controlled trial of a couples-based sexuality intervention for men with localised prostate cancer and their female partners.

PubMed

Chambers, Suzanne K; Occhipinti, Stefano; Schover, Leslie; Nielsen, Lisa; Zajdlewicz, Leah; Clutton, Samantha; Halford, Kim; Gardiner, Robert A; Dunn, Jeff

2015-07-01

The diagnosis and treatment of prostate cancer is followed by substantive sexual morbidity. The optimal approach for intervening remains unclear. A three-arm randomised control trial was undertaken with 189 heterosexual couples where the man had been diagnosed with prostate cancer and treated surgically. The efficacy of peer-delivered telephone support versus nurse-delivered telephone counselling versus usual care in improving both men's and women's sexual adjustment was investigated. Assessments were undertaken at baseline (pre-test) with follow-up at 3, 6 and 12 months. At 12 months, men in the peer (p = 0.016) and nurse intervention (p = 0.008) were more likely to use medical treatments for erectile dysfunction (ED) than men in the usual care arm. Men in the nurse intervention more frequently used oral medication for ED than men in usual care (p = 0.002). No significant effects were found for sexual function, sexuality needs, sexual self-confidence, masculine self-esteem, marital satisfaction or intimacy. Although peer and nurse couples-based interventions can increase use of medical treatments for ED, this may not translate into better sexual or relationship outcomes. More research is needed into the optimal timing of interventions to improve sexual outcomes for men with prostate cancer and to identify the subpopulations that will benefit from them. Copyright © 2014 John Wiley & Sons, Ltd.

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

PubMed

Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

2018-04-01

Guidelines from the NCCN ® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Physical activity, alcohol consumption, BMI and smoking status before and after prostate cancer diagnosis in the ProtecT trial: opportunities for lifestyle modification.

PubMed

Hackshaw-McGeagh, Lucy E; Penfold, Chris M; Walsh, Eleanor; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Jeffreys, Mona; Martin, Richard M; Lane, J Athene

2015-09-15

Associations between certain lifestyle characteristics and prostate cancer risk have been reported, and continuation post-diagnosis can adversely affect prognosis. We explored whether men make spontaneous changes to their physical activity and alcohol intake, body mass index (BMI) and smoking status, following a diagnosis of localised prostate cancer. A detailed diet, health and lifestyle questionnaire was completed by 511 participants within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial, both before and 9 months after a diagnosis of prostate cancer. Of 177 men who were insufficiently active before their diagnosis (median 0 activity units/week; IQR 0-9), 40.7% had increased their activity by a median of 22 U week(-1) (IQR 15-35) 9 months later, and there was weak evidence that men were more active after diagnosis than before (p = 0.07). Men categorised as "working" occupational social class and who were insufficiently active before diagnosis were 2.03 (95%, CI = 1.03-3.99, p = 0.04) times more likely to have increased their physical activity levels compared to men classified as "managerial or professional." Similarly, men who were insufficiently active pre-diagnosis and with T-stage 2 compared with T-stage 1 prostate cancer were 2.47 (95%, CI = 1.29-4.71, p = 0.006) times more likely to be sufficiently active post-diagnosis. Following diagnosis, there was an overall reduction in alcohol intake (p = 0.03) and the proportion of current smokers (p = 0.09), but no overall change in BMI. We conclude that some men spontaneously change certain lifestyle behaviours on receiving a diagnosis of prostate cancer. For many men, however, additional support through lifestyle interventions is probably required to facilitate and maintain these changes. © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

[Prostate cancer. Epidemiology. Risk factors. Pathology].

PubMed

Fournier, G; Valeri, A; Mangin, P; Cussenot, O

2004-10-01

Prostate cancer (prostate adenocarcinoma) has become an important concern in terms of public health these past fifteen years; recent French epidemiological data revealed 10,104 deaths due to this disease in 2000. The two main factors involved are the serum prostatic specific antigen (PSA), routinely used since late 1980's and which allows early diagnosis (before symptom onset), and the lengthened duration of life. Such cancer is rare before the age of 50, but its frequency increases with age, making it the most frequent type of cancer in French men. Although the aetiology of this disease is unknown, the ethnic origin, and a familial history of prostate or breast cancer are known risk factors. Predisposing genes to such hereditary types remain to be identified. Other genetic factors (polymorphisms), combined with environmental factors such as nutrition, have been incriminated, which is likely to explain the geographical variations of this affection. At the molecular level, the mechanisms involved in the tumoral initiation and progression remain unclear. Various genetic alterations have been identified among the genome of cancerous cells, at various stages of the affection: intraepithelial neoplasia, localized, locally advanced, metastatic or hormone refractory stage -, hormonal escape). However, the precise sequence and nature of the complex molecular events remain to be determined prior to their routine utilisation in the determination of subjects at risk, or as prognostic factors, and even as therapeutic targets. The anatomopathology is a key for the diagnosis. Intraepithelial neoplasia is the pre-cancerous lesion observed in most adenocarcinomas; these are localized in the peripheral part of the prostate gland in 70% of the cases. Gleason's classification is the current gold standard for the determination of tumoral aggressiveness and categorisation of the adenocarcinomas which are basically heterogeneous (coexistence of tumors cells with different degrees of differenciation in the same tumor). This anatomopathological classification allows distinguishing the tumours in terms of potential progressiveness and prognosis, and hence, to orientate the therapeutic strategy in case of localised or locally advanced prostate cancer.

The surgical manegement of metastases to humerus-clinical evaluation.

PubMed

Chrobok, Adam; Spindel, Jerzy; Miszczyk, Leszek; Koczy, Bogdan; Pilecki, Bogdan; Jarosz, Adam; Mrozek, Tomasz

2003-06-30

Background. The humerus is a common localisation of cancer metastases. The restoration of anatomical order and tumor resection within humerus is important for patients quality of everyday life and for their pain relief. The surgical treatment is one of the most important part of the whole oncological ways of tratment.
The study objective was a clinical assesment of tumor resection and reconstruction within humerus according to matastasis localisation and the choice of surgical technique.
Material and methods. In the years 1999-2002 19 patients underwent surgery due to pathological fracture or/and cancer metastasis within humerus. The shaft localisation of the tumor was found in 8 cases and in 11 patients the metastatic foci were found in proximnal diaphysis. In patients with proximal diaphysis localisation of the tumor the partial resection with subsequent joint exchange procedure was made. The humeral shaft metastatic cancer changes were treated by the segmental resection with subsequent surgical cement filling or auto/allogenical bone grafting combined with intramedullary nail or AO/ASIF plate stabilisation. The average follow-up period was 8,5 months.
Results. In patients after resection with shoulder joint alloplasty according to the Enneking test a very good result was found in 7 and very good in 4 cases.
In patients with femoral shaft metastatic tumor locaslisation, 6 good and 2 fair results were found. In 1 patient after 2 months rehabilitation a reoperation was needed due to the mechanical destabilisation. The best results were found in patients after intramedullary nailing.An acute soft tissue inflamation requiering surgical treatment was found in 1 patient after shoulder joint replacement.
Conclusions. After clinical analysis of the material we highly recomend the partial humeral bone resection with subsequent shoulder alloplasty in patients with proximal humeral diaphysis metastatic localisation. In cases with shaft localisation a better results were found after intramedullary nailing compared to common plate technique.

Nuclear localisation of LASP-1 correlates with poor long-term survival in female breast cancer.

PubMed

Frietsch, J J; Grunewald, T G P; Jasper, S; Kammerer, U; Herterich, S; Kapp, M; Honig, A; Butt, E

2010-05-25

LIM and SH3 protein 1 (LASP-1) is a nucleo-cytoplasmatic signalling protein involved in cell proliferation and migration and is upregulated in breast cancer in vitro studies have shown that LASP-1 might be regulated by prostate-derived ETS factor (PDEF), p53 and/or LASP1 gene amplification. This current study analysed the prognostic significance of LASP-1 on overall survival (OS) in 177 breast cancer patients and addressed the suggested mechanisms of LASP-1-regulation. Nucleo-cytoplasmatic LASP-1-positivity of breast carcinoma samples was correlated with long-term survival, clinicopathological parameters, Ki67-positivity and PDEF expression. Rate of LASP1 amplification was determined in micro-dissected primary breast cancer cells using quantitative RT-PCR. Cell-phase dependency of nuclear LASP-1-localisation was studied in synchronised cells. In addition, LASP-1, PDEF and p53 expression was compared in cell lines of different tumour entities to define principles for LASP-1-regulation. We showed that LASP-1 overexpression is not due to LASP1 gene amplification. Moreover, no correlation between p53-mutations or PDEF-expression and LASP-1-status was observed. However, nuclear LASP-1-localisation in breast carcinomas is increased during proliferation with peak in G2/M-phase and correlated significantly with Ki67-positivity and poor OS. Our results provide evidence that nuclear LASP-1-positivity may serve as a negative prognostic indicator for long-term survival of breast cancer patients.

Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum.

PubMed

Chen, Mao Xiang; Gorman, Shelby A; Benson, Bill; Singh, Kuljit; Hieble, J Paul; Michel, Martin C; Tate, Simon N; Trezise, Derek J

2004-06-01

The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in human tissues and their cellular localisation in samples of colon and corpus cavernosum. SK1 mRNA was detected almost exclusively in neuronal tissues. SK2 mRNA distribution was restricted but more widespread than SK1, and was detected in adrenal gland, brain, prostate, bladder, liver and heart. SK3 mRNA was detected in almost every tissue examined. It was highly expressed in brain and in smooth muscle-rich tissues including the clitoris and the corpus cavernosum, and expression in the corpus cavernosum was upregulated up to 5-fold in patients undergoing sex-change operations. IK1 mRNA was present in surface-rich, secretory and inflammatory cell-rich tissues, highest in the trachea, prostate, placenta and salivary glands. In detailed immunohistochemical studies of the colon and the corpus cavernosum, SK1-like immunoreactivity was observed in the enteric neurons. SK3-like immunoreactivity was observed strongly in smooth muscle and vascular endothelium. IK1-like immunoreactivity was mainly observed in inflammatory cells and enteric neurons of the colon, but absent in corpus cavernosum. These distinctive patterns of distribution suggest that these channels are likely to have different biological functions and could be specifically targeted for a number of human diseases, such as irritable bowel syndrome, hypertension and erectile dysfunction.

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China.

PubMed

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-02

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China

PubMed Central

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-01

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients. PMID:29416625

The management of anterior tooth wear using gold palatal veneers in canine guidance.

PubMed

Eliyas, S; Martin, N

2013-03-01

Localised anterior tooth wear can be managed using minimally invasive techniques with conservation of tooth structure and preservation of pulp vitality. This article describes and illustrates with two clinical cases, the management of localised tooth wear, with the restoration of canine guidance by a combination of gold palatal veneers and direct composite restorations.

Lower urinary tract symptoms in benign prostatic hyperplasia patients: orchestrated by chronic prostatic inflammation and prostatic calculi?.

PubMed

Kim, Sang Hoon; Jung, Kyu In; Koh, Jun Sung; Min, Ki Ouk; Cho, Su Yeon; Kim, Hyun Woo

2013-01-01

This study aims to examine the relationship between chronic prostatic inflammation and prostatic calculi, and clinical parameters of benign prostatic hyperplasia (BPH). This study was based on 225 patients who underwent transurethral resection of the prostate for BPH. Chronic inflammation was graded as 0 (n = 44), I (n = 54), II (n = 88) or III (n = 39) according to severity. Prostatic calculi were classified into types A (n = 66), B (n = 44), M (n = 77) and N (n = 38). The relationship between inflammation and calculus type was analyzed, and clinical parameters of BPH were compared for each group. There was no correlation between severity of inflammation and calculus type. Prostatic volume increased with the severity of inflammation and showed significant differences between G2, G3 and G0. The International Prostate Symptom Score also increased with increasing inflammation. There was no significant difference between each clinical parameter according to calculus type. Prostatic calculi had no significant association with chronic inflammation and clinical parameters of BPH. Chronic inflammation was associated with the volume of the prostate and storage symptoms; thus, it is not only presumed to be related to the progression of BPH, but may also be one of the causes of lower urinary tract symptoms. Copyright © 2012 S. Karger AG, Basel.

Combining immunotherapies for the treatment of prostate cancer.

PubMed

Redman, Jason M; Gulley, James L; Madan, Ravi A

2017-12-01

Sipuleucel-T, a therapeutic dendritic-cell vaccine, was Food and Drug Administration-approved for prostate cancer in 2010. No new immunotherapies for prostate cancer have been approved since. However, novel agents and combination approaches offer great promise for improving outcomes for prostate cancer patients. Here we review the latest developments in immunotherapy for prostate cancer. Sipuleucel-T has demonstrated a survival advantage of 4.1 months in metastatic castration-resistant prostate cancer. PSA-TRICOM (PROSTVAC), a prostate-specific antigen-targeted vaccine platform, showed evidence of clinical and immunologic efficacy in early-phase clinical trials, and results from a phase III trial in advanced disease are pending. While immune checkpoint inhibitors appear to have modest activity as monotherapy, preclinical and clinical data suggest that they may synergize with vaccines, poly [ADP-ribose] polymerase inhibitors, and other agents. Several clinical studies that combine these therapies are underway. Combining prostate cancer vaccines with immune checkpoint inhibitors has great potential for improving clinical outcomes in prostate cancer. Such combination approaches may create and then recruit tumor-specific T cells to tumor while also increasing their effector function. Other emerging agents may also enhance immune-mediated tumor destruction. Copyright © 2017. Published by Elsevier Inc.

Current status of 5α-reductase inhibitors in prostate disease management.

PubMed

Kang, Dong Il; Chung, Jae Il

2013-04-01

The key enzyme in the androgen synthesis and androgen receptor pathways is 5α-reductase (5-AR), which occurs as three isoenzymes. Types I and II 5-ARs the most important clinically, and two different 5-AR inhibitors (5-ARIs), finasteride and dutasteride, have been developed. Several urology associations have recommended and upgraded the use of 5-ARIs for an enlarged prostate with lower urinary tract symptoms. In the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events Trial, 5-ARIs reduced the incidence of low-grade prostate cancer. However, despite the documented reductions in the overall incidence of prostate cancer, 5-ARIs are at the center of a dispute. The American Society of Clinical Oncology (ASCO) and the American Urology Association (AUA) presented clinical guidelines for the use of 5-ARIs for chemoprevention of prostate cancer in 2008. However, ASCO/AUA has eliminated these from the main "Clinical Guidelines" in 2012, because the U.S. Food and Drug Administration denied a supplemental New Drug Application for the use of dutasteride for prostate cancer chemoprevention. The 5-ARIs can also be used to manage hemospermia and prostatic hematuria, and to prevent intraoperative bleeding, although there is insufficient evidence for a standard strategy. This review summarizes the current use of 5-ARIs for prostate disease, including benign prostate hyperplasia, prostate cancer, prostate-related bleeding, and hemospermia.

Prostate Cancer Clinical Consortium Clinical Research Site:Targeted Therapies

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5b. GRANT NUMBER... therapy resistance/sensitivity, identification of new therapeutic targets through high quality genomic analyses, providing access to the highest quality

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.

78 FR 24750 - Scientific Information Request Therapies for Clinically Localized Prostate Cancer

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... and benefits of the following therapies for clinically localized prostate cancer? a. Radical... prostate cancer: radical prostatectomy (including retropubic, perineal, laparoscopic, robotic-assisted..., biochemical (PSA) progression, metastatic and/or clinical progression-free survival, health status, and...

Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.

PubMed

Bonilla, Carolina; Lewis, Sarah J; Rowlands, Mari-Anne; Gaunt, Tom R; Davey Smith, George; Gunnell, David; Palmer, Tom; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Grönberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; 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; Lathrop, Mark; Martin, Richard M; Holly, Jeff M P

2016-10-01

Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. © 2016 UICC.

BrachyView: Combining LDR seed positions with transrectal ultrasound imaging in a prostate gel phantom.

PubMed

Alnaghy, S; Cutajar, D L; Bucci, J A; Enari, K; Safavi-Naeini, M; Favoino, M; Tartaglia, M; Carriero, F; Jakubek, J; Pospisil, S; Lerch, M; Rosenfeld, A B; Petasecca, M

2017-02-01

BrachyView is a novel in-body imaging system which aims to provide LDR brachytherapy seeds position reconstruction within the prostate in real-time. The first prototype is presented in this study: the probe consists of a gamma camera featuring three single cone pinhole collimators embedded in a tungsten tube, above three, high resolution pixelated detectors (Timepix). The prostate was imaged with a TRUS system using a sagittal crystal with a 2.5mm slice thickness. Eleven needles containing a total of thirty 0.508U 125 I seeds were implanted under ultrasound guidance. A CT scan was used to localise the seed positions, as well as provide a reference when performing the image co-registration between the BrachyView coordinate system and the TRUS coordinate system. An in-house visualisation software interface was developed to provide a quantitative 3D reconstructed prostate based on the TRUS images and co-registered with the LDR seeds in situ. A rigid body image registration was performed between the BrachyView and TRUS systems, with the BrachyView and CT-derived source locations compared. The reconstructed seed positions determined by the BrachyView probe showed a maximum discrepancy of 1.78mm, with 75% of the seeds reconstructed within 1mm of their nominal location. An accurate co-registration between the BrachyView and TRUS coordinate system was established. The BrachyView system has shown its ability to reconstruct all implanted LDR seeds within a tissue equivalent prostate gel phantom, providing both anatomical and seed position information in a single interface. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

[Prostatic localization revealing an acute myeloid leukemia. Apropos of a case].

PubMed

Smaoui, S; Lecomte, M J; Peraldi, R; Pernin, F

1998-09-01

The authors report an original case of acute myeloid leukaemia (AML) presenting in the form of acute urinary retention, confirmed by prostatic biopsy, with complete absence of any non-urological clinical features. Prostatic sites of leukaemia are frequent and classically reported, but often occur during the course of known leukaemia, and are rarely symptomatic, justifying biopsies in the presence of any prostatic symptoms. Immunolabelling represents the key to the diagnosis in the presence of undifferentiated cells demonstrated on prostatic biopsies. The outcome was fatal in this case, despite early chemotherapy. The clinical features, clinical course and therapeutic aspects of prostatic leukaemia are discussed.

Clutter elimination for deep clinical optoacoustic imaging using localised vibration tagging (LOVIT)☆

PubMed Central

Jaeger, Michael; Bamber, Jeffrey C.; Frenz, Martin

2013-01-01

This paper investigates a novel method which allows clutter elimination in deep optoacoustic imaging. Clutter significantly limits imaging depth in clinical optoacoustic imaging, when irradiation optics and ultrasound detector are integrated in a handheld probe for flexible imaging of the human body. Strong optoacoustic transients generated at the irradiation site obscure weak signals from deep inside the tissue, either directly by propagating towards the probe, or via acoustic scattering. In this study we demonstrate that signals of interest can be distinguished from clutter by tagging them at the place of origin with localised tissue vibration induced by the acoustic radiation force in a focused ultrasonic beam. We show phantom results where this technique allowed almost full clutter elimination and thus strongly improved contrast for deep imaging. Localised vibration tagging by means of acoustic radiation force is especially promising for integration into ultrasound systems that already have implemented radiation force elastography. PMID:25302147

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...AND SUBTITLE Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Characterization of Desmoglein Expression in the Normal Prostatic Gland. Desmoglein 2 Is an Independent Prognostic Factor for Aggressive Prostate Cancer

PubMed Central

Barber, Alison G.; Castillo-Martin, Mireia; Bonal, Dennis M.; Rybicki, Benjamin A.; Christiano, Angela M.; Cordon-Cardo, Carlos

2014-01-01

Purpose The expression of desmogleins (DSGs), which are known to be crucial for establishing and maintaining the cell-cell adhesion required for tissue integrity, has been well characterized in the epidermis and hair follicle; however, their expression in other epithelial tissues such as prostate is poorly understood. Although downregulation of classical cadherins, such as E-cadherin, has been described in prostate cancer tissue samples, the expression of desmogleins has only been previously reported in prostate cancer cell lines. In this study we characterized desmoglein expression in normal prostate tissues, and further investigated whether Desmoglein 2 (DSG2) expression specifically can serve as a potential clinical prognostic factor for patients diagnosed with primary prostate cancer. Experimental Design We utilized immunofluorescence to examine DSG2 expression in normal prostate (n = 50) and in a clinically well-characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2 expression with clinico-pathological characteristics and biochemical recurrence was analyzed to assess its clinical significance. Results These studies revealed that DSG2 and DSG4 were specifically expressed in prostatic luminal cells, whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not expressed in normal prostate epithelium. Further analyses of DSG2 expression in prostate cancer revealed that reduced levels of this biomarker were a significant independent marker of poor clinical outcome. Conclusion Here we report for the first time that a low DSG2 expression phenotype is a useful prognostic biomarker of tumor aggressiveness and may serve as an aid in identifying patients with clinically significant prostate cancer. PMID:24896103

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.

A phase and frequency alignment protocol for 1H MRSI data of the prostate.

PubMed

Wright, Alan J; Buydens, Lutgarde M C; Heerschap, Arend

2012-05-01

(1)H MRSI of the prostate reveals relative metabolite levels that vary according to the presence or absence of tumour, providing a sensitive method for the identification of patients with cancer. Current interpretations of prostate data rely on quantification algorithms that fit model metabolite resonances to individual voxel spectra and calculate relative levels of metabolites, such as choline, creatine, citrate and polyamines. Statistical pattern recognition techniques can potentially improve the detection of prostate cancer, but these analyses are hampered by artefacts and sources of noise in the data, such as variations in phase and frequency of resonances. Phase and frequency variations may arise as a result of spatial field gradients or local physiological conditions affecting the frequency of resonances, in particular those of citrate. Thus, there are unique challenges in developing a peak alignment algorithm for these data. We have developed a frequency and phase correction algorithm for automatic alignment of the resonances in prostate MRSI spectra. We demonstrate, with a simulated dataset, that alignment can be achieved to a phase standard deviation of 0.095  rad and a frequency standard deviation of 0.68  Hz for the citrate resonances. Three parameters were used to assess the improvement in peak alignment in the MRSI data of five patients: the percentage of variance in all MRSI spectra explained by their first principal component; the signal-to-noise ratio of a spectrum formed by taking the median value of the entire set at each spectral point; and the mean cross-correlation between all pairs of spectra. These parameters showed a greater similarity between spectra in all five datasets and the simulated data, demonstrating improved alignment for phase and frequency in these spectra. This peak alignment program is expected to improve pattern recognition significantly, enabling accurate detection and localisation of prostate cancer with MRSI. Copyright © 2011 John Wiley & Sons, Ltd.

The PSA testing dilemma: GPs' reports of consultations with asymptomatic men: a qualitative study.

PubMed

Clements, Alison; Watson, Eila; Rai, Tanvi; Bukach, Colleen; Shine, Brian; Austoker, Joan

2007-06-25

The National Health Service Prostate Cancer Risk Management Programme (PCRMP) has recommended that screening for prostate cancer is available for asymptomatic men, on the understanding that they have been provided with full and balanced information about the advantages and limitations of the prostate-specific antigen (PSA) test. Guidance has been distributed to all GPs in England and Wales to assist in the provision of information to men. This study aimed to elicit GPs' accounts of their discussions with asymptomatic men who consult with concerns about prostate cancer in order to identify the degree to which the PCRMP guidance was reflected in these consultations. Qualitative interview study. Semi-structured telephone interviews with 21 GPs from 18 GP practices in Oxfordshire. All GPs reported undertaking some discussion with asymptomatic men about the PSA test. They described focussing most of the discussion on the false-positive and false-negative rates of the test, and the risks associated with a prostate biopsy. They reported less discussion of the potential for diagnosing indolent cancers, the dilemmas regarding treatment options for localised prostate cancer and the potential benefits of testing. Considerable variation existed between GPs in their accounts of the degree of detail given, and GP's presentation of information appeared to be affected by their personal views of the PSA test. The GPs in this study appear to recognise the importance of discussions regarding PSA testing; however, a full and balanced picture of the associated advantages and limitations does not seem to be consistently conveyed. Factors specific to PSA testing which appeared to have an impact on the GPs' discussions were the GP's personal opinions of the PSA test, and the need to counter men's primarily positive views of the benefits of PSA testing. Awareness of the impact of their views on the consultations may help GPs give men a more balanced presentation of the benefits and limitations of the PSA test.

Prostate Cancer: Serum and Tissue Markers

PubMed Central

Miller, Gary J; Brawer, Michael K; Sakr, Wael A; Thrasher, J Brantley; Townsend, Ronald

2001-01-01

The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the “gold standard,” has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and the clinical emergence of prostate cancer; the possible correlation of serum insulin-like growth factor levels with the risk for developing prostate cancer; and the latest advances in radiologic staging. PMID:16985995

Characterizing the Hypermutated Subtype of Advanced Prostate Cancer as a Predictive Biomarker for Precision Medicine

DTIC Science & Technology

2017-10-01

goal of this research is to characterize the mechanisms leading to hypermutated prostate cancer and to integrate tumor hypermutation status with... integrate tumor hypermutation status with clinical decision making and therapy to improve the care of men with advanced prostate cancer. Using Next-Gen...preparation of presentations that integrate prostate cancer patient clinical histories with genomic findings 1-36 Yes, see Prostate Precision Tumor

General Information about Prostate Cancer

MedlinePlus

... Research Prostate Cancer Treatment (PDQ®)–Patient Version General Information About Prostate Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Assessment of localisation to auditory stimulation in post-comatose states: use the patient’s own name

PubMed Central

2013-01-01

Background At present, there is no consensus on how to clinically assess localisation to sound in patients recovering from coma. We here studied auditory localisation using the patient’s own name as compared to a meaningless sound (i.e., ringing bell). Methods Eighty-six post-comatose patients diagnosed with a vegetative state/unresponsive wakefulness syndrome or a minimally conscious state were prospectively included. Localisation of auditory stimulation (i.e., head or eyes orientation toward the sound) was assessed using the patient’s own name as compared to a ringing bell. Statistical analyses used binomial testing with bonferroni correction for multiple comparisons. Results 37 (43%) out of the 86 studied patients showed localisation to auditory stimulation. More patients (n=34, 40%) oriented the head or eyes to their own name as compared to sound (n=20, 23%; p<0.001). Conclusions When assessing auditory function in disorders of consciousness, using the patient’s own name is here shown to be more suitable to elicit a response as compared to neutral sound. PMID:23506054

Proposed morphologic classification of prostate cancer with neuroendocrine differentiation.

PubMed

Epstein, Jonathan I; Amin, Mahul B; Beltran, Himisha; Lotan, Tamara L; Mosquera, Juan-Miguel; Reuter, Victor E; Robinson, Brian D; Troncoso, Patricia; Rubin, Mark A

2014-06-01

On July 31, 2013, the Prostate Cancer Foundation assembled a working committee on the molecular biology and pathologic classification of neuroendocrine (NE) differentiation in prostate cancer. New clinical and molecular data emerging from prostate cancers treated by contemporary androgen deprivation therapies, as well as primary lesions, have highlighted the need for refinement of diagnostic terminology to encompass the full spectrum of NE differentiation. The classification system consists of: Usual prostate adenocarcinoma with NE differentiation; 2) Adenocarcinoma with Paneth cell NE differentiation; 3) Carcinoid tumor; 4) Small cell carcinoma; 5) Large cell NE carcinoma; and 5) Mixed NE carcinoma - acinar adenocarcinoma. The article also highlights "prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma" and "castrate-resistant prostate cancer with small cell cancer-like clinical presentation". It is envisioned that specific criteria associated with the refined diagnostic terminology will lead to clinically relevant pathologic diagnoses that will stimulate further clinical and molecular investigation and identification of appropriate targeted therapies.

Prostatic cancers: understanding their molecular pathology and the 2016 WHO classification

PubMed Central

Inamura, Kentaro

2018-01-01

Accumulating evidence suggests that prostatic cancers represent a group of histologically and molecularly heterogeneous diseases with variable clinical courses. In accordance with the increased knowledge of their clinicopathologies and genetics, the World Health Organization (WHO) classification of prostatic cancers has been revised. Additionally, recent data on their comprehensive molecular characterization have increased our understanding of the genomic basis of prostatic cancers and enabled us to classify them into subtypes with distinct molecular pathologies and clinical features. Our increased understanding of the molecular pathologies of prostatic cancers has permitted their evolution from a poorly understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes that allow the implementation of personalized therapies and better patient management. This review provides perspectives on the new 2016 WHO classification of prostatic cancers as well as recent knowledge of their molecular pathologies. The WHO classification of prostatic cancers will require additional revisions to allow for reliable and clinically meaningful cancer diagnoses as a better understanding of their molecular characteristics is obtained. PMID:29581876

Metabolomic signatures of aggressive prostate cancer.

PubMed

McDunn, Jonathan E; Li, Zhen; Adam, Klaus-Peter; Neri, Bruce P; Wolfert, Robert L; Milburn, Michael V; Lotan, Yair; Wheeler, Thomas M

2013-10-01

Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. Prostate tumors had significantly altered metabolite profiles compared to cancer-free prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NAD+ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests. Copyright © 2013 Wiley Periodicals, Inc.

Prognostic Significance of Digital Rectal Examination and Prostate Specific Antigen in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Arm.

PubMed

Halpern, Joshua A; Shoag, Jonathan E; Mittal, Sameer; Oromendia, Clara; Ballman, Karla V; Hershman, Dawn L; Wright, Jason D; Shih, Ya-Chen Tina; Nguyen, Paul L; Hu, Jim C

2017-02-01

The absence of definitive data or explicit guidelines regarding the use of digital rectal examination for prostate cancer screening may lead to confusion for physicians and patients alike. We evaluated the prognostic value of abnormal digital rectal examination and prostate specific antigen following the widespread dissemination of prostate specific antigen testing in the U.S. Collectively, men comprising the screening arm of the PLCO cancer screening trial who underwent digital rectal examination screening (35,350) were followed for 314,033 person-years. Adjusted analyses with competing risks regression were performed to assess the association of suspicious (nodularity, induration, asymmetry) digital rectal examination and abnormal prostate specific antigen (4 ng/ml or greater) with the detection of clinically significant prostate cancer, prostate cancer specific mortality and overall mortality. Among all screening encounters with a suspicious digital rectal examination only 15.4% had a concurrently abnormal prostate specific antigen (McNemar's test p <0.001). During followup there were 1,612 clinically significant prostate cancers detected, 64 prostate cancer specific deaths and 4,600 deaths. On multivariable analysis suspicious digital rectal examination and abnormal prostate specific antigen were associated with a greater risk of clinically significant prostate cancer (HR 2.21, 95% CI 1.99-2.44 vs HR 5.48, 95% CI 5.05-5.96, p <0.001 and p <0.001) and prostate cancer specific mortality (HR 2.54, 95% CI 1.41-4.58 vs HR 5.23, 95% CI 3.08-8.88, p=0.002 and p <0.001), respectively. In a secondary analysis of a contemporary U.S. cohort, suspicious digital rectal examination and abnormal prostate specific antigen on routine screening were independently associated with clinically significant prostate cancer and prostate cancer specific mortality. However, additional research is needed to optimize screening protocols. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate-specific antigen velocity is not better than total prostate-specific antigen in predicting prostate biopsy diagnosis.

PubMed

Gorday, William; Sadrzadeh, Hossein; de Koning, Lawrence; Naugler, Christopher T

2015-12-01

1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3+4 and a 4+3 group. Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7-10. The Gleason grade 7-10 group was further divided into 4+3 and 3+4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. 4622 men between the ages of 40-89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC=0.570-0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC=0.572-0.699). There were marked increases in the area under curves when 3+4 and 4+3 Gleason 7 cancers were separated. Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3+4 and 4+3 group. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

DTIC Science & Technology

2015-10-01

with Cancer in Non-Neoplastic Prostate Tissue PRINCIPAL INVESTIGATOR: Farhad Kosari, Ph.D. CONTRACTING ORGANIZATION: Mayo Clinic Rochester, MN...E-Mail: kosari.farhad@mayo.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Mayo Clinic Rochester, MN 55905-0002 8...with the Tissue Request Acquisition Group (TRAG) at the Mayo Clinic , a process was implemented for the collection of resected prostates from

Emerging proteomics biomarkers and prostate cancer burden in Africa

PubMed Central

Adeola, Henry A.; Blackburn, Jonathan M.; Rebbeck, Timothy R.; Zerbini, Luiz F.

2017-01-01

Various biomarkers have emerged via high throughput omics-based approaches for use in diagnosis, treatment, and monitoring of prostate cancer. Many of these have yet to be demonstrated as having value in routine clinical practice. Moreover, there is a dearth of information on validation of these emerging prostate biomarkers within African cohorts, despite the huge burden and aggressiveness of prostate cancer in men of African descent. This review focusses of the global landmark achievements in prostate cancer proteomics biomarker discovery and the potential for clinical implementation of these biomarkers in Africa. Biomarker validation processes at the preclinical, translational and clinical research level are discussed here, as are the challenges and prospects for the evaluation and use of novel proteomic prostate cancer biomarkers. PMID:28388542

Emerging proteomics biomarkers and prostate cancer burden in Africa.

PubMed

Adeola, Henry A; Blackburn, Jonathan M; Rebbeck, Timothy R; Zerbini, Luiz F

2017-06-06

Various biomarkers have emerged via high throughput omics-based approaches for use in diagnosis, treatment, and monitoring of prostate cancer. Many of these have yet to be demonstrated as having value in routine clinical practice. Moreover, there is a dearth of information on validation of these emerging prostate biomarkers within African cohorts, despite the huge burden and aggressiveness of prostate cancer in men of African descent. This review focusses of the global landmark achievements in prostate cancer proteomics biomarker discovery and the potential for clinical implementation of these biomarkers in Africa. Biomarker validation processes at the preclinical, translational and clinical research level are discussed here, as are the challenges and prospects for the evaluation and use of novel proteomic prostate cancer biomarkers.

Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients.

PubMed

Washino, Satoshi; Okochi, Tomohisa; Saito, Kimitoshi; Konishi, Tsuzumi; Hirai, Masaru; Kobayashi, Yutaka; Miyagawa, Tomoaki

2017-02-01

To assess the value of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system, for prostate multi-parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate-specific antigen (PSA) level, prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer. Patients who underwent mpMRI at our hospital, and who had their first prostate biopsy between July 2010 and April 2014, were analysed retrospectively. The prostate biopsies were taken transperineally under transrectal ultrasonography guidance. In all, 14 cores were biopsied as a systematic biopsy in all patients. Two cognitive fusion-targeted biopsy cores were added for each lesion in patients who had suspicious or equivocal lesions on mpMRI. The PI-RADS scoring system version 2.0 (PI-RADS v2) was used to describe the MRI findings. Univariate and multivariate analyses were performed to determine significant predictors of prostate cancer and clinically significant prostate cancer. In all, 288 patients were analysed. The median patient age, PSA level, prostate volume and PSA density were 69 years, 7.5 ng/mL, 28.7 mL, and 0.26 ng/mL/mL, respectively. The biopsy results were benign, clinically insignificant, and clinically significant prostate cancer in 129 (45%), 18 (6%) and 141 (49%) patients, respectively. The multivariate analysis revealed that PI-RADS v2 score and PSA density were independent predictors for prostate cancer and clinically significant prostate cancer. When PI-RADS v2 score and PSA density were combined, a PI-RADS v2 score of ≥4 and PSA density ≥0.15 ng/mL/mL, or PI-RADS v2 score of 3 and PSA density of ≥0.30 ng/mL/mL, was associated with the highest clinically significant prostate cancer detection rates (76-97%) on the first biopsy. Of the patients in this group with negative biopsy results, 22% were subsequently diagnosed as prostate cancer. In contrast, a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL yielded no clinically significant prostate cancer and no additional detection of prostate cancer on further biopsies. A combination of PI-RADS v2 score and PSA density can help in the decision-making process before prostate biopsy and in the follow-up strategy in biopsy naïve patients. Patients with a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL may avoid unnecessary biopsies. © 2016 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Bacterial prostatitis.

PubMed

Gill, Bradley C; Shoskes, Daniel A

2016-02-01

The review provides the infectious disease community with a urologic perspective on bacterial prostatitis. Specifically, the article briefly reviews the categorization of prostatitis by type and provides a distillation of new findings published on bacterial prostatitis over the past year. It also highlights key points from the established literature. Cross-sectional prostate imaging is becoming more common and may lead to more incidental diagnoses of acute bacterial prostatitis. As drug resistance remains problematic in this condition, the reemergence of older antibiotics such as fosfomycin, has proven beneficial. With regard to chronic bacterial prostatitis, no clear clinical risk factors emerged in a large epidemiological study. However, bacterial biofilm formation has been associated with more severe cases. Surgery has a limited role in bacterial prostatitis and should be reserved for draining of a prostatic abscess or the removal of infected prostatic stones. Prostatitis remains a common and bothersome clinical condition. Antibiotic therapy remains the basis of treatment for both acute and chronic bacterial prostatitis. Further research into improving prostatitis treatment is indicated.

Department of Defense prostate cancer clinical trials consortium: a new instrument for prostate cancer clinical research.

PubMed

Morris, Michael J; Basch, Ethan M; Wilding, George; Hussain, Maha; Carducci, Michael A; Higano, Celestia; Kantoff, Philip; Oh, William K; Small, Eric J; George, Daniel; Mathew, Paul; Beer, Tomasz M; Slovin, Susan F; Ryan, Charles; Logothetis, Christopher; Scher, Howard I

2009-01-01

In 2005, the US Department of Defense, through the US Army Medical Research and Materiel Command, Office of the Congressionally Directed Medical Research Programs, created a funding mechanism to form a clinical trials consortium to conduct phase I and II studies in prostate cancer. This is the first report of the Prostate Cancer Clinical Trials Consortium (PCCTC). The Department of Defense award supports a consortium of 10 prostate cancer research centers. Memorial Sloan-Kettering Cancer Center was awarded the Coordinating Center grant for the consortium and charged with creating an infrastructure to conduct early-phase multicenter clinical trials. Each participating center was required to introduce >or=1 clinical trial per year and maintain accrual of a minimum of 35 patients per year. The PCCTC was launched in 2006 and now encompasses 10 leading prostate cancer research centers. Fifty-one trials have been opened, and 1386 patients have been accrued at member sites. Members share an online clinical trial management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, an administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review are established. The PCCTC fulfills a congressional directive to create a clinical trials instrument dedicated to early-phase prostate cancer studies. The member institutions have built an administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. Clinical trials are open and accruing in excess of federally mandated goals.

Towards 3D ultrasound image based soft tissue tracking: a transrectal ultrasound prostate image alignment system.

PubMed

Baumann, Michael; Mozer, Pierre; Daanen, Vincent; Troccaz, Jocelyne

2007-01-01

The emergence of real-time 3D ultrasound (US) makes it possible to consider image-based tracking of subcutaneous soft tissue targets for computer guided diagnosis and therapy. We propose a 3D transrectal US based tracking system for precise prostate biopsy sample localisation. The aim is to improve sample distribution, to enable targeting of unsampled regions for repeated biopsies, and to make post-interventional quality controls possible. Since the patient is not immobilized, since the prostate is mobile and due to the fact that probe movements are only constrained by the rectum during biopsy acquisition, the tracking system must be able to estimate rigid transformations that are beyond the capture range of common image similarity measures. We propose a fast and robust multi-resolution attribute-vector registration approach that combines global and local optimization methods to solve this problem. Global optimization is performed on a probe movement model that reduces the dimensionality of the search space and thus renders optimization efficient. The method was tested on 237 prostate volumes acquired from 14 different patients for 3D to 3D and 3D to orthogonal 2D slices registration. The 3D-3D version of the algorithm converged correctly in 96.7% of all cases in 6.5s with an accuracy of 1.41mm (r.m.s.) and 3.84mm (max). The 3D to slices method yielded a success rate of 88.9% in 2.3s with an accuracy of 1.37mm (r.m.s.) and 4.3mm (max).

Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging and Fusion Guided Targeted Biopsy Evaluated by Transperineal Template Saturation Prostate Biopsy for the Detection and Characterization of Prostate Cancer.

PubMed

Mortezavi, Ashkan; Märzendorfer, Olivia; Donati, Olivio F; Rizzi, Gianluca; Rupp, Niels J; Wettstein, Marian S; Gross, Oliver; Sulser, Tullio; Hermanns, Thomas; Eberli, Daniel

2018-02-21

We evaluated the diagnostic accuracy of multiparametric magnetic resonance imaging and multiparametric magnetic resonance imaging/transrectal ultrasound fusion guided targeted biopsy against that of transperineal template saturation prostate biopsy to detect prostate cancer. We retrospectively analyzed the records of 415 men who consecutively presented for prostate biopsy between November 2014 and September 2016 at our tertiary care center. Multiparametric magnetic resonance imaging was performed using a 3 Tesla device without an endorectal coil, followed by transperineal template saturation prostate biopsy with the BiopSee® fusion system. Additional fusion guided targeted biopsy was done in men with a suspicious lesion on multiparametric magnetic resonance imaging, defined as Likert score 3 to 5. Any Gleason pattern 4 or greater was defined as clinically significant prostate cancer. The detection rates of multiparametric magnetic resonance imaging and fusion guided targeted biopsy were compared with the detection rate of transperineal template saturation prostate biopsy using the McNemar test. We obtained a median of 40 (range 30 to 55) and 3 (range 2 to 4) transperineal template saturation prostate biopsy and fusion guided targeted biopsy cores, respectively. Of the 124 patients (29.9%) without a suspicious lesion on multiparametric magnetic resonance imaging 32 (25.8%) were found to have clinically significant prostate cancer on transperineal template saturation prostate biopsy. Of the 291 patients (70.1%) with a Likert score of 3 to 5 clinically significant prostate cancer was detected in 129 (44.3%) by multiparametric magnetic resonance imaging fusion guided targeted biopsy, in 176 (60.5%) by transperineal template saturation prostate biopsy and in 187 (64.3%) by the combined approach. Overall 58 cases (19.9%) of clinically significant prostate cancer would have been missed if fusion guided targeted biopsy had been performed exclusively. The sensitivity of multiparametric magnetic resonance imaging and fusion guided targeted biopsy for clinically significant prostate cancer was 84.6% and 56.7% with a negative likelihood ratio of 0.35 and 0.46, respectively. Multiparametric magnetic resonance imaging alone should not be performed as a triage test due to a substantial number of false-negative cases with clinically significant prostate cancer. Systematic biopsy outperformed fusion guided targeted biopsy. Therefore, it will remain crucial in the diagnostic pathway of prostate cancer. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Prostate histopathology of NIH category IV prostatitis detected by sextant prostate needle biopsy from the patients with high prostatic specific antigen].

PubMed

Shimomura, Tatsuya; Kiyota, Hiroshi; Takahashi, Hiroyuki; Madarame, Jun; Kimura, Takahiro; Onodera, Shouichi

2003-08-01

Asymptomatic prostatitis is classified as category IV in NIH classification of prostatitis syndrome (1999). No report concerning this category has been present. We investigated this category histopathologically and clinically, in order to clarify the histopathological distribution and its correlation to the clinical features, in this study. Among 785 patients who were suspected prostate cancer because of their high prostatic specific antigen (PSA) values and to have a sextant prostate needle biopsy was performed between January, 1996 and December, 2000, 88 patients (11.2%) were diagnosed as NIH category IV prostatitis (asymptomatic prostatitis). We observed all pathological specimens stained with Hematoxylin-Eosine, and classified them into subtypes according to the classification criteria for prostatitis defined by True et al. (1999). We also investigated the relationship between histopathological distribution and clinical features such as PSA values, PSA density, the incidence of pyuria or bacteriuria. In the histopathological study, grade distributions were 12.5% (11/88) in mild, 71.6% (63/88) in moderate, and 15.9% (14/88) in severe. Location distributions were 2.3% (2/88) in glandular, 68.2% (60/88) in periglandular, and 29.5% (26/88) in stromal. No relationship between these subtypes and clinical features was recognized statistically. However, 7 patients (7.95%) were diagnosed as prostate cancers, later. Pyuria was found in 29.1% (23/79). Bacteriuria was present in 14.3% (11/77). Isolated bacteria were 4 strains of Enterococcus faccalis, 2 strains of each of Pseudomonas aeruginosa and Staphylococcus aureus, and one strain of each of Escherichia coli, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Staphylococcus haemolyticus, and Staphylococcus epidermidis. Gram positive rod, and Candida sp. No relationship between these subtypes and bacterial species was recognized. These results indicated that the incidence of NIII category IV prostatits was not low without correlation to any clinical features. However, we should pay attention to the presence of prostate cancer, because a small number of the patients were diagnosed as prostate cancer, later.

[Recognition and thoughts for diagnosis and treatment of chronic prostatitis in integrated traditional Chinese and Western medicine].

PubMed

Song, Shu-qi; Zhang, Ya-qiang

2009-12-01

The etiology, pathogenesis, and diagnostic criteria of chronic prostatitis were reviewed in this article. Based on clinical practice, the authors systematically discussed the thoughts and methods for the treatment of chronic prostatitis by integrated traditional Chinese and Western medicine. Meanwhile, advice on disputed problems in clinical study of prostatits were given, such as curative effect estimation value of the number of leukocytes in expressed prostatic secretion (EPS) and bacterial culture in EPS, the opportunity and treatment course of antibiotics, National Institutes of Health chronic prostatitis symptom index, classification of syndromes of traditional Chinese medicine (TCM), TCM symptom score, and clinical study period.

1.5-Tesla Multiparametric-Magnetic Resonance Imaging for the detection of clinically significant prostate cancer.

PubMed

Popita, Cristian; Popita, Anca Raluca; Sitar-Taut, Adela; Petrut, Bogdan; Fetica, Bogdan; Coman, Ioan

2017-01-01

Multiparametric-magnetic resonance imaging (mp-MRI) is the main imaging modality used for prostate cancer detection. The aim of this study is to evaluate the diagnostic performance of mp-MRI at 1.5-Tesla (1.5-T) for the detection of clinically significant prostate cancer. In this ethical board approved prospective study, 39 patients with suspected prostate cancer were included. Patients with a history of positive prostate biopsy and patients treated for prostate cancer were excluded. All patients were examined at 1.5-T MRI, before standard transrectal ultrasonography-guided biopsy. The overall sensitivity, specificity, positive predictive value and negative predictive value for mp-MRI were 100%, 73.68%, 80% and 100%, respectively. Our results showed that 1.5 T mp-MRI has a high sensitivity for detection of clinically significant prostate cancer and high negative predictive value in order to rule out significant disease.

Prostate Zonal Volumetry as a Predictor of Clinical Outcomes for Prostate Artery Embolization

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

Assis, André Moreira de, E-mail: andre.assis@criep.com.br, E-mail: andre.maa@gmail.com; Maciel, Macello Sampaio, E-mail: macielmjs@gmail.com; Moreira, Airton Mota, E-mail: airton.mota@criep.com.br

PurposeTo determine prostate baseline zonal volumetry and correlate these findings with clinical outcomes for patients who underwent prostate artery embolization (PAE) for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH).Materials and MethodsThis is a retrospective study that included patients treated by PAE from 2010 to 2014. Baseline and 6-month follow-up evaluations included prostate MRI with whole prostate (WP) and central gland (CG) volume measurements—as well as prostate zonal volumetry index (ZVi) calculation, defined as the CG/WP volumes relation—the International Prostate Symptom Score (IPSS), and the Quality of life (QoL) index. Baseline WP, CG, and ZVi were statistical compared to IPSS andmore » QoL values at 6 months.ResultsA total of 93 consecutive patients were included, with mean age of 63.4 years (range, 51–86). Clinical failure, defined as IPSS > 7 or QoL > 2, was seen in four cases (4.3%). Mean reductions in prostate volumes after PAE were of 30.6% and 31.2% for WP and CG, respectively (p < 0.0001). Clinical parameters had mean decrease from 21 to 3.3 points for IPSS, and from 4.7 to 1.2 points for QoL (p < 0.0001). Baseline WP, CG, and ZVi correlated to the degree of clinical improvement (p < 0.05 for all). The baseline ZVi cut-off calculated for better clinical outcomes was > 0.45, with 85% sensitivity and 75% specificity.ConclusionsBaseline CG and WP volumes as well as ZVi presented strong correlation with clinical outcomes in patients undergoing PAE, and its assessment should be considered in pre-treatment evaluation whenever possible. Both patients and medical team should be aware of the possibility of less favorable outcomes when ZVi < 0.45.« less

Influence of gross specimen sampling on the incidence of incidental prostatic carcinoma in cystoprostatectomy specimens of patients with bladder carcinoma.

PubMed

Mlakar, J; Volavšek, M

2016-03-01

Reported prostate cancer incidence rates vary greatly among cystoprostatectomy samples. We investigated how the thoroughness of prostate sampling influences prostatic carcinoma incidence in bladder cancer patients. In a retrospective study, 313 cystoprostatectomy cases of urinary bladder carcinoma were analysed for the presence of concurrent prostatic carcinoma. Patients were divided into two groups: patients who had undergone the operation before and after 2007, when a policy of preferably complete prostate sampling in cystoprostatectomy specimens was introduced at our institution. Cases processed after the 2007 recommended sampling changes had a significantly higher rate of incidental prostatic carcinoma and clinically significant prostatic carcinoma than the pre-2007 group (p < 0.0001 and p = 0.003, respectively). Complete prostate processing in cystoprostatectomy specimens results in a higher incidence of incidental prostatic carcinoma than with partial processing. More patients with clinically significant prostate cancer are consequently discovered. In conclusion, we believe that complete prostate sampling should be mandatory.

Identification of threshold prostate specific antigen levels to optimize the detection of clinically significant prostate cancer by magnetic resonance imaging/ultrasound fusion guided biopsy.

PubMed

Shakir, Nabeel A; George, Arvin K; Siddiqui, M Minhaj; Rothwax, Jason T; Rais-Bahrami, Soroush; Stamatakis, Lambros; Su, Daniel; Okoro, Chinonyerem; Raskolnikov, Dima; Walton-Diaz, Annerleim; Simon, Richard; Turkbey, Baris; Choyke, Peter L; Merino, Maria J; Wood, Bradford J; Pinto, Peter A

2014-12-01

Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effectiveness, cost-utility and implementation of a decision aid for patients with localised prostate cancer and their partners: study protocol of a stepped-wedge cluster randomised controlled trial.

PubMed

Al-Itejawi, Hoda H M; van Uden-Kraan, Cornelia F; van de Ven, Peter M; Coupé, Veerle M H; Vis, André N; Nieuwenhuijzen, Jakko A; van Moorselaar, Jeroen A; Verdonck-de Leeuw, Irma M

2017-09-15

Patient decision aids (PDAs) have been developed to help patients make an informed choice for a treatment option. Despite proven benefits, structural implementation falls short of expectations. The present study aims to assess the effectiveness and cost-utility of the PDA among newly diagnosed patients with localised prostate cancer and their partners, alongside implementation of the PDA in routine care. A stepped-wedge cluster randomised trial will be conducted. The PDA will be sequentially implemented in 18 hospitals in the Netherlands, over a period of 24 months. Every 3 or 6 months, a new cluster of hospitals will switch from usual care to care including a PDA.The primary outcome measure is decisional conflict experienced by the patient. Secondary outcomes comprise the patient's quality of life, treatment preferences, role in the decision making, expectations of treatment, knowledge, need for supportive care and decision regret. Furthermore, societal cost-utility will be valued. Other outcome measures considered are the partner's treatment preferences, experienced participation to decision making, quality of life, communication between patient, partner and health care professional, and the effect of prostate cancer on the relationship, social contacts and their role as caregiver. Patients and partners receiving the PDA will also be asked about their satisfaction with the PDA.Baseline assessment takes place after the treatment choice and before the start of a treatment, with follow-up assessments at 3, 6 and 12 months following the end of treatment or the day after deciding on active surveillance. Outcome measures on implementation include the implementation rate (defined as the proportion of all eligible patients who will receive a PDA) and a questionnaire for health care professionals on determinants of implementing an innovation. This study will be conducted in accordance with local laws and regulations of the Medical Ethics Committee of VU University Medical Center, Amsterdam, The Netherlands. The results from this stepped-wedge trial will be presented at scientific meetings and published in peer-reviewed journals. Nederlands Trial Register NTR TC5177, registration date: May 28 th 2015.Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effectiveness, cost-utility and implementation of a decision aid for patients with localised prostate cancer and their partners: study protocol of a stepped-wedge cluster randomised controlled trial

PubMed Central

Al-Itejawi, Hoda H M; van Uden-Kraan, Cornelia F; van de Ven, Peter M; Coupé, Veerle M H; Vis, André N; Nieuwenhuijzen, Jakko A; van Moorselaar, Jeroen A; Verdonck-de Leeuw, Irma M

2017-01-01

Introduction Patient decision aids (PDAs) have been developed to help patients make an informed choice for a treatment option. Despite proven benefits, structural implementation falls short of expectations. The present study aims to assess the effectiveness and cost-utility of the PDA among newly diagnosed patients with localised prostate cancer and their partners, alongside implementation of the PDA in routine care. Methods/analysis A stepped-wedge cluster randomised trial will be conducted. The PDA will be sequentially implemented in 18 hospitals in the Netherlands, over a period of 24 months. Every 3 or 6 months, a new cluster of hospitals will switch from usual care to care including a PDA. The primary outcome measure is decisional conflict experienced by the patient. Secondary outcomes comprise the patient’s quality of life, treatment preferences, role in the decision making, expectations of treatment, knowledge, need for supportive care and decision regret. Furthermore, societal cost-utility will be valued. Other outcome measures considered are the partner’s treatment preferences, experienced participation to decision making, quality of life, communication between patient, partner and health care professional, and the effect of prostate cancer on the relationship, social contacts and their role as caregiver. Patients and partners receiving the PDA will also be asked about their satisfaction with the PDA. Baseline assessment takes place after the treatment choice and before the start of a treatment, with follow-up assessments at 3, 6 and 12 months following the end of treatment or the day after deciding on active surveillance. Outcome measures on implementation include the implementation rate (defined as the proportion of all eligible patients who will receive a PDA) and a questionnaire for health care professionals on determinants of implementing an innovation. Ethics and dissemination This study will be conducted in accordance with local laws and regulations of the Medical Ethics Committee of VU University Medical Center, Amsterdam, The Netherlands. The results from this stepped-wedge trial will be presented at scientific meetings and published in peer-reviewed journals. Trial registration Nederlands Trial Register NTR TC5177, registration date: May 28th 2015. Pre-results. PMID:28918408

Pancreatic cancer: Are "liquid biopsies" ready for prime-time?

PubMed Central

Lewis, Alexandra R; Valle, Juan W; McNamara, Mairead G

2016-01-01

Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells (CTCs) have been investigated as a potential “liquid biopsy” in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms. Circulating tumour DNA (ctDNA) has also been detected in pancreas cancer with a sensitivity ranging from 26%-100% in studies across different platforms and using different genetic markers. However, there is no clear consensus on which platform is the most effective for detection, nor which genetic markers are the most useful to use. Potential roles of liquid biopsies include diagnosis, screening, guiding therapies and prognosis. The presence of CTCs or ctDNA has been shown to be of prognostic value both at diagnosis and after treatment in patients with pancreatic cancer. However, more prospective studies are required before this promising technology is ready for adoption into routine clinical practice. PMID:27621566

A single microfocus (5% or less) of Gleason 6 prostate cancer at biopsy--can we predict adverse pathological outcomes?

PubMed

Thong, Alan E; Shikanov, Sergey; Katz, Mark H; Gofrit, Ofer N; Eggener, Scott; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2008-12-01

Patients with Gleason score 6 microfocal prostate cancer, defined as 5% or less in 1 biopsy core, are often considered to have favorable disease. Few studies have addressed clinical parameters that predict pathological upgrading or up staging at radical prostatectomy. From a prospective database of 1,271 consecutive robot assisted laparoscopic prostatectomies performed from 2003 to 2008 patients with Gleason score 6 microfocal prostate cancer were identified. Adverse pathological outcome was defined as any upgrading and/or up staging on prostatectomy pathological findings. Multivariate logistic regression was used to evaluate the ability of patient age, clinical stage, the total number of biopsy cores, preoperative prostate specific antigen, prostate volume and pathological prostate specific antigen density to predict adverse pathological outcomes. A total of 192 patients with a median age of 59 years (range 42 to 73) were identified with Gleason score 6 prostate cancer involving 5% or less of 1 biopsy core, including 177 (92%) with clinical T1c disease. Mean +/- SD preoperative prostate specific antigen was 6.0 +/- 3.9 ng/ml (range 0.8 to 35). Overall 42 patients (22%) had adverse pathological outcomes, including upgrading in 35 (18%) and up staging in 16 (8%). Multivariate logistic regression revealed that age more than 65 years and pathological prostate specific antigen density greater than 0.20 ng/ml/gm were predictive of an increased risk of adverse pathological results (p = 0.0081 and 0.0169, respectively). While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.

Transrectal ultrasound (TRUS) findings of the prostate gland in late onset hypogonadism with testosterone supplementation in correlation with clinical outcome.

PubMed

Phongkitkarun, Sith; Rassameepong, Apinan; Permpongkosol, Sompol; Taphey, Mayureewan; Wibulpolprasert, Bussanee

2012-07-01

To determine the TRUS findings of the prostate and correlation of ultrasoundfindings with clinical outcomes in late-onset hypogonadal (LOH) men with testosterone supplementation. Between January 2007 and September 2010, TRUS findings and clinical outcomes of 16 from 226 subjects were studied The demographic data, ultrasound parameters as prostate volume and vascularity, and clinical parameters were evaluated Correlation between ultrasound and clinical parameters were analyzed using Pearson correlation analysis. During mean time follow-up of 6.48 months, the volume of the central gland (CG) significantly increased (p = 0.02), the volume of the total gland (TG) increased, and the volume of the peripheral zone (PZ) slightly decreased. The vascularity of the TG, CG, and PZ were significantly increased. The periurethral region vascularity was not significantly increased (p = 0.06), whereas total serum testosterone, prostate specific antigen (PSA), and PSA density were increased The International Prostate Symptom Score (IPSS) was significantly decreased (p < 0.001). There was a significant correlation between increased prostate volume and increased serum PSA. Testosterone supplementation in LOH men was found to cause an increase in TG volume during the first six months. The preferentially increased CG volume and prostatic vascularity might be due to exogenous testosterone. The authors observed a significantly increased PSA with a strong correlation between serum PSA and prostate volume.

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

Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

DTIC Science & Technology

2017-10-01

publication delineating key methodological components of pain studies in prostate cancer. KEYWORDS Pain, metastatic castrate resistant prostate cancer...pain palliation and pain progression in prostate cancer clinical trials that are feasible, methodologically rigorous, and meet regulatory...requirements for drug approval and labeling. The primary aim of this award is to conduct an observational longitudinal study in men with castrate-resistant

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.

Prostate-specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer.

PubMed

Hashimoto, Takeshi; Ohori, Makoto; Shimodaira, Kenji; Kaburaki, Naoto; Hirasawa, Yosuke; Satake, Naoya; Gondo, Tatsuo; Nakagami, Yoshihiro; Namiki, Kazunori; Ohno, Yoshio

2018-06-01

To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer. Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group 1, prostate-specific antigen screening; group 2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ 2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival. In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study. Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer. © 2018 The Japanese Urological Association.

Clinical and microbiological characteristics of spontaneous acute prostatitis and transrectal prostate biopsy-related acute prostatitis: Is transrectal prostate biopsy-related acute prostatitis a distinct acute prostatitis category?

PubMed

Kim, Jong Wook; Oh, Mi Mi; Bae, Jae Hyun; Kang, Seok Ho; Park, Hong Seok; Moon, Du Geon

2015-06-01

This study aimed to compare the clinical and microbiological characteristics between acute bacterial prostatitis and transrectal biopsy-related acute prostatitis. We retrospectively reviewed the records of 135 patients hospitalized for acute prostatitis in three urological centers between 2004 and 2013. Acute bacterial prostatitis was diagnosed according to typical symptoms, findings of physical examination, and laboratory test results. Clinical variables, laboratory test results, and anti-microbial susceptibility results were reviewed. Patients were classified into the spontaneous acute prostatitis group (S-ABP) or biopsy-related acute prostatitis (Bx-ABP) for comparison of their clinical, laboratory, and microbiological findings. The mean age of all patients was 61.7 ± 12.9 years. Compared with S-ABP patients, Bx-ABP patients were significantly older, had larger prostate volumes, higher PSA values, higher peak fever temperatures, and higher incidence of septicemia and antibiotic-resistant bacteria. Overall, of the 135 patients, 57.8% had positive bacterial urine and/or blood cultures. Bx-ABP patients had a higher incidence of bacterial (urine and/or blood) positive cultures compared to S-ABP patients (66.7% versus 55.6%). Escherichia coli was the predominant organism in both groups, but it was more common in Bx-ABP (88.9%) than in S-ABP (66.7%). Extended spectrum beta-lactamase -producing bacteria accounted for 64.7% of culture-positive patients in the Bx-ABP group compared to 13.3% in the S-ABP group. Bx-ABP patients showed a higher incidence of septicemia and antibiotic-resistant bacteria than S-ABP patients. These results have important implications for the management and antimicrobial treatment of Bx-ABP, which may well deserve to be considered a distinct prostatitis category. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Long non-coding RNA lnc-MX1-1 is associated with poor clinical features and promotes cellular proliferation and invasiveness in prostate cancer

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

Jiang, Chen-Yi; Gao, Yuan; Wang, Xing-Jie

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined bymore » real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer. - Highlights: • LncRNA lnc-MX1-1 is up-regulated in prostate cancer. • Overexpression of lnc-MX1-1 is correlated with poor prostate cancer clinical features. • Knockdown of lnc-MX1-1 reduces proliferation and invasiveness of prostate cancer cells.« less

Targeted vs systematic robot-assisted transperineal magnetic resonance imaging-transrectal ultrasonography fusion prostate biopsy.

PubMed

Mischinger, Johannes; Kaufmann, Sascha; Russo, Giorgio I; Harland, Niklas; Rausch, Steffen; Amend, Bastian; Scharpf, Marcus; Loewe, Lorenz; Todenhoefer, Tilman; Notohamiprodjo, Mike; Nikolaou, Konstantin; Stenzl, Arnulf; Bedke, Jens; Kruck, Stephan

2018-05-01

To evaluate the performance of transperineal robot-assisted (RA) targeted (TB) and systematic (SB) prostate biopsy in primary and repeat biopsy settings. Patients underwent RA biopsy between 2014 and 2016. Before RA-TB, multiparametric magnetic resonance imaging (mpMRI) was performed. Prostate lesions were scored (Prostate Imaging, Reporting and Data System, version 2) and used for RA-TB planning. In addition, RA-SB was performed. Available, whole-gland pathology was analysed. In all, 130 patients were biopsy naive and 72 had had a previous negative transrectal ultrasonography-guided biopsy. In total, 202 patients had suspicious mpMRI lesions. Clinically significant prostate cancer was found in 85% of all prostate cancer cases (n = 123). Total and clinically significant prostate cancer detection rates for RA-TB vs RA-SB were not significantly different at 77% vs 84% and 80% vs 82%, respectively. RA-TB demonstrated a better sampling performance compared to RA-SB (26.4% vs 13.9%; P < 0.001). Transperineal RA-TB and -SB showed similar clinically significant prostate cancer detection rates in primary and repeat biopsy settings. However, RA-TB offered a 50% reduction in biopsy cores. Omitting RA-SB is associated with a significant risk of missing clinically significant prostate cancer. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

PSA and beyond: alternative prostate cancer biomarkers

PubMed Central

2016-01-01

Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

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.

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.

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

Clinicopathological Overview of Granulomatous Prostatitis: An Appraisal

PubMed Central

Dravid, Nandkumar; Nikumbh, Dhiraj; Patil, Ashish; Nagappa, Karibasappa Gundabaktha

2016-01-01

Introduction Granulomatous prostatitis is a rare inflammatory condition of the prostate. Granulomatous prostatitis is important because, it mimics prostatic carcinoma clinically and hence the diagnosis can be made only by histopathological examination. Aim To study the histomorphological features and to know the prevalence of granulomatous prostatitis. Materials and Methods Histopathological records of 1,203 prostatic specimens received in the Department of the Pathology over a period of five years (June 2009 – June 2014). Seventeen cases of histopathologically, diagnosed granulomatous prostatitis were retrieved and reterospective data was collected from the patient’s records. Results Out of 17 cases of granulomatous prostatitis, we encountered 9 cases of non-specific granulomatous prostatitis, 5 cases of xanthogranulomatous prostatitis and 3 cases of specific tubercular prostatitis. The common age ranged from 51-75 years (mean 63 years) with mean PSA level of 15.8ng/ml. Six patients showed focal hypoechoic areas on TRUS and 11 cases revealed hard and fixed nodule on DRE. Conclusion Non-specific granulomatous prostatitis is the most common type of granulomatous prostatitis. There is no specific pattern of clinical, biochemical and ultrasound findings that allows the diagnosis of granulomatous prostatitis or differentiates it from prostatic carcinoma. Hence, histomorphological diagnosis is the gold standard in differentiating various prostatic lesions. PMID:27014642

Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer: Report From the 2015 Coffey-Holden Prostate Cancer Academy Meeting

PubMed Central

Miyahira, Andrea K.; Lang, Joshua M.; Den, Robert B.; Garraway, Isla P.; Lotan, Tamara L.; Ross, Ashley E.; Stoyanova, Tanya; Cho, Steve Y.; Simons, Jonathan W.; Pienta, Kenneth J.; Soule, Howard R.

2018-01-01

BACKGROUND The 2015 Coffey-Holden Prostate Cancer Academy Meeting, themed: “Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer,” was held in La Jolla, California from June 25 to 28, 2015. METHODS The Prostate Cancer Foundation (PCF) sponsors an annual, invitation-only, action-tank-structured meeting on a critical topic concerning lethal prostate cancer. The 2015 meeting was attended by 71 basic, translational, and clinical investigators who discussed the current state of the field, major unmet needs, and ideas for addressing earlier diagnosis and treatment of men with lethal prostate cancer for the purpose of extending lives and making progress toward a cure. RESULTS The questions addressed at the meeting included: cellular and molecular mechanisms of tumorigenesis, evaluating, and targeting the microenvironment in the primary tumor, advancing biomarkers for clinical integration, new molecular imaging technologies, clinical trials, and clinical trial design in localized high-risk and oligometastatic settings, targeting the primary tumor in advanced disease, and instituting multi-modal care of high risk and oligometastatic patients. DISCUSSION This article highlights the current status, greatest unmet needs, and anticipated field changes that were discussed at the meeting toward the goal of optimizing earlier interventions to potentiate cures in high-risk and oligometastatic prostate cancer patients. PMID:26477609

Multidisciplinary intervention of early, lethal metastatic prostate cancer: Report from the 2015 Coffey-Holden Prostate Cancer Academy Meeting.

PubMed

Miyahira, Andrea K; Lang, Joshua M; Den, Robert B; Garraway, Isla P; Lotan, Tamara L; Ross, Ashley E; Stoyanova, Tanya; Cho, Steve Y; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2016-02-01

The 2015 Coffey-Holden Prostate Cancer Academy Meeting, themed: "Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer," was held in La Jolla, California from June 25 to 28, 2015. The Prostate Cancer Foundation (PCF) sponsors an annual, invitation-only, action-tank-structured meeting on a critical topic concerning lethal prostate cancer. The 2015 meeting was attended by 71 basic, translational, and clinical investigators who discussed the current state of the field, major unmet needs, and ideas for addressing earlier diagnosis and treatment of men with lethal prostate cancer for the purpose of extending lives and making progress toward a cure. The questions addressed at the meeting included: cellular and molecular mechanisms of tumorigenesis, evaluating, and targeting the microenvironment in the primary tumor, advancing biomarkers for clinical integration, new molecular imaging technologies, clinical trials, and clinical trial design in localized high-risk and oligometastatic settings, targeting the primary tumor in advanced disease, and instituting multi-modal care of high risk and oligometastatic patients. This article highlights the current status, greatest unmet needs, and anticipated field changes that were discussed at the meeting toward the goal of optimizing earlier interventions to potentiate cures in high-risk and oligometastatic prostate cancer patients. © 2015 Wiley Periodicals, Inc.

Treating Localized Prostate Cancer

MedlinePlus

... Prostate Cancer: Update of a 2008 Systematic Review . Comparative Effectiveness Review No. 146. (Prepared by the ECRI ... Prostate Cancer Research Protocol Archived March 29, 2013 Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer: ...

Microarray Data Mining for Potential Selenium Targets in Chemoprevention of Prostate Cancer

PubMed Central

ZHANG, HAITAO; DONG, YAN; ZHAO, HONGJUAN; BROOKS, JAMES D.; HAWTHORN, LESLEYANN; NOWAK, NORMA; MARSHALL, JAMES R.; GAO, ALLEN C.; IP, CLEMENT

2008-01-01

Background A previous clinical trial showed that selenium supplementation significantly reduced the incidence of prostate cancer. We report here a bioinformatics approach to gain new insights into selenium molecular targets that might be relevant to prostate cancer chemoprevention. Materials and Methods We first performed data mining analysis to identify genes which are consistently dysregulated in prostate cancer using published datasets from gene expression profiling of clinical prostate specimens. We then devised a method to systematically analyze three selenium microarray datasets from the LNCaP human prostate cancer cells, and to match the analysis to the cohort of genes implicated in prostate carcinogenesis. Moreover, we compared the selenium datasets with two datasets obtained from expression profiling of androgen-stimulated LNCaP cells. Results We found that selenium reverses the expression of genes implicated in prostate carcinogenesis. In addition, we found that selenium could counteract the effect of androgen on the expression of a subset obtained from androgen-regulated genes. Conclusions The above information provides us with a treasure of new clues to investigate the mechanism of selenium chemoprevention of prostate cancer. Furthermore, these selenium target genes could also serve as biomarkers in future clinical trials to gauge the efficacy of selenium intervention. PMID:18548127

Precision medicine for advanced prostate cancer

PubMed Central

Mullane, Stephanie A.; Van Allen, Eliezer M.

2016-01-01

Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

Precision medicine for advanced prostate cancer.

PubMed

Mullane, Stephanie A; Van Allen, Eliezer M

2016-05-01

Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

1.5-Tesla Multiparametric-Magnetic Resonance Imaging for the detection of clinically significant prostate cancer

PubMed Central

POPITA, CRISTIAN; POPITA, ANCA RALUCA; SITAR-TAUT, ADELA; PETRUT, BOGDAN; FETICA, BOGDAN; COMAN, IOAN

2017-01-01

Background and aim Multiparametric-magnetic resonance imaging (mp-MRI) is the main imaging modality used for prostate cancer detection. The aim of this study is to evaluate the diagnostic performance of mp-MRI at 1.5-Tesla (1.5-T) for the detection of clinically significant prostate cancer. Methods In this ethical board approved prospective study, 39 patients with suspected prostate cancer were included. Patients with a history of positive prostate biopsy and patients treated for prostate cancer were excluded. All patients were examined at 1.5-T MRI, before standard transrectal ultrasonography–guided biopsy. Results The overall sensitivity, specificity, positive predictive value and negative predictive value for mp-MRI were 100%, 73.68%, 80% and 100%, respectively. Conclusion Our results showed that 1.5 T mp-MRI has a high sensitivity for detection of clinically significant prostate cancer and high negative predictive value in order to rule out significant disease. PMID:28246496

MD-miniRNA could be a more accurate biomarker for prostate cancer screening compared with serum prostate-specific antigen level.

PubMed

Xue, Dong; Zhou, Cui-Xing; Shi, Yun-Bo; Lu, Hao; He, Xiao-Zhou

2015-05-01

Prostate cancer and prostatic hyperplasia detection remains a great challenge, lacking of effective non-invasive and specific diagnostic biomarkers. In the current study, we aimed to identify the relative expression of plasma MD-miniRNA and its diagnostic performance in differentiating prostate cancer and prostatic hyperplasia patients from healthy controls, compared with serum prostate-specific antigen (PSA) level. All of the clinical participants (63 prostate cancer patients, 32 prostatic hyperplasia patients, and 50 healthy controls) were obtained from the Third Affiliated Hospital of Suzhou University in China between January 2013 and April 2014. Clinical characteristics were well matched. Plasma samples were extracted to test the relative expression of MD-miniRNA using the method of qRT-PCR. SPSS 22.0 statistical software package was used to analyze the data and GraphPad Prism 6.0 was used to generate the graphs. Relativity expression of plasma MD-miniRNA was significantly upregulated in prostate cancer, compared with prostatic hyperplasia patients and healthy controls. Serum PSA level revealed similar differences among these groups. MD-miniRNA presented a relatively high diagnostic accuracy with AUC of 0.86 (95 % CI 0.80-0.93) in differentiating prostate cancer patients from healthy controls. Simultaneously, MD-miniRNA was able to discriminate prostate cancer patients from prostatic hyperplasia controls with AUC of 0.79 (95 % CI 0.70-0.88). In addition, MD-miniRNA displayed a better diagnostic performance than PSA level. However, the panel of these two biomarkers revealed the best diagnostic performance, compared with either single biomarker. Results of this study showed that plasma MD-miniRNA could serve as a promising and noninvasive biomarker for diagnosing prostate cancer. Further large-scale studies are needed to confirm its clinical diagnosis accuracy.

Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer*

PubMed Central

Khan, Amjad P.; Poisson, Laila M.; Bhat, Vadiraja B.; Fermin, Damian; Zhao, Rong; Kalyana-Sundaram, Shanker; Michailidis, George; Nesvizhskii, Alexey I.; Omenn, Gilbert S.; Chinnaiyan, Arul M.; Sreekumar, Arun

2010-01-01

Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of biomarkers of cancer invasion and disease aggressiveness. Although alterations in gene expression have been extensively quantified during neoplastic progression, complementary analyses of proteomic changes have been limited. Here we interrogate the proteomic alterations in a cohort of 15 prostate-derived tissues that included five each from adjacent benign prostate, clinically localized prostate cancer, and metastatic disease from distant sites. The experimental strategy couples isobaric tags for relative and absolute quantitation with multidimensional liquid phase peptide fractionation followed by tandem mass spectrometry. Over 1000 proteins were quantified across the specimens and delineated into clinically localized and metastatic prostate cancer-specific signatures. Included in these class-specific profiles were both proteins that were known to be dysregulated during prostate cancer progression and new ones defined by this study. Enrichment analysis of the prostate cancer-specific proteomic signature, to gain insight into the functional consequences of these alterations, revealed involvement of miR-128-a/b regulation during prostate cancer progression. This finding was validated using real time PCR analysis for microRNA transcript levels in an independent set of 15 clinical specimens. miR-128 levels were elevated in benign prostate epithelial cell lines compared with invasive prostate cancer cells. Knockdown of miR-128 induced invasion in benign prostate epithelial cells, whereas its overexpression attenuated invasion in prostate cancer cells. Taken together, our profiles of the proteomic alterations of prostate cancer progression revealed miR-128 as a potentially important negative regulator of prostate cancer cell invasion. PMID:19955085

Men's experiences of regaining urinary continence following robotic-assisted laparoscopic prostatectomy (RALP) for localised prostate cancer: a qualitative phenomenological study.

PubMed

Waller, Jo; Pattison, Natalie

2013-02-01

To understand how men interpret their experiences of regaining continence following robotic-assisted laparoscopic prostatectomy (RALP). RALP is an innovative surgical technique intended to minimise the risk of long-term postoperative urinary incontinence in localised prostate cancer. Studies have shown that urinary function and quality of life domains can be adversely affected following RALP; however, the impact on men's lives has been hitherto unreported. A qualitative study using hermeneutic phenomenology Face-to-face, in-depth audio-recorded interviews with seven men (aged 57-71) who had recently undergone RALP and defined themselves as continent of urine. Data were inductively analysed for themes using an adapted version of Diekelmann et al. [1989, The NLN Criteria of Appraisal of Baccalaureate Programs: A Critical Hermeneutic Analysis, 1st edn. National League for Nursing (NLN) Press, New York, NY] framework. Men's experiences of regaining continence were situated within a wider network of personal and social relationships, and cultural structures. Themes included 'what was forecast', 'after-sales service', 'new plumbing', 'sense of self'. Men adopted a variety of practical coping strategies: preventing incontinence; improving incontinence; and dealing with lack of bladder control. The need to regain a sense of control over their lives resulted in all men developing coping mechanisms in order that they could resume their societal roles, which were salient to their personal identity, inferring that men's ability to cope with incontinence after RALP was dependent on factors other than urinary leakage alone. Knowledge of the potential impact of RALP could help nurses tailor appropriate interventions. Incontinence is individually interpreted and may not be well-addressed by traditional 'one-size fits all' preoperative programmes or information. Flexible and imaginative options (e.g., activity-focused interventions; buddy systems; internet programmes; telephone follow-up) for preoperative and postoperative support and activities for men may improve men's uptake of such services, through specialist nurse or peer support. © 2013 Blackwell Publishing Ltd.

Incidental prostate cancer at the time of cystectomy: the incidence and clinicopathological features in Chinese patients.

PubMed

Pan, Jiahua; Xue, Wei; Sha, Jianjun; Yang, Hu; Xu, Fan; Xuan, Hanqing; Li, Dong; Huang, Yiran

2014-01-01

To evaluate the incidence and the clinicopathological features of incidental prostate cancer detected in radical cystoprostatectomy (RCP) specimens in Chinese men and to estimate the oncological risk of prostate apex-sparing surgery for such patients. The clinical data and pathological feature of 504 patients who underwent RCP for bladder cancer from January 1999 to March 2013 were retrospectively reviewed. Whole mount serial section of the RCP specimens were cut transversely at 3-4 mm intervals and examined in same pathological institution. Thirty-four out of 504 patients (6.8%) had incidental prostate cancer with a mean age of 70.3 years. 12 cases (35.2%) were diagnosed as significant disease. 4 cases were found to have apex involvement of adenocarcinoma of the prostate while in 5 cases the prostate stroma invasion by urothelial carcinoma were identified (one involved prostate apex). The mean follow-up time was 46.4±33.8 months. Biochemical recurrence occurred in 3 patients but no prostate cancer-related death during the follow-up. There was no statistical significance in cancer specific survival between the clinically significant and insignificant cancer group. The prevalence of incidental prostate cancer in RCP specimens in Chinese patients was remarkably lower than in western people. Most of the incidental prostate cancer was clinically insignificant and patient's prognosis was mainly related to the bladder cancer. Sparing the prostate apex was potentially associated with a 1.0% risk of leaving significant cancer of the prostate or urothelial carcinoma.

Meeting report from the Prostate Cancer Foundation PSMA-directed radionuclide scientific working group.

PubMed

Miyahira, Andrea K; Pienta, Kenneth J; Morris, Michael J; Bander, Neil H; Baum, Richard P; Fendler, Wolfgang P; Goeckeler, William; Gorin, Michael A; Hennekes, Hartwig; Pomper, Martin G; Sartor, Oliver; Tagawa, Scott T; Williams, Scott; Soule, Howard R

2018-05-01

The Prostate Cancer Foundation (PCF) convened a PSMA-Directed Radionuclide Scientific Working Group on November 14, 2017, at Weill Cornell Medicine, New York, NY. The meeting was attended by 35 global investigators with expertise in prostate cancer biology, radionuclide therapy, molecular imaging, prostate-specific membrane antigen (PSMA)-targeted agents, drug development, and prostate cancer clinical trials. The goal of this meeting was to discuss the potential for using PSMA-targeted radionuclide agents for the treatment of advanced prostate cancer and to define the studies and clinical trials necessary for validating and optimizing the use of these agents. Several major topic areas were discussed including the overview of PSMA biology, lessons and applications of PSMA-targeted PET imaging, the nuances of designing PSMA-targeted radionuclide agents, clinical experiences with PSMA-targeted radionuclides, PCF-funded projects to accelerate PSMA-targeted radionuclide therapy, and barriers to the use of radionuclide treatments in widespread clinical practice. This article reviews the major topics discussed at the meeting with the goal of promoting research that will validate and optimize the use of PSMA-targeted radionuclide therapies for the treatment of advanced prostate cancer. © 2018 Wiley Periodicals, Inc.

Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

NASA Astrophysics Data System (ADS)

Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

2016-05-01

Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

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.

[Prostate biopsy under magnetic resonance imaging guidance].

PubMed

Kuplevatskiy, V I; CherkashiN, M A; Roshchin, D A; Berezina, N A; Vorob'ev, N A

2016-01-01

Prostate cancer (PC) is one of the most important problems in modern oncology. According to statistical data, PC ranks second in the cancer morbidity structure in the Russian Federation and developed countries and its prevalence has been progressively increasing over the past decade. A need for early diagnosis and maximally accurate morphological verification of the diagnosis in difficult clinical cases (inconvenient tumor location for standard transrectal biopsy; gland scarring changes concurrent with prostatitis and hemorrhage; threshold values of prostate-specific antigen with unclear changes in its doubling per unit time; suspicion of biochemical recurrence or clinical tumor progression after special treatment) leads to revised diagnostic algorithms and clinically introduced new high-tech invasive diagnostic methods. This paper gives the first analysis of literature data on Russian practice using one of the new methods to verify prostate cancer (transrectal prostate cancer under magnetic resonance imaging (MRI) guidance). The have sought the 1995-2015 data in the MEDLINE and Pubmed.

α-blockade, apoptosis, and prostate shrinkage: how are they related?

PubMed

Chłosta, Piotr; Drewa, Tomasz; Kaplan, Steven

2013-01-01

The α1-adrenoreceptor antagonists, such as terazosin and doxazosin, induce prostate programmed cell death (apoptosis) within prostate epithelial and stromal cells in vitro. This treatment should cause prostate volume decrease, However, this has never been observed in clinical conditions. The aim of this paper is to review the disconnect between these two processes. PubMed and DOAJ were searched for papers related to prostate, apoptosis, and stem cell death. The following key words were used: prostate, benign prostate hyperplasia, programmed cell death, apoptosis, cell death, α1-adrenoreceptor antagonist, α-blockade, prostate epithelium, prostate stroma, stem cells, progenitors, and in vitro models. We have shown how discoveries related to stem cells can influence our understanding of α-blockade treatment for BPH patients. Prostate epithelial and mesenchymal compartments have stem (progenitors) and differentiating cells. These compartments are described in relation to experimental in vitro and in vivo settings. Apoptosis is observed within prostate tissue, but this effect has no clinical significance and cannot lead to prostate shrinkage. In part, this is due to stem cells that are responsible for prostate tissue regeneration and are resistant to apoptosis triggered by α1-receptor antagonists.

Physical activity, alcohol consumption, BMI and smoking status before and after prostate cancer diagnosis in the ProtecT trial: Opportunities for lifestyle modification

PubMed Central

Hackshaw-McGeagh, Lucy E; Penfold, Chris M; Walsh, Eleanor; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Jeffreys, Mona; Martin, Richard M; Lane, J Athene

2015-01-01

Associations between certain lifestyle characteristics and prostate cancer risk have been reported, and continuation post-diagnosis can adversely affect prognosis. We explored whether men make spontaneous changes to their physical activity and alcohol intake, body mass index (BMI) and smoking status, following a diagnosis of localised prostate cancer. A detailed diet, health and lifestyle questionnaire was completed by 511 participants within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial, both before and 9 months after a diagnosis of prostate cancer. Of 177 men who were insufficiently active before their diagnosis (median 0 activity units/week; IQR 0–9), 40.7% had increased their activity by a median of 22 U week−1 (IQR 15–35) 9 months later, and there was weak evidence that men were more active after diagnosis than before (p = 0.07). Men categorised as “working” occupational social class and who were insufficiently active before diagnosis were 2.03 (95%, CI = 1.03–3.99, p = 0.04) times more likely to have increased their physical activity levels compared to men classified as “managerial or professional.” Similarly, men who were insufficiently active pre-diagnosis and with T-stage 2 compared with T-stage 1 prostate cancer were 2.47 (95%, CI = 1.29–4.71, p = 0.006) times more likely to be sufficiently active post-diagnosis. Following diagnosis, there was an overall reduction in alcohol intake (p = 0.03) and the proportion of current smokers (p = 0.09), but no overall change in BMI. We conclude that some men spontaneously change certain lifestyle behaviours on receiving a diagnosis of prostate cancer. For many men, however, additional support through lifestyle interventions is probably required to facilitate and maintain these changes. What’s new? Does cancer diagnosis lead individuals to consider making healthy lifestyle changes? These authors studied men diagnosed with prostate cancer to find out whether they changed their activity level, alcohol consumption, body mass index, or smoking habits after being diagnosed with prostate cancer. They found that some men increased their activity level and/or decreased their alcohol consumption, but not all. As making positive lifestyle changes may improve prognosis, it’s worth looking for ways to encourage newly diagnosed patients to make healthy changes. PMID:25761662

Vegetarianism and breast, colorectal and prostate cancer risk: an overview and meta-analysis of cohort studies.

PubMed

Godos, J; Bella, F; Sciacca, S; Galvano, F; Grosso, G

2017-06-01

Vegetarian diets may be associated with certain benefits toward human health, although current evidence is scarce and contrasting. In the present study, a systematic review and meta-analysis of prospective cohort studies was performed with respect to the association between vegetarian diets and breast, colorectal and prostate cancer risk. Studies were systematically searched in Pubmed and EMBASE electronic databases. Eligible studies had a prospective design and compared vegetarian, semi- and pesco-vegetarian diets with a non-vegetarian diet. Random-effects models were applied to calculate relative risks (RRs) of cancer between diets. Statistical heterogeneity and publication bias were explored. A total of nine studies were included in the meta-analysis. Studies were conducted on six cohorts accounting for 686 629 individuals, and 3441, 4062 and 1935 cases of breast, colorectal and prostate cancer, respectively. None of the analyses showed a significant association of vegetarian diet and a lower risk of either breast, colorectal, and prostate cancer compared to a non-vegetarian diet. By contrast, a lower risk of colorectal cancer was associated with a semi-vegetarian diet (RR = 0.86, 95% confidence interval = 0.79-0.94; I 2 = 0%, P heterogeneity = 0.82) and a pesco-vegetarian diet (RR = 0.67, 95% confidence interval = 0.53, 0.83; I 2 = 0%, P heterogeneity = 0.46) compared to a non-vegetarian diet. The subgroup analysis by cancer localisation showed no differences in summary risk estimates between colon and rectal cancer. A summary of the existing evidence from cohort studies on vegetarian diets showed that complete exclusion of any source of protein from the diet is not associated with further benefits for human health. © 2016 The British Dietetic Association Ltd.

Automated Patient Positioning Guided by Cone-Beam CT for Prostate Radiotherapy

DTIC Science & Technology

2009-01-01

clinically implemented an automated patient positioning strategy and tested with phantom experiments; (2) developed image-to-projection deformable...31st, 2008). The goal of this project is to develop a clinically practical technique for prostate patient positioning based on newly emerged CBCT...tissue organs; Secondly, it considers both the prostate target and the organs at risk (OARs) simultaneously, thus a better clinical decision can be

Emerging Vaccine Therapy Approaches for Prostate Cancer

PubMed Central

Sonpavde, Guru; Slawin, Kevin M; Spencer, David M; Levitt, Jonathan M

2010-01-01

Prostate cancer vaccines attempt to induce clinically relevant, cancer-specific systemic immune responses in patients with prostate cancer and represent a new class of targeted, nontoxic therapies. With a growing array of vaccine technologies in preclinical or clinical development, autologous antigen-presenting cell vaccines loaded with the antigen, prostate acid phosphatase, and poxvirus vaccines targeting prostate-specific antigen have recently demonstrated a significant survival benefit in randomized trials of patients with metastatic castration-resistant prostate cancer, whereas others have failed to demonstrate any benefit. The combination of vaccines with chemotherapy, radiotherapy, and other biologic agents is also being evaluated. Efforts to optimize vaccine approaches and select ideal patient populations need to continue to build on these early successes. PMID:20428291

High-Intensity Focused Ultrasound (HIFU) Using Sonablate® Devices for the Treatment of Benign Prostatic Hyperplasia and Localized Prostate Cancer: 18-year experience

NASA Astrophysics Data System (ADS)

Uchida, Toyoaki

2011-09-01

From 1993 to 2010, we have treated 156 patients benign prostatic hyperplasia (BPH) and 1,052 patients localized prostate cancer high-intensity focused ultrasound (HIFU). Four different HIFU devices, SonablateR-200, SonablateR-500, SonablateR-500 version 4 and Sonablate® TCM, have been used for this study. Clinical outcome of HIFU for BPH did not show any superior effects to transurethral resection of the prostate, laser surgery or transurethral vapolization of the prostate. However, HIFU appears to be a safe and minimally invasive therapy for patients with localized prostate cancer, especially low- and intermediate-risk patients. The rate of clinical outcome has significantly improved over the years due to technical improvements in the device.

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.

Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

USDA-ARS?s Scientific Manuscript database

Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

Development of New Treatments for Prostate Cancer

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

DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

2005-02-01

The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center ofmore » excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention are underway. The specific goals of this program are: (1) To investigate the molecular mechanisms underlying normal prostate growth and differentiation and elucidate the molecular mechanisms underlying prostate oncogenesis. (2) To build on fundamental knowledge to develop effective therapeutic approaches for the treatment of prostate cancer. (3) To improve the control of prostate cancer through early detection, chemoprevention, and outreach and education. This new disease-based program is structured to improve interdisciplinary interactions and translational results. Already, through the dynamic leadership of Drs. Cory Abate-Shen and Robert DiPaola, new investigators were attracted to the field, new collaborations engendered, and numerous investigator-initiated trials implemented. Progress in GPCC and the program overall has been outstanding. The Center has success in uniting investigators with broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer in patients and populations at risk. Members wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Studies in cell culture and powerful animal models developed recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention are underway.« less

External beam radiation therapy for clinically localized prostate cancer: when and how we optimize with concurrent hormonal deprivation.

PubMed

Koontz, Bridget F; Lee, W Robert

2011-10-01

Androgen deprivation plays a major role in the treatment of prostate cancer.Preclinical studies have shown that androgen deprivation provides both an independent cytotoxic effect and radiosensitization on prostate tumors. For men with non-metastatic prostate cancer, the addition of androgen deprivation to radiotherapy has been shown to improve survival for intermediate and high risk disease compared to radiation alone.This review discusses the clinical trial data regarding combination of androgen deprivation and radiation and provides recommendations for its use in men undergoing radiotherapy for localized prostate cancer.

Detection of sexually transmitted pathogens in patients with chronic prostatitis/chronic pelvic pain: a prospective clinical study.

PubMed

Papeš, Dino; Pasini, Miram; Jerončić, Ana; Vargović, Martina; Kotarski, Viktor; Markotić, Alemka; Škerk, Višnja

2017-05-01

In <10% of patients with prostatitis syndrome, a causative uropathogenic organism can be detected. It has been shown that certain organisms that cause sexually transmitted infections can also cause chronic bacterial prostatitis, which can be hard to diagnose and treat appropriately because prostatic samples obtained by prostatic massage are not routinely tested to detect them. We conducted a clinical study to determine the prevalence of Chlamydia, mycoplasma, and trichomonas infection in 254 patients that were previously diagnosed and treated for chronic prostatitis/chronic pelvic pain syndrome due to negative urethral swab, urine, and prostate samples. Urethral swabs and standard Meares-Stamey four-glass tests were done. Detailed microbiological analysis was conducted to detect the above organisms. Thirty-five (13.8%) patients had positive expressed prostatic secretions/VB3 samples, of which 22 (10.1%) were sexually transmitted organisms that were not detected on previous tests.

Heterobivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2011-04-01

specific membrane antigen (PSMA), showed promise in the clinic for identifying candidates for salvage radiotherapy. (4, 5) Because of the important...removed benzyl group to afford the Lys- Urea-Glu 14 in 85% yield. Compound 14 was conjugated with the suberic acid bis-(N- hydroxysuccinimide ( DSS ) in...directed against human and mouse prostate-specific membrane antigen. Prostate 2004; 61: 1-11. 4. Chang SS, Heston WD. The clinical role of prostate

KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer.

PubMed

Alshareeda, A T; Negm, O H; Green, A R; Nolan, C C; Tighe, P; Albarakati, N; Sultana, R; Madhusudan, S; Ellis, I O; Rakha, E A

2015-06-09

It is recognised that modulations of the nuclear import of macromolecules have a role in changing cellular phenotypes and carcinogenesis. We and others have noticed that aberrant subcellular localisation of DNA damage response (DDR) proteins in breast cancer (BC) is associated with loss-of-function phenotype. This study aims to investigate the biological and clinical significance of the nucleocytoplasmic transport protein karyopherin α-2 (KPNA2), and its role in controlling DDR proteins subcellular localisation in BC. A large (n=1494) and well-characterised series of early-stage invasive BC with a long-term follow-up was assessed for KPNA2 protein by using immunohistochemistry. KPNA2 expression was associated with the subcellular localisation of key DDR proteins that showed cytoplasmic expression including BRCA1, RAD51, SMC6L1, γH2AX, BARD1, UBC9, PIAS1 and CHK1. High level of KPNA2 was associated not only with cytoplasmic localisation of these proteins but also with their low/negative nuclear expression. Positive KPNA2 expression was associated with negative oestrogen receptor and triple-negative phenotype. Survival analysis showed that KPNA2 was associated with poor outcome (P<0.0001), but this effect was not independent of other prognostic variables. This study provides further evidence for the complexity of DDR mechanism in BC, and that KNPA2 has a role in the aberrant subcellular localisation of DDR proteins with subsequent impaired function.

African American Participation in Oncology Clinical Trials--Focus on Prostate Cancer: Implications, Barriers, and Potential Solutions.

PubMed

Ahaghotu, Chiledum; Tyler, Robert; Sartor, Oliver

2016-04-01

In the United States, the incidence and mortality rates of many cancers, especially prostate cancer, are disproportionately high among African American men compared with Caucasian men. Recently, mortality rates for prostate cancer have declined more rapidly in African American versus Caucasian men, but prostate cancer is still the most common cancer and the second leading cause of cancer deaths in African American men in the United States. Compared with Caucasian men, prostate cancer occurs at younger ages, has a higher stage at diagnosis, and is more likely to progress after definitive treatments in African American men. Reasons for racial discrepancies in cancer are multifactorial and potentially include socioeconomic, cultural, nutritional, and biologic elements. In addition to improving access to novel therapies, clinical trial participation is essential to adequately establish the risks and benefits of treatments in African American populations. Considering the disproportionately high mortality rates noted in these groups, our understanding of the natural history and responses to therapies is limited. This review will explore African American underrepresentation in clinical trials with a focus on prostate cancer, and potentially effective strategies to engage African American communities in prostate cancer research. Solutions targeting physicians, investigators, the community, and health care systems are identified. Improvement of African American participation in prostate cancer clinical trials will benefit all stakeholders. Published by Elsevier Inc.

Development of disulfiram-loaded vaginal rings for the localised treatment of cervical cancer.

PubMed

Boyd, Peter; Major, Ian; Wang, Weiguang; McConville, Christopher

2014-11-01

Cervical cancer is the third most prevalent cancer in women and disproportionately affects those in low resource settings due to limited programs for screening and prevention. In the developed world treatment for the disease in the non-metastasised state usually takes the form of surgical intervention and/or radiotherapy. In the developing world such techniques are less widely available. This paper describes the development of an intravaginal ring for the localised delivery of a chemotherapeutic drug to the cervix that has the potential to reduce the need for surgical intervention and will also provide a novel anti-cancer therapy for women in low resource settings. Disulfiram has demonstrated antineoplastic action against prostate, breast and lung cancer. Both PEVA and silicone elastomer were investigated for suitability as materials in the manufacture of DSF eluting intravaginal rings. DSF inhibited the curing process of the silicone elastomer, therefore PEVA was chosen as the material to manufacture the DSF-loaded vaginal rings. The vaginal rings had an excellent content uniformity while the DSF remained stable throughout the manufacturing process. Furthermore, the rings provided diffusion controlled release of DSF at levels well in excess of the IC50 value for the HeLa cervical cancer cell line. Copyright © 2014 Elsevier B.V. All rights reserved.

The Use of Biomarkers in Prostate Cancer Screening and Treatment

PubMed Central

Alford, Ashley V.; Brito, Joseph M.; Yadav, Kamlesh K.; Yadav, Shalini S.; Tewari, Ashutosh K.; Renzulli, Joseph

2017-01-01

Prostate cancer screening and diagnosis has been guided by prostate-specific antigen levels for the past 25 years, but with the most recent US Preventive Services Task Force screening recommendations, as well as concerns regarding overdiagnosis and overtreatment, a new wave of prostate cancer biomarkers has recently emerged. These assays allow the testing of urine, serum, or prostate tissue for molecular signs of prostate cancer, and provide information regarding both diagnosis and prognosis. In this review, we discuss 12 commercially available biomarker assays approved for the diagnosis and treatment of prostate cancer. The results of clinical validation studies and clinical decision-making studies are presented. This information is designed to assist urologists in making clinical decisions with respect to ordering and interpreting these tests for different patients. There are numerous fluid and biopsy-based genomic tests available for prostate cancer patients that provide the physician and patient with different information about risk of future disease and treatment outcomes. It is important that providers be able to recommend the appropriate test for each individual patient; this decision is based on tissue availability and prognostic information desired. Future studies will continue to emphasize the important role of genomic biomarkers in making individualized treatment decisions for prostate cancer patients. PMID:29472826

Bacterial Prostatitis: Bacterial Virulence, Clinical Outcomes, and New Directions.

PubMed

Krieger, John N; Thumbikat, Praveen

2016-02-01

Four prostatitis syndromes are recognized clinically: acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatitis. Because Escherichia coli represents the most common cause of bacterial prostatitis, we investigated the importance of bacterial virulence factors and antimicrobial resistance in E. coli strains causing prostatitis and the potential association of these characteristics with clinical outcomes. A structured literature review revealed that we have limited understanding of the virulence-associated characteristics of E. coli causing acute prostatitis. Therefore, we completed a comprehensive microbiological and molecular investigation of a unique strain collection isolated from healthy young men. We also considered new data from an animal model system suggesting certain E. coli might prove important in the etiology of chronic prostatitis/chronic pelvic pain syndrome. Our human data suggest that E. coli needs multiple pathogenicity-associated traits to overcome anatomic and immune responses in healthy young men without urological risk factors. The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these E. coli strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance confers little added advantage to E. coli strains in these healthy outpatients. Our animal model data also suggest that certain pathogenic E. coli may be important in the etiology of chronic prostatitis/chronic pelvic pain syndrome through mechanisms that are dependent on the host genetic background and the virulence of the bacterial strain.

Detection rate of prostate cancer following biopsy among the northern Han Chinese population: a single-center retrospective study of 1022 cases.

PubMed

Jia, Yong; Zhu, Lei-Yi; Xian, Yu-Xin; Sun, Xiao-Qing; Gao, Jian-Gang; Zhang, Xin-Hong; Hou, Si-Chuan; Zhang, Chang-Cun; Liu, Zhao-Xu

2017-08-29

Prostate cancer is known to have ethnic and regional differences. The study aimed to clinically evaluate the detection rate of prostate cancer on transrectal ultrasonography (TRUS)-guided prostate biopsy and analyze its characteristics among the northern Han Chinese population at a single center. Between October 2009 and September 2016, a total of 1027 Chinese men, who had undergone TRUS-guided prostate biopsy at Qingdao Municipal Hospital, were retrospectively analyzed. Prostate biopsies were performed in the case of an abnormally elevated serum PSA level, and/or abnormal digital rectal examination (DRE) findings, and/or suspicious prostatic imaging findings. Of the 1022 men enrolled in the analysis, 438 patients (42.8%) were diagnosed with prostate adenocarcinoma histologically. When serum PSA levels were divided into five subgroups (less than 4.0, 4.0 to 10.0, 10.0 to 20.0, 20.0 to 100.0, and ≥ 100.0 ng/ml), the detection rates of prostate cancer were 12.4, 15.9, 34.1, 66.2, and 93.8%, respectively. With serum PSA levels of 4.0 to 10.0 ng/ml, the cancer detection rates for a normal DRE and a suspect DRE finding were 13.5 and 58.2%, respectively. Accordingly, the cancer detection rates for a normal imaging and a suspect imaging finding were 13.5 and 58.2%, respectively. Besides, a large proportion of the patients were in the clinically advanced stage. The present study data reported a relatively higher prostate cancer detection rate of 42.8% and that the majority of the patients presented with clinically advanced prostate cancers within a local clinical urologic practice. An early detection and screening program for prostate cancer is of great need to reduce the burden from this disease among the northern Han Chinese population.

Long-term Treatment with Finasteride Resulted in a Significant Improvement Relative to Placebo in Clinical Progression of Benign Prostatic Hyperplasia (BPH) in Men with Enlarged Prostates (≥30 mL), But Not in Those with Smaller Prostates (<30 mL): Data from the Medical Therapy of Prostatic Symptoms (MTOPS) Trial

PubMed Central

Kaplan, Steven A.; Lee, Jeannette Y.; Meehan, Alan G.; Kusek, John W.

2013-01-01

Purpose This post hoc analysis of the Medical Therapy of Prostatic Symptoms (MTOPS) trial examined the effect of finasteride alone compared to placebo on clinical progression of benign prostatic hyperplasia (BPH) in men with baseline prostate volume (PV) <30 mL and ≥30 mL. Materials and Methods Men were randomized to placebo (n=737), doxazosin alone (4 to 8 mg) (n=756), finasteride alone (5 mg) (n=768), or doxazosin plus finasteride (n=786) (average duration of follow-up was 4.5 yrs); ~50% of patients had a baseline PV ≥30 mL. The present analysis was based on the finasteride alone and placebo arms only and included patients for whom baseline and end of study data were available. We examined the effect of treatment on the cumulative percentage of men who did not experience clinical progression of BPH by study end. Results In men with baseline PV ≥30 mL, treatment with finasteride produced a significant (p<0.001) increase relative to placebo in the cumulative percentage of patients who did not experience clinical progression of BPH (finasteride, 88.1%, versus placebo, 77.8%). There was no significant (p=0.441) between-group difference in men with baseline PV <30 mL (91.4% versus 89.1%, respectively). Conclusions Long-term treatment with finasteride led to a significant beneficial effect compared to placebo on clinical progression of BPH in LUTS patients with enlarged prostates (baseline PV ≥30 mL). Finasteride had no significant effect, compared to placebo on clinical progression of BPH in LUTS patients with smaller prostates (baseline PV <30 mL). PMID:21334655

Nutraceuticals for prostate cancer chemoprevention: from molecular mechanisms to clinical application.

PubMed

Wang, Zhijun; Fan, Jeffery; Liu, Mandy; Yeung, Steven; Chang, Andy; Chow, Moses S S; Pon, Doreen; Huang, Ying

2013-12-01

Nutraceutical is a food, or part of a food, used for the prevention and/or treatment of diseases. A number of nutraceuticals serve as candidates for development of prostate cancer chemopreventive agents because of promising epidemiological, preclinical and pilot clinical findings. Their mechanisms of action may involve an ability to target multiple molecular pathways in carcinogenesis without eliciting toxic side effects. This review provides an overview of several nutraceuticals, including green tea polyphenol, omega-3 fatty acids, vitamin D, lycopene, genistein, quercetin, resveratrol and sulforaphane, for the clinical relevance to chemoprevention of prostate cancer. Their mechanisms of action on regulating key processes of carcinogenesis are also discussed. For each of these agents, a brief summary of completed or currently ongoing clinical trials related to the chemopreventive efficacy on prostate cancer is given. Even though a few clinical trials have been conducted, review of these results indicate that further studies are required to confirm the clinical efficacy and safety, and to provide a guidance on how to use nutraceuticals for optimal effect. Future cancer prevention clinical trials for the nutraceuticals should recruit men with an increased risk of prostate cancer.

Multiparametric magnetic resonance imaging predicts the presence of prostate cancer in patients with negative prostate biopsy.

PubMed

Lista, F; Castillo, E; Gimbernat, H; Rodríguez-Barbero, J M; Panizo, J; Angulo, J C

2015-03-01

To assess the ability of multiparametric prostate magnetic resonance imaging (mpMRI) to detect prostate cancer in patients with prior negative transrectal prostate biopsy (TPB). mpMRI (TSE-T2-w, DWI and DCE sequences) was performed on 1.5T (Magnetom Avanto; Siemens Healthcare Solutions) in 150 patients suspicious of prostate cancer and with negative TPB. European Society of Urogenital Radiology (ESUR) criteria were used (score 1: clinically significant disease is highly unlikely to be present; score 2: clinically significant cancer is unlikely to be present; score 3: clinically significant cancer is equivocal; score 4: clinically significant cancer is likely to be present; score 5: clinically significant cancer is highly likely to be present). PSA measurement (total and free), digital rectal examination (DRE), transrectal ultrasound (TRU) and a second TPB (at least 14 cylinders) were performed in all patients. Variables were submitted for independent blind analysis. The accuracy of each test was measured. Stepwise selection model for prediction of prostate cancer in second TPB was developed. Mean age was 66.2± 5 years (51-77), mean PSA 11.3± 9.6ng/mL (0.9-75) and mean prostatic volume 82.2±42 (20-250) cc. DRE was suspicious in 11 (7.3%) patients. The mean number of cylinders per patient sampled in second TRB was 17.6±2.7(14-22). Second TRB was positive in 28 patients (18.7%). mpMRI was positive (score 3-5) in 102 (68%), test sensibility was 92.9% and the NPV was 95.8%. The risk of prostate cancer diagnosis in second TPB is modified by: PSA velocity > 0.75 (OR 1.04 [0.99-1.08]; P=0.06), free/total ratio PSA <15% (OR 0.37 [0.13-1.05]; P=0.06), each cc. of prostate volume (OR 0.98 [0.97-1]; P=0.017) and mpMRI 3-5 (OR 7.87 [1.78-34.7]; P=0.006). Multivariate analysis reveals that mpMRI (OR 7.41 [1.65-33.28]; P=0.009) and prostatic volume (OR 0.31 [0.12-0.78]; P=0.01) are independent risk predictors of prostate cancer. According to ESUR guidelines and in patients with prior negative prostate biopsy, mpMRI is a valuable tool for the prediction of prostate cancer in second TPB. Lower prostate volume, the higher reliability. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Meeting Report From the Prostate Cancer Foundation Scientific Working Group on Radium-223.

PubMed

Miyahira, Andrea K; Morris, Michael; Soule, Howard R

2017-02-01

The Prostate Cancer Foundation (PCF) convened a Scientific Working Group Meeting on Radium-223 on September 8, 2016, at The Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center. The meeting was attended by 18 investigators with expertise in radium-223, bone biology, molecular imaging, biomarkers, and prostate cancer clinical trials. The goal of this meeting was to discuss the known and unknown surroundings the therapeutic effects of the bone targeting agent radium-223, in bone metastatic prostate cancer therapy, and to outline the most critical studies needed to improve the clinical use of this agent. Three major topic areas were discussed: (1) the basic science of radium; (2) immuno-adjuvant properties of radium therapy; and (3) high impact clinical trials and correlative science. This article reviews the major topics discussed at the meeting for the purpose of accelerating studies that will improve the use of radium-223 in the treatment of prostate cancer patients. Prostate 77:245-254, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Diagnostic tests in urology: magnetic resonance imaging (MRI) for the staging of prostate cancer.

PubMed

Preston, Mark A; Harisinghani, Mukesh G; Mucci, Lorelei; Witiuk, Kelsey; Breau, Rodney H

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The use of MRI for prostate cancer diagnosis and staging is increasing. Indications for prostate MRI are not defined and many clinicians are unsure of how best to use MRI to aid clinical decisions. This evidence-based medicine article addresses the clinical utility of prostate MRI for preoperative staging. Based on a common patient scenario, a guide to calculating the probability of extraprostatic extension is provided. © 2013 BJU International.

Prostate Cancer Screening: Should You Get a PSA Test?

MedlinePlus

... Mayo Clinic Staff Cancer screening tests — including the prostate-specific antigen (PSA) test to look for signs of prostate ... of harm to the person undergoing the testing. Prostate-specific antigen (PSA) is a protein produced by both cancerous ( ...

Clinical trial combines enzalutamide with immunotherapy for advanced prostate cancer | Center for Cancer Research

Cancer.gov

Dr. Ravi Madan, Clinical Director of the Genitourinary Malignancies Branch, is conducting a clinical trial for men who have metastatic prostate cancer but have not yet been treated with chemotherapy, abiraterone or enzalutamide.

METastasis Reporting and Data System for Prostate Cancer: Practical Guidelines for Acquisition, Interpretation, and Reporting of Whole-body Magnetic Resonance Imaging-based Evaluations of Multiorgan Involvement in Advanced Prostate Cancer.

PubMed

Padhani, Anwar R; Lecouvet, Frederic E; Tunariu, Nina; Koh, Dow-Mu; De Keyzer, Frederik; Collins, David J; Sala, Evis; Schlemmer, Heinz Peter; Petralia, Giuseppe; Vargas, H Alberto; Fanti, Stefano; Tombal, H Bertrand; de Bono, Johann

2017-01-01

Comparative reviews of whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography/computed tomography (CT; with different radiotracers) have shown that metastasis detection in advanced cancers is more accurate than with currently used CT and bone scans. However, the ability of WB-MRI and positron emission tomography/CT to assess therapeutic benefits has not been comprehensively evaluated. There is also considerable variability in the availability and quality of WB-MRI, which is an impediment to clinical development. Expert recommendations for standardising WB-MRI scans are needed, in order to assess its performance in advanced prostate cancer (APC) clinical trials. To design recommendations that promote standardisation and diminish variations in the acquisition, interpretation, and reporting of WB-MRI scans for use in APC. An international expert panel of oncologic imagers and oncologists with clinical and research interests in APC management assessed biomarker requirements for clinical care and clinical trials. Key requirements for a workable WB-MRI protocol, achievable quality standards, and interpretation criteria were identified and synthesised in a white paper. The METastasis Reporting and Data System for Prostate Cancer guidelines were formulated for use in all oncologic manifestations of APC. Uniformity in imaging data acquisition, quality, and interpretation of WB-MRI are essential for assessing the test performance of WB-MRI. The METastasis Reporting and Data System for Prostate Cancer standard requires validation in clinical trials of treatment approaches in APC. METastasis Reporting and Data System for Prostate Cancer represents the consensus recommendations on the performance, quality standards, and reporting of whole-body magnetic resonance imaging, for use in all oncologic manifestations of advanced prostate cancer. These new criteria require validation in clinical trials of established and new treatment approaches in advanced prostate cancer. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Development and preliminary evaluation of an ultrasonic motor actuated needle guide for 3T MRI-guided transperineal prostate interventions

NASA Astrophysics Data System (ADS)

Song, Sang-Eun; Tokuda, Junichi; Tuncali, Kemal; Tempany, Clare; Hata, Nobuhiko

2012-02-01

Image guided prostate interventions have been accelerated by Magnetic Resonance Imaging (MRI) and robotic technologies in the past few years. However, transrectal ultrasound (TRUS) guided procedure still remains as vast majority in clinical practice due to engineering and clinical complexity of the MRI-guided robotic interventions. Subsequently, great advantages and increasing availability of MRI have not been utilized at its maximum capacity in clinic. To benefit patients from the advantages of MRI, we developed an MRI-compatible motorized needle guide device "Smart Template" that resembles a conventional prostate template to perform MRI-guided prostate interventions with minimal changes in the clinical procedure. The requirements and specifications of the Smart Template were identified from our latest MRI-guided intervention system that has been clinically used in manual mode for prostate biopsy. Smart Template consists of vertical and horizontal crossbars that are driven by two ultrasonic motors via timing-belt and mitergear transmissions. Navigation software that controls the crossbar position to provide needle insertion positions was also developed. The software can be operated independently or interactively with an open-source navigation software, 3D Slicer, that has been developed for prostate intervention. As preliminary evaluation, MRI distortion and SNR test were conducted. Significant MRI distortion was found close to the threaded brass alloy components of the template. However, the affected volume was limited outside the clinical region of interest. SNR values over routine MRI scan sequences for prostate biopsy indicated insignificant image degradation during the presence of the robotic system and actuation of the ultrasonic motors.

Can exercise suppress tumour growth in advanced prostate cancer patients with sclerotic bone metastases? A randomised, controlled study protocol examining feasibility, safety and efficacy

PubMed Central

Newton, Robert U; Spry, Nigel A; Taaffe, Dennis R; Chambers, Suzanne K; Feeney, Kynan T; Joseph, David J; Redfern, Andrew D; Ferguson, Tom; Galvão, Daniel A

2017-01-01

Introduction Exercise may positively alter tumour biology through numerous modulatory and regulatory mechanisms in response to a variety of modes and dosages, evidenced in preclinical models to date. Specifically, localised and systemic biochemical alterations produced during and following exercise may suppress tumour formation, growth and distribution by virtue of altered epigenetics and endocrine–paracrine activity. Given the impressive ability of targeted mechanical loading to interfere with metastasis-driven tumour formation in human osteolytic tumour cells, it is of equal interest to determine whether a similar effect is observed in sclerotic tumour cells. The study aims to (1) establish the feasibility and safety of a combined modular multimodal exercise programme with spinal isometric training in advanced prostate cancer patients with sclerotic bone metastases and (2) examine whether targeted and supervised exercise can suppress sclerotic tumour growth and activity in spinal metastases in humans. Methods and analysis A single-blinded, two-armed, randomised, controlled and explorative phase I clinical trial combining spinal isometric training with a modular multimodal exercise programme in 40 men with advanced prostate cancer and stable sclerotic spinal metastases. Participants will be randomly assigned to (1) the exercise intervention or (2) usual medical care. The intervention arm will receive a 3-month, supervised and individually tailored modular multimodal exercise programme with spinal isometric training. Primary endpoints (feasibility and safety) and secondary endpoints (tumour morphology; biomarker activity; anthropometry; musculoskeletal health; adiposity; physical function; quality of life; anxiety; distress; fatigue; insomnia; physical activity levels) will be measured at baseline and following the intervention. Statistical analyses will include descriptive characteristics, t-tests, effect sizes and two-way (group × time) repeated-measures analysis of variance (or analysis of covariance) to examine differences between groups over time. The data-set will be primarily examined using an intention-to-treat approach with multiple imputations, followed by a secondary sensitivity analysis to ensure data robustness using a complete cases approach. Ethics and dissemination Ethics approval was obtained from the Human Research Ethics Committee (HREC) of Edith Cowan University and the Sir Charles Gairdner and Osborne Park Health Care Group. If proven to be feasible and safe, this study will form the basis of future phase II and III trials in human patients with advanced cancer. To reach a maximum number of clinicians, practitioners, patients and scientists, outcomes will be disseminated through national and international clinical, conference and patient presentations, as well as publication in high-impact, peer-reviewed academic journals. Trial registration number ACTRN 12616000179437. PMID:28559456

Exploiting Epigenetic Alterations in Prostate Cancer.

PubMed

Baumgart, Simon J; Haendler, Bernard

2017-05-09

Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

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.

Prostate cancer diagnostics: Clinical challenges and the ongoing need for disruptive and effective diagnostic tools.

PubMed

Sharma, Shikha; Zapatero-Rodríguez, Julia; O'Kennedy, Richard

The increased incidence and the significant health burden associated with carcinoma of the prostate have led to substantial changes in its diagnosis over the past century. Despite technological advancements, the management of prostate cancer has become progressively more complex and controversial for both early and late-stage disease. The limitations and potential harms associated with the use of prostate-specific antigen (PSA) as a diagnostic marker have stimulated significant investigation of numerous novel biomarkers that demonstrate varying capacities to detect prostate cancer and can decrease unnecessary biopsies. However, only a few of these markers have been approved for specific clinical settings while the others have not been adequately validated for use. This review systematically and critically assesses ongoing issues and emerging challenges in the current state of prostate cancer diagnostic tools and the need for disruptive next generation tools based on analysis of combinations of these biomarkers to enhance predictive accuracy which will benefit clinical diagnostics and patient welfare. Copyright © 2016. Published by Elsevier Inc.

Real-time photoacoustic imaging of prostate brachytherapy seeds using a clinical ultrasound system.

PubMed

Kuo, Nathanael; Kang, Hyun Jae; Song, Danny Y; Kang, Jin U; Boctor, Emad M

2012-06-01

Prostate brachytherapy is a popular prostate cancer treatment option that involves the permanent implantation of radioactive seeds into the prostate. However, contemporary brachytherapy procedure is limited by the lack of an imaging system that can provide real-time seed-position feedback. While many other imaging systems have been proposed, photoacoustic imaging has emerged as a potential ideal modality to address this need, since it could easily be incorporated into the current ultrasound system used in the operating room. We present such a photoacoustic imaging system built around a clinical ultrasound system to achieve the task of visualizing and localizing seeds. We performed several experiments to analyze the effects of various parameters on the appearance of brachytherapy seeds in photoacoustic images. We also imaged multiple seeds in an ex vivo dog prostate phantom to demonstrate the possibility of using this system in a clinical setting. Although still in its infancy, these initial results of a photoacoustic imaging system for the application of prostate brachytherapy seed localization are highly promising.

Target motion tracking in MRI-guided transrectal robotic prostate biopsy.

PubMed

Tadayyon, Hadi; Lasso, Andras; Kaushal, Aradhana; Guion, Peter; Fichtinger, Gabor

2011-11-01

MRI-guided prostate needle biopsy requires compensation for organ motion between target planning and needle placement. Two questions are studied and answered in this paper: 1) is rigid registration sufficient in tracking the targets with an error smaller than the clinically significant size of prostate cancer and 2) what is the effect of the number of intraoperative slices on registration accuracy and speed? we propose multislice-to-volume registration algorithms for tracking the biopsy targets within the prostate. Three orthogonal plus additional transverse intraoperative slices are acquired in the approximate center of the prostate and registered with a high-resolution target planning volume. Both rigid and deformable scenarios were implemented. Both simulated and clinical MRI-guided robotic prostate biopsy data were used to assess tracking accuracy. average registration errors in clinical patient data were 2.6 mm for the rigid algorithm and 2.1 mm for the deformable algorithm. rigid tracking appears to be promising. Three tracking slices yield significantly high registration speed with an affordable error.

CaP CURE Initiatives and Projects

PubMed Central

Soule, Howard R

2003-01-01

CaP CURE was founded in 1993 to help find better treatments and a cure for prostate cancer. By reducing the time and complexity required to apply for funding, and by funding many first-time applicants, CaP CURE has attracted a large number of high-level investigators to the field of prostate cancer research. The organization’s Therapy Consortium meets regularly to address major issues that impede progress in clinical development of new treatments for prostate cancer. CaP CURE has also sponsored an initiative to standardize clinical trial design scenarios for the clinical state of rising prostate-specific antigen and intends to present them to the Food and Drug Administration in partnership with the National Dialogue on Cancer. Finally, CaP CURE’s efforts have resulted in a significant increase in federal funding of prostate cancer research programs. PMID:16986049

A multidisciplinary prostate cancer clinic for newly diagnosed patients: developing the role of the advanced practice nurse.

PubMed

Madsen, Lydia T; Craig, Catherine; Kuban, Deborah

2009-06-01

Newly diagnosed patients with prostate cancer have various treatment options, and a multidisciplinary prostate cancer clinic (MPCC) can present all options in a single setting. An MPCC was started in 2004 at the University of Texas M.D. Anderson Cancer Center, and 258 patients with prostate cancer were evaluated in its first year. The clinic expanded in 2006 and an oncology advanced practice nurse (APN) was recruited to address specific objectives. The APN role was used to implement a quality-of-life protocol, provide detailed patient education (including a treatment summary and care plan), and serve as a single point of contact as patients move toward a treatment decision. Formal evaluation of the MPCC showed that patients were satisfied with this approach to the complex decision-making process in prostate cancer.

Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique.

PubMed

Johannsen, M; Gneveckow, U; Eckelt, L; Feussner, A; Waldöfner, N; Scholz, R; Deger, S; Wust, P; Loening, S A; Jordan, A

2005-11-01

The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100 kHz and variable field strength (0-18 kA m(-1)). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anaesthesia. In the first patient treated, maximum and minimum intra-prostatic temperatures measured at a field strength of 4.0-5.0 kA m(-1) were 48.5 degrees C and 40.0 degrees C during the 1st treatment and 42.5 degrees C and 39.4 degrees C during the 6th treatment, respectively. These first clinical experiences prompted us to initiate a phase I study to evaluate feasibility, toxicity and quality of life during hyperthermia using magnetic nanoparticles in patients with biopsy-proven local recurrence of prostate cancer following radiotherapy with curative intent. To the authors' knowledge, this is the first report on clinical application of interstitial hyperthermia using magnetic nanoparticles in the treatment of human cancer.

Can TRUS Power Doppler Predict the Preservation of Erectile Function in HIFU Treatment of Localised Prostate Cancer? — A Preliminary Study

NASA Astrophysics Data System (ADS)

Hoh, I. M.; Calleary, J. G.; Moore, C.; Emberton, M.; Allen, C.

2006-05-01

Perhaps the single most significant unifying feature in men diagnosed with organ confined prostate cancer is the hope of erectile preservation in the treatment that offers cure. Although it is not 100% certain that the preservation of neurovascular bundle (NVB) can actually lead to intact sexual function, there is evidence that non-sparing nerve radical prostatectomy has a much higher incidence of impotence compared to nerve-sparing ones. The idea to monitor NVB flow can be realized using a simple power Doppler technique that was done before and after HIFU. The NVB flow was found intact in all patients (n=14). Tumescence returned in 93% of patients with a mean time of 6 weeks for this to occur. The erectile function score, IIEF-15 decreased by a third but shows a trend towards recovery. This preliminary study demonstrates the feasibility of transrectal power Doppler as a monitoring tool to provide immediate feedback on the NVB flow which was found intact in all patients. Although early reports of the tumescence proved encouraging, its full impact on erectile function will require longer follow-up.

Reliability of horizontal and vertical tube shift techniques in the localisation of supernumerary teeth.

PubMed

Mallineni, S K; Anthonappa, R P; King, N M

2016-12-01

To assess the reliability of the vertical tube shift technique (VTST) and horizontal tube shift technique (HTST) for the localisation of unerupted supernumerary teeth (ST) in the anterior region of the maxilla. A convenience sample of 83 patients who attended a major teaching hospital because of unerupted ST was selected. Only non-syndromic patients with ST and who had complete clinical and radiographic and surgical records were included in the study. Ten examiners independently rated the paired set of radiographs for each technique. Chi-square test, paired t test and kappa statistics were employed to assess the intra- and inter-examiner reliability. Paired sets of 1660 radiographs (830 pairs for each technique) were available for the analysis. The overall sensitivity for VTST and HTST was 80.6 and 72.1% respectively, with slight inter-examiner and good intra-examiner reliability. Statistically significant differences were evident between the two localisation techniques (p < 0.05). Localisation of unerupted ST using VTST was more successful than HTST in the anterior region of the maxilla.

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma.

PubMed

McNeel, Douglas G; Bander, Neil H; Beer, Tomasz M; Drake, Charles G; Fong, Lawrence; Harrelson, Stacey; Kantoff, Philip W; Madan, Ravi A; Oh, William K; Peace, David J; Petrylak, Daniel P; Porterfield, Hank; Sartor, Oliver; Shore, Neal D; Slovin, Susan F; Stein, Mark N; Vieweg, Johannes; Gulley, James L

2016-01-01

Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly.

Factors Predicting a Good Symptomatic Outcome After Prostate Artery Embolisation (PAE).

PubMed

Maclean, D; Harris, M; Drake, T; Maher, B; Modi, S; Dyer, J; Somani, B; Hacking, N; Bryant, T

2018-02-26

As prostate artery embolisation (PAE) becomes an established treatment for benign prostatic obstruction, factors predicting good symptomatic outcome remain unclear. Pre-embolisation prostate size as a predictor is controversial with a handful of papers coming to conflicting conclusions. We aimed to investigate if an association existed in our patient cohort between prostate size and clinical benefit, in addition to evaluating percentage volume reduction as a predictor of symptomatic outcome following PAE. Prospective follow-up of 86 PAE patients at a single institution between June 2012 and January 2016 was conducted (mean age 64.9 years, range 54-80 years). Multiple linear regression analysis was performed to assess strength of association between clinical improvement (change in IPSS) and other variables, of any statistical correlation, through Pearson's bivariate analysis. No major procedural complications were identified and clinical success was achieved in 72.1% (n = 62) at 12 months. Initial prostate size and percentage reduction were found to have a significant association with clinical improvement. Multiple linear regression analysis (r 2  = 0.48) demonstrated that percentage volume reduction at 3 months (r = 0.68, p < 0.001) had the strongest correlation with good symptomatic improvement at 12 months after adjusting for confounding factors. Both the initial prostate size and percentage volume reduction at 3 months predict good symptomatic outcome at 12 months. These findings therefore aid patient selection and counselling to achieve optimal outcomes for men undergoing prostate artery embolisation.

Poster - Thur Eve - 06: Comparison of an open source genetic algorithm to the commercially used IPSA for generation of seed distributions in LDR prostate brachytherapy.

PubMed

McGeachy, P; Khan, R

2012-07-01

In early stage prostate cancer, low dose rate (LDR) prostate brachytherapy is a favorable treatment modality, where small radioactive seeds are permanently implanted throughout the prostate. Treatment centres currently rely on a commercial optimization algorithm, IPSA, to generate seed distributions for treatment plans. However, commercial software does not allow the user access to the source code, thus reducing the flexibility for treatment planning and impeding any implementation of new and, perhaps, improved clinical techniques. An open source genetic algorithm (GA) has been encoded in MATLAB to generate seed distributions for a simplified prostate and urethra model. To assess the quality of the seed distributions created by the GA, both the GA and IPSA were used to generate seed distributions for two clinically relevant scenarios and the quality of the GA distributions relative to IPSA distributions and clinically accepted standards for seed distributions was investigated. The first clinically relevant scenario involved generating seed distributions for three different prostate volumes (19.2 cc, 32.4 cc, and 54.7 cc). The second scenario involved generating distributions for three separate seed activities (0.397 mCi, 0.455 mCi, and 0.5 mCi). Both GA and IPSA met the clinically accepted criteria for the two scenarios, where distributions produced by the GA were comparable to IPSA in terms of full coverage of the prostate by the prescribed dose, and minimized dose to the urethra, which passed straight through the prostate. Further, the GA offered improved reduction of high dose regions (i.e hot spots) within the planned target volume. © 2012 American Association of Physicists in Medicine.

Bilateral Arterial Embolization of the Prostate Through a Single Prostatic Artery: A Case Series

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

Amouyal, Gregory, E-mail: gregamouyal@hotmail.com; Pellerin, Olivier, E-mail: olivier.pellerin@aphp.fr; Giudice, Costantino Del, E-mail: costantino.delgiudice@aphp.fr

Peri-prostatic shunts are frequent during PAE, carrying the risk of non-target embolization of penis/corpus cavernosum or rectum but also the potential advantage to irrigate the contralateral lobe. Sometimes, bilateral embolization is impossible, carrying the risk of limited clinical success. The possibility to reach contralateral prostatic territory from the ipsilateral prostatic artery (PA) and embolize it via peri/intra-prostatic anastomoses could be of interest in this situation. We describe a series of three consecutive patients (among 89 consecutive patients treated by PAE for symptomatic BPH) who underwent successful embolization of both prostatic lobes through catheterization of a PA on only one side.more » All patients had clinical success after a mean follow-up of 3.3 months. Dosimetry of these three procedures indicates that there may be radiation dose savings.« less

A pilot study on understanding the journey of advanced prostate cancer patients.

PubMed

Wagholikar, Amol; Fung, Maggie; Nelson, Colleen

2011-01-01

To understand the journey of advanced prostate cancer patients for supporting development of an innovative patient journey browser. Prostate cancer is one of the common cancers in Australia. Due to the chronic nature of the disease, it is important to have effective disease management strategy and care model. Multi-disciplinary care is a well-proven approach for chronic disease management. The Multi-disciplinary team (MDT) can function more effectively if all the required information is available for the clinical decision support. The development of innovative technology relies on an accurate understanding of the advanced prostate cancer patient's journey over a prolonged period. This need arises from the fact that advanced prostate cancer patients may follow various treatment paths and change their care providers. As a result of this, it is difficult to understand the actual sources of patient's clinical records and their treatment patterns. The aim of the research is to understand variable sources of clinical records, treatment patterns, alternative therapies, over the counter (OTC) medications of advanced prostate cancer patients. This study provides better and holistic understanding of advanced prostate cancer journey. The study was conducted through an on-line survey developed to seek and analyse the responses from the participants. The on-line questionnaire was carefully developed through consultations with the clinical researchers at the Australian Prostate Cancer Research Centre-Queensland, prostate cancer support group representatives and health informaticians at the Australian E-Health Research Centre. The non-identifying questionnaire was distributed to the patients through prostate cancer support groups in Queensland, Australia. The pilot study was carried out between August 2010 and December 2010. The research made important observations about the advanced prostate cancer journey. It showed that General Practitioner (GP) was the common source of patient's clinical records (41%) followed by Urologist (14%) and other clinicians (14%). The data analysis also showed that selenium was the common complementary supplement (55%) used by the patients and about 48% patients did not use any OTC drugs. The most common OTC used by the patients was Paracetamol (about 45%). The results have provided a foundation to the architecture of the proposed technology solution. The outcomes of this study are incorporated in design of the proposed patient journey browser system. A basic version of the system is currently being used at the advanced prostate cancer MDT meetings.

Clinical Usefulness of the Histoculture Drug Response Assay for Prostate Cancer and Benign Prostate Hypertrophy (BPH).

PubMed

Hoffman, Robert M

2018-01-01

The histoculture drug response assay (HDRA) has been adapted to determine androgen sensitivity in Gelfoam histoculture of human benign prostatic tissue as well as prostate cancer. Gelfoam histoculture was used to measure androgen-independent and androgen-dependent growth of benign and malignant prostate tissue. The androgen-sensitivity index was significantly higher in 23 paired specimens of prostate cancer compared to benign prostate hypertrophy (BPH). Genistein decreased the androgen-sensitivity index of BPH and prostate cancer in Gelfoam ® histoculture in a dose-dependent manner.

Point/Counterpoint: early detection of prostate cancer: do the benefits outweigh the consequences?

PubMed

Carroll, Peter R; Vickers, Andrew J

2014-05-01

Few clinical issues have polarized the oncology community as much as screening for prostate cancer, with advocates of prostate-specific antigen (PSA) testing vocal on one side and skeptics just as vocal on the other. At the NCCN 19th Annual Conference, Dr. Peter R. Carroll and Dr. Andrew J. Vickers tackled the controversy surrounding early detection of prostate cancer, focusing attention on the randomized trial results at the heart of the matter; over-detection (the Achilles' heel of screening); and the rationale behind the new, streamlined 2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection, which emphasize selective early detection and treatment and are tightly aligned with the NCCN Guidelines for Prostate Cancer. Copyright © 2014 by the National Comprehensive Cancer Network.

Vitamin D in prostate cancer.

PubMed

Trump, Donald L; Aragon-Ching, Jeanny B

2018-01-01

Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.

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.

ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer.

PubMed

Lev, Avital; Lulla, Amriti R; Ross, Brian C; Ralff, Marie D; Makhov, Petr B; Dicker, David T; El-Deiry, Wafik S

2018-05-01

Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target. Out of at least 15 AR-Vs described thus far, AR-V7 is the most abundant, and its expression correlates with ADT resistance. ONC201/TIC10 is the founding member of the imipridone class of small molecules and has shown anticancer activity in a broad range of tumor types. ONC201 is currently being tested in phase I/II clinical trials for advanced solid tumors, including mCRPC, and hematologic malignancies. There has been promising activity observed in patients in early clinical testing. This study demonstrates preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in both castration-resistant and -sensitive prostate cancer cells. Furthermore, the data demonstrate that ONC201 downregulates the expression of key drivers of prostate cancer such as AR-V7 and downstream target genes including the clinically used biomarker PSA (KLK3). Finally, the data also provide a preclinical rationale for combination of ONC201 with approved therapeutics for prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or docetaxel. Implications: The preclinical efficacy of ONC201 as a single agent or in combination, in hormone-sensitive or castration-resistant prostate cancer, suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5); 754-66. ©2018 AACR . ©2018 American Association for Cancer Research.

Can prostatic arterial embolisation (PAE) reduce the volume of the peripheral zone? MRI evaluation of zonal anatomy and infarction after PAE.

PubMed

Lin, Yen-Ting; Amouyal, Grégory; Correas, Jean-Michel; Pereira, Héléna; Pellerin, Olivier; Del Giudice, Costantino; Déan, Carole; Thiounn, Nicolas; Sapoval, Marc

2016-10-01

To assess the impact of prostatic arterial embolisation (PAE) on various prostate gland anatomical zones. We retrospectively reviewed paired MRI scans obtained before and after PAE for 25 patients and evaluated changes in volumes of the median lobe (ML), central gland (CG), peripheral zone (PZ) and whole prostate gland (WPV) following PAE. We used manual segmentation to calculate volume on axial view T2-weighted images for ML, CG and WPV. We calculated PZ volume by subtracting CG volume from WPV. Enhanced phase on dynamic contrasted-enhanced MRI was used to evaluate the infarction areas after PAE. Clinical results of International Prostate Symptom Score and International Index of Erectile Function questionnaires and the urodynamic study were evaluated before and after PAE. Significant reductions in volume were observed after PAE for ML (26.2 % decrease), CG (18.8 %), PZ (16.4 %) and WPV (19.1 %; p < 0.001 for all these volumes). Patients with clinical failure had smaller volume reductions for WPV, ML and CG (all p < 0.05). Patients with significant CG infarction after PAE displayed larger WPV, ML and CG volume reductions (all p < 0.01). PAE can significantly decrease WPV, ML, CG and PZ volumes, and poor clinical outcomes are associated with smaller volume reductions. • The MRI segmentation method provides detailed comparisons of prostate volume change. • Prostatic arterial embolisation (PAE) decreased central gland and peripheral zone volumes. • Prostates with infarction after PAE showed larger decreases in volume. • A larger decrease in prostate volume is associated with clinical success.

Early post-interventional sonographic evaluation of prostatic artery embolization. A promising role for contrast-enhanced ultrasonography (CEUS).

PubMed

Moschouris, Hippocrates; Stamatiou, Konstantinos; Kalokairinou Motogna, Mariana; Vrakas, Spyros; Kiltenis, Michail; Kladis-Kalentzis, Konstantinos; Tsavdaroglou, Avraam; Papadogeorgopoulos, Nikolaos; Marmaridou, Kyriaki; Malagari, Katerina

2018-05-02

To assess the feasibility, findings and potential value of early post-interventional, contrast-enhanced ultrasonographic (CEUS) study of prostate artery embolization (PAE). Fourteen patients treated with PAE for symptomatic benign prostatic hyperplasia were prospectively included in the study. Sonographic evaluation of the prostate included: 1) baseline transabdominal and transrectal CEUS (ta-CEUS and tr-CEUS, respectively) 1-3 days prior to PAE; 2) early post PAE CEUS, with ta-CEUS immediately post PAE and tr-CEUS 3 days post PAE; and 3) follow-up with ta-CEUS and tr-CEUS 3 months post PAE. A brief unenhanced US study preceded each CEUS. Post-therapeutic changes in size, echogenicity and enhancement of the prostate were recorded and were correlated with clinical outcomes. PAE resulted in clinical success in 11/14 patients (78.5%). All sonographic studies were technically adequate, with the exception of ta-CEUS immediately post PAE in 2/14 (14.2%) patients. CEUS studies immediately post PAE and 3 days post PAE showed non-enhancing, welldefined infarctions of the prostate in 10/14 patients (71.4%). There was a strong correlation between ta-CEUS immediately post PAE and tr-CEUS 3 days post PAE regarding the measurements of prostatic infarctions (r =0.98, p< 0.01). The presence of infarctions on early post PAE CEUS was associated with clinical success (p=0.01) and their extent correlated with the degree of prostate shrinkage on 3-month follow-up (r=0.84, p<0.05). The 3 cases of failed PAE showed no infarctions and no prostate shrinkage. Early post-interventional CEUS of PAE is feasible and may have clinical and prognostic value.

Neurophysiological localisation of ulnar neuropathy at the elbow: Validation of diagnostic criteria developed by a taskforce of the Danish Society of clinical neurophysiology.

PubMed

Pugdahl, K; Beniczky, S; Wanscher, B; Johnsen, B; Qerama, E; Ballegaard, M; Benedek, K; Juhl, A; Ööpik, M; Selmar, P; Sønderborg, J; Terney, D; Fuglsang-Frederiksen, A

2017-11-01

This study validates consensus criteria for localisation of ulnar neuropathy at elbow (UNE) developed by a taskforce of the Danish Society of Clinical Neurophysiology and compares them to the existing criteria from the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). The Danish criteria are based on combinations of conduction slowing in the segments of the elbow and forearm expressed in Z-scores, and difference between the segments in m/s. Examining fibres to several muscles and sensory fibres can increase the certainty of the localisation. Diagnostic accuracy for UNE was evaluated on 181 neurophysiological studies of the ulnar nerve from 171 peer-reviewed patients from a mixed patient-group. The diagnostic reference standard was the consensus diagnosis based on all available clinical, laboratory, and electrodiagnostic information reached by a group of experienced Danish neurophysiologists. The Danish criteria had high specificity (98.4%) and positive predictive value (PPV) (95.2%) and fair sensitivity (76.9%). Compared to the AANEM criteria, the Danish criteria had higher specificity (p<0.001) and lower sensitivity (p=0.02). The Danish consensus criteria for UNE are very specific and have high PPV. The Danish criteria for UNE are reliable and well suited for use in different centres as they are based on Z-scores. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

AEG-1 promoter-mediated imaging of prostate cancer

PubMed Central

Bhatnagar, Akrita; Wang, Yuchuan; Mease, Ronnie C.; Gabrielson, Matthew; Sysa, Polina; Minn, Il; Green, Gilbert; Simmons, Brian; Gabrielson, Kathleen; Sarkar, Siddik; Fisher, Paul B.; Pomper, Martin G.

2014-01-01

We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single photon emission-computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for non-invasive clinical imaging. Further, the approach compares favorably to accepted and emerging clinical standards, including positron emission tomography with [18F]fluorodeoxyglucose and [18F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer. PMID:25145668

Keratin 13 expression reprograms bone and brain metastases of human prostate cancer cells.

PubMed

Li, Qinlong; Yin, Lijuan; Jones, Lawrence W; Chu, Gina C-Y; Wu, Jason B-Y; Huang, Jen-Ming; Li, Quanlin; You, Sungyong; Kim, Jayoung; Lu, Yi-Tsung; Mrdenovic, Stefan; Wang, Ruoxiang; Freeman, Michael R; Garraway, Isla; Lewis, Michael S; Chung, Leland W K; Zhau, Haiyen E

2016-12-20

Lethal progression of prostate cancer metastasis can be improved by developing animal models that recapitulate the clinical conditions. We report here that cytokeratin 13 (KRT13), an intermediate filament protein, plays a directive role in prostate cancer bone, brain, and soft tissue metastases. KRT13 expression was elevated in bone, brain, and soft tissue metastatic prostate cancer cell lines and in primary and metastatic clinical prostate, lung, and breast cancer specimens. When KRT13 expression was determined at a single cell level in primary tumor tissues of 44 prostate cancer cases, KRT13 level predicted bone metastasis and the overall survival of prostate cancer patients. Genetically enforced KRT13 expression in human prostate cancer cell lines drove metastases toward mouse bone, brain and soft tissues through a RANKL-independent mechanism, as KRT13 altered the expression of genes associated with EMT, stemness, neuroendocrine/neuromimicry, osteomimicry, development, and extracellular matrices, but not receptor activator NF-κB ligand (RANKL) signaling networks in prostate cancer cells. Our results suggest new inhibitors targeting RANKL-independent pathways should be developed for the treatment of prostate cancer bone and soft tissue metastases.

Design and End Points of Clinical Trials for Patients With Progressive Prostate Cancer and Castrate Levels of Testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group

PubMed Central

Scher, Howard I.; Halabi, Susan; Tannock, Ian; Morris, Michael; Sternberg, Cora N.; Carducci, Michael A.; Eisenberger, Mario A.; Higano, Celestia; Bubley, Glenn J.; Dreicer, Robert; Petrylak, Daniel; Kantoff, Philip; Basch, Ethan; Kelly, William Kevin; Figg, William D.; Small, Eric J.; Beer, Tomasz M.; Wilding, George; Martin, Alison; Hussain, Maha

2014-01-01

Purpose To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. Methods A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. Results The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as “new lesions” or “no new lesions,” changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group. Conclusion PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit. PMID:18309951

Can one blood draw replace transrectal ultrasonography-estimated prostate volume to predict prostate cancer risk?

PubMed

Carlsson, Sigrid V; Peltola, Mari T; Sjoberg, Daniel; Schröder, Fritz H; Hugosson, Jonas; Pettersson, Kim; Scardino, Peter T; Vickers, Andrew J; Lilja, Hans; Roobol, Monique J

2013-09-01

To explore whether a panel of kallikrein markers in blood: total, free and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2, could be used as a non-invasive alternative for predicting prostate cancer on biopsy in a screening setting. The study cohort comprised previously unscreened men who underwent sextant biopsy owing to elevated PSA (≥3 ng/mL) in two different centres of the European Randomized Study of Screening for Prostate Cancer, Rotterdam (n = 2914) and Göteborg (n = 740). A statistical model, based on kallikrein markers, was compared with one based on established clinical factors for the prediction of biopsy outcome. The clinical tests were found to be no better than blood markers, with an area under the curve in favour of the blood measurements of 0.766 vs. 0.763 in Rotterdam and 0.809 vs. 0.774 in Göteborg. Adding digital rectal examination (DRE) or DRE plus transrectal ultrasonography (TRUS) volume to the markers improved discrimination, although the increases were small. Results were similar for predicting high-grade cancer. There was a strong correlation between the blood measurements and TRUS-estimated prostate volume (Spearman's correlation 0.60 in Rotterdam and 0.57 in Göteborg). In previously unscreened men, each with indication for biopsy, a statistical model based on kallikrein levels was similar to a clinical model in predicting prostate cancer in a screening setting, outside the day-to-day clinical practice. Whether a clinical approach can be replaced by laboratory analyses or used in combination with decision models (nomograms) is a clinical judgment that may vary from clinician to clinician depending on how they weigh the different advantages and disadvantages (harms, costs, time, invasiveness) of both approaches. © 2013 BJU International.

Prostate cancer risk prediction in a urology clinic in Mexico

PubMed Central

Liang, Yuanyuan; Messer, Jamie C; Louden, Christopher; Jimenez-Rios, Miguel A; Thompson, Ian M; Camarena-Reynoso, Hector R

2012-01-01

Objectives To evaluate factors affecting the risk of prostate cancer (PCa) and high-grade disease (HGPCa, Gleason score ≥7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC). Methods and Materials From a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerología, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of PCa, and history of a prior prostate biopsy on PCa and HGPCa separately. Internal discrimination, goodness-of-fit and clinical utility of the resulting models were assessed with comparison to the PCPTRC. Results Rates of both PCa (73.2%) and HGPCa (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of PCa but overestimated the risk of HGPCa. Four factors influencing PCa on biopsy were logPSA, DRE, family history and a prior biopsy history (all p<0.001). The internal AUC of the logistic model was 0.823 compared to 0.785 of the PCPTRC for PCa (p<0.001). The same four factors were significantly associated with HGPCa as well and the AUC was 0.779 compared to 0.766 of the PCPTRC for HGPCa (p=0.13). Conclusions Lack of screening programs or regular urological checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics. PMID:22306115

Magnetic resonance microscopy of prostate tissue: How basic science can inform clinical imaging development

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

Bourne, Roger

2013-03-15

This commentary outlines how magnetic resonance imaging (MRI) microscopy studies of prostate tissue samples and whole organs have shed light on a number of clinical imaging mysteries and may enable more effective development of new clinical imaging methods.

Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model

PubMed Central

Scher, Howard I.; Solo, Kirk; Valant, Jason; Todd, Mary B.; Mehra, Maneesha

2015-01-01

Objective To identify patient populations most in need of treatment across the prostate cancer disease continuum, we developed a novel dynamic transition model based on risk of disease progression and mortality. Design and Outcome Measurements We modeled the flow of patient populations through eight prostate cancer clinical states (PCCS) that are characterized by the status of the primary tumor, presence of metastases, prior and current treatment, and testosterone levels. Simulations used published US incidence rates for each year from 1990. Progression and mortality rates were derived from published clinical trials, meta-analyses, and observational studies. Model outputs included the incidence, prevalence, and mortality for each PCCS. The impact of novel treatments was modeled in three distinct scenarios: metastatic castration-resistant prostate cancer (mCRPC), non-metastatic CRPC (nmCRPC), or both. Results and Limitations The model estimated the prevalence of prostate cancer as 2,219,280 in the US in 2009 and 3,072,480 in 2020, and incidence of mCRPC as 36,100 and 42,970, respectively. All-cause mortality in prostate cancer was estimated at 168,290 in 2009 and 219,360 in 2020, with 20.5% and 19.5% of these deaths, respectively, occurring in men with mCRPC. The majority (86%) of incidence flow into mCRPC states was from the nmCRPC clinical state. In the scenario with novel interventions for nmCRPC states, the progression to mCRPC is reduced, thus decreasing mCRPC incidence by 12% in 2020, with a sustained decline in mCRPC mortality. A limitation of the model is that it does not estimate prostate cancer—specific mortality. Conclusion The model informs clinical trial design for prostate cancer by quantifying outcomes in PCCS, and demonstrates the impact of an effective therapy applied in an earlier clinical state of nmCRPC on the incidence of mCRPC morbidity and subsequent mortality. PMID:26460686

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

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

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance.more » BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.« less

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications.

PubMed

Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M

2016-01-01

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

Predicting the Presence of Clinically Significant Prostate Cancer using Multiparametric MRI and MR-US Fusion Biopsy | Division of Cancer Prevention

Cancer.gov

Prostate cancer is the second leading cause of cancer death in American men, accounting for 26% of new cancer diagnoses and 9% of cancer deaths in men. Active surveillance, radical prostatectomy and radiotherapy are commonly used treatments for clinically localized prostate cancer. However, current risk stratification methods cannot be used effectively to avoid subjecting

The clinical effectiveness and cost-effectiveness of the PROGENSA® prostate cancer antigen 3 assay and the Prostate Health Index in the diagnosis of prostate cancer: a systematic review and economic evaluation.

PubMed

Nicholson, Amanda; Mahon, James; Boland, Angela; Beale, Sophie; Dwan, Kerry; Fleeman, Nigel; Hockenhull, Juliet; Dundar, Yenal

2015-10-01

There is no single definitive test to identify prostate cancer in men. Biopsies are commonly used to obtain samples of prostate tissue for histopathological examination. However, this approach frequently misses cases of cancer, meaning that repeat biopsies may be necessary to obtain a diagnosis. The PROGENSA(®) prostate cancer antigen 3 (PCA3) assay (Hologic Gen-Probe, Marlborough, MA, USA) and the Prostate Health Index (phi; Beckman Coulter Inc., Brea, CA, USA) are two new tests (a urine test and a blood test, respectively) that are designed to be used to help clinicians decide whether or not to recommend a repeat biopsy. To evaluate the clinical effectiveness and cost-effectiveness of the PCA3 assay and the phi in the diagnosis of prostate cancer. Multiple publication databases and trial registers were searched in May 2014 (from 2000 to May 2014), including MEDLINE, EMBASE, The Cochrane Library, ISI Web of Science, Medion, Aggressive Research Intelligence Facility database, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number Register and World Health Organization International Clinical Trials Registry Platform. The assessment of clinical effectiveness involved three separate systematic reviews, namely reviews of the analytical validity, the clinical validity of these tests and the clinical utility of these tests. The assessment of cost-effectiveness comprised a systematic review of full economic evaluations and the development of a de novo economic model. The perspective of the evaluation was the NHS in England and Wales. Men suspected of having prostate cancer for whom the results of an initial prostate biopsy were negative or equivocal. The use of the PCA3 score or phi in combination with existing tests (including histopathology results, prostate-specific antigen level and digital rectal examination), multiparametric magnetic resonance imaging and clinical judgement. In addition to documents published by the manufacturers, six studies were identified for inclusion in the analytical validity review. The review identified issues concerning the precision of the PCA3 assay measurements. It also highlighted issues relating to the storage requirements and stability of samples intended for analysis using the phi assay. Fifteen studies met the inclusion criteria for the clinical validity review. These studies reported results for 10 different clinical comparisons. There was insufficient evidence to enable the identification of appropriate test threshold values for use in a clinical setting. In addition, the implications of adding either the PCA3 assay or the phi to clinical assessment were not clear. Furthermore, the addition of the PCA3 assay or the phi to clinical assessment plus magnetic resonance imaging was not found to improve discrimination. No published papers met the inclusion criteria for either the clinical utility review or the cost-effectiveness review. The results from the cost-effectiveness analyses indicated that using either the PCA3 assay or the phi in the NHS was not cost-effective. The main limitations of the systematic review of clinical validity are that the review conclusions are over-reliant on findings from one study, the descriptions of clinical assessment vary widely within reviewed studies and many of the reported results for the clinical validity outcomes do not include either standard errors or confidence intervals. The clinical benefit of using the PCA3 assay or the phi in combination with existing tests, scans and clinical judgement has not yet been confirmed. The results from the cost-effectiveness analyses indicate that the use of these tests in the NHS would not be cost-effective. This study is registered as PROSPERO CRD42014009595. The National Institute for Health Research Health Technology Assessment programme.

The impact of prostate artery embolization (PAE) on the the physical history and pathophysiology of benign prostatic hyperplasia (BPH).

PubMed

Stamatiou, Konstantinos

2018-03-31

Prostate artery embolization (PAE) is a non invasive modality for the treatment of benign prostate hypertrophy (BPH) related lower urinary tract symptoms (LUTS). As a relatively new procedure, data determining the clinical success is somehow scarce. In the present article we examine the current clinical outcome measures in order to identify the most accurate. Current imaging outcome measures are consistent with clinical ones only in the group of patients with adenomatous- dominant BPH while are inconsistent in patients with small sized adenomas. Additional studies and/or evaluation tools are needed in order to provide accurate evaluation of clinical success in the subgroup of patients with non- adenomatous-dominant BPH while they may inspire new options and novel techniques for both BPH treatment and treatment-follow up.

Malakoplakia of the Prostate as a Mimicker of Prostate Cancer on Prostate Health Index and Magnetic Resonance Imaging-Fusion Prostate Biopsy: A Case Report.

PubMed

Heah, Nathaniel H; Tan, Teck Wei; Tan, Yung Khan

2017-01-01

Background: Isolated malakoplakia of the prostate is a rare inflammatory condition that has been clinically mistaken for prostatic malignancies. The development of Prostate Imaging Reporting and Data System (PI-RADS) classifications, and Prostate Health Index (PHI) has led to more accurate diagnosis of clinically significant disease and stratification of patients that may be at risk of prostate cancer. Case Presentation: We present a case of a 75-year-old male who was on follow-up with our hospital for elevated prostate specific antigen (PSA). He was admitted for an episode of urosepsis, which was treated with antibiotics and subsequently underwent further workup and was found to have a raised PHI, as well as a high PI-RADS classification and was later found to have malakoplakia based on histology of prostate tissue obtained during targeted magnetic resonance imaging (MRI)-guided fusion prostate biopsy. Conclusion: To our understanding, this is the first case where a prostate lesion has been labeled as a PI-RADS 5 lesion, with elevated PHI that has subsequently been proven histologically to be malakoplakia. An important possible confounder is the interval between the MRI and the episode of urosepsis and it is well known that urosepsis can affect the PSA and MRI result. We present this case to highlight the potential for a false diagnosis of prostate cancer, in spite of laboratory and radiological findings.

Genetics of Prostate Cancer (PDQ®)—Health Professional Version

Cancer.gov

Familial prostate cancer is associated with certain inherited gene mutations (variants). Learn about the hereditary prostate cancer genes, genetic testing, clinical management, and psychosocial issues in this expert-reviewed summary.

Prostate cancer in young adults-Seventeen-year clinical experience of a single center.

PubMed

Huang, Tzu-Hao; Kuo, Junne-Yih; Huang, Yi-Hsiu; Chung, Hsiao-Jen; Huang, William J S; Wu, Howard H H; Chang, Yen-Hwa; Lin, Alex T L; Chen, Kuang-Kuo

2017-01-01

In the general population, prostate adenocarcinoma affects predominately older men. If fact, most current guidelines suggest that males over the age of 50 years should undergo prostate cancer screening. However, the clinical behavior and prognosis of prostate cancer in young adults is not well defined. The aim of this study was to evaluate the clinical behavior, pathological characteristics, and prognosis of prostate cancer in young adults. We retrospectively reviewed the records of young patients (age, ≤50 years) in our hospital with prostate adenocarcinoma between 1997 and 2013. We compared data including initial presentation, cancer cell type, Gleason score, disease stage, prostate-specific antigen (PSA) level, prostate volume, treatment, and survival between patients both younger and older than 50 years. Data were analyzed using the Kaplan-Meier method to assess survival. Twenty-six patients were enrolled in our study, accounting for 0.55% of all patients with a diagnosis of prostate cancer at our facility. All 26 patients had a pathology diagnosis of adenocarcinoma, with a mean age on diagnosis of 46.8±2.8 years (range, 39-50 years). On initial presentation, patients older than 50 years more frequently displayed lower urinary tract symptoms (LUTS) than younger patients (62.3% vs. 30.4%, p=0.008). There was no statistical difference in histological grade, disease stage, PSA level, overall survival, and biochemical-free survival between the two groups. The result of our investigation indicated that prostate adenocarcinoma patients younger than 50 years had similar histological grade, disease stage, PSA level, overall survival, and biochemical-free survival as the older population. However, patients younger than 50 years with prostate cancer less frequently showed initial symptoms of LUTS. Copyright © 2016. Published by Elsevier Taiwan LLC.

Clinical and histopathological characteristics of patients with prostate cancer in the BioBank Japan project.

PubMed

Ukawa, Shigekazu; Nakamura, Koshi; Okada, Emiko; Hirata, Makoto; Nagai, Akiko; Yamagata, Zentaro; Muto, Kaori; Matsuda, Koichi; Ninomiya, Toshiharu; Kiyohara, Yutaka; Kamatani, Yoichiro; Kubo, Michiaki; Nakamura, Yusuke; Tamakoshi, Akiko

2017-03-01

Prostate cancer is the sixth leading cause of cancer-related deaths in Japan. We aimed to elucidate the clinical and histopathological characteristics of patients with prostate cancer in the BioBank Japan (BBJ) project. Four thousand, seven hundred and ninety-three patients diagnosed with prostate cancer in the BBJ project were included. Clinical and histopathological data, including causes of death, were analyzed. Relative survival (RS) rates of prostate cancer were calculated. Four thousand, one hundred and seventy-one prostate cancer patients with available histological data had adenocarcinoma. The mean age of the patients was 72.5 years. The proportion of patients who were non-smokers, non-drinkers, had a normal body mass index, did not exercise, had a normal prostate-specific antigen level, and had a family history of prostate cancer were 30.7%, 28.0%, 66.6%, 58.1%, 67.6%, and 6.5%, respectively. The proportion of patients with Stage II, III, and IV disease were 24.4%, 7.3%, and 4.4%, respectively. After limiting to patients with a time from the initial diagnosis of prostate cancer to entry into the study cohort of ≤90 days (n = 869), the 5- and 10-year RS rates were 96.3% and 100.5%, respectively, although we were unable to consider management strategies due to a plenty of data missing. We provide an overview of patients with prostate cancer in the BBJ project. Our findings, coupled with those from various high throughput "omics" technologies, will contribute to the implementation of prevention interventions and medical management of prostate cancer patients. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Prostate ultrasound--for urologists only?

PubMed

Frauscher, Ferdinand; Gradl, Johann; Pallwein, Leo

2005-11-23

The value of ultrasound (US) in the diagnosis of prostate cancer has dramatically increased in the past decade. This is mainly related to the increasing incidence of prostate cancer, the most common cancer in men and one of the most important causes of death from cancer in men. The value of conventional gray-scale US for prostate cancer detection has been extensively investigated, and has shown a low sensitivity and specificity. Therefore conventional gray-scale US is mainly used by urologists for guiding systematic prostate biopsies. With the development of new US techniques, such as color and power Doppler US, and the introduction of US contrast agents, the role of US for prostate cancer detection has dramatically changed. Advances in US techniques were introduced to further increase the value of US contrast agents. Although most of these developments in US techniques, which use the interaction of the contrast agent with the transmitted US waves, are very sensitive for the detection of microbubbles, they are mostly unexplored, in particular for prostate applications. Early reports of contrast-enhanced US investigations of blood flow of the prostate have shown that contrast-enhanced US adds important information to the conventional gray-scale US technique. Furthermore, elastography or 'strain imaging' seems to have great potential in prostate cancer detection. Since these new advances in US are very sophisticated and need a long learning curve, radiologists, who are overall better trained with these new US techniques, will play a more important role in prostate cancer diagnosis. Current trends show that these new US techniques may allow for targeted biopsies and therefore replace the current 'gold standard' for prostate cancer detection--the systematic biopsy. Consequently the use of these new US techniques for the detection and clinical staging of prostate cancer is promising. However, future clinical trials will be needed to determine if the promise of these new US advances of the prostate evolves into clinical application. International Cancer Imaging Society.

Alteration of Antithrombin III and D-dimer Levels in Clinically Localized Prostate Cancer

PubMed Central

Ko, Dong Woo; Park, Juhyun; Kim, In Sung; Doo, Seung Hwan; Yoon, Cheol Yong; Park, Hongzoo; Lee, Won Ki; Kim, Dae Sung; Jeong, Seong Jin; Byun, Seok-Soo; Lee, Sang Eun

2010-01-01

Purpose We performed a comparative analysis of the plasma levels of antithrombin (AT) III, plasminogen, fibrinogen, and D-dimer among patients with and without clinically localized prostate cancer to investigate the clinical significance of the coagulation profile in prostate cancer. Materials and Methods A prospective study was performed in which plasma levels of AT III, plasminogen, fibrinogen, and D-dimer were assessed in patients before they underwent prostate biopsy. According to the results of the biopsy, the patients were categorized into the cancer group or the control group. Levels of the four coagulation factors were then compared between the cancer and control groups. Also, levels of the four coagulation factors were correlated with tumor stage and grade in the cancer group. Results The cancer group had significantly lower levels of AT III activity and higher plasma D-dimer levels than did the control group (p=0.007 and p=0.018, respectively). Within the cancer group, no significant differences were observed in the levels of AT III, plasminogen, fibrinogen, or D-dimer between those with a pathological Gleason score of ≥7 and otherwise. Regarding pathologic stage of prostate cancer, the subjects with organ-confined disease and those with extraprostatic extension of a tumor demonstrated no significant differences in the preoperative levels of the four coagulation factors analyzed. Conclusions Our results suggest that plasma levels of AT III and D-dimer are altered in patients with prostate cancer. Further study is needed to elucidate the underlying mechanism and clinical significances of such a phenomenon among patients with clinically localized prostate cancer. PMID:20414406

Nc886 is epigenetically repressed in prostate cancer and acts as a tumor suppressor through the inhibition of cell growth.

PubMed

Fort, Rafael Sebastián; Mathó, Cecilia; Geraldo, Murilo Vieira; Ottati, María Carolina; Yamashita, Alex Shimura; Saito, Kelly Cristina; Leite, Katia Ramos Moreira; Méndez, Manuel; Maedo, Noemí; Méndez, Laura; Garat, Beatriz; Kimura, Edna Teruko; Sotelo-Silveira, José Roberto; Duhagon, María Ana

2018-02-02

Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer. Nc886 promoter methylation status and its correlation with patient clinical parameters or DNMTs levels were evaluated in TCGA and specific GEO prostate tissue datasets. Nc886 level was measured by RT-qPCR to compare normal/neoplastic prostate cells from radical prostatectomies and cell lines, and to assess nc886 response to demethylating agents. The effect of nc886 recovery in cell proliferation (in vitro and in vivo) and invasion (in vitro) was evaluated using lentiviral transduced DU145 and LNCaP cell lines. The association between the expression of nc886 and selected genes was analyzed in the TCGA-PRAD cohort. Nc886 promoter methylation increases in tumor vs. normal prostate tissue, as well as in metastatic vs. normal prostate tissue. Additionally, nc886 promoter methylation correlates with prostate cancer clinical staging, including biochemical recurrence, Clinical T-value and Gleason score. Nc886 transcript is downregulated in tumor vs. normal tissue -in agreement with its promoter methylation status- and increases upon demethylating treatment. In functional studies, the overexpression of nc886 in the LNCaP and DU145 cell line leads to a decreased in vitro cell proliferation and invasion, as well as a reduced in vivo cell growth in NUDE-mice tumor xenografts. Finally, nc886 expression associates with the prostate cancer cell cycle progression gene signature in TCGA-PRAD. Our data suggest a tumor suppressor role for nc886 in the prostate, whose expression is epigenetically silenced in cancer leading to an increase in cell proliferation and invasion. Nc886 might hold clinical value in prostate cancer due to its association with clinical parameters and with a clinically validated gene signature.

Prostate-specific membrane antigen-based imaging in prostate cancer: impact on clinical decision making process.

PubMed

Demirkol, Mehmet Onur; Acar, Ömer; Uçar, Burcu; Ramazanoğlu, Sultan Rana; Sağlıcan, Yeşim; Esen, Tarık

2015-05-01

There is an ongoing need for an accurate imaging modality which can be used for staging purposes, metastatic evaluation, predicting biologic aggresiveness and investigating recurrent disease in prostate cancer. Prostate specific membrane antigen, given its favorable molecular characteristics, holds a promise as an ideal target for prostate cancer-specific nuclear imaging. In this study, we evaluated our initial results of PSMA based PET/CT imaging in prostate cancer. A total of 22 patients with a median age and serum PSA level of 68 years and 4.15 ng/ml, respectively underwent Ga-68 PSMA PET/CT in our hospital between Februrary and August 2014. Their charts were retrospectively reviewed in order to document the clinical characteristics, the indications for and the results of PSMA based imaging and the impact of Ga-68 PSMA PET/CT findings on disease management. The most common indications were rising PSA after local ± adjuvant treatment followed by staging and metastatic evaluation before definitive or salvage treatment. All except 2 patients had prostatic ± extraprostatic PSMA positive lesions. For those who had a positive result; treatment strategies were tailored accordingly. Above the PSA level of 2 ng/ml, none of the PSMA based nuclear imaging studies revealed negative results. PSMA based nuclear imaging has significantly impacted our way of handling patients with prostate cancer. Its preliminary performance in different clinical scenarios and ability to detect lesions even in low PSA values seems fairly promising and deserves to be supplemented with further clinical studies. © 2015 Wiley Periodicals, Inc.

A Pitfall in Transrectal Prostate Biopsy: Malakoplakia Evaluation of Two Cases Based on the Literature Review

PubMed Central

Solakoglu Kahraman, Dudu; Sayhan, Sevil; Diniz, Gulden; Ayaz, Duygu; Karadeniz, Tugba; Can, Ertan

2014-01-01

Malakoplakia is a rarely seen inflammatory condition that is considered to develop secondary to a chronic Escherichia coli infection. Although malakoplakia usually affects the genitourinary tract, it may also be observed in the colon, stomach, lungs, liver, bones, uterus, and skin. Malakoplakia of the genitourinary system usually involves the bladder, whereas it may also affect the prostate along with the bladder. Malakoplakia of the prostate is very rare, and it may be clinically mistaken for prostatic malignancies. Definitive diagnosis is only possible through histopathological examination. This study elaborates on two patients who presented to our hospital in 2013 with high PSA levels. The primary clinical consideration was prostate carcinoma. However, these two cases were diagnosed as malakoplakia based on the results of histopathological analysis of the transrectal prostate biopsy specimen. PMID:24868476

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

Vitamin D in prostate cancer

PubMed Central

Trump, Donald L; Aragon-Ching, Jeanny B

2018-01-01

Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited. PMID:29667615

Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

PubMed

Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

2015-05-01

The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

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

A Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous Cohorts.

PubMed

Ankerst, Donna P; Straubinger, Johanna; Selig, Katharina; Guerrios, Lourdes; De Hoedt, Amanda; Hernandez, Javier; Liss, Michael A; Leach, Robin J; Freedland, Stephen J; Kattan, Michael W; Nam, Robert; Haese, Alexander; Montorsi, Francesco; Boorjian, Stephen A; Cooperberg, Matthew R; Poyet, Cedric; Vertosick, Emily; Vickers, Andrew J

2018-05-16

Prostate cancer prediction tools provide quantitative guidance for doctor-patient decision-making regarding biopsy. The widely used online Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) utilized data from the 1990s based on six-core biopsies and outdated grading systems. We prospectively gathered data from men undergoing prostate biopsy in multiple diverse North American and European institutions participating in the Prostate Biopsy Collaborative Group (PBCG) in order to build a state-of-the-art risk prediction tool. We obtained data from 15 611 men undergoing 16 369 prostate biopsies during 2006-2017 at eight North American institutions for model-building and three European institutions for validation. We used multinomial logistic regression to estimate the risks of high-grade prostate cancer (Gleason score ≥7) on biopsy based on clinical characteristics, including age, prostate-specific antigen, digital rectal exam, African ancestry, first-degree family history, and prior negative biopsy. We compared the PBCG model to the PCPTRC using internal cross-validation and external validation on the European cohorts. Cross-validation on the North American cohorts (5992 biopsies) yielded the PBCG model area under the receiver operating characteristic curve (AUC) as 75.5% (95% confidence interval: 74.2-76.8), a small improvement over the AUC of 72.3% (70.9-73.7) for the PCPTRC (p<0.0001). However, calibration and clinical net benefit were far superior for the PBCG model. Using a risk threshold of 10%, clinical use of the PBCG model would lead to the equivalent of 25 fewer biopsies per 1000 patients without missing any high-grade cancers. Results were similar on external validation on 10 377 European biopsies. The PBCG model should be used in place of the PCPTRC for prediction of prostate biopsy outcome. A contemporary risk tool for outcomes on prostate biopsy based on the routine clinical risk factors is now available for informed decision-making. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Long-term outcomes in younger men following permanent prostate brachytherapy.

PubMed

Shapiro, Edan Y; Rais-Bahrami, Soroush; Morgenstern, Carol; Napolitano, Barbara; Richstone, Lee; Potters, Louis

2009-04-01

We reviewed the long-term outcomes in men undergoing permanent prostate brachytherapy with a focus on those presenting before age 60 years. Between 1992 and 2005 a total of 2,119 patients with clinical stage T1-T2, N0, M0 prostate cancer treated with permanent prostate brachytherapy were included in this study. Treatment regimens consisted of permanent prostate brachytherapy with or without hormone therapy, permanent prostate brachytherapy with external beam radiotherapy, or all 3 modalities. Biochemical recurrence was defined using the Phoenix definition. Multivariate analysis was performed to determine if age and/or other clinicopathological features were associated with disease progression. The Kaplan-Meier method was used to calculate rates of freedom from progression with the log rank test to compare patients younger than 60 vs 60 years or older. Median followup was 56.1 months. In the study population 237 patients were younger than 60 years at diagnosis (11%). The 5 and 10-year freedom from progression rates were 90.1% and 85.6%, respectively, for the entire population. Multivariate analysis demonstrated that prostate specific antigen (p <0.01), biopsy Gleason score (p <0.0001) and year of treatment (p <0.001) were associated with freedom from progression while age (p = 0.95) and clinical stage (p = 0.11) were not. There was no significant difference in freedom from progression between men younger than 60, or 60 years or older (log rank p = 0.46). In the younger cohort the 10-year freedom from progression for patients presenting with low, intermediate and high risk disease was 91.3%, 80.0% and 70.2% compared to 91.8%, 83.4% and 72.1%, respectively, for men 60 years or older. Our long-term results confirm favorable outcomes after permanent prostate brachytherapy in men younger than 60 years. Outcomes are impacted by disease related risk factors but not by age or clinical stage. Definitive treatment options for younger men with clinically localized prostate cancer should include permanent prostate brachytherapy.

Evaluation of a novel label-free photonic-crystal biosensor imaging system for the detection of prostate cancer cells

NASA Astrophysics Data System (ADS)

DeLuna, Frank; Ding, XiaoFie; Sun, Lu-Zhe; Ye, Jing Yong

2017-02-01

Biomarker screening for prostate-specific antigen (PSA) is the current clinical standard for detection of prostate cancer. However this method has shown many limitations, mainly in its specificity, which can lead to a high false positive rate. Thus, there is a growing need in developing a more specific detection system for prostate cancer. Using a Photonic- Crystal-based biosensor in a Total-Internal-Reflection (PC-TIR) configuration, we demonstrate the use of refractive index (RI) to accomplish label-free detection of prostate cancer cells against non-cancerous prostate epithelial cells. The PC-TIR biosensor possesses an open microcavity, which in contrast to traditional closed microcavities, allows for easier access of analyte molecules or cells to interact with its sensing surface. In this study, an imaging system was designed using the PC-TIR biosensor to quantify cell RI as the contrast parameter for prostate cancer detection. Non-cancerous BPH-1 prostate epithelial cells and prostate cancer PC-3 cells were placed on a single biosensor and measured concurrently. Recorded image data was then analyzed through a home-built MatLab program. Results demonstrate that RI is a suitable variable for differentiation between prostate cancer cells and non-cancerous prostate epithelial cells. Our study shows clinical potential in utilizing RI test for the detection of prostate cancer.

Beyond immune checkpoint blockade: new approaches to targeting host-tumor interactions in prostate cancer: report from the 2014 Coffey-Holden prostate cancer academy meeting.

PubMed

Miyahira, Andrea K; Kissick, Haydn T; Bishop, Jennifer L; Takeda, David Y; Barbieri, Christopher E; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2015-03-01

The 2014 Coffey-Holden Prostate Cancer Academy Meeting, held in La Jolla, CA from June 26 to 29, 2014, was themed: "Beyond Immune Checkpoint Blockade: New Approaches to Targeting Host-Tumor Interactions in Prostate Cancer." Sponsored by the Prostate Cancer Foundation (PCF), this annual, invitation-only meeting is structured as an action-tank, and brought together 72 investigators with diverse academic backgrounds to discuss the most relevant topics in the fields of prostate cancer immunotherapy and the tumor microenvironment. The questions addressed at the meeting included: mechanisms underlying the successes and failures of prostate cancer immunotherapies, how to trigger an effective immune response against prostate cancer, the tumor microenvironment and its role in therapy resistance and tumor metastasis, clinically relevant prostate cancer mouse models, how host-tumor interactions affect current therapies and tumor phenotypes, application of principles of precision medicine to prostate cancer immunotherapy, optimizing immunotherapy clinical trial design, and complex multi-system interactions that affect prostate cancer and immune responses including the effects of obesity and the potential role of the host microbiome. This article highlights the most significant recent progress and unmet needs that were discussed at the meeting toward the goal of speeding the development of optimal immunotherapies for the treatment of prostate cancer. © 2014 Wiley Periodicals, Inc.

Diagnosis and treatment of bacterial prostatitis.

PubMed

Videčnik Zorman, Jerneja; Matičič, Mojca; Jeverica, Samo; Smrkolj, Tomaž

2015-01-01

Prostate inflammation is a common syndrome, especially in men under 50. It usually presents with voiding symptoms and pain in the genitourinary area, and sometimes as sexual dysfunction. Based on clinical and laboratory characteristics, prostatitis is classified as acute bacterial prostatitis, chronic bacterial prostatitis, chronic inflammatory and non-inflammatory prostatitis or chronic pelvic pain syndrome, and asymptomatic inflammatory prostatitis. Bacterial prostatitis is most often caused by infection with uropathogens, mainly Gram-negative bacilli, but Gram-positive and atypical microorganisms have also been identified as causative organisms of chronic prostatitis. According to reports by several authors, Chlamydia trachomatis and Trichomonas vaginalis are some of the most common pathogens, making chronic prostatitis a sexually transmitted disease. Diagnosis and treatment of acute and chronic bacterial prostatitis in particular can be challenging.

Fear of new or recurrent melanoma after treatment for localised melanoma.

PubMed

Bell, Katy J L; Mehta, Yachna; Turner, Robin M; Morton, Rachael L; Dieng, Mbathio; Saw, Robyn; Guitera, Pascale; McCaffery, Kirsten; Low, Donald; Low, Cynthia; Jenkins, Marisa; Irwig, Les; Webster, Angela C

2017-11-01

To estimate the amount of fear of new or recurrent melanoma among people treated for localised melanoma in an Australian specialist centre. We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores. Two hundred fifteen people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was 15.0 (95% CI 14.0-16.1). A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores ≥13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores ≥16). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma. There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

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 .).

21 CFR 862.1020 - Acid phosphatase (total or prostatic) test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Acid phosphatase (total or prostatic) test system. 862.1020 Section 862.1020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1020 - Acid phosphatase (total or prostatic) test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Acid phosphatase (total or prostatic) test system. 862.1020 Section 862.1020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1020 - Acid phosphatase (total or prostatic) test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Acid phosphatase (total or prostatic) test system. 862.1020 Section 862.1020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1020 - Acid phosphatase (total or prostatic) test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Acid phosphatase (total or prostatic) test system. 862.1020 Section 862.1020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1020 - Acid phosphatase (total or prostatic) test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Acid phosphatase (total or prostatic) test system. 862.1020 Section 862.1020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

Biomarkers for Early Detection of Clinically Relvant Prostate Cancer: A Multi-Institutional Validation Trial - Genomic Health, Inc. — EDRN Public Portal

Cancer.gov

Validate a panel of tissue-based biomarkers to determine the presence of or progression to clinically relevant prostate cancer at the time of diagnosis. Utilize a novel, biopsy based multi-gene quantitative RT-PCR assay developed by Genomic Health, Oncotype DX Prostate Cancer Assay, which discriminates aggressive from indolent cancer on multivariate modeling of PCa patients.

Prevalence of Trichomonas vaginalis by PCR in men attending a primary care urology clinic in South Korea.

PubMed

Seo, Jun-Hyeok; Yang, Hye-Won; Joo, So-Young; Song, Su-Min; Lee, Yu-Ran; Ryu, Jae-Sook; Yoo, Eun Sang; Lee, Won Kee; Kong, Hyun-Hee; Lee, Sang-Eun; Lee, Won-Ja; Goo, Youn-Kyoung; Chung, Dong-Il; Hong, Yeonchul

2014-10-01

Trichomonas vaginalis, a causative agent of trichomoniasis, may trigger symptomatic or asymptomatic nongonococcal urethritis and chronic prostatitis in men. Despite the availability of highly sensitive diagnostic tests, such as nucleic acid amplification tests, including PCR, few prospective studies present data on male T. vaginalis infection in South Korea. In the present study, the prevalence of T. vaginalis and associated clinical conditions were evaluated in 201 male patients from a primary care urology clinic in South Korea. The prevalence of T. vaginalis infection in our cohort was 4% (8/201) by PCR. T. vaginalis infection was common in men older than 40 years (median age, 52 years). Among the 8 Trichomonas-positive patients, 87.5% (7/8) had prostatic diseases, such as prostatitis and benign prostatic hyperplasia, and 25.0% (2/8) and 12.5% (1/8) were coinfected with Chlamydia trachomatis and Mycoplasma genitalium, respectively. Our results suggest that T. vaginalis infection is not rare in men attending primary care urology clinics in South Korea, especially in those older than 40 years, in whom it may explain the presence of prostatic disease. The possibility of T. vaginalis infection should be routinely considered in older male patients with prostatic diseases in South Korea.

Prostate Cancer Screening Results from PLCO

Cancer.gov

Learn the results of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a large-scale clinical trial to determine whether certain cancer screening tests can help reduce deaths from prostate, lung, colorectal, and ovarian cancer.

Physical examination and history-taking skills in a prostate clinic.

PubMed

Wareing, Mark

The proliferation of nurse-led initiatives arising from nurse specialist/practitioner posts in urology is reflected in areas such as the management of bladder cancer, erectile dysfunction, stoma care, and prostate disease. The establishment of the role of urology specialist nurse in one North Oxfordshire hospital led to the development of a nurse-led prostate assessment clinic for male patients with lower urinary tract symptoms arising from benign prostatic hyperplasia. A description of how training was conducted, and the subsequent reappraisal of competency, is given in relation to physical examination and history-taking skills necessary for the development of this initiative.

Cabazitaxel for the treatment of prostate cancer.

PubMed

Michielsen, Dirk P J; Braeckman, Johan G; Denis, Louis

2011-04-01

Prostate cancer is a frequently diagnosed male cancer. In men presenting locally advanced or metastatic disease, the mainstay of treatment is hormonal suppression. Despite the castrate levels of testosterone, with time, prostate cancer gradually evolves into a castration-refractory state. Chemotherapeutic agents are able to influence the natural history of metastatic castration-resistant prostate cancer. Docetaxel is a clinically relevant, FDA-approved taxane. Today, it is the first-line chemotherapeutic agent in castration-refractory prostate cancer (CRPC). There is no standard second-line chemotherapeutic regimen. This review provides information on the efficacy of cabazitaxel as a second-line treatment for CRPC. The medline database was searched for clinical trials on chemotherapeutical treatment options of castration-resistant prostate cancer. All available data on the efficacy of cabazitaxel are summarized. New treatment strategies for castration-resistant prostate cancer should primarily focus on quality of life. In this view, vaccination therapy seems promising because of the acceptable level of toxicity. However, more research is needed to prove their efficacy in the treatment of castration-resistant prostate cancer. Cabazitaxel seems to be a promising second-line therapy in CRPC.

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.

Role of prostate artery embolization in the management of refractory haematuria of prostatic origin.

PubMed

Pereira, Keith; Halpern, Joshua A; McClure, Timothy D; Lewis, Nicholas A; Kably, Isaam; Bhatia, Shivank; Hu, Jim C

2016-09-01

Prostatic haematuria is among the most common genitourinary complaints of emergency room visits, distressing and troublesome to men and a challenging clinical problem to the treating physician. The most common aetiologies of prostatic haematuria include benign prostatic hyperplasia and prostate cancer. Prostatic haematuria usually resolves with conservative and medical methods; failure of these interventions results in refractory haematuria of prostatic origin (RHPO), a potentially life-threatening scenario. Several different treatments have been described, with varying degrees of success. Patients with RHPO are often elderly and unfit for radical surgery. Prostate artery embolization (PAE) has evolved as a safe and effective technique in the management of RHPO. Use of a superselective approach optimizes clinical success while minimizing complications. This minimally invasive approach improves patients with haemodynamic instability, serves as a bridge to elective surgery, and is a highly effective treatment for RHPO. It may obviate the need for more invasive and morbid surgical therapies. The aim of the present review was to describe the current management of RHPO and the technique of PAE and to review its efficacy and associated morbidity. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Lessons Learned from Implementing a Prostate Cancer Risk Assessment Program for Underserved High-Risk Men in the Community: the Prostate REACH Project.

PubMed

Fleisher, Linda; Davis, Stacy N; Gross, Laura; Bagden, Loretta; Zakrzewski, Debra; González, Evelyn; Kandadai, Venk; Rusten, Cheryl; Baskett, Jerilyn; Obeid, Elias; Giri, Veda N

2016-03-01

Prostate cancer disproportionately affects Black men, who may also encounter barriers to participation in prostate cancer risk assessment. The Prostate Risk, Education and Assessment in the Community with Help (REACH) project was a community-based extension of a comprehensive prostate cancer risk assessment program at a comprehensive cancer center. The goals of the REACH project were the following: (1) establish a community prostate cancer risk assessment clinic, (2) conduct targeted recruitment, and (3) provide navigation services including follow-up for uninsured men. Key implementation steps included the following: (1) choosing a clinic site, (2) establishing patient access procedures, (3) establishing navigator services, (4) developing subsidy fund use guidelines, and (5) designing recruitment and promotion. Through community-based promotion, 64 men inquired about the program and 26 (41 %) participated. Of those screened, 46 % had abnormal results, and 2 men were diagnosed with prostate cancer. Here, we describe a unique demonstration project to implement a comprehensive prostate cancer risk assessment program in an underserved Black community and describe successes and challenges to inform future efforts to promote access to underserved men.

Canine prostate models in preclinical studies of minimally invasive interventions: part II, benign prostatic hyperplasia models

PubMed Central

Báez-Díaz, Claudia; Sánchez-Margallo, Francisco Miguel

2017-01-01

Canine prostate is widely used as animal model in the preclinical evaluation of emerging therapeutic interventions. Spontaneous benign prostatic hyperplasia (BPH) is common in adult intact male dogs with two distinct pathological types: glandular and complex form of prostatic hyperplasia. The complex form of prostatic hyperplasia, usually occurring in older dogs, represents an ideal model because of its unique pathologic feature, including not only glandular hyperplasia but also an increase in prostate stromal components. The limited commercial availability of adult dogs with spontaneous BPH motivates experimentally induced BPH in young dogs. Hormone-induced canine BPH model has been well established with various hormonal treatment regimens and administration approaches. The goal of this review is to provide the veterinary background in spontaneous BPH in dogs, summarize the techniques in hormonal induction of canine BPH, and highlight the pathological and clinical limitations of the canine models that may lead to distinct therapeutic responses compared to clinical trials in humans. PMID:28725598

Non-coding RNAs in Prostate Cancer: From Discovery to Clinical Applications.

PubMed

Ceder, Yvonne

2016-01-01

Prostate cancer is a heterogeneous disease for which the molecular mechanisms are still not fully elucidated. Prostate cancer research has traditionally focused on genomic and epigenetic alterations affecting the proteome, but over the last decade non-coding RNAs, especially microRNAs, have been recognized to play a key role in prostate cancer progression. A considerable number of individual microRNAs have been found to be deregulated in prostate cancer and their biological significance elucidated in functional studies. This review will delineate the current advances regarding the involvement of microRNAs and their targets in prostate cancer biology as well as their potential usage in the clinical management of the disease. The main focus will be on microRNAs contributing to initiation and progression of prostate cancer, including androgen signalling, cellular plasticity, stem cells biology and metastatic processes. To conclude, implications on potential future microRNA-based therapeutics based on the recent advances regarding the interplay between microRNAs and their targets are discussed.

[New Radiopharmaceuticals Based on Prostate-Specific Inhibitors of Membrane Antigen for Diagnostics and Therapy of Metastatic Prostate Cancer].

PubMed

Vlasova, O P; German, K E; Krilov, V V; Petriev, V M; Epstein, N B

2015-01-01

About 10.7% cases of prostate cancer were registered in Russia in 2011 (40,000 patients). More than half of cancer cases were revealed in advanced (III-IV) stages when metastases inevitably developed quickly. Clinical problem of early diagnostics and treatment of metastatic prostate cancer is still not solved. Anatomical imaging techniques have low sensitivity and specificity for the detection of this disease. Metabolic visualization methods which use prostate specific antigen (PSA) as a marker are also ineffective. This article describes prostate-specific membrane antigens (PSMA) that are proposed as a marker for diagnostics and therapy of prostate cancer. The most promising PSMA-based radiopharmaceutical agent for diagnostics has been developed and clinically tested in the European countries. These pharmaceuticals are based on small peptide molecules modified with urea, and have the highest affinity to PSMA. Favorable phannacokinetics, rapid accumulation in the tumor and rapid excretion from the body are beneficial features of these pharmaceuticals.

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

PubMed Central

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

2016-01-01

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

PubMed

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

2016-02-29

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

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

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

Dendritic cell based vaccines: progress in immunotherapy studies for prostate cancer.

PubMed

Ragde, Haakon; Cavanagh, William A; Tjoa, Benjamin A

2004-12-01

No effective treatment is currently available for metastatic prostate cancer. Dendritic cell (DC) based cancer vaccine research has emerged from the laboratories to human clinical trials. We describe progress in the development of DC based prostate cancer vaccine. The literature was reviewed for major contributions to a growing number of studies that demonstrate the potential of DC based immunotherapeutics for prostate cancer. Background topics relating to DC based immunotherapy theory and practice are also addressed. DCs have been recognized as the most efficient antigen presenting cells that have the capacity to initiate naive T cell response in vitro and in vivo. During their differentiation and maturation pathways, dendritic cells can efficiently capture, process and present antigens for T cell activation. These characteristics make DC an attractive choice as the cellular adjuvant for cancer vaccines. Advances in DC generation, loading, and maturation methodologies have made it possible to generate clinical grade vaccines for various human trials. More than 100 DC vaccine trials, including 7 studies of patients with advanced prostate cancer have been reported to date. These vaccines were generally well tolerated with no significant adverse toxicity reported. Clinical responders have been identified in these studies. The new prospects opened by DC based vaccines for prostate cancer are fascinating. When compared to conventional treatments, DC vaccinations have few side effects. Improvements in patient selection, vaccine delivery strategies, immune monitoring and vaccine manufacturing will be crucial in moving DC based prostate cancer vaccines closer to the clinics.

Risk Stratification Among Men With Prostate Imaging Reporting and Data System Version 2 Category 3 Transition Zone Lesions: Is Biopsy Always Necessary?

PubMed Central

Felker, Ely R.; Raman, Steven S.; Margolis, Daniel J.; Lu, David S. K.; Shaheen, Nicholas; Natarajan, Shyam; Sharma, Devi; Huang, Jiaoti; Dorey, Fred; Marks, Leonard S.

2017-01-01

OBJECTIVE The objective of our study was to determine the clinical and MRI characteristics of clinically significant prostate cancer (PCA) (Gleason score ≥ 3 + 4) in men with Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 3 transition zone (TZ) lesions. MATERIALS AND METHODS From 2014 to 2016, 865 men underwent prostate MRI and MRI/ultrasound (US) fusion biopsy (FB). A subset of 90 FB-naïve men with 96 PI-RADSv2 category 3 TZ lesions was identified. Patients were imaged at 3 T using a body coil. Images were assigned a PI-RADSv2 category by an experienced radiologist. Using clinical data and imaging features, we performed univariate and multivariate analyses to identify predictors of clinically significant PCA. RESULTS The mean patient age was 66 years, and the mean prostate-specific antigen density (PSAD) was 0.13 ng/mL2. PCA was detected in 34 of 96 (35%) lesions, 14 of which (15%) harbored clinically significant PCA. In univariate analysis, DWI score, prostate volume, and PSAD were significant predictors (p < 0.05) of clinically significant PCA with a suggested significance for apparent diffusion coefficient (ADC) and prostate-specific antigen value (p < 0.10). On multivariate analysis, PSAD and lesion ADC were the most important covariates. The combination of both PSAD of 0.15 ng/mL2 or greater and an ADC value of less than 1000 mm2/s yielded an AUC of 0.91 for clinically significant PCA (p < 0.001). If FB had been restricted to these criteria, only 10 of 90 men would have undergone biopsy, resulting in diagnosis of clinically significant PCA in 60% with eight men (9%) misdiagnosed (false-negative). CONCLUSION The yield of FB in men with PI-RADSv2 category 3 TZ lesions for clinically significant PCA is 15% but significantly improves to 60% (AUC > 0.9) among men with PSAD of 0.15 ng/mL2 or greater and lesion ADC value of less than 1000 mm2/s. PMID:28858541

King's Health Partners' Prostate Cancer Biobank (KHP PCaBB).

PubMed

Saifuddin, S R; Devlies, W; Santaolalla, A; Cahill, F; George, G; Enting, D; Rudman, S; Cathcart, P; Challacombe, B; Dasgupta, P; Galustian, C; Chandra, A; Chowdhury, S; Gillett, C; Van Hemelrijck, M

2017-11-22

The KHP PCaBB was established in 2013 and recruits donors from the Urology or Oncology Departments at Guy's Hospital in London (UK). Prostate cancer patients may be approached to give their consent for biobanking at any point in their treatment pathway, which allows residual material from their earlier diagnosis to be transferred and used by the Biobank. Currently, patients are specifically asked to donate samples of blood and surplus prostate tissue as well as permitting access to their clinical and pathological data that continues to be added throughout the course of their disease. Between 2013 and 2015, 549 prostate cancer patients gave their consent to the biobank and, the tissue repository collected 489 blood samples, 120 frozen prostate tissue samples and 1064 formalin fixed paraffin embedded diagnostic blocks.Prostate cancer has become a chronic disease in a large proportion of men, with many men receiving multiple subsequent treatments, and their treatment trajectory often spanning over decades. Therefore, this resource aims to provide an ideal research platform to explore potential variations in treatment response as well as disease markers in the different risk categories for prostate cancer.A recent audit of the KHP PCaBB revealed that between 2013 and 2015, 1796 patients were diagnosed with prostate cancer at King's Health Partners (KHP), out of which 549 (30.6%) gave their consent to KHP PCaBB. Comparisons between demographic and clinical characteristics of patients who had consented compared to the total patient population revealed that the KHP PCaBB is demographically representative of the total prostate cancer patient population seen in Guy's and St Thomas' NHS Foundation Trust (GSTT). We observed no differences in distribution of ethnicity (p = 0.507) and socioeconomic status (p = 0.097). Some differences were observed in clinical characteristics, specifically with treatment type - which differed significantly between the patients who had given consent and total patient population.The KHP PCaBB has thereby amassed a rich data and tissue repository that is largely reflective of both the demographic and clinical diversity within the total prostate cancer patient population seen at KHP, making it an ideal platform for prostate cancer research.

Increased Bisecting N-Acetylglucosamine and Decreased Branched Chain Glycans of N-linked Glycoproteins in Expressed Prostatic Secretions Associated with Prostate Cancer Progression

PubMed Central

Nyalwidhe, Julius O.; Betesh, Lucy R.; Powers, Thomas W.; Jones, E. Ellen; White, Krista Y.; Burch, Tanya C.; Brooks, Jasmin; Watson, Megan T.; Lance, Raymond S.; Troyer, Dean A.; Semmes, O. John; Mehta, Anand; Drake, Richard R.

2013-01-01

Purpose Using prostatic fluids rich in glycoproteins like prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) , the goal of this study was to identify the structural types and relative abundance of glycans associated with prostate cancer status for subsequent use in emerging mass spectrometry-based glycopeptide analysis platforms. Experimental Design A series of pooled samples of expressed prostatic secretions (EPS) and exosomes reflecting different stages of prostate cancer disease were used for N-linked glycan profiling by three complementary methods, MALDI-TOF profiling, normal-phase HPLC separation, and triple quadropole MS analysis of PAP glycopeptides. Results Glycan profiling of N-linked glycans from different EPS fluids indicated a global decrease in larger branched tri- and tetra-antennary glycans. Differential exoglycosidase treatments indicated a substantial increase in bisecting N-acetylglucosamines correlated with disease severity. A triple quadrupole MS analysis of the N-linked glycopeptides sites from PAP in aggressive prostate cancer pools was done to cross-reference with the glycan profiling data. Conclusion and clinical relevance Changes in glycosylation as detected in EPS fluids reflect the clinical status of prostate cancer. Defining these molecular signatures at the glycopeptide level in individual samples could improve current approaches of diagnosis and prognosis. PMID:23775902

Is there a link between BPH and prostate cancer?

PubMed

Chang, R T M; Kirby, Roger; Challacombe, B J

2012-04-01

BPH is one of the most common diseases of older men, with more than 70% of men over 70 years affected, and prostate cancer is the most common cancer in men in the UK. Prostate cancer generally presents in one of three ways: asymptomatic patients who are screened (usually by a PSA test); men with LUTS who are investigated and undergo prostate biopsy; or patients with symptoms of metastasis such as bone pain. Men can be reassured that the main cause of LUTS is BPH. Only a small proportion of men have LUTS that are directly attributable to prostate cancer. Digital rectal examination (DRE) gives an evaluation of prostate size, which is relevant in particular to BPH management, and along with PSA testing it is one of the only ways of differentiating clinically between BPH and prostate cancer. If a nodular abnormality is present there is around a 50% chance of a diagnosis of prostate cancer being made on biopsy. Raised levels of serum PSA may be suggestive of prostate cancer, but diagnosis requires histological confirmation in almost every case. A normal PSA, PSA density and DRE can give reasonable confidence with regards to excluding clinically significant prostate cancer. BPH is not a known risk factor for prostate cancer, although the two frequently coexist. Age is the strongest predictor of prostate cancer risk, along with family history. BPH is not considered to be a precursor of prostate cancer. It is likely that although BPH may not make prostate cancer more likely to occur, it may increase the chance of diagnosing an incidental cancer.

Prostate cancer characteristics in the World Trade Center cohort, 2002-2013.

PubMed

Hashim, Dana; Boffetta, Paolo; Galsky, Matthew; Oh, William; Lucchini, Roberto; Crane, Michael; Luft, Benjamin; Moline, Jaqueline; Udasin, Iris; Harrison, Denise; Taioli, Emanuela

2018-07-01

An increased incidence of prostate cancer was reported in three cohorts of World Trade Center (WTC) respondents. It is uncertain whether this increase is because of WTC-related exposures or enhanced surveillance. Prostate cancer cases (2002-2013) were obtained from the WTC Health Program. Age, race, and Gleason score distribution were compared with New York State Cancer Registry cases from the same time period. Multivariate models were adjusted for age and race. Analyses of clinical characteristics of prostate cancer cases within the cohort were also carried out, adjusting for age, race, and WTC exposure categories. WTC respondents had a prostate cancer age-standardized rate ratio of 1.65 [95% confidence interval (CI): 1.37-1.93] compared with New York State; age-specific ratios were highest for ages 30-49 (2.28; 95% CI: 1.51-3.43), 70-74 (2.05; 95% CI: 1.03-4.10), and 80-84 years (5.65; 95% CI: 1.41-22.58). High WTC exposure was associated with advanced clinical stage (5.58; 95% CI: 1.05-29.76; Ptrend=0.03). WTC respondents continue to have a higher prostate cancer rate compared with New York State as a whole. Respondents with a higher WTC exposure level may have had more advanced clinical stage of prostate cancer.

Prostate Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... or routine screening test for prostate cancer. Screening tests for prostate cancer are under study, and there are screening clinical trials taking place ...

Targeted proteomics identifies liquid-biopsy signatures for extracapsular prostate cancer

PubMed Central

Kim, Yunee; Jeon, Jouhyun; Mejia, Salvador; Yao, Cindy Q; Ignatchenko, Vladimir; Nyalwidhe, Julius O; Gramolini, Anthony O; Lance, Raymond S; Troyer, Dean A; Drake, Richard R; Boutros, Paul C; Semmes, O. John; Kislinger, Thomas

2016-01-01

Biomarkers are rapidly gaining importance in personalized medicine. Although numerous molecular signatures have been developed over the past decade, there is a lack of overlap and many biomarkers fail to validate in independent patient cohorts and hence are not useful for clinical application. For these reasons, identification of novel and robust biomarkers remains a formidable challenge. We combine targeted proteomics with computational biology to discover robust proteomic signatures for prostate cancer. Quantitative proteomics conducted in expressed prostatic secretions from men with extraprostatic and organ-confined prostate cancers identified 133 differentially expressed proteins. Using synthetic peptides, we evaluate them by targeted proteomics in a 74-patient cohort of expressed prostatic secretions in urine. We quantify a panel of 34 candidates in an independent 207-patient cohort. We apply machine-learning approaches to develop clinical predictive models for prostate cancer diagnosis and prognosis. Our results demonstrate that computationally guided proteomics can discover highly accurate non-invasive biomarkers. PMID:27350604

The prostate cancer screening clinic in the Bahamas: a model for low- and middle-income countries.

PubMed

Roberts, Robin; Mitchell, Corydon; Tancawan, Ana Lourdes; Pedican, Mandi; Jones, Glenn Wayne

2017-11-01

Grand Bahama (pop. 51,000) is an island within the Bahamas archipelago. A local chapter of International Us TOO Prostate Cancer Support Group (UTGB) has led an annual community-based prostate cancer screening clinic in Grand Bahama each September since 2009. Features of this initiative, characteristics of attendees, and a description of found cancers were summarized to determine the clinic's value and to guide improvements. We analyzed the established clinic from 2012 to 2015, wherein UTGB attracted corporate funding, volunteers managed clinics, and health professionals provided healthcare services. An explicit algorithm was used to sort clients by age, comorbidities, and findings from digital rectal examinations, and prostate-specific antigen (PSA) values, to determine which clients would undergo secondary assessment and prostate biopsy. Overall, 1,844 males were registered (mean age 57.6 years), and only 149 men attended on more than one occasion for a total of 1,993 clinic visit. The urologist reviewed 315 men in secondary follow-up, for elevated PSA and/or an abnormal digital rectal examination. Of these, 45 men fulfilled criteria for trans-rectal ultrasound biopsy, and there were 40 found cases of prostate cancer, for a positive-predictive value of 89%. By D'Amico risk-stratification, these 40 cases were low (10%), intermediate (40%), and high risk (50%). The urologist counseled all 40 cases and facilitated access to standard care. This study suggests that low-resource countries can advance cost-effective screening clinics, apply policy guidelines, and provide services within acceptable standards of care. It is the expectation, with a sustained effort and community participation over the ensuing years, that earlier disease presentation will occur and, consequently, a concomitant decrease in the disease-specific mortality.

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.

Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer.

PubMed

Haffner, Michael C; Guner, Gunes; Taheri, Diana; Netto, George J; Palsgrove, Doreen N; Zheng, Qizhi; Guedes, Liana Benevides; Kim, Kunhwa; Tsai, Harrison; Esopi, David M; Lotan, Tamara L; Sharma, Rajni; Meeker, Alan K; Chinnaiyan, Arul M; Nelson, William G; Yegnasubramanian, Srinivasan; Luo, Jun; Mehra, Rohit; Antonarakis, Emmanuel S; Drake, Charles G; De Marzo, Angelo M

2018-06-01

Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases. The study included 539 primary prostate cancers comprising 508 acinar adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining. Increased levels of PD-L1 expression were noted in 42.9% of small-cell carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In conclusion, in this comprehensive evaluation of PD-L1 expression in prostate cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in mCRPC. These results will be important for the future clinical development of programmed cell death protein 1/PD-L1-targeting therapies in prostate cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Vitamin D deficiency and insufficiency among patients with prostate cancer

PubMed Central

Trump, Donald L.; Chadha, Manpreet K.; Sunga, Annette Y.; Fakih, Marwan G.; Ashraf, Umeer; Silliman, Carrie G.; Hollis, Bruce W.; Nesline, Mary K.; Tian, Lili; Tan, Wei; Johnson, Candace S.

2009-01-01

Objective To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. Patients, subjects and methods The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. Results The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (< 20 ng/mL) and insufficiency (20–31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32–100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Conclusions Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region. PMID:19426195

Vitamin D deficiency and insufficiency among patients with prostate cancer.

PubMed

Trump, Donald L; Chadha, Manpreet K; Sunga, Annette Y; Fakih, Marwan G; Ashraf, Umeer; Silliman, Carrie G; Hollis, Bruce W; Nesline, Mary K; Tian, Lili; Tan, Wei; Johnson, Candace S

2009-10-01

To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (<20 ng/mL) and insufficiency (20-31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32-100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region.

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

Zoberi, J.

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

Molecular and Clinical Predictors of Aggressive Prostate Cancer

DTIC Science & Technology

2007-09-01

AD_________________ Award Number: W81XWH-05-1-0562 TITLE: Molecular and Clinical Predictors of...DATES COVERED (From - To) 1 SEP 2006 - 31 AUG 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Molecular And Clinical Predictors Of Aggressive...course. We are evaluating molecular and clinical predictors at diagnosis to distinguish lethal and indolent prostate cancer. In a related project, we

A Preliminary Analysis of Calcifying Particles in the Serum and Prostates of Patients with Prostatic Inflammation

NASA Technical Reports Server (NTRS)

Jones, Jeffrey A.; Carlson, Grant; Kajander, E. Olavi; Warmflash, David; Taylor, Karen; Ayala, Gustavo; Shoskes, Daniel; Everett, Meg; Feedback, Dan; Ciftcioglu, Neva

2006-01-01

Chronic diseases of the prostate such as benign prostatic hyperplasia (BPH) & chronic pelvic pain syndrome (CPPS) have associated findings of chronic inflammation, despite a lack of causal relationship. Numerous attempts to define an infectious agent responsible for the clinical findings have been inconsistent. The possibility of an infectious agent, that has not been uncovered with routine culturing methods, forms the basis for this study. Serum from 940 healthy Finnish men were compared with serum from 40 Crohn's, 40 path dx prostatitis, & 40 with path dx carcinoma, using an enzyme-linked immunosorbant assay (ELISA), to detect antigens specific to Nanobacteria(NB) utilizing monoclonal antibodies (Ab) 5/3 and 8D10. This ELISA has not been validated for detecting NB-associated with clinical prostatic disease, yet cross-reactivity with other bacterial species is low. Immunohistochemistry was performed on de-paraffinized prostatic tissue slides, de-calcified with EDTA and stained with the DAKO Catalyzed Signal Amplification kit, employing 8D10 as the primary (target/antigen-detecting) Ab. The mean (plus or minus SD) & median concentrations of NB antigen (U/50 L) were 379.59 (plus or minus 219.28) & 640.00 for patients with prostatitis (BPH) vs 3.31 (plus or minus 3.55) & 2.94 for prostate adenocarcinoma, 1.88 (plus or minus 2.94) & 0.80 for Crohn's disease, & 7.43 (plus or minus 25.57) & 0.00 for patients with no clinical prostatic disease. Unpaired t-tests revealed statistically significant differences between the prostatitis (BPH) sera & each of the other groups with p less than 0.005, but no differences between the other groups themselves. Preliminary studies with immunohistochemistry & 3-D confocal microscopy reveal 16/24 tissue sections + for NB Ag in BPH vs. only 2/22 tissue sections with prostate cancer. The preliminary findings of this serum screening study suggest that NB antigen may be commonly found in the serum of patients with the pathological diagnosis of prostatitis. Preliminary immunohistologic studies, suggest that NB may be found within the gland itself at a higher rate in patients with BPH relative to patients with adenocarcinoma, however confirmatory studies with a more specific ELISA technique, primary cultures, & with larger numbers of patients in a prospective design are required to determine if 1) NB are a causative organism for clinical hyperplastic and inflammatory disease, & if 2) serological testing can be used to discriminate patients with nanobacterial-associated prostatic disease.

Effectiveness of the combined evaluation of KLK3 genetics and free-to-total prostate specific antigen ratio for prostate cancer diagnosis.

PubMed

Zambon, Carlo-Federico; Prayer-Galetti, Tommaso; Basso, Daniela; Padoan, Andrea; Rossi, Elisa; Secco, Silvia; Pelloso, Michela; Fogar, Paola; Navaglia, Filippo; Moz, Stefania; Zattoni, Filiberto; Plebani, Mario

2012-10-01

Of serum prostate specific antigen variability 40% depends on inherited factors. We ascertained whether the knowledge of KLK3 genetics would enhance prostate specific antigen diagnostic performance in patients with clinical suspicion of prostate cancer. We studied 1,058 men who consecutively underwent prostate biopsy for clinical suspicion of prostate cancer. At histology prostate cancer was present in 401 cases and absent in 657. Serum total prostate specific antigen and the free-to-total prostate specific antigen ratio were determined. Four polymorphisms of the KLK3 gene (rs2569733, rs2739448, rs925013 and rs2735839) and 1 polymorphism of the SRD5A2 gene (rs523349) were studied. The influence of genetics on prostate specific antigen variability was evaluated by multivariate linear regression analysis. The performance of total prostate specific antigen and the free-to-total prostate specific antigen ratio alone or combined with a genetically based patient classification were defined by ROC curve analyses. For prostate cancer diagnosis the free-to-total prostate specific antigen ratio index alone (cutoff 11%) was superior to total prostate specific antigen (cutoff 4 ng/ml) and to free-to-total prostate specific antigen ratio reflex testing (positive predictive value 61%, 43% and 54%, respectively). Prostate specific antigen correlated with KLK3 genetics (rs2735839 polymorphism p = 0.001, and rs2569733, rs2739448 and rs925013 haplotype combination p = 0.003). In patients with different KLK3 genetics 2 optimal free-to-total prostate specific antigen ratio cutoffs (11% and 14.5%) were found. For free-to-total prostate specific antigen ratio values between 11% and 14.5% the prostate cancer probability ranged from 30.0% to 47.4% according to patient genetics. The free-to-total prostate specific antigen ratio is superior to total prostate specific antigen for prostate cancer diagnosis, independent of total prostate specific antigen results. Free-to-total prostate specific antigen ratio findings below 11% are positively associated with prostate cancer and those above 14.5% are negatively associated with prostate cancer, while the interpretation of those between 11% and 14.5% is improved by patient KLK3 genetic analysis. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate Cancer Clinical Trials Group: The University of Michigan Site

DTIC Science & Technology

2012-04-01

and fusion-negative strata. UM will be the lead site for this trial with the Univ. of Chicago N01 Phase II consortium as the coordinating center. Ten...sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study. JE Ward, T...N01 contract with CTEP (University of Chicago – Early Therapeutics Development with Phase II emphasis group). The Program is committed to creating

The impact of introducing intensity modulated radiotherapy into routine clinical practice.

PubMed

Miles, Elizabeth A; Clark, Catharine H; Urbano, M Teresa Guerrero; Bidmead, Margaret; Dearnaley, David P; Harrington, Kevin J; A'Hern, Roger; Nutting, Christopher M

2005-12-01

Intensity modulated radiotherapy (IMRT) at the Royal Marsden Hospital London was introduced in July 2001. Treatment delivery was dynamic using a single-phase technique. Concerns were raised regarding increased clinical workload due to introduction of new technology. The potential increased use of resources was assessed. IMRT patient selection was within guidelines of clinical trials and included patients undergoing prostate plus pelvic lymph node (PPN) irradiation and head and neck cancer (HNC) treatment. Patient planning, quality assurance and treatment times were collected for an initial IMRT patient group. A comparative group of patients with advanced HNC undergoing two- or three-phase conventional radiotherapy, requiring matched photon and electron fields, were also timed. The median overall total planning time for IMRT was greater for HNC patients compared to the PPN cohort. For HNC the overall IMRT planning time was significantly longer than for conventional. The median treatment time for conventional two- or three-phase HNC treatments, encompassing similar volumes to those treated with IMRT, was greater than that for the IMRT HNC patient cohort. A reduction in radiographer man hours per patient of 4.8h was recorded whereas physics time was increased by 4.9h per patient. IMRT currently increases overall planning time. Additional clinician input is required for target volume localisation. Physics time is increased, a significant component of this being patient specific QA. Radiographer time is decreased. For HNC a single phase IMRT treatment has proven to be more efficient than a multiple phase conventional treatment. IMRT has been integrated smoothly and efficiently into the existing treatment working day. This preliminary study suggests that IMRT could be a routine treatment with efficient use of current radiotherapy resources.

Reporting combined outcomes with Trifecta and survival, continence, and potency (SCP) classification in 337 patients with prostate cancer treated with image-guided hypofractionated radiotherapy.

PubMed

Jereczek-Fossa, Barbara A; Zerini, Dario; Fodor, Cristiana; Santoro, Luigi; Maucieri, Andrea; Gerardi, Marianna A; Vischioni, Barbara; Cambria, Raffaella; Garibaldi, Cristina; Cattani, Federica; Vavassori, Andrea; Matei, Deliu V; Musi, Gennaro; De Cobelli, Ottavio; Orecchia, Roberto

2014-12-01

To report the image-guided hypofractionated radiotherapy (hypo-IGRT) outcome for patients with localised prostate cancer according to the new outcome models Trifecta (cancer control, urinary continence, and sexual potency) and SCP (failure-free survival, continence and potency). Between August 2006 and January 2011, 337 patients with cT1-T2N0M0 prostate cancer (median age 73 years) were eligible for a prospective longitudinal study on hypo-IGRT (70.2 Gy/26 fractions) in our Department. Patients completed four questionnaires before treatment, and during follow-up: the International Index of Erectile Function-5 (IIEF-5), the International Prostate Symptom Score (IPSS), and the European Organization for Research and Treatment of Cancer prostate-cancer-specific Quality of Life Questionnaires (QLQ) QLQ-PR25 and QLQ-C30. Baseline and follow-up patient data were analysed according to the Trifecta and SCP outcome models. Cancer control, continence and potency were defined respectively as no evidence of disease, score 1 or 2 for item 36 of the QLQ-PR25 questionnaire, and total score of >16 on the IIEF-5 questionnaire. Patients receiving androgen-deprivation therapy (ADT) at any time were excluded. Trifecta criteria at baseline were met in 72 patients (42% of all ADT-free patients with completed questionnaires). Both at 12 and 24 months after hypo-IGRT, 57% of the Trifecta patients at baseline were still meeting the Trifecta criteria (both oncological and functional success according to the SCP model). The main reason for failing the Trifecta criteria during follow-up was erectile dysfunction: in 18 patients after 6 months follow-up, in 12 patients after 12 months follow-up, and in eight patients after 24 months. Actuarial 2-year Trifecta failure-free survival rate was 44% (95% confidence interval 27-60%). In multivariate analysis no predictors of Trifecta failure were identified. Missing questionnaires was the main limitation of the study. The Trifecta and SCP classifications can be used as tools to report RT outcome. © 2013 The Authors. BJU International © 2013 BJU International.

Prostate Stem Cell Antigen: A Prospective Therapeutic and Diagnostic Target

PubMed Central

Raff, Adam B.; Gray, Andrew; Kast, W. Martin

2009-01-01

The development of novel clinical tools to combat cancer is an intense field of research and recent efforts have been directed at the identification of proteins that may provide diagnostic, prognostic and/or therapeutic applications due to their restricted expression. To date, a number of protein candidates have emerged as potential clinical tools in the treatment of prostate cancer. Discovered over ten year ago, prostate stem cell antigen (PSCA) is a cell surface antigen that belongs to the Ly-6/Thy-1 family of glycosylphosphatidylinositol-anchored proteins. PSCA is highly overexpressed in human prostate cancer, with limited expression in normal tissues, making it an ideal target for both diagnosis and therapy. Several studies have now clearly correlated the expression of PSCA with relevant clinical benchmarks, such as Gleason score and metastasis, while others have demonstrated the efficacy of PSCA targeting in treatment through various modalities. The purpose of this review is to present the current body of knowledge about PSCA and its potential role in the treatment of human prostate cancer. PMID:18838214

Development of a 3D ultrasound-guided prostate biopsy system

NASA Astrophysics Data System (ADS)

Cool, Derek; Sherebrin, Shi; Izawa, Jonathan; Fenster, Aaron

2007-03-01

Biopsy of the prostate using ultrasound guidance is the clinical gold standard for diagnosis of prostate adenocarinoma. However, because early stage tumors are rarely visible under US, the procedure carries high false-negative rates and often patients require multiple biopsies before cancer is detected. To improve cancer detection, it is imperative that throughout the biopsy procedure, physicians know where they are within the prostate and where they have sampled during prior biopsies. The current biopsy procedure is limited to using only 2D ultrasound images to find and record target biopsy core sample sites. This information leaves ambiguity as the physician tries to interpret the 2D information and apply it to their 3D workspace. We have developed a 3D ultrasound-guided prostate biopsy system that provides 3D intra-biopsy information to physicians for needle guidance and biopsy location recording. The system is designed to conform to the workflow of the current prostate biopsy procedure, making it easier for clinical integration. In this paper, we describe the system design and validate its accuracy by performing an in vitro biopsy procedure on US/CT multi-modal patient-specific prostate phantoms. A clinical sextant biopsy was performed by a urologist on the phantoms and the 3D models of the prostates were generated with volume errors less than 4% and mean boundary errors of less than 1 mm. Using the 3D biopsy system, needles were guided to within 1.36 +/- 0.83 mm of 3D targets and the position of the biopsy sites were accurately localized to 1.06 +/- 0.89 mm for the two prostates.

Determination of optimal drug dose and light dose index to achieve minimally invasive focal ablation of localised prostate cancer using WST11-vascular-targeted photodynamic (VTP) therapy.

PubMed

Moore, Caroline M; Azzouzi, Abel-Rahmene; Barret, Eric; Villers, Arnauld; Muir, Gordon H; Barber, Neil J; Bott, Simon; Trachtenberg, John; Arumainayagam, Nimalan; Gaillac, Bertrand; Allen, Clare; Schertz, Avigdor; Emberton, Mark

2015-12-01

To determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD Soluble) for vascular-targeted photodynamic (VTP) therapy in men with low-risk prostate cancer. In all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months. In all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP. Treatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%). © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

Comparison of prostate cancer survival in Germany and the USA: can differences be attributed to differences in stage distributions?

PubMed

Winter, Alexander; Sirri, Eunice; Jansen, Lina; Wawroschek, Friedhelm; Kieschke, Joachim; Castro, Felipe A; Krilaviciute, Agne; Holleczek, Bernd; Emrich, Katharina; Waldmann, Annika; Brenner, Hermann

2017-04-01

To better understand the influence of prostate-specific antigen (PSA) screening and other health system determinants on prognosis of prostate cancer, up-to-date relative survival (RS), stage distributions, and trends in survival and incidence in Germany were evaluated and compared with the United States of America (USA). Incidence and mortality rates for Germany and the USA for the period 1999-2010 were obtained from the Centre for Cancer Registry Data at the Robert Koch Institute and the USA Surveillance Epidemiology and End Results (SEER) database. For analyses on stage and survival, data from 12 population-based cancer registries in Germany and from the SEER-13 database were analysed. Patients (aged ≥ 15 years) diagnosed with prostate cancer (1997-2010) and mortality follow-up to December 2010 were included. The 5- and 10-year RS and survival trends (2002-2010) were calculated using standard and model-based period analysis. Between 1999 and 2010, prostate cancer incidence decreased in the USA but increased in Germany. Nevertheless, incidence remained higher in the USA throughout the study period (99.8 vs 76.0 per 100,000 in 2010). The proportion of localised disease significantly increased from 51.9% (1998-2000) to 69.6% (2007-2010) in Germany and from 80.5% (1998-2000) to 82.6% (2007-2010) in the USA. Mortality slightly decreased in both countries (1999-2010). Overall, 5- and 10-year RS was lower in Germany (93.3%; 90.7%) than in the USA (99.4%; 99.6%) but comparable after adjustment for stage. The same patterns were seen in age-specific analyses. Improvements seen in prostate cancer survival between 2002-2004 and 2008-2010 (5-year RS: 87.4% and 91.2%; +3.8% units) in Germany disappeared after adjustment for stage (P = 0.8). The survival increase in Germany and the survival advantage in the USA might be explained by differences in incidence and stage distributions over time and across countries. Effects of early detection or a lead-time bias due to the more widespread utilisation and earlier introduction of PSA testing in the USA are likely to explain the observed patterns. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

MO-B-BRC-04: MRI-Based Prostate HDR

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

Mourtada, F.

2016-06-15

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

MO-B-BRC-00: Prostate HDR Treatment Planning - Considering Different Imaging Modalities

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

NONE

2016-06-15

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

MO-B-BRC-02: Ultrasound Based Prostate HDR

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

Chang, Z.

2016-06-15

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

Prostate Cancer Pathology Resource Network

DTIC Science & Technology

2012-07-01

microarrays (TMAs), serum, plasma , buffy coat, prostatic fluid, and derived specimens (DNA and RNA); these specimens are linked to clinical and...research community. The specimens in the PCBN include tissues from prostatectomies, serum, plasma , buffy coat, prostatic fluid, derived specimens such...prostatectomy, seminal vesicles), body fluids (serum, plasma , buffy coat, prostatic fluid; most can be matched to tumor and benign tissue), and

Risks of Prostate Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... or routine screening test for prostate cancer. Screening tests for prostate cancer are under study, and there are screening clinical trials taking place ...

Development of three-dimensional radiotherapy techniques in breast cancer

NASA Astrophysics Data System (ADS)

Coles, Charlotte E.

Radiotherapy following conservation surgery decreases local relapse and death from breast cancer. Currently, the challenge is to minimise the morbidity caused by this treatment without losing efficacy. Despite many advances in radiation techniques in other sites of the body, the majority of breast cancer patients are still planned and treated using 2-dimensional simple radiotherapy techniques. In addition, breast irradiation currently consumes 30% of the UK's radiotherapy workload. Therefore, any change to more complex treatment should be of proven benefit. The primary objective of this research is to develop and evaluate novel radiotherapy techniques to decrease irradiation of normal structures and improve localisation of the tumour bed. I have developed a forward-planned intensity modulated (IMRT) breast radiotherapy technique, which has shown improved dosimetry results compared to standard breast radiotherapy. Subsequently, I have developed and implemented a phase III randomised controlled breast IMRT trial. This National Cancer Research Network adopted trial will answer an important question regarding the clinical benefit of breast IMRT. It will provide DNA samples linked with high quality clinical outcome data, for a national translational radiogenomics study investigating variation in normal tissue toxicity. Thus, patients with significant late normal tissue side effects despite good dose homogeneity will provide the best model for finding differences due to underlying genetics. I evaluated a novel technique using high definition free-hand 3-dimensional (3D) ultrasound in a phantom study, and the results suggested that this is an accurate and reproducible method for tumour bed localisation. I then compared recognised methods of tumour bed localisation with the 3D ultrasound method in a clinical study. The 3D ultrasound technique appeared to accurately represent the shape and spatial position of the tumour cavity. This tumour bed localisation research facilitated protocol development of a proposed national breast radiotherapy trial investigating IMRT and partial breast irradiation.

Expression of the cancer-testis antigen BORIS correlates with prostate cancer.

PubMed

Cheema, Zubair; Hari-Gupta, Yukti; Kita, Georgia-Xanthi; Farrar, Dawn; Seddon, Ian; Corr, John; Klenova, Elena

2014-02-01

BORIS, a paralogue of the transcription factor CTCF, is a member of the cancer-testis antigen (CT) family. BORIS is normally present at high levels in the testis; however it is aberrantly expressed in various tumors and cancer cell lines. The main objectives of this study were to investigate BORIS expression together with sub-cellular localization in both prostate cell lines and tumor tissues, and assess correlations between BORIS and clinical/pathological characteristics. We examined BORIS mRNA expression, protein levels and cellular localization in a panel of human prostate tissues, cancer and benign, together with a panel prostate cell lines. We also compared BORIS levels and localization with clinical/pathological characteristics in prostate tumors. BORIS was detected in all inspected prostate cancer cell lines and tumors, but was absent in benign prostatic hyperplasia. Increased levels of BORIS protein positively correlated with Gleason score, T-stage and androgen receptor (AR) protein levels in prostate tumors. The relationship between BORIS and AR was further highlighted in prostate cell lines by the ability of ectopically expressed BORIS to activate the endogenous AR mRNA and protein. BORIS localization in the nucleus plus cytoplasm was also associated with higher BORIS levels and Gleason score. Detection of BORIS in prostate tumors suggests potential applications of BORIS as a biomarker for prostate cancer diagnosis, as an immunotherapy target and, potentially, a prognostic marker of more aggressive prostate cancer. The ability of BORIS to activate the AR gene indicates BORIS involvement in the growth and development of prostate tumors. © 2013 Wiley Periodicals, Inc.

Development of a real-time clinical decision support system upon the web mvc-based architecture for prostate cancer treatment

PubMed Central

2011-01-01

Background A real-time clinical decision support system (RTCDSS) with interactive diagrams enables clinicians to instantly and efficiently track patients' clinical records (PCRs) and improve their quality of clinical care. We propose a RTCDSS to process online clinical informatics from multiple databases for clinical decision making in the treatment of prostate cancer based on Web Model-View-Controller (MVC) architecture, by which the system can easily be adapted to different diseases and applications. Methods We designed a framework upon the Web MVC-based architecture in which the reusable and extractable models can be conveniently adapted to other hospital information systems and which allows for efficient database integration. Then, we determined the clinical variables of the prostate cancer treatment based on participating clinicians' opinions and developed a computational model to determine the pretreatment parameters. Furthermore, the components of the RTCDSS integrated PCRs and decision factors for real-time analysis to provide evidence-based diagrams upon the clinician-oriented interface for visualization of treatment guidance and health risk assessment. Results The resulting system can improve quality of clinical treatment by allowing clinicians to concurrently analyze and evaluate the clinical markers of prostate cancer patients with instantaneous clinical data and evidence-based diagrams which can automatically identify pretreatment parameters. Moreover, the proposed RTCDSS can aid interactions between patients and clinicians. Conclusions Our proposed framework supports online clinical informatics, evaluates treatment risks, offers interactive guidance, and provides real-time reference for decision making in the treatment of prostate cancer. The developed clinician-oriented interface can assist clinicians in conveniently presenting evidence-based information to patients and can be readily adapted to an existing hospital information system and be easily applied in other chronic diseases. PMID:21385459

Development of a real-time clinical decision support system upon the Web MVC-based architecture for prostate cancer treatment.

PubMed

Lin, Hsueh-Chun; Wu, Hsi-Chin; Chang, Chih-Hung; Li, Tsai-Chung; Liang, Wen-Miin; Wang, Jong-Yi Wang

2011-03-08

A real-time clinical decision support system (RTCDSS) with interactive diagrams enables clinicians to instantly and efficiently track patients' clinical records (PCRs) and improve their quality of clinical care. We propose a RTCDSS to process online clinical informatics from multiple databases for clinical decision making in the treatment of prostate cancer based on Web Model-View-Controller (MVC) architecture, by which the system can easily be adapted to different diseases and applications. We designed a framework upon the Web MVC-based architecture in which the reusable and extractable models can be conveniently adapted to other hospital information systems and which allows for efficient database integration. Then, we determined the clinical variables of the prostate cancer treatment based on participating clinicians' opinions and developed a computational model to determine the pretreatment parameters. Furthermore, the components of the RTCDSS integrated PCRs and decision factors for real-time analysis to provide evidence-based diagrams upon the clinician-oriented interface for visualization of treatment guidance and health risk assessment. The resulting system can improve quality of clinical treatment by allowing clinicians to concurrently analyze and evaluate the clinical markers of prostate cancer patients with instantaneous clinical data and evidence-based diagrams which can automatically identify pretreatment parameters. Moreover, the proposed RTCDSS can aid interactions between patients and clinicians. Our proposed framework supports online clinical informatics, evaluates treatment risks, offers interactive guidance, and provides real-time reference for decision making in the treatment of prostate cancer. The developed clinician-oriented interface can assist clinicians in conveniently presenting evidence-based information to patients and can be readily adapted to an existing hospital information system and be easily applied in other chronic diseases.

Late-onset granulomatous prostatitis following intravesical bacille Calmette-Guerin therapy: case report.

PubMed

Castillo Cádiz, Octavio; Villasenín Parrado, Lorena; Borgna Christie, Vincenzo; Gallegos Méndez, Iván; Martínez Corta, Virginia

2016-06-20

Bacille Calmette-Guerin intravesical treatment is the most effective treatment for reducing the recurrence of non-muscle-invasive urothelial carcinomas. This treatment can sometimes have side effects and serious complications. Granulomatous prostatitis is a common histological finding but it rarely has a clinical presentation. We report a case of a 75-year-old, type 2 diabetic, male patient who was diagnosed with urothelial in situ carcinoma, for which he began treatment with Bacille Calmette-Guerin instillations. Five years later the patient presented nocturia, pollakiuria, severe urgency, and intense and recurrent perineal pain associated with marked elevation of prostatic specific antigen. A prostatic biopsy was performed that showed a moderate to severe granulomatous prostatitis related to bacille Calmette-Guerin. The patient received full antituberculosis combination drugs with a favorable clinical response.

A clinical data validated mathematical model of prostate cancer growth under intermittent androgen suppression therapy

NASA Astrophysics Data System (ADS)

Portz, Travis; Kuang, Yang; Nagy, John D.

2012-03-01

Prostate cancer is commonly treated by a form of hormone therapy called androgen suppression. This form of treatment, while successful at reducing the cancer cell population, adversely affects quality of life and typically leads to a recurrence of the cancer in an androgen-independent form. Intermittent androgen suppression aims to alleviate some of these adverse affects by cycling the patient on and off treatment. Clinical studies have suggested that intermittent therapy is capable of maintaining androgen dependence over multiple treatment cycles while increasing quality of life during off-treatment periods. This paper presents a mathematical model of prostate cancer to study the dynamics of androgen suppression therapy and the production of prostate-specific antigen (PSA), a clinical marker for prostate cancer. Preliminary models were based on the assumption of an androgen-independent (AI) cell population with constant net growth rate. These models gave poor accuracy when fitting clinical data during simulation. The final model presented hypothesizes an AI population with increased sensitivity to low levels of androgen. It also hypothesizes that PSA production is heavily dependent on androgen. The high level of accuracy in fitting clinical data with this model appears to confirm these hypotheses, which are also consistent with biological evidence.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI.

PubMed

Sheridan, Alison D; Nath, Sameer K; Syed, Jamil S; Aneja, Sanjay; Sprenkle, Preston C; Weinreb, Jeffrey C; Spektor, Michael

2018-02-01

The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to perform biopsy.

Combination immunotherapy with prostate GVAX and ipilimumab: safety and toxicity.

PubMed

Karan, Dev; Van Veldhuizen, Peter

2012-06-01

Evaluation of: van den Eertwegh AJ, Versluis J, van den Berg HP et al. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a Phase 1 dose-escalation trial. Lancet Oncol. 13(5), 509 – 517 (2012). A significant interest in the development of therapeutic cancer vaccines over the last decade has led to an improvement in overall survival of cancer patients in several clinical trials. As a result, two active immunotherapy agents, sipuleucel-T and ipilimumab, have been approved by the US FDA for the treatment of prostate cancer and melanoma, respectively. GVAX(®) cellular vaccine (Cell Genesysis, Inc., CA, USA) is another active immunotherapy agent targeting prostate cancer and it has been well studied in various clinical trials. The current publication, by van den Eertwegh et al., demonstrated a combination of two active immunotherapy approaches, using GVAX and ipilimumab for the treatment of metastatic castration-resistant prostate cancer. While GVAX is designed to amplify the antitumor response specific to prostate cancer cells, ipilimumab contributes to T-cell activation. Thus, the authors presented the possibility of augmenting antitumor T-cell activity in two different ways. They successfully demonstrated a tolerable dose and safety profile of ipilimumab in combination with GVAX for patients with metastatic castration-resistant prostate cancer. However, further studies of such immunotherapy combinations and detailed analysis of their immunological effects are needed to observe clinical benefit.

Simple case definition of clinical benign prostatic hyperplasia, based on International Prostate Symptom Score, predicts general practitioner consultation rates.

PubMed

Kok, Esther T; Bohnen, Arthur M; Jonkheijm, Rikkert; Gouweloos, Jochem; Groeneveld, Frans P M J; Thomas, Siep; Bosch, J L H Ruud

2006-10-01

To determine which case-definition of clinical benign prostatic hyperplasia (BPH) has the best predictive value for general practitioner visits for lower urinary tract symptoms (LUTS) suggestive of BPH. The incidence and prevalence rates of general practitioner visits for LUTS were also determined. A longitudinal, population-based study from 1995 to 2003 was conducted among 1688 men aged 50 to 78 years old. Data were collected on physical urologic parameters, quality of life, and symptom severity as determined from the International Prostate Symptom Score. Information on health-care-seeking behavior of all participants was collected from the general practitioner (GP) record using a computerized search engine and an additional manual check of the electronically selected files. The incidence and prevalence rate of the men at risk was 19.6% and 14.0%, respectively, and these rates increased with age. For sensitivity and the positive predictive value, the case-definition of clinical BPH as an International Prostate Symptom Score greater than 7 had the best predictive value for GP visits for LUTS within 2 years after baseline. Because only marginal improvement (greater specificity but lower sensitivity) in the prediction of GP visits for LUTS was possible by adding information on prostate volume and flow, for the prediction of future GP visits for LUTS suggestive of BPH, we suggest that the International Prostate Symptom Score questionnaire be used and that estimation of the prostate volume and flow is not required.

Photoselective vaporization of the prostate (PVP) with green light KTP laser in the management of symptomatic benign prostatic enlargement (BPE): does the anatomy of the TURP-like cavity predict the clinical outcome?

NASA Astrophysics Data System (ADS)

Nseyo, Unyime

2005-04-01

Photoselective vaporization of the prostate (PVP) is evolving as an alternative outpatient surgical treatment to transurethral resection of the prostate (TURP) in the management of patients with symptomatic benign prostatic hypertrophy/enlargement (BPH/BPE). The purported benefits of PVP include rapid vaporization of the prostate with an instant creation of TURP-like anatomic defect, an excellent hemostasis, shorter (<24 hours) duration of catheterization, short (< 24 hours) hospital stay, and quick return to work. We retrospectively reviewed the video clips of our cases to determine whether or not the anatomic appearance of the post-PVP prostatic cavity per se could predict clinical outcome. Forty-three, non-consecutive patients, diagnosed with symptomatic BPH have been treated with PVP using the 80W KTP laser and followed for at least 18 months (range 18-24). A majority (N=32) of the patients was enrolled under an Institutional Review Board approved multi-center protocol at the Hunter McGuire Veterans Administration Medical Center, Richmond, Virginia. We reviewed the urodynamic parameters: AUA-SI, QOL, Qmax and PVR at 3, 6, 12, 18 and 24 months postoperatively. We plan to present video documentations of the various anatomic appearances of the TURP-like prostatic cavity at the conclusion of the PVP treatment along with summaries of the short and long term clinical outcomes.

Racial differences in clinically localized prostate cancers of black and white men.

PubMed

deVere White, R W; Deitch, A D; Jackson, A G; Gandour-Edwards, R; Marshalleck, J; Soares, S E; Toscano, S N; Lunetta, J M; Stewart, S L

1998-06-01

Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences. A total of 117 prostate cancers (43 black and 74 white patients) obtained at radical prostatectomy for clinically localized disease were assigned Gleason scores by a single pathologist. Enzymatically dissociated nuclei from archival prostate cancers were examined by DNA flow cytometry using propidium iodide staining and the multicycle program to remove debris and sliced nuclei and to perform cell cycle analysis. For immunostaining after microwave antigen retrieval we used a DO-1/DO-7 monoclonal antibody cocktail for p53 and the clone 124 antibody for bcl-2. Significantly more black than white men had Gleason score 7 tumors. The DNA ploidy distribution of Gleason 6 or less tumors was similar for both races. As anticipated, the ploidy distribution of higher grade prostate cancer in white men was more abnormal but, unexpectedly, this was not found for higher grade prostate cancer in black men. No significant racial differences were found in S phase fractions, p53 or bcl-2 immunopositivity. However, for prostate cancer in black men there was a significant association between bcl-2 immunopositivity and higher S-phase fractions. The aggressive prostate cancers of black men may be characterized by the 2 features of high proliferation and a block to programmed cell death.

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.

Prostate cancer risk prediction in a urology clinic in Mexico.

PubMed

Liang, Yuanyuan; Messer, Jamie C; Louden, Christopher; Jimenez-Rios, Miguel A; Thompson, Ian M; Camarena-Reynoso, Hector R

2013-10-01

To evaluate factors affecting the risk of prostate cancer (CaP) and high-grade disease (HGCaP, Gleason score ≥ 7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC). From a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerología, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of CaP, and history of a prior prostate biopsy on CaP and HGCaP, separately. Internal discrimination, goodness-of-fit, and clinical utility of the resulting models were assessed with comparison to the PCPTRC. Rates of both CaP (73.2%) and HGCaP (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of CaP but overestimated the risk of HGCaP. Four factors influencing CaP on biopsy were logPSA, DRE, family history and a prior biopsy history (all P < 0.001). The internal AUC of the logistic model was 0.823 compared with 0.785 of the PCPTRC for CaP (P < 0.001). The same 4 factors were significantly associated with HGCaP as well and the AUC was 0.779 compared with 0.766 of the PCPTRC for HGCaP (P = 0.13). Lack of screening programs or regular urologic checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics. Copyright © 2013 Elsevier Inc. 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.

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics and their Environment

DTIC Science & Technology

2012-07-01

sites to assess their discussions with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about...with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about such trials, and barriers to and...calculated and compared across race/ethnicity. Examination of major outcomes included willingness to participate in, knowledge of, and attitudes towards

Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction

DTIC Science & Technology

2016-10-01

clinical oncology , cancer genetics, genomic science/bioinformatics, clinical pathology, social and behavioral sciences, and bioethics in order to...Interpret and translate sequence variants into clinical oncology setting; 5) Assess and evaluate costs associated with clinical sequencing. Role...Lethal Prostate Cancer Goal(s): Radiation Therapy Oncology Group (RTOG) 96-01 represents a phase III trial of of salvage radiation therapy (RT) alone

Chronic prostatitis/chronic pelvic pain syndrome: a review of evaluation and therapy.

PubMed

Polackwich, A S; Shoskes, D A

2016-06-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as NIH Category III Prostatitis is a highly prevalent syndrome with significant impact on quality of life. As a heterogeneous syndrome, there exists no 'one size fits all' therapy with level 1 evidence to guide therapy. This often leads to a nihilistic approach to patients and clinical outcomes are poor. In this review, we examine the evidence for CP/CPPS therapies and discuss our technique of clinical phenotyping combined with multimodal therapy. Review of Medline articles with terms 'non-bacterial prostatitis', 'abacterial prostatitis' and 'chronic pelvic pain syndrome'. Many individual therapies have been evaluated in the treatment of CP/CPPS; antibiotics, anti-inflammatory medications (including bioflavonoids), neuromodulators, alpha blockers, pelvic floor physical therapy and cognitive behavior therapy. Each of these has been found to have varying success in alleviating symptoms. UPOINT is a system of clinical phenotyping for CP/CPPS patients that has 6 defined domains, which guide multimodal therapy. It has been validated to correlate with symptom burden and therapy guided by UPOINT leads to significant symptom improvement in 75-84% of patients based on three independent studies. CP/CPPS is a heterogeneous condition and, much like with prostate cancer, optimal therapy can only be achieved by classifying patients into clinically meaningful phenotypic groups (much like TNM) and letting the phenotype drive therapy.

CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations.

PubMed

Khanna, Anchit; Rane, Jayant K; Kivinummi, Kati K; Urbanucci, Alfonso; Helenius, Merja A; Tolonen, Teemu T; Saramäki, Outi R; Latonen, Leena; Manni, Visa; Pimanda, John E; Maitland, Norman J; Westermarck, Jukka; Visakorpi, Tapio

2015-08-14

Residual androgen receptor (AR)-signaling and presence of cancer stem-like cells (SCs) are the two emerging paradigms for clinically challenging castration-resistant prostate cancer (CRPC). Therefore, identification of AR-target proteins that are also overexpressed in the cancer SC population would be an attractive therapeutic approach.Our analysis of over three hundred clinical samples and patient-derived prostate epithelial cultures (PPECs), revealed Cancerous inhibitor of protein phosphatase 2A (CIP2A) as one such target. CIP2A is significantly overexpressed in both hormone-naïve prostate cancer (HN-PC) and CRPC patients . CIP2A is also overexpressed, by 3- and 30-fold, in HN-PC and CRPC SCs respectively. In vivo binding of the AR to the intronic region of CIP2A and its functionality in the AR-moderate and AR-high expressing LNCaP cell-model systems is also demonstrated. Further, we show that AR positively regulates CIP2A expression, both at the mRNA and protein level. Finally, CIP2A depletion reduced cell viability and colony forming efficiency of AR-independent PPECs as well as AR-responsive LNCaP cells, in which anchorage-independent growth is also impaired.These findings identify CIP2A as a common denominator for AR-signaling and cancer SC functionality, highlighting its potential therapeutic significance in the most clinically challenging prostate pathology: castration-resistant prostate cancer.

Category III chronic prostatitis/chronic pelvic pain syndrome: insights from the National Institutes of Health Chronic Prostatitis Collaborative Research Network studies.

PubMed

Nickel, J Curtis; Alexander, Richard B; Anderson, Rodney; Berger, Richard; Comiter, Craig V; Datta, Nand S; Fowler, Jackson E; Krieger, John N; Landis, J Richard; Litwin, Mark S; McNaughton-Collins, Mary; O'Leary, Michael P; Pontari, Michel A; Schaeffer, Anthony J; Shoskes, Daniel A; White, Paige; Kusek, John; Nyberg, Leroy

2008-07-01

Chronic prostatitis/chronic pelvic pain syndrome remains an enigmatic medical condition. Creation of the National Institutes of Health-funded Chronic Prostatitis Collaborative Research Network (CPCRN) has stimulated a renewed interest in research on and clinical aspects of chronic prostatitis/chronic pelvic pain syndrome. Landmark publications of the CPCRN document a decade of progress. Insights from these CPCRN studies have improved our management of chronic prostatitis/chronic pelvic pain syndrome and offer hope for continued progress.

Prostate atypia: does repeat biopsy detect clinically significant prostate cancer?

PubMed

Dorin, Ryan P; Wiener, Scott; Harris, Cory D; Wagner, Joseph R

2015-05-01

While the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia. We reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service. Ten thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein's criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient. ASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. © 2015 Wiley Periodicals, Inc.

Variation in prostate cancer treatment associated with population density of the county of residence.

PubMed

Cary, C; Odisho, A Y; Cooperberg, M R

2016-06-01

We sought to assess variation in the primary treatment of prostate cancer by examining the effect of population density of the county of residence on treatment for clinically localized prostate cancer and quantify variation in primary treatment attributable to the county and state level. A total 138 226 men with clinically localized prostate cancer in the Surveillance, Epidemiology and End Result (SEER) database in 2005 through 2008 were analyzed. The main association of interest was between prostate cancer treatment and population density using multilevel hierarchical logit models while accounting for the random effects of counties nested within SEER regions. To quantify the effect of county and SEER region on individual treatment, the percent of total variance in treatment attributable to county of residence and SEER site was estimated with residual intraclass correlation coefficients. Men with localized prostate cancer in metropolitan counties had 23% higher odds of being treated with surgery or radiation compared with men in rural counties, controlling for number of urologists per county as well as clinical and sociodemographic characteristics. Three percent (95% confidence interval (CI): 1.2-6.2%) of the total variation in treatment was attributable to SEER site, while 6% (95% CI: 4.3-9.0%) of variation was attributable to county of residence, adjusting for clinical and sociodemographic characteristics. Variation in treatment for localized prostate cancer exists for men living in different population-dense counties of the country. These findings highlight the importance of comparative effectiveness research to improve understanding of this variation and lead to a reduction in unwarranted variation.

Impact of Lesion Visibility on Transrectal Ultrasound on the Prediction of Clinically Significant Prostate Cancer (Gleason Score 3 + 4 or Greater) with Transrectal Ultrasound-Magnetic Resonance Imaging Fusion Biopsy.

PubMed

Garcia-Reyes, Kirema; Nguyen, Hao G; Zagoria, Ronald J; Shinohara, Katsuto; Carroll, Peter R; Behr, Spencer C; Westphalen, Antonio C

2017-09-20

The purpose of this study was to estimate the impact of lesion visibility with transrectal ultrasound on the prediction of clinically significant prostate cancer with transrectal ultrasound-magnetic resonance imaging fusion biopsy. This HIPAA (Health Insurance Portability and Accountability Act) compliant, institutional review board approved, retrospective study was performed in 178 men who were 64.7 years old with prostate specific antigen 8.9 ng/ml. They underwent transrectal ultrasound-magnetic resonance imaging fusion biopsy from January 2013 to September 2016. Visible lesions on magnetic resonance imaging were assigned a PI-RADS™ (Prostate Imaging Reporting and Data System), version 2 score of 3 or greater. Transrectal ultrasound was positive when a hypoechoic lesion was identified. We used a 3-level, mixed effects logistic regression model to determine how transrectal ultrasound-magnetic resonance imaging concordance predicted the presence of clinically significant prostate cancer. The diagnostic performance of the 2 methods was estimated using ROC curves. A total of 1,331 sextants were targeted by transrectal ultrasound-magnetic resonance imaging fusion or systematic biopsies, of which 1,037 were negative, 183 were Gleason score 3 + 3 and 111 were Gleason score 3 + 4 or greater. Clinically significant prostate cancer was diagnosed by transrectal ultrasound and magnetic resonance imaging alone at 20.5% and 19.7% of these locations, respectively. Men with positive imaging had higher odds of clinically significant prostate cancer than men without visible lesions regardless of modality (transrectal ultrasound OR 14.75, 95% CI 5.22-41.69, magnetic resonance imaging OR 12.27, 95% CI 6.39-23.58 and the 2 modalities OR 28.68, 95% CI 14.45-56.89, all p <0.001). The ROC AUC to detect clinically significant prostate cancer using the 2 methods (0.85, 95% CI 0.81-0.89) was statistically greater than that of transrectal ultrasound alone (0.80, 95% CI 0.76-0.85, p = 0.001) and magnetic resonance imaging alone (0.83, 95% CI 0.79-0.87, p = 0.04). The sensitivity and specificity of transrectal ultrasound were 42.3% and 91.6%, and the sensitivity and specificity of magnetic resonance imaging were 62.2% and 84.1%, respectively. Lesion visibility on magnetic resonance imaging or transrectal ultrasound denotes a similar probability of clinically significant prostate cancer. This probability is greater when each examination is positive. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

68Ga-PSMA-11 PET/CT in Newly Diagnosed Carcinoma of the Prostate: Correlation of Intraprostatic PSMA Uptake with Several Clinical Parameters.

PubMed

Koerber, Stefan A; Utzinger, Maximilian T; Kratochwil, Clemens; Kesch, Claudia; Haefner, Matthias F; Katayama, Sonja; Mier, Walter; Iagaru, Andrei H; Herfarth, Klaus; Haberkorn, Uwe; Debus, Juergen; Giesel, Frederik L

2017-12-01

68 Ga-prostate-specific membrane antigen (PSMA) PET/CT is a promising diagnostic tool for patients with prostate cancer. Our study evaluates SUVs in benign prostate tissue and malignant, intraprostatic tumor lesions and correlates results with several clinical parameters. Methods: One hundred four men with newly diagnosed prostate carcinoma and no previous therapy were included in this study. SUV max was measured and correlated with biopsy findings and MRI. Afterward, data were compared with current prostate-specific antigen (PSA) values, Gleason score (GS), and d'Amico risk classification. Results: In this investigation a mean SUV max of 1.88 ± 0.44 in healthy prostate tissue compared with 10.77 ± 8.45 in malignant prostate lesions ( P < 0.001) was observed. Patients with higher PSA, higher GS, and higher d'Amico risk score had statistically significant higher PSMA uptake on PET/CT ( P < 0.001 each). Conclusion: PSMA PET/CT is well suited for detecting the intraprostatic malignant lesion in patients with newly diagnosed prostate cancer. Our findings indicate a significant correlation of PSMA uptake with PSA, GS, and risk classification according to the d'Amico scale. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Benign Prostatic Hyperplasia: from Bench to Clinic

PubMed Central

Cho, Hee Ju

2012-01-01

Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options. PMID:22468207

SHBG Is an Important Factor in Stemness Induction of Cells by DHT In Vitro and Associated with Poor Clinical Features of Prostate Carcinomas

PubMed Central

Ma, Yuanyuan; Liang, Dongming; Liu, Jian; Wen, Jian-Guo; Servoll, Einar; Waaler, Gudmund; Sæter, Thorstein; Axcrona, Karol; Vlatkovic, Ljiljana; Axcrona, Ulrika; Paus, Elisabeth; Yang, Yue; Zhang, Zhiqian; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

2013-01-01

Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression. PMID:23936228

Clinical implications of prostate-specific antigen in men and women.

PubMed

Yu, H

2000-01-01

Prostate-specific antigen (PSA) is a valuable tumor marker for prostate cancer. Although it is indeed produced at an extremely high level by the prostate, PSA is also expressed in many female tissues, especially those regulated by sex steroid hormones. PSA is detected in both normal and abnormal breast tissue, as well as in various breast fluids, including milk, nipple aspirate, and cyst fluid. Clinical studies suggest that the presence of PSA in breast tissue may indicate a favorable prognosis for breast cancer patients. Levels of PSA in nipple aspirate fluid, however, may be indicative of breast cancer risk. Concentrations of PSA in serum are elevated in pregnant women as well as in women who have excess androgens. More studies are necessary to determine the clinical implications of the presence of PSA in amniotic fluid and female serum.

Real World Evidence: A Quantitative and Qualitative Glance at Participant Feedback from a Free-Response Survey Investigating Experiences of a Structured Exercise Intervention for Men with Prostate Cancer.

PubMed

Fox, L; Cahill, F; Burgess, C; Peat, N; Rudman, S; Kinsella, J; Cahill, D; George, G; Santaolalla, A; Van Hemelrijck, M

2017-01-01

To explore patient experiences of a structured exercise intervention for men with prostate cancer (PCa). 41 men with either localised or advanced PCa who had been referred for a structured exercise programme by their physician and then subsequently consented to a telephone survey. Participants underwent a 10-week supervised exercise programme within a large cancer centre hospital consisting of 8 sessions. They then completed a short multiple choice telephone survey, elaborating on their responses where appropriate. Views expressed by participants were analysed using an affinity diagram and common themes were identified. Feedback from our telephone surveys was consistently positive and suggests that the structured exercise intervention provides exercise confidence, motivation to exercise, and social support and promotes positive health behaviour change in the context of exercise. Individual differences arose amongst participants in their perceived utility of the intervention, with 73.3% expressing a preference for structured exercise classes and 19.5% expressing a preference for exercising independently. Design of a structured exercise intervention for patients with PCa should embrace the positive aspects outlined here but consider patients' individual differences. Ongoing feedback from patients should be utilised alongside traditional study designs to inform intervention design in this area.

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.

[Giant prostatic calculus with neurogenic bladder disease and prostate diverticulum: a case report and review of the literature].

PubMed

Li, Xiao-Shi; Quan, Chang-Yi; Li, Gang; Cai, Qi-Liang; Hu, Bin; Wang, Jiu-Wei; Niu, Yuan-Jie

2013-02-01

To study the etiology, clinical manifestation, diagnosis and treatment of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum. We retrospectively analyzed the clinical data of a case of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum and reviewed the relevant literature. The patient was a 37-year-old man, with urinary incontinence for 22 years and intermittent dysuria with frequent micturition for 9 years, aggravated in the past 3 months. He had received surgery for spina bifida and giant vesico-prostatic calculus. The results of preoperative routine urinary examination were as follows: WBC 17 -20/HPF, RBC 12 - 15/HPF. KUB, IVU and pelvic CT revealed spina bifida occulta, neurogenic bladder and giant prostatic calculus. The patient underwent TURP and transurethral lithotripsy with holmium-YAG laser. The prostatic calculus was carbonate apatite in composition. Urinary dynamic images at 2 weeks after surgery exhibited significant improvement in the highest urine flow rate and residual urine volume. Seventeen months of postoperative follow-up showed dramatically improved urinary incontinence and thicker urine stream. Prostate diverticulum with prostatic giant calculus is very rare, and neurogenic bladder may play a role in its etiology. Cystoscopy is an accurate screening method for its diagnosis. For the young patients and those who wish to retain sexual function, TURP combined with holmium laser lithotripsy can be employed, and intraoperative rectal examination should be taken to ensure complete removal of calculi.

MO-B-BRC-01: Introduction [Brachytherapy

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

Prisciandaro, J.

2016-06-15

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

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.

Co-Expression of Putative Cancer Stem Cell Markers CD44 and CD133 in Prostate Carcinomas.

PubMed

Kalantari, Elham; Asgari, Mojgan; Nikpanah, Seyedehmoozhan; Salarieh, Naghme; Asadi Lari, Mohammad Hossein; Madjd, Zahra

2017-10-01

Cancer stem cells (CSCs) are the main players of prostate tumorigenesis thus; characterization of CSCs can pave the way for understanding the early detection, drug resistance, metastasis and relapse. The current study was conducted to evaluate the expression level and clinical significance of the potential CSC markers CD44 and CD133 in a series of prostate tissues. One hundred and forty eight prostate tissues composed of prostate cancer (PCa), high-grade prostatic intraepithelial neoplasia (HGPIN), and benign prostate hyperplasia (BPH) were immunostained for the putative CSC markers CD44 and CD133. Subsequently, the correlation between the expression of these markers and the clinicopathological variables was examined. A higher level of CD44 expression was observed in 42% of PCa, 57% of HGPIN, and 42% BPH tissues. In the case of CD133 expression PCa, HGPIN, and BPH samples demonstrated high immunoreactivity in 46%, 43%, and 42% of cells, respectively. Statistical analysis showed an inverse significant correlation between CD44 expression with Gleason score of PCa (P = 0.02), while no significant correlation was observed between CD133 expression and clinicopathological parameters. A significant reciprocal correlation was observed between the expression of two putative CSC markers CD44 and CD133 in PCa specimens while not indicating clinical significance. Further clinical investigation is required to consider these markers as targets of new therapeutic strategies for PCa.

The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients

PubMed Central

Pascale, Mariarosa; Aversa, Cinzia; Barbazza, Renzo; Marongiu, Barbara; Siracusano, Salvatore; Stoffel, Flavio; Sulfaro, Sando; Roggero, Enrico; Stanta, Giorgio

2016-01-01

Abstract Background Neuroendocrine markers, which could indicate for aggressive variants of prostate cancer and Ki67 (a well-known marker in oncology for defining tumor proliferation), have already been associated with clinical outcome in prostate cancer. The aim of this study was to investigate the prognostic value of those markers in primary prostate cancer patients. Patients and methods NSE (neuron specific enolase), ChrA (chromogranin A), Syp (Synaptophysin) and Ki67 staining were performed by immunohistochemistry. Then, the prognostic impact of their expression on overall survival was investigated in 166 primary prostate cancer patients by univariate and multivariate analyses. Results NSE, ChrA, Syp and Ki67 were positive in 50, 45, 54 and 146 out of 166 patients, respectively. In Kaplan-Meier analysis only diffuse NSE staining (negative vs diffuse, p = 0.004) and Ki67 (≤ 10% vs > 10%, p < 0.0001) were significantly associated with overall survival. Ki67 expression, but not NSE, resulted as an independent prognostic factor for overall survival in multivariate analysis. Conclusions A prognostic model incorporating Ki67 expression with clinical-pathological covariates could provide additional prognostic information. Ki67 may thus improve prediction of prostate cancer outcome based on standard clinical-pathological parameters improving prognosis and management of prostate cancer patients. PMID:27679548

Molecular and Clinical Predictors of Aggressive Prostate Cancer

DTIC Science & Technology

2008-09-01

Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiology Biomarkers and Prevention 2006;15: 939-45. 12. Urisman A, Molinaro...combined with the findings of serologic evidence of T vaginalis and prostate cancer mortality provide supportive evidence for the study hypothesis

Efficient 3D multi-region prostate MRI segmentation using dual optimization.

PubMed

Qiu, Wu; Yuan, Jing; Ukwatta, Eranga; Sun, Yue; Rajchl, Martin; Fenster, Aaron

2013-01-01

Efficient and accurate extraction of the prostate, in particular its clinically meaningful sub-regions from 3D MR images, is of great interest in image-guided prostate interventions and diagnosis of prostate cancer. In this work, we propose a novel multi-region segmentation approach to simultaneously locating the boundaries of the prostate and its two major sub-regions: the central gland and the peripheral zone. The proposed method utilizes the prior knowledge of the spatial region consistency and employs a customized prostate appearance model to simultaneously segment multiple clinically meaningful regions. We solve the resulted challenging combinatorial optimization problem by means of convex relaxation, for which we introduce a novel spatially continuous flow-maximization model and demonstrate its duality to the investigated convex relaxed optimization problem with the region consistency constraint. Moreover, the proposed continuous max-flow model naturally leads to a new and efficient continuous max-flow based algorithm, which enjoys great advantages in numerics and can be readily implemented on GPUs. Experiments using 15 T2-weighted 3D prostate MR images, by inter- and intra-operator variability, demonstrate the promising performance of the proposed approach.

Clinical characteristics and prognostic factors of prostate cancer with liver metastases.

PubMed

Wang, HaiTao; Li, BaoGuo; Zhang, PengYu; Yao, YanHong; Chang, JiWu

2014-01-01

Liver metastasis from prostate cancer is uncommon and remains poorly understood. We computer searched the clinical records of all our patients registered into a database to identify patients that presented or developed liver metastases. A total of 27 prostate cancer patients with ultrasound or CT/MR imaging evidence of liver metastases were included in our analysis. The liver metastasis rate from metastatic prostate cancer was 4.29%. Eight (29.63%) patients had previously untreated, hormone-naive prostate cancer (synchronous liver metastases at diagnosis of prostate cancer), whereas 19 (70.37%) patients had already been diagnosed as having hormone-refractory prostate cancer. In the hormone-naive group, the median overall survival after liver metastases diagnosis was 38 months and half of the patients were still alive at the latest follow-up, whereas only 6 months in the hormone-refractory group (p = 0.003). High concentration of serum neuron-specific enolase and previous chemotherapy were associated with a significantly poor overall survival after liver metastases in the hormone-refractory group using Kaplan–Meier curves and logrank tests for univariate analysis.

Evaluation of apoptosis indexes in currently used oral alpha- blockers in prostate: a pilot study

PubMed Central

Demir, Mehmet; Akin, Yigit; Terim, Kubra Asena Kapakin; Gulum, Mehmet; Buyukfirat, Evren; Ciftci, Halil; Yeni, Ercan

2018-01-01

ABSTRACT Objectives: Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Materials and Methods: Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Pa- tients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analy- sis in Java were used for evaluations. Statistical significant p was p<0.05. Results: There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statisti- cal significant difference apoptosis index in immunochemical TUNEL dyeing and im- age software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Conclusions: Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis. PMID:29617082

Evaluation of apoptosis indexes in currently used oral alpha-blockers in prostate: a pilot study.

PubMed

Demir, Mehmet; Akin, Yigit; Terim, Kubra Asena Kapakin; Gulum, Mehmet; Buyukfirat, Evren; Ciftci, Halil; Yeni, Ercan

2018-01-01

Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Patients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analysis in Java were used for evaluations. Statistical significant p was p<0.05. There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statistical significant difference apoptosis index in immunochemical TUNEL dyeing and image software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis. Copyright® by the International Brazilian Journal of Urology.

[Significance of PSMA imaging in prostate cancer].

PubMed

Gasch, C; Düwel, C; Kopka, K; Kratochwil, C; Vinsensia, M; Eiber, M; Maurer, T; Haberkorn, U; Hadaschik, B; Giesel, F L

2017-01-01

Prostate cancer (PCa) is one of the most common malignancies of men in developed countries. To improve clinical diagnostics of PCa, 68 Ga-PSMA-11 was recently introduced as a new PET tracer. 68 Ga-PSMA-11 is able to specifically bind to the prostate-specific membrane antigen (PSMA), which is upregulated on the surface of prostate cancer cells in most patients. To analyse the current significance of 68 Ga-PSMA-11 PET imaging in prostate cancer in relation to staging of men with initial diagnosis, biochemical recurrence and metastatic disease. Retrospective analysis of current literature (PubMed search) regarding 68 Ga-PSMA-11 PET diagnostics in primary staging, in biochemical recurrence and in metastasized disease. Compared to conventional imaging, 68 Ga-PSMA-11 PET/CT reaches a higher sensitivity with an excellent specificity in the clinical diagnosis of primary staging as well as staging for recurrence and advanced, metastasized disease. In biochemical recurrence, 68 Ga-PSMA-11 PET/CT shows significantly higher detection rates in comparison to choline PET/CT, especially in patients with low PSA values. In the clinical diagnosis of recurrent disease, therapy concepts were changed in more than a quarter of the patients due to the use of 68 Ga-PSMA-11 PET/CT. The significance of staging with 68 Ga-PSMA-11 PET/CT in advanced metastasized patients remains uncertain. Due to the excellent results of 68 Ga-PSMA-11 PET imaging, even in patients with slightly elevated PSA levels, it will continue to play an important role in clinical diagnostics of prostate cancer and, thus, its clinical utilization will become more widely spread.

Multiparametric MRI followed by targeted prostate biopsy for men with suspected prostate cancer: a clinical decision analysis

PubMed Central

Willis, Sarah R; Ahmed, Hashim U; Moore, Caroline M; Donaldson, Ian; Emberton, Mark; Miners, Alec H; van der Meulen, Jan

2014-01-01

Objective To compare the diagnostic outcomes of the current approach of transrectal ultrasound (TRUS)-guided biopsy in men with suspected prostate cancer to an alternative approach using multiparametric MRI (mpMRI), followed by MRI-targeted biopsy if positive. Design Clinical decision analysis was used to synthesise data from recently emerging evidence in a format that is relevant for clinical decision making. Population A hypothetical cohort of 1000 men with suspected prostate cancer. Interventions mpMRI and, if positive, MRI-targeted biopsy compared with TRUS-guided biopsy in all men. Outcome measures We report the number of men expected to undergo a biopsy as well as the numbers of correctly identified patients with or without prostate cancer. A probabilistic sensitivity analysis was carried out using Monte Carlo simulation to explore the impact of statistical uncertainty in the diagnostic parameters. Results In 1000 men, mpMRI followed by MRI-targeted biopsy ‘clinically dominates’ TRUS-guided biopsy as it results in fewer expected biopsies (600 vs 1000), more men being correctly identified as having clinically significant cancer (320 vs 250), and fewer men being falsely identified (20 vs 50). The mpMRI-based strategy dominated TRUS-guided biopsy in 86% of the simulations in the probabilistic sensitivity analysis. Conclusions Our analysis suggests that mpMRI followed by MRI-targeted biopsy is likely to result in fewer and better biopsies than TRUS-guided biopsy. Future research in prostate cancer should focus on providing precise estimates of key diagnostic parameters. PMID:24934207

Biomarkers in prostate cancer - Current clinical utility and future perspectives.

PubMed

Kretschmer, Alexander; Tilki, Derya

2017-12-01

Current tendencies in the treatment course of prostate cancer patients increase the need for reliable biomarkers that help in decision-making in a challenging clinical setting. Within the last decade, several novel biomarkers have been introduced. In the following comprehensive review article, we focus on diagnostic (PHI ® , 4K score, SelectMDx ® , ConfirmMDx ® , PCA3, MiPS, ExoDX ® , mpMRI) and prognostic (OncotypeDX GPS ® , Prolaris ® , ProMark ® , DNA-ploidy, Decipher ® ) biomarkers that are in widespread clinical use and are supported by evidence. Hereby, we focus on multiple clinical situations in which innovative biomarkers may guide decision-making in prostate cancer therapy. In addition, we describe novel liquid biopsy approaches (circulating tumor cells, cell-free DNA) that have been described as predictive biomarkers in metastatic castration-resistant prostate cancer and might support an individual patient-centred oncological approach in the nearer future. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

DTIC Science & Technology

2016-10-01

consensus meeting, with input from investigators in the Prostate Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study...Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study Endpoint and Label Development Team, and FDA Division of...Abstract. American Society of Clinical Oncology . Chicago IL, June 1-5, 2013. INVENTIONS, PATENTS AND LICENSES None 11 REPORTABLE OUTCOMES

[Concomitant oncopathological changes in the prostate of urinary bladder cancer patients undergoing radical cystoprostateectomy].

PubMed

Komyakov, B K; Sergeev, A V; Fadeev, V A; Ismailov, K I; Ulyanov, A Yu; Shmelev, A Yu; Onoshko, M V

2017-09-01

To determine the incidence of spreading bladder transitional cell carcinoma and primary adenocarcinoma to the prostate in patients with bladder cancer undergoing radical cystectomy. From 1995 to 2016, 283 men underwent radical cystectomy with removal of the bladder, perivesical tissue, prostate, seminal vesicles and pelvic lymph nodes. Prostate sparing cystectomy was performed in 45 (13.7%) patients. The whole prostate and the apex of the prostate were preserved in 21 (6.4%) and 24 (7.3%) patients, respectively. The spread of transitional cell cancer of the bladder to the prostate occurred in 50 (15.2%) patients. Twelve (3.6%) patients were found to have primary prostate adenocarcinoma. Clinically significant prostate cancer was diagnosed in 4 (33.3%) patients. We believe that the high oncological risk of prostate sparing cystectomy, despite some functional advantages, dictates the need for complete removal of the prostate in the surgical treatment of bladder cancer.

Tuberculous prostatitis: mimicking a cancer.

PubMed

Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay

2016-01-01

Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions.

Development and clinical introduction of automated radiotherapy treatment planning for prostate cancer

NASA Astrophysics Data System (ADS)

Winkel, D.; Bol, G. H.; van Asselen, B.; Hes, J.; Scholten, V.; Kerkmeijer, L. G. W.; Raaymakers, B. W.

2016-12-01

To develop an automated radiotherapy treatment planning and optimization workflow to efficiently create patient specifically optimized clinical grade treatment plans for prostate cancer and to implement it in clinical practice. A two-phased planning and optimization workflow was developed to automatically generate 77Gy 5-field simultaneously integrated boost intensity modulated radiation therapy (SIB-IMRT) plans for prostate cancer treatment. A retrospective planning study (n  =  100) was performed in which automatically and manually generated treatment plans were compared. A clinical pilot (n  =  21) was performed to investigate the usability of our method. Operator time for the planning process was reduced to  <5 min. The retrospective planning study showed that 98 plans met all clinical constraints. Significant improvements were made in the volume receiving 72Gy (V72Gy) for the bladder and rectum and the mean dose of the bladder and the body. A reduced plan variance was observed. During the clinical pilot 20 automatically generated plans met all constraints and 17 plans were selected for treatment. The automated radiotherapy treatment planning and optimization workflow is capable of efficiently generating patient specifically optimized and improved clinical grade plans. It has now been adopted as the current standard workflow in our clinic to generate treatment plans for prostate cancer.

Multiparametric MRI of Prostate Cancer: An Update on State-of-the-Art Techniques and Their Performance in Detecting and Localizing Prostate Cancer

PubMed Central

Hegde, John V.; Mulkern, Robert V.; Panych, Lawrence P.; Fennessy, Fiona M.; Fedorov, Andriy; Maier, Stephan E.; Tempany, Clare M.C.

2013-01-01

Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided. PMID:23606141

Contralateral routing of signals disrupts monaural level and spectral cues to sound localisation on the horizontal plane.

PubMed

Pedley, Adam J; Kitterick, Pádraig T

2017-09-01

Contra-lateral routing of signals (CROS) devices re-route sound between the deaf and hearing ears of unilaterally-deaf individuals. This rerouting would be expected to disrupt access to monaural level cues that can support monaural localisation in the horizontal plane. However, such a detrimental effect has not been confirmed by clinical studies of CROS use. The present study aimed to exercise strict experimental control over the availability of monaural cues to localisation in the horizontal plane and the fitting of the CROS device to assess whether signal routing can impair the ability to locate sources of sound and, if so, whether CROS selectively disrupts monaural level or spectral cues to horizontal location, or both. Unilateral deafness and CROS device use were simulated in twelve normal hearing participants. Monaural recordings of broadband white noise presented from three spatial locations (-60°, 0°, and +60°) were made in the ear canal of a model listener using a probe microphone with and without a CROS device. The recordings were presented to participants via an insert earphone placed in their right ear. The recordings were processed to disrupt either monaural level or spectral cues to horizontal sound location by roving presentation level or the energy across adjacent frequency bands, respectively. Localisation ability was assessed using a three-alternative forced-choice spatial discrimination task. Participants localised above chance levels in all conditions. Spatial discrimination accuracy was poorer when participants only had access to monaural spectral cues compared to when monaural level cues were available. CROS use impaired localisation significantly regardless of whether level or spectral cues were available. For both cues, signal re-routing had a detrimental effect on the ability to localise sounds originating from the side of the deaf ear (-60°). CROS use also impaired the ability to use level cues to localise sounds originating from straight ahead (0°). The re-routing of sounds can restrict access to the monaural cues that provide a basis for determining sound location in the horizontal plane. Perhaps encouragingly, the results suggest that both monaural level and spectral cues may not be disrupted entirely by signal re-routing and that it may still be possible to reliably identify sounds originating on the hearing side. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

VPAC1-targeted PET/CT scan: improved molecular imaging for the diagnosis of prostate cancer using a novel cell surface antigen.

PubMed

Truong, Hong; Gomella, Leonard G; Thakur, Mathew L; Trabulsi, Edouard J

2018-05-01

Current approaches to prostate cancer screening and diagnosis are plagued with limitations in diagnostic accuracy. There is a compelling need for biomolecular imaging that will not only detect prostate cancer early but also distinguish prostate cancer from benign lesions accurately. In this topic paper, we review evidence that supports further investigation of VPAC1-targeted PET/CT imaging in the primary diagnosis of prostate cancer. A non-systematic review of Medline/PubMed was performed. English language guidelines on prostate cancer diagnosis and management, original articles, and review articles were selected based on their clinical relevance. VPAC1 receptors were overexpressed 1000 times more in prostate cancer than benign prostatic stromal tissue. In vitro and in vivo studies showed that Copper-64 labeled analogs of VPAC1 ligands can be synthesized with high radiochemical efficiency and purity. The radioactive probes had excellent VPAC1 receptor binding specificity and affinity. They had good biochemical stability in vitro and in mouse and human serum. They had minimal urinary excretion, which made them favorable for prostate cancer imaging. Initial feasibility study in men with prostate cancer showed that the probes were safe with no reported adverse reaction. 64 Cu-TP3805 PET/CT detected 98% of prostate cancer lesions and nodal metastasis as confirmed with whole mount histopathological evaluation. VPAC1 receptors are promising targets for biomolecular imaging of primary prostate cancer that can distinguish malignant from benign lesions non-invasively. Further investigations are warranted to validate initial findings and define the clinical utilities of VPAC1-targeted PET imaging for prostate cancer diagnosis and management.

Optical coherence elastography (OCE) as a method for identifying benign and malignant prostate biopsies

NASA Astrophysics Data System (ADS)

Li, Chunhui; Guan, Guangying; Ling, Yuting; Lang, Stephen; Wang, Ruikang K.; Huang, Zhihong; Nabi, Ghulam

2015-03-01

Objectives. Prostate cancer is the most frequently diagnosed malignancy in men. Digital rectal examination (DRE) - a known clinical tool based on alteration in the mechanical properties of tissues due to cancer has traditionally been used for screening prostate cancer. Essentially, DRE estimates relative stiffness of cancerous and normal prostate tissue. Optical coherence elastography (OCE) are new optical imaging techniques capable of providing cross-sectional imaging of tissue microstructure as well as elastogram in vivo and in real time. In this preliminary study, OCE was used in the setting of the human prostate biopsies ex vivo, and the images acquired were compared with those obtained using standard histopathologic methods. Methods. 120 prostate biopsies were obtained by TRUS guided needle biopsy procedures from 9 patients with clinically suspected cancer of the prostate. The biopsies were approximately 0.8mm in diameter and 12mm in length, and prepared in Formalin solution. Quantitative assessment of biopsy samples using OCE was obtained in kilopascals (kPa) before histopathologic evaluation. The results obtained from OCE and standard histopathologic evaluation were compared provided the cross-validation. Sensitivity, specificity, and positive and negative predictive values were calculated for OCE (histopathology was a reference standard). Results. OCE could provide quantitative elasticity properties of prostate biopsies within benign prostate tissue, prostatic intraepithelial neoplasia, atypical hyperplasia and malignant prostate cancer. Data analysed showed that the sensitivity and specificity of OCE for PCa detection were 1 and 0.91, respectively. PCa had significantly higher stiffness values compared to benign tissues, with a trend of increasing in stiffness with increasing of malignancy. Conclusions. Using OCE, microscopic resolution elastogram is promising in diagnosis of human prostatic diseases. Further studies using this technique to improve the detection and staging of malignant cancer of the prostate are ongoing.

The Stockholm-3 (STHLM3) Model can Improve Prostate Cancer Diagnostics in Men Aged 50-69 yr Compared with Current Prostate Cancer Testing.

PubMed

Eklund, Martin; Nordström, Tobias; Aly, Markus; Adolfsson, Jan; Wiklund, Peter; Brandberg, Yvonne; Thompson, James; Wiklund, Fredrik; Lindberg, Johan; Presti, Joseph C; StLezin, Mark; Clements, Mark; Egevad, Lars; Grönberg, Henrik

2016-11-23

Prostate cancer screening is associated with low specificity, unnecessary biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA) ≥3ng/ml as an indication for biopsy. Urologists in today's current prostate cancer testing (CPT) have access to numerous variables in addition to PSA (eg, age, ethnicity, family history, free PSA, PSA velocity, digital rectal examination, and prostate volume) to support biopsy decisions. We estimated the number of prostate cancers diagnosed and prostate biopsies performed if S3M replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men enrolled in the STHLM3 validation cohort 2012-2015. With the same sensitivity as CPT to diagnose Gleason score ≥7 prostate cancer, S3M was estimated to reduce the number of men biopsied by 53% (95% confidence interval [CI]: 41-65%), avoid 76% (95% CI: 67-81%) of negative biopsies, and reduce Gleason score 6 cancers by 23% (95% CI: 6-40%). S3M has the potential to improve prostate cancer diagnostics by better selecting men with high risk of GS ≥7 prostate cancer. We modeled the effect the Stockholm-3 model would have on prostate cancer diagnostics if it replaced current clinical practice. We found that Stockholm-3 model may substantially reduce the number of biopsies, while maintaining the same sensitivity to diagnose clinically significant prostate cancer. Copyright © 2016. Published by Elsevier B.V.

Interfraction Prostate Movement in Bone Alignment After Rectal Enema for Radiotherapy

PubMed Central

Seo, Young Eun; Kim, Tae Hyo; Lee, Ki Soo; Cho, Won Yeol; Lee, Hyung-Sik; Hur, Won-Joo

2014-01-01

Purpose To assess the effect of a rectal enema on interfraction prostate movement in bone alignment (BA) for prostate radiotherapy (RT), we analyzed the spatial difference in prostates in a bone-matched setup. Materials and Methods We performed BA retrospectively with data from prostate cancer patients who underwent image-guided RT (IGRT). The prostate was identified with implanted fiducial markers. The setup for the IGRT was conducted with the matching of three fiducial markers on RT planning computed tomography images and those on two oblique kV x-ray images. Offline BA was performed at the same position. The coordinates of a virtual prostate in BA and a real prostate were obtained by use of the ExaxTrac/NovalisBody system, and the distance between them was calculated as the spatial difference. Interfraction prostate displacement was drawn from the comparison of the spatial differences. Results A total of 15 patients with localized prostate cancer treated with curative hypofractionated IGRT were enrolled. A total of 420 fractions were analyzed. The mean of the interfraction prostate displacements after BA was 3.12±2.00 mm (range, 0.20-10.53 mm). The directional difference was profound in the anterior-posterior and supero-inferior directions (2.14±1.73 mm and 1.97±1.44 mm, respectively) compared with the right-left direction (0.26±0.22 mm, p<0.05). The required margin around the clinical target volume was 4.97 mm with the formula of van Herk et al. Conclusions The interfraction prostate displacement was less frequent when a rectal enema was performed before the procedure. A rectal enema can be used to reduce interfraction prostate displacement and resulting clinical target volume-to-planning target volume margin. PMID:24466393

Building a high-resolution T2-weighted MR-based probabilistic model of tumor occurrence in the prostate.

PubMed

Nagarajan, Mahesh B; Raman, Steven S; Lo, Pechin; Lin, Wei-Chan; Khoshnoodi, Pooria; Sayre, James W; Ramakrishna, Bharath; Ahuja, Preeti; Huang, Jiaoti; Margolis, Daniel J A; Lu, David S K; Reiter, Robert E; Goldin, Jonathan G; Brown, Matthew S; Enzmann, Dieter R

2018-02-19

We present a method for generating a T2 MR-based probabilistic model of tumor occurrence in the prostate to guide the selection of anatomical sites for targeted biopsies and serve as a diagnostic tool to aid radiological evaluation of prostate cancer. In our study, the prostate and any radiological findings within were segmented retrospectively on 3D T2-weighted MR images of 266 subjects who underwent radical prostatectomy. Subsequent histopathological analysis determined both the ground truth and the Gleason grade of the tumors. A randomly chosen subset of 19 subjects was used to generate a multi-subject-derived prostate template. Subsequently, a cascading registration algorithm involving both affine and non-rigid B-spline transforms was used to register the prostate of every subject to the template. Corresponding transformation of radiological findings yielded a population-based probabilistic model of tumor occurrence. The quality of our probabilistic model building approach was statistically evaluated by measuring the proportion of correct placements of tumors in the prostate template, i.e., the number of tumors that maintained their anatomical location within the prostate after their transformation into the prostate template space. Probabilistic model built with tumors deemed clinically significant demonstrated a heterogeneous distribution of tumors, with higher likelihood of tumor occurrence at the mid-gland anterior transition zone and the base-to-mid-gland posterior peripheral zones. Of 250 MR lesions analyzed, 248 maintained their original anatomical location with respect to the prostate zones after transformation to the prostate. We present a robust method for generating a probabilistic model of tumor occurrence in the prostate that could aid clinical decision making, such as selection of anatomical sites for MR-guided prostate biopsies.

Prostate cancer localization with endorectal MR imaging and MR spectroscopic imaging: effect of clinical data on reader accuracy.

PubMed

Dhingsa, Rajpal; Qayyum, Aliya; Coakley, Fergus V; Lu, Ying; Jones, Kirk D; Swanson, Mark G; Carroll, Peter R; Hricak, Hedvig; Kurhanewicz, John

2004-01-01

To determine the effect of digital rectal examination findings, sextant biopsy results, and prostate-specific antigen (PSA) levels on reader accuracy in the localization of prostate cancer with endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging. This was a retrospective study of 37 patients (mean age, 57 years) with biopsy-proved prostate cancer. Transverse T1-weighted, transverse high-spatial-resolution, and coronal T2-weighted MR images and MR spectroscopic images were obtained. Two independent readers, unaware of clinical data, recorded the size and location of suspicious peripheral zone tumor nodules on a standardized diagram of the prostate. Readers also recorded their degree of diagnostic confidence for each nodule on a five-point scale. Both readers repeated this interpretation with knowledge of rectal examination findings, sextant biopsy results, and PSA level. Step-section histopathologic findings were the reference standard. Logistic regression analysis with generalized estimating equations was used to correlate tumor detection with clinical data, and alternative free-response receiver operating characteristic (AFROC) curve analysis was used to examine the overall effect of clinical data on all positive results. Fifty-one peripheral zone tumor nodules were identified at histopathologic evaluation. Logistic regression analysis showed awareness of clinical data significantly improved tumor detection rate (P <.02) from 15 to 19 nodules for reader 1 and from 13 to 19 nodules for reader 2 (27%-37% overall) by using both size and location criteria. AFROC analysis showed no significant change in overall reader performance because there was an associated increase in the number of false-positive findings with awareness of clinical data, from 11 to 21 for reader 1 and from 16 to 25 for reader 2. Awareness of clinical data significantly improves reader detection of prostate cancer nodules with endorectal MR imaging and MR spectroscopic imaging, but there is no overall change in reader accuracy, because of an associated increase in false-positive findings. A stricter definition of a true-positive result is associated with reduced sensitivity for prostate cancer nodule detection. Copyright RSNA, 2004

Emerging Therapies in Metastatic Prostate Cancer.

PubMed

Sonnenburg, Daniel W; Morgans, Alicia K

2018-04-11

In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy. A single-arm phase 2 study of the PARP inhibitor olaparib demonstrated high response rates and more favorable progression-free and overall survival for men with metastatic castration-resistant prostate cancer and DNA repair defects treated with olaparib compared with men without DNA repair defects. Multiple ongoing clinical trials are investigating novel hormonal therapies and combinations of chemotherapy, targeted small molecules, immunotherapy, and radiopharmaceuticals. Progress continues to be made in the treatment of metastatic prostate cancer, and ongoing clinical trials continue to investigate novel agents and approaches to treatment.

MR-CT registration using a Ni-Ti prostate stent in image-guided radiotherapy of prostate cancer.

PubMed

Korsager, Anne Sofie; Carl, Jesper; Østergaard, Lasse Riis

2013-06-01

In image-guided radiotherapy of prostate cancer defining the clinical target volume often relies on magnetic resonance (MR). The task of transferring the clinical target volume from MR to standard planning computed tomography (CT) is not trivial due to prostate mobility. In this paper, an automatic local registration approach is proposed based on a newly developed removable Ni-Ti prostate stent. The registration uses the voxel similarity measure mutual information in a two-step approach where the pelvic bones are used to establish an initial registration for the local registration. In a phantom study, the accuracy was measured to 0.97 mm and visual inspection showed accurate registration of all 30 data sets. The consistency of the registration was examined where translation and rotation displacements yield a rotation error of 0.41° ± 0.45° and a translation error of 1.67 ± 2.24 mm. This study demonstrated the feasibility for an automatic local MR-CT registration using the prostate stent.

Finasteride Reduces the Risk of Incident Clinical Benign Prostatic Hyperplasia

PubMed Central

Parsons, J. Kellogg; Schenk, Jeannette M.; Arnold, Kathryn B.; Messer, Karen; Till, Cathee; Thompson, Ian M.; Kristal, Alan R.

2014-01-01

Background Despite the high prevalence of clinical benign prostatic hyperplasia (BPH) among older men, there remains a notable absence of studies focused on BPH prevention. Objective To determine if finasteride prevents incident clinical BPH in healthy older men. Design, setting, and participants Data for this study are from the Prostate Cancer Prevention Trial. After excluding those with a history of BPH diagnosis or treatment, or an International Prostate Symptom Score (IPSS) ≥8 at study entry, 9253 men were available for analysis. Outcome measurements and statistical analysis The primary outcome was incident clinical BPH, defined as the initiation of medical treatment, surgery, or sustained, clinically significant urinary symptoms (IPSS >14). Finasteride efficacy was estimated using Cox proportional regression models to generate hazards ratios (HRs). Results and limitations Mean length of follow-up was 5.3 yr. The rate of clinical BPH was 19 per 1000 person-years in the placebo arm and 11 per 1000 person-years in the finasteride arm (p < 0.001). In a covariate-adjusted model, finasteride reduced the risk of incident clinical BPH by 40% (HR: 0.60; 95% confidence interval, 0.51–0.69; p < 0.001). The effect of finasteride on incident clinical BPH was attenuated in men with a body mass index ≥30 kg/m2 (pinteraction = 0.04) but otherwise did not differ significantly by physical activity, age, race, current diabetes, or current smoking. The post hoc nature of the analysis is a potential study limitation. Conclusions Finasteride substantially reduces the risk of incident clinical BPH in healthy older men. These results should be considered in formulating recommendations for the use of finasteride to prevent prostate diseases in asymptomatic older men. PMID:22459892

Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

DTIC Science & Technology

2007-12-01

anticancer drug effectiveness. PDT is currently in worldwide multicenter clinical trials for the localized prostate cancer therapy. The available results...indicate that PDT employing advanced laser fiber technology and sophisticated light dosimetry is able to treat localized prostate cancer in an...treatment for localized prostate cancer patients that accounts for more than 90% of total prostate cancer population. 15. SUBJECT TERMS Photodynamic

Unusual Giant Prostatic Urethral Calculus

PubMed Central

Bello, A.; Maitama, H. Y.; Mbibu, N. H.; Kalayi, G. D.; Ahmed, A.

2010-01-01

Giant vesico-prostatic urethral calculus is uncommon. Urethral stones rarely form primarily in the urethra, and they are usually associated with urethral strictures, posterior urethral valve or diverticula. We report a case of a 32-year-old man with giant vesico-prostatic (collar-stud) urethral stone presenting with sepsis and bladder outlet obstruction. The clinical presentation, management, and outcome of the giant prostatic urethral calculus are reviewed. PMID:22091328

Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study.

PubMed

Abrate, Alberto; Lazzeri, Massimo; Lughezzani, Giovanni; Buffi, Nicolòmaria; Bini, Vittorio; Haese, Alexander; de la Taille, Alexandre; McNicholas, Thomas; Redorta, Joan Palou; Gadda, Giulio M; Lista, Giuliana; Kinzikeeva, Ella; Fossati, Nicola; Larcher, Alessandro; Dell'Oglio, Paolo; Mistretta, Francesco; Freschi, Massimo; Guazzoni, Giorgio

2015-04-01

To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer. © 2014 The Authors. BJU International © 2014 BJU International.

SRD5A1 and SRD5A2 are associated with treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic receptor antagonists.

PubMed

Gu, Xin; Na, Rong; Huang, Tao; Wang, Li; Tao, Sha; Tian, Lu; Chen, Zhuo; Jiao, Yang; Kang, Jian; Zheng, Siqun; Xu, Jianfeng; Sun, Jielin; Qi, Jun

2013-08-01

Common treatments for benign prostatic hyperplasia include 5α-reductase inhibitors and α-adrenergic receptor antagonists. However, these treatments can only partially decrease the risk of benign prostatic hyperplasia progression. SRD5A1 and SRD5A2 are 5α-reductase inhibitor targets. We investigated the association between drug efficacy and single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a Chinese population. We genotyped 11 tagging single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a total of 426 benign prostatic hyperplasia cases and 1,008 controls from Xinhua Hospital, Shanghai, People's Republic of China. Cases were treated with type II 5α-reductase inhibitors and α-adrenergic receptor antagonists. We tested the association of tagging single nucleotide polymorphisms with benign prostatic hyperplasia risk/progression, clinical characteristics at baseline, including the I-PSS (International Prostate Symptom Score) and total prostate volume, and changes in clinical characteristics after treatment. The 11 tagging single nucleotide polymorphisms were not significantly associated with benign prostatic hyperplasia risk or progression (each p >0.05). In the SRD5A1 gene rs6884552 and rs3797177 were significantly associated with baseline I-PSS (p = 0.04 and 0.003, respectively). In the SRD5A2 gene rs523349 (V89L) and rs9332975 were significantly associated with baseline total prostate volume (p = 0.01 and 0.001, respectively). In SRD5A1 rs166050 was significantly associated with the posttreatment change in total prostate volume (p = 0.04). In SRD5A2 rs523349 and rs612224 were significantly associated with the posttreatment I-PSS change (p = 0.03 and 0.009, respectively). SRD5A1 and SRD5A2 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Investigating the prostate specific antigen, body mass index and age relationship: is an age-BMI-adjusted PSA model clinically useful?

PubMed

Harrison, Sean; Tilling, Kate; Turner, Emma L; Lane, J Athene; Simpkin, Andrew; Davis, Michael; Donovan, Jenny; Hamdy, Freddie C; Neal, David E; Martin, Richard M

2016-12-01

Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age-BMI-adjusted PSA model would be clinically useful for detecting prostate cancer. Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50-69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m 2 . Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status. In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7-2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m 2 (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m 2 increase in BMI (95% CI 3.4-6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0-15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age-BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer. Age and BMI were associated with small changes in PSA. An age-BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics, and Their Environment

DTIC Science & Technology

2011-07-01

cancer clinical trials, attitudes and knowledge about such trials, and barriers to and facilitators of participation, b) Conduct a self-administered...facilitate or hinder participation in prostate cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of...cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of prostate trials and sites, and broader community

Can exercise suppress tumour growth in advanced prostate cancer patients with sclerotic bone metastases? A randomised, controlled study protocol examining feasibility, safety and efficacy.

PubMed

Hart, Nicolas H; Newton, Robert U; Spry, Nigel A; Taaffe, Dennis R; Chambers, Suzanne K; Feeney, Kynan T; Joseph, David J; Redfern, Andrew D; Ferguson, Tom; Galvão, Daniel A

2017-05-30

Exercise may positively alter tumour biology through numerous modulatory and regulatory mechanisms in response to a variety of modes and dosages, evidenced in preclinical models to date. Specifically, localised and systemic biochemical alterations produced during and following exercise may suppress tumour formation, growth and distribution by virtue of altered epigenetics and endocrine-paracrine activity. Given the impressive ability of targeted mechanical loading to interfere with metastasis-driven tumour formation in human osteolytic tumour cells, it is of equal interest to determine whether a similar effect is observed in sclerotic tumour cells. The study aims to (1) establish the feasibility and safety of a combined modular multimodal exercise programme with spinal isometric training in advanced prostate cancer patients with sclerotic bone metastases and (2) examine whether targeted and supervised exercise can suppress sclerotic tumour growth and activity in spinal metastases in humans. A single-blinded, two-armed, randomised, controlled and explorative phase I clinical trial combining spinal isometric training with a modular multimodal exercise programme in 40 men with advanced prostate cancer and stable sclerotic spinal metastases. Participants will be randomly assigned to (1) the exercise intervention or (2) usual medical care. The intervention arm will receive a 3-month, supervised and individually tailored modular multimodal exercise programme with spinal isometric training. Primary endpoints (feasibility and safety) and secondary endpoints (tumour morphology; biomarker activity; anthropometry; musculoskeletal health; adiposity; physical function; quality of life; anxiety; distress; fatigue; insomnia; physical activity levels) will be measured at baseline and following the intervention. Statistical analyses will include descriptive characteristics, t-tests, effect sizes and two-way (group × time) repeated-measures analysis of variance (or analysis of covariance) to examine differences between groups over time. The data-set will be primarily examined using an intention-to-treat approach with multiple imputations, followed by a secondary sensitivity analysis to ensure data robustness using a complete cases approach. Ethics approval was obtained from the Human Research Ethics Committee (HREC) of Edith Cowan University and the Sir Charles Gairdner and Osborne Park Health Care Group. If proven to be feasible and safe, this study will form the basis of future phase II and III trials in human patients with advanced cancer. To reach a maximum number of clinicians, practitioners, patients and scientists, outcomes will be disseminated through national and international clinical, conference and patient presentations, as well as publication in high-impact, peer-reviewed academic journals. ACTRN 12616000179437. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Epidemiology of senile prostatic enlargement among elderly men in Arar, Kingdom of Saudi Arabia

PubMed Central

Alanazi, Abdullah Barghash; Alshalan, Anfal Muaddi; Alanazi, Omar Ayed; Alanazi, Munif Salah; Alanazi, Abdulaziz Inad; Alanazi, Abdullah Hussain; Alhadhari, Anwar Mohammed; Alanazi, Ahmed Saad; Alanazi, Rahmah Abdulhadi; Alanazi, Ibtisam Matan; Alanazi, Mohammed Abdullah; Alkhidhr, Mohammed Abdullah; Aldehneen, Hassan Ali; Alanazi, Raed Khalid

2017-01-01

Background and aim Senile prostatic enlargement due to benign prostatic hyperplasia (BPH) is a common problem among older men, and is responsible for considerable disability. This study was conducted to determine the prevalence and determinants of the clinically diagnosed prostatic enlargement among elderly men in Arar, Northern Saudi Arabia. Methods This cross-sectional study was carried out on all consented elderly males attending the outpatient clinic of the urology department of Arar Central Hospital from February 2017 to July 30, 2017. Each participant underwent a general examination and digital per rectal to detect general chronic diseases, obesity and prostatic enlargement. Data were analyzed by SPSS version 16, using descriptive statistics and Chi-squared test. Results Among 81 elderly male participants in the study, 19.8% had clinically diagnosed senile prostatic enlargement (SPE) and 3.7% had prostatic tumors. There was significant relation between SPE and age as 6.2% of cases were 60–69 years, 43.8% were 70–79 years and 44.0% were 80 years or more (p<0.05). There was also significant relation between SPE and obesity as 62.5% of cases were obese and 37.5% were non obese (p<0.05). There was no significant relation with marital status, smoking or diabetes mellitus (p<0.05). Conclusion Senile prostatic enlargement is one of the significant important issues in public health in Arar city, Northern Saudi Arabia. The prevalence of this condition reaches 19.3%, thereby placing even greater burden on the quality of life of the elderly and on the health system in the region. PMID:29038720

Towards clinical application of RayStretch for heterogeneity corrections in LDR permanent 125I prostate brachytherapy.

PubMed

Hueso-González, Fernando; Ballester, Facundo; Perez-Calatayud, Jose; Siebert, Frank-André; Vijande, Javier

RayStretch is a simple algorithm proposed for heterogeneity corrections in low-dose-rate brachytherapy. It is built on top of TG-43 consensus data, and it has been validated with Monte Carlo (MC) simulations. In this study, we take a real clinical prostate implant with 71 125 I seeds as reference and we apply RayStretch to analyze its performance in worst-case scenarios. To do so, we design two cases where large calcifications are located in the prostate lobules. RayStretch resilience under various calcification density values is also explored. Comparisons against MC calculations are performed. Dose-volume histogram-related parameters like prostate D 90 , rectum D 2cc , or urethra D 10 obtained with RayStretch agree within a few percent with the detailed MC results for all cases considered. The robustness and compatibility of RayStretch with commercial treatment planning systems indicate its applicability in clinical practice for dosimetric corrections in prostate calcifications. Its use during intraoperative ultrasound planning is foreseen. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Long Non-Coding RNA as Potential Biomarker for Prostate Cancer: Is It Making a Difference?

PubMed

Deng, Junli; Tang, Jie; Wang, Guo; Zhu, Yuan-Shan

2017-03-07

Whole genome transcriptomic analyses have identified numerous long non-coding RNA (lncRNA) transcripts that are increasingly implicated in cancer biology. LncRNAs are found to promote essential cancer cell functions such as proliferation, invasion, and metastasis, with the potential to serve as novel biomarkers of various cancers and to further reveal uncharacterized aspects of tumor biology. However, the biological and molecular mechanisms as well as the clinical applications of lncRNAs in diverse diseases are not completely understood, and remain to be fully explored. LncRNAs may be critical players and regulators in prostate cancer carcinogenesis and progression, and could serve as potential biomarkers for prostate cancer. This review focuses on lncRNA biomarkers that are already available for clinical use and provides an overview of lncRNA biomarkers that are under investigation for clinical development in prostate cancer.

Proposed Morphologic Classification of Prostate Cancer With Neuroendocrine Differentiation

PubMed Central

Epstein, Jonathan I.; Amin, Mahul B.; Beltran, Himisha; Lotan, Tamara L.; Mosquera, Juan-Miguel; Reuter, Victor E.; Robinson, Brian D.; Troncoso, Patricia; Rubin, Mark A.

2014-01-01

On July 31, 2013, the Prostate Cancer Foundation assembled a working committee on the molecular biology and pathologic classification of neuroendocrine differentiation in prostate cancer. The committee consisted of genitourinary oncologists, urologists, urological surgical pathologists, basic scientists, and translational researchers, with expertise in this field. It was concluded that the proceedings of the meeting should be reported in 2 manuscripts appealing to different target audiences, one to focus on surgical pathology and the other to review the molecular aspects of this disease. New clinical and molecular data emerging from prostate cancers treated by contemporary androgen deprivation therapies, as well as primary lesions, have highlighted the need for refinement of diagnostic terminology to encompass the full spectrum of neuroendocrine differentiation. It is envisioned that specific criteria associated with the refined diagnostic terminology will lead to clinically relevant pathologic diagnoses that will stimulate further clinical and molecular investigation and identification of appropriate targeted therapies. PMID:24705311

A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer

PubMed Central

Lunardi, Andrea; Ala, Ugo; Epping, Mirjam T.; Salmena, Leonardo; Clohessy, John G.; Webster, Kaitlyn A.; Wang, Guocan; Mazzucchelli, Roberta; Bianconi, Maristella; Stack, Edward C.; Lis, Rosina; Patnaik, Akash; Cantley, Lewis C.; Bubley, Glenn; Cordon-Cardo, Carlos; Gerald, William L.; Montironi, Rodolfo; Signoretti, Sabina; Loda, Massimo; Nardella, Caterina; Pandolfi, Pier Paolo

2013-01-01

Here we report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. We show that castration counteracts tumor progression in a Pten-loss driven mouse model of prostate cancer through the induction of apoptosis and proliferation block. Conversely, this response is bypassed upon deletion of either Trp53 or Lrf together with Pten, leading to the development of castration resistant prostate cancer (CRPC). Mechanistically, the integrated acquisition of data from mouse models and patients identifies the expression patterns of XAF1-XIAP/SRD5A1 as a predictive and actionable signature for CRPC. Importantly, we show that combined inhibition of XIAP, SRD5A1, and AR pathways overcomes castration resistance. Thus, our co-clinical approach facilitates stratification of patients and the development of tailored and innovative therapeutic treatments. PMID:23727860

CCR study: evidence for benefit of TARP vaccine for men with early stage prostate cancer | Center for Cancer Research

Cancer.gov

Results from a pilot clinical trial found that TARP, or T-cell receptor gamma chain alternate reading frame protein, vaccination slowed prostate-specific antigen (PSA) rise in the majority of patients with early stage prostate cancer.

Antioxidant Prophylaxis in the Prevention of Prostatic Epithelial Neoplasia

DTIC Science & Technology

2009-02-01

of antioxidants such as selenium, tocopherols , lycopene, β-carotene etc. have been found to be effective in lowering prostate cancer risk. Although...3ng/ml; 2). The α- tocopherol , β-carotene (ATBC) cancer prevention trial in Finland found that consumption of vitamin E reduced clinical prostate

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.

Incidental prostate cancer in patients with muscle-invasive bladder cancer who underwent radical cystoprostatectomy.

PubMed

Tanaka, Toshikazu; Koie, Takuya; Ohyama, Chikara; Hashimoto, Yasuhiro; Imai, Atsushi; Tobisawa, Yuki; Hatakeyama, Shingo; Yamamoto, Hayato; Yoneyama, Tohru; Horiguchi, Hirotaka; Kodama, Hirotake; Yoneyama, Takahiro

2017-11-01

The aim of this study was to analyze the features of incidentally detected prostate cancer (PCa) in radical cystoprostatectomy (RCP) specimens to determine their pathological characteristics and clinical significance. In this retrospective study, we reviewed the clinical and pathological records of 431 consecutive patients with muscle-invasive bladder cancer who underwent RCP at Hirosaki University. Of these, we focused on 237 male patients with prostate-specific antigen (PSA) measurements and digital rectal examinations (DRE) that were recorded prior to the RCP. Significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, pathological T3 or higher stage, lymph node involvement or three or more multifocal lesions within the prostate specimen. We compared clinically significant and insignificant PCa. In this study, a total of 43 patients (18.1%) were diagnosed with incidental PCa via RCP specimens. Age, preoperative PSA levels and pathological T stage in patients with clinically significant PCa were considerably higher than in those with insignificant cancer. Apical involvement was found in 16 patients, including 11 of those with clinically significant PCa. By the end of the follow-up period, none of the enrolled patients had a biochemical recurrence after surgery or died from PCa. According to our findings, preoperative risk factors were not reliable enough to accurately predict clinically significant PCa. Although there was no biochemical relapse or clinical recurrence of PCa in this study, the potential oncologic risk of prostate-sparing RCP must be considered. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Minimally important difference for the Expanded Prostate Cancer Index Composite Short Form.

PubMed

Skolarus, Ted A; Dunn, Rodney L; Sanda, Martin G; Chang, Peter; Greenfield, Thomas K; Litwin, Mark S; Wei, John T

2015-01-01

To establish a score threshold that constitutes a clinically relevant change for each domain of the Expanded Prostate Cancer Index Composite (EPIC) Short Form (EPIC-26). Although its use in clinical practice and clinical trials has increased worldwide, the clinical interpretation of this 26-item disease-specific patient-reported quality of life questionnaire for men with localized prostate cancer would be facilitated by characterization of score thresholds for clinically relevant change (the minimally important differences [MIDs]). We used distribution- and anchor-based approaches to establish the MID range for each EPIC-26 domain (urinary, sexual, bowel, and vitality/hormonal) based on a prospective multi-institutional cohort of 1201 men treated for prostate cancer between 2003 and 2006 and followed up for 3 years after treatment. For the anchor-based approach, we compared within-subject and between-subject score changes for each domain to an external "anchor" measure of overall cancer treatment satisfaction. We found the bowel and vitality/hormonal domains to have the lowest MID range (a 4-6 point change should be considered clinically relevant), whereas the sexual domain had the greatest MID values (10-12). Urinary incontinence appeared to have a greater MID range (6-9) than the urinary irritation/obstruction domain (5-7). Using 2 independent approaches, we established the MIDs for each EPIC-26 domain. A definition of these MID values is essential for the researcher or clinician to understand when changes in symptom burden among prostate cancer survivors are clinically relevant. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers

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

Koontz, Bridget F., E-mail: bridget.koontz@duke.edu; Tsivian, Matvey; Mouraviev, Vladimir

Purpose: To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. Methods: One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Results: Nine hundred seventy-nine patientsmore » had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Conclusions: Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.« less

Impact of primary Gleason grade on risk stratification for Gleason score 7 prostate cancers.

PubMed

Koontz, Bridget F; Tsivian, Matvey; Mouraviev, Vladimir; Sun, Leon; Vujaskovic, Zeljko; Moul, Judd; Lee, W Robert

2012-01-01

To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Nine hundred seventy-nine patients had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities. Copyright © 2012 Elsevier Inc. All rights reserved.

Methodology to study the three-dimensional spatial distribution of prostate cancer and their dependence on clinical parameters

PubMed Central

Rojas, Kristians Diaz; Montero, Maria L.; Yao, Jorge; Messing, Edward; Fazili, Anees; Joseph, Jean; Ou, Yangming; Rubens, Deborah J.; Parker, Kevin J.; Davatzikos, Christos; Castaneda, Benjamin

2015-01-01

Abstract. A methodology to study the relationship between clinical variables [e.g., prostate specific antigen (PSA) or Gleason score] and cancer spatial distribution is described. Three-dimensional (3-D) models of 216 glands are reconstructed from digital images of whole mount histopathological slices. The models are deformed into one prostate model selected as an atlas using a combination of rigid, affine, and B-spline deformable registration techniques. Spatial cancer distribution is assessed by counting the number of tumor occurrences among all glands in a given position of the 3-D registered atlas. Finally, a difference between proportions is used to compare different spatial distributions. As a proof of concept, we compare spatial distributions from patients with PSA greater and less than 5  ng/ml and from patients older and younger than 60 years. Results suggest that prostate cancer has a significant difference in the right zone of the prostate between populations with PSA greater and less than 5  ng/ml. Age does not have any impact in the spatial distribution of the disease. The proposed methodology can help to comprehend prostate cancer by understanding its spatial distribution and how it changes according to clinical parameters. Finally, this methodology can be easily adapted to other organs and pathologies. PMID:26236756

Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

PubMed

Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Kadono, Yoshifumi; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

2016-03-01

To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

Impact of Body Mass Index, Age, Prostate Volume, and Genetic Polymorphisms on Prostate-specific Antigen Levels in a Control Population.

PubMed

Cornu, Jean-Nicolas; Cancel-Tassin, Geraldine; Cox, David G; Roupret, Morgan; Koutlidis, Nicolas; Bigot, Pierre; Valeri, Antoine; Ondet, Valerie; Gaffory, Cécile; Fournier, Georges; Azzouzi, Abdel-Rahmene; Cormier, Luc; Cussenot, Olivier

2016-07-01

Prostate-specific antigen (PSA) is still the cornerstone of prostate cancer (PCa) screening and diagnosis in both research and current clinical practice. Inaccuracy of PSA is partly due to the influence of a number of genetic, clinical, and biological factors modifying PSA blood levels. In the present study, we detailed the respective influence of each factor among age, body mass index (BMI), prostate volume, and five single-nucleotide polymorphisms-rs10788160 (10q26), rs10993994 (10q11), rs11067228 (12q24), rs17632542 (19q13.33), and rs2928679 (8p21)-on PSA values in a cohort of 1374 men without PCa. Our results show that genetic factors, when risk variants are combined, influence PSA levels with an effect size similar to that of BMI. Taken together, the respective correlations of clinical parameters and genetic parameters would make it possible to correct and adjust PSA values more effectively in each individual. These results establish the basis to understand and implement a more personalised approach for the interpretation of PSA blood levels in the context of PCa screening and diagnosis. Prostate-specific antigen (PSA) values in an individual may vary according to genetic predisposition. The effect size of this variation can be significant, comparable with those resulting from clinical characteristics. Personalised PSA testing should take this into account. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Differentiation among prostate cancer patients with Gleason score of 7 using histopathology whole-slide image and genomic data

NASA Astrophysics Data System (ADS)

Ren, Jian; Karagoz, Kubra; Gatza, Michael; Foran, David J.; Qi, Xin

2018-03-01

Prostate cancer is the most common non-skin related cancer affecting 1 in 7 men in the United States. Treatment of patients with prostate cancer still remains a difficult decision-making process that requires physicians to balance clinical benefits, life expectancy, comorbidities, and treatment-related side effects. Gleason score (a sum of the primary and secondary Gleason patterns) solely based on morphological prostate glandular architecture has shown as one of the best predictors of prostate cancer outcome. Significant progress has been made on molecular subtyping prostate cancer delineated through the increasing use of gene sequencing. Prostate cancer patients with Gleason score of 7 show heterogeneity in recurrence and survival outcomes. Therefore, we propose to assess the correlation between histopathology images and genomic data with disease recurrence in prostate tumors with a Gleason 7 score to identify prognostic markers. In the study, we identify image biomarkers within tissue WSIs by modeling the spatial relationship from automatically created patches as a sequence within WSI by adopting a recurrence network model, namely long short-term memory (LSTM). Our preliminary results demonstrate that integrating image biomarkers from CNN with LSTM and genomic pathway scores, is more strongly correlated with patients recurrence of disease compared to standard clinical markers and engineered image texture features. The study further demonstrates that prostate cancer patients with Gleason score of 4+3 have a higher risk of disease progression and recurrence compared to prostate cancer patients with Gleason score of 3+4.

How accurate is our clinical prediction of "minimal prostate cancer"?

PubMed

Leibovici, Dan; Shikanov, Sergey; Gofrit, Ofer N; Zagaja, Gregory P; Shilo, Yaniv; Shalhav, Arieh L

2013-07-01

Recommendations for active surveillance versus immediate treatment for low risk prostate cancer are based on biopsy and clinical data, assuming that a low volume of well-differentiated carcinoma will be associated with a low progression risk. However, the accuracy of clinical prediction of minimal prostate cancer (MPC) is unclear. To define preoperative predictors for MPC in prostatectomy specimens and to examine the accuracy of such prediction. Data collected on 1526 consecutive radical prostatectomy patients operated in a single center between 2003 and 2008 included: age, body mass index, preoperative prostate-specific antigen level, biopsy Gleason score, clinical stage, percentage of positive biopsy cores, and maximal core length (MCL) involvement. MPC was defined as < 5% of prostate volume involvement with organ-confined Gleason score < or = 6. Univariate and multivariate logistic regression analyses were used to define independent predictors of minimal disease. Classification and Regression Tree (CART) analysis was used to define cutoff values for the predictors and measure the accuracy of prediction. MPC was found in 241 patients (15.8%). Clinical stage, biopsy Gleason's score, percent of positive biopsy cores, and maximal involved core length were associated with minimal disease (OR 0.42, 0.1, 0.92, and 0.9, respectively). Independent predictors of MPC included: biopsy Gleason score, percent of positive cores and MCL (OR 0.21, 095 and 0.95, respectively). CART showed that when the MCL exceeded 11.5%, the likelihood of MPC was 3.8%. Conversely, when applying the most favorable preoperative conditions (Gleason < or = 6, < 20% positive cores, MCL < or = 11.5%) the chance of minimal disease was 41%. Biopsy Gleason score, the percent of positive cores and MCL are independently associated with MPC. While preoperative prediction of significant prostate cancer was accurate, clinical prediction of MPC was incorrect 59% of the time. Caution is necessary when implementing clinical data as selection criteria for active surveillance.

Is the Ellipsoid Formula the New Standard for 3-Tesla MRI Prostate Volume Calculation without Endorectal Coil?

PubMed

Haas, Matthias; Günzel, Karsten; Miller, Kurt; Hamm, Bernd; Cash, Hannes; Asbach, Patrick

2017-01-01

Prostate volume in multiparametric MRI (mpMRI) is of clinical importance. For 3-Tesla mpMRI without endorectal coil, there is no distinctive standard for volume calculation. We tested the accuracy of the ellipsoid formula with planimetric volume measurements as reference and investigated the correlation of gland volume and cancer detection rate on MRI/ultrasound (MRI/US) fusion-guided biopsy. One hundred forty-three patients with findings on 3-Tesla mpMRI suspicious of cancer and subsequent MRI/US fusion-guided targeted biopsy and additional systematic biopsy were analyzed. T2-weighted images were used for measuring the prostate diameters and for planimetric volume measurement by a segmentation software. Planimetric and calculated prostate volumes were compared with clinical data. The median prostate volume was 48.1 ml (interquartile range (IQR) 36.9-62.1 ml). Volume calculated by the ellipsoid formula showed a strong concordance with planimetric volume, with a tendency to underestimate prostate volume (median volume 43.1 ml (IQR 31.2-58.8 ml); r = 0.903, p < 0.001). There was a moderate, significant inverse correlation of prostate volume to a positive biopsy result (r = -0.24, p = 0.004). The ellipsoid formula gives sufficient approximation of prostate volume on 3-Tesla mpMRI without endorectal coil. It allows a fast, valid volume calculation in prostate MRI datasets. © 2016 S. Karger AG, Basel.

Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) in prostate cancer.

PubMed

Avgeris, Margaritis; Koutalellis, Georgios; Fragoulis, Emmanuel G; Scorilas, Andreas

2008-10-01

L-Dopa decarboxylase (DDC) is a pyridoxal 5'-phosphate-dependent enzyme that was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of DDC in prostate tissues and to evaluate its clinical utility in prostate cancer (CaP). Total RNA was isolated from 118 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients and a highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDC mRNA quantification has been developed using the SYBR Green chemistry. LNCaP prostate cancer cell line was used as a calibrator and GAPDH as a housekeeping gene. DDC was found to be overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (p<0.001). Logistic regression and ROC analysis have demonstrated that the DDC expression has significant discriminatory value between CaP and BPH (p<0.001). DDC expression status was compared with other established prognostic factors, in prostate cancer. High expression levels of DDC were found more frequently in high Gleason's score tumors (p=0.022) as well as in advanced stage patients (p=0.032). Our data reveal the potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer.

Recent Advances in Prostate Cancer Treatment and Drug Discovery.

PubMed

Nevedomskaya, Ekaterina; Baumgart, Simon J; Haendler, Bernard

2018-05-04

Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC). Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA) targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.

Nomograms to predict the pathological stage of clinically localized prostate cancer in Korean men: comparison with western predictive tools using decision curve analysis.

PubMed

Jeong, Chang Wook; Jeong, Seong Jin; Hong, Sung Kyu; Lee, Seung Bae; Ku, Ja Hyeon; Byun, Seok-Soo; Jeong, Hyeon; Kwak, Cheol; Kim, Hyeon Hoe; Lee, Eunsik; Lee, Sang Eun

2012-09-01

To develop and evaluate nomograms to predict the pathological stage of clinically localized prostate cancer after radical prostatectomy in Korean men. We reviewed the medical records of 2041 patients who had clinical stages T1c-T3a prostate cancer and were treated solely with radical prostatectomy at two hospitals. Logistic regressions were carried out to predict organ-confined disease, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis using preoperative variables and resulting nomograms. Internal validations were assessed using the area under the receiver operating characteristic curve and calibration plot, and then external validations were carried out on 129 patients from another hospital. Head-to-head comparisons with 2007 Partin tables and Cancer of the Prostate Risk Assessment score were carried out using the area under the curve and decision curve analysis. The significant predictors for organ-confined disease and extraprostatic extension were clinical stage, prostate-specific antigen, Gleason score and a percent positive core of biopsy. Significant predictors for seminal vesicle invasion were prostate-specific antigen, Gleason score and percent positive core, and those for lymph node metastasis were prostate-specific antigen and percent positive core. The area under the curve of established nomograms for organ-confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were 0.809, 0.804, 0.889 and 0.838, respectively. The nomograms were well calibrated and externally validated. These nomograms showed significantly higher accuracies and net benefits than two Western tools in Korean men. This is the first study to have developed and fully validated nomograms to predict the pathological stage of prostate cancer in an Asian population. These nomograms might be more accurate and useful for Korean men than other predictive models developed using Western populations. © 2012 The Japanese Urological Association.

Psychometric Assessment of the Chinese Version of the Abbreviated Expanded Prostate Cancer Index Composite (EPIC-26) and the Clinical Practice Version (EPIC-CP) in Chinese Men With Prostate Cancer.

PubMed

Lam, Wendy W T; Tse, Michael A; Ng, Chris N L; Chung, Edward K M; Fielding, Richard

2017-06-01

The Expanded Prostate Cancer Index Composite (EPIC) instrument was designed to assess a range of health-related quality-of-life issues specifically relevant to patients with prostate cancer. This study examined the validity and reliability of Chinese versions of the 26-item EPIC and of the 16-item EPIC for Clinical Practice (EPIC-CP) in Chinese patients with prostate cancer. A Chinese version of the 26-item EPIC and the 16-item EPIC-CP were self-completed by 252 Chinese patients with prostate cancer who were recruited from three community-based cancer service centers. Confirmatory factors analysis assessed the factor structures of the EPIC and the EPIC-CP. Internal consistency and construct and clinical validities of the factor structures were assessed. Confirmatory factor analysis revealed that the original factor structure of both EPIC-26 and EPIC-CP showed good fit to this sample. A correlated model was superior to a hierarchical model in both EPIC-26 and EPIC-CP supporting the utility of the domain scores over the total scores. Cronbach α ranged from 0.55 to 0.91 for EPIC-26 and 0.44 to 0.67 for EPIC-CP. Construct validity was supported by correlations between EPIC-26/EPIC-CP and psychological distress measures. Clinical validity was supported by differentiation between patients with and without prostatectomy. These Chinese versions of the five-factor EPIC-26 and the EPIC-CP are valid and practical measures for assessing a range of health-related quality-of-life issues related to the diagnosis and treatment of prostate cancer, highlighting their utility in assessing health-related quality of life for patients diagnosed with prostate cancer. Copyright © 2017 American Academy of Hospice and Palliative Medicine. 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.

[Morphea or juvenile localised scleroderma: Case report].

PubMed

Strickler, Alexis; Gallo, Silvanna; Jaramillo, Pedro; de Toro, Gonzalo

2016-01-01

Morphea or juvenile localised scleroderma (JLS) is an autoimmune, inflammatory, chronic, slowly progressive connective tissue disease of unknown cause that preferably affects skin and underlying tissues. To report a case of Juvenil Localised scleroderma in an 8-year old girl, contributing to an early diagnosis and treatment. The case is presented of an 8 year-old girl who presented with indurated hypopigmented plaques, of linear distribution in the right upper extremity of two years onset, together with papery texture hyperpigmented indurated plaques with whitish areas of thinned skin in right lower extremity, and leg and ankle swelling. The clinical features and diagnostic tests, including histology were compatible with linear and pansclerotic JLS. She started with immunosuppressive therapy, physiotherapy, and occupational therapy. We report a case of linear and pansclerotic ELJ type, in which there was a 2 year delay in diagnosis, however the response to treatment was positive as expected. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

A Review of Non-Invasive Techniques to Detect and Predict Localised Muscle Fatigue

PubMed Central

Al-Mulla, Mohamed R.; Sepulveda, Francisco; Colley, Martin

2011-01-01

Muscle fatigue is an established area of research and various types of muscle fatigue have been investigated in order to fully understand the condition. This paper gives an overview of the various non-invasive techniques available for use in automated fatigue detection, such as mechanomyography, electromyography, near-infrared spectroscopy and ultrasound for both isometric and non-isometric contractions. Various signal analysis methods are compared by illustrating their applicability in real-time settings. This paper will be of interest to researchers who wish to select the most appropriate methodology for research on muscle fatigue detection or prediction, or for the development of devices that can be used in, e.g., sports scenarios to improve performance or prevent injury. To date, research on localised muscle fatigue focuses mainly on the clinical side. There is very little research carried out on the implementation of detecting/predicting fatigue using an autonomous system, although recent research on automating the process of localised muscle fatigue detection/prediction shows promising results. PMID:22163810

[Clinical epidemiological assessments on 3521 patients suffering from road traffic injuries, in relation with trauma localisation and severity, assisted in "Sf. Ioan" Emergency Unit, during 2002-2009].

PubMed

Manole, M; Ciuhodaru, T; Zanoschi, Georgeta; Manole, Alina; Ivan, A

2011-01-01

The aim of study was to assess road traffic injuries in relation with their localisation and severity. A sample of 3521 patients suffering from road traffic injuries and assisted in "Sf. Ioan" Emergency Unit, Iaşi, Romania was assess regarding age group, sex and residence area, type of lesions and ther localisation and severity, between 2002-2009. Data were collected using a special epidemiological inquiry and processed using SPSS and MS Excel statistical softs. The incidence of road traffic injuries increased during the last decade, with a report men/women of 1.5, urban and 21-30 age group predominance. The most frequent were leg fractures (16.7%) and thoracal contusions (19.1%), cranial and facial trauma (32.4%), with open injuries (10.5%). Prevention programmes with a high efficiency at the national level, as well as a concret identification of risk factors with a multidisciplinar approach of road traffic accidents, are needed.

Anti-tumour activity of platinum compounds in advanced prostate cancer-a systematic literature review.

PubMed

Hager, S; Ackermann, C J; Joerger, M; Gillessen, S; Omlin, A

2016-06-01

For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents. To systematically identify and analyse clinical trials that have evaluated platinum agents in advanced prostate cancer patients. PubMed was searched to identify published clinical trials of platinum agents in advanced prostate cancer. The PRIMSA statement was followed for the systematic review process. Identified trials are analysed for study design, statistical plan, assessments of anti-tumour activity and the potential value of predictive biomarkers. A total of 163 references were identified by the literature search and 72 publications that met the selection criteria were included in this review; of these 33 used carboplatin, 27 cisplatin, 6 satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall, anti-tumour activity varies in the range of 10%-40% for objective response and 20%-70% for PSA decline ≥50%. Response seemed highest for the combinations of carboplatin with taxanes or oxaliplatin with gemcitabine. The interpretation of the clinical data is limited by differences in response criteria used and patient populations studied. Platinum compounds have moderate anti-tumour activity in molecularly unselected patients with advanced prostate cancer. Translational evidence of DNA repair deficiency should be leveraged in future studies to select prostate cancer patients most likely to benefit from platinum-based therapy. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Clinically localized prostate cancer in 2017: A review of comparative effectiveness.

PubMed

Lavery, Hugh J; Cooperberg, Matthew R

2017-02-01

Introducing the topic of comparative effectiveness for prostate cancer treatments with a reminder of the disease's heterogeneity risks tautology. However, the profound variation both in this cancer's biology and its clinical course is increasingly widely recognized, while management alternatives for clinically localized prostate cancer have exploded. Available options now include active surveillance, multiple surgical approaches to prostatectomy, various forms of external-beam and interstitial radiation, and a growing list of energy ablative technologies. Each treatment option has its own efficacy rate as well as its own set of complications, side effects and financial costs. Difficulties comparing these options, together with the high prevalence of the disease, led the Institute of Medicine to include localized prostate cancer among the top 25 priority conditions for future comparative effectiveness research. The sheer volume of possible treatment options, with their individual risks and benefits, can be confusing for patients and clinicians to research, understand and explain. To help clinicians navigate these treatment options, we have assembled this Urologic Oncology Seminar on the comparative effectiveness of treatments for clinically localized prostate cancer. The articles focus on high quality evidence-based medicine and most have included useful tables summarizing seminal trials and available resources. Copyright © 2017 Elsevier Inc. All rights reserved.

Using circulating tumor cells to inform on prostate cancer biology and clinical utility

PubMed Central

Li, Jing; Gregory, Simon G.; Garcia-Blanco, Mariano A.; Armstrong, Andrew J.

2016-01-01

Substantial advances in the molecular biology of prostate cancer have led to the approval of multiple new systemic agents to treat men with metastatic castration-resistant prostate cancer (mCRPC). These treatments encompass androgen receptor directed therapies, immunotherapies, bone targeting radiopharmaceuticals and cytotoxic chemotherapies. There is, however, great heterogeneity in the degree of patient benefit with these agents, thus fueling the need to develop predictive biomarkers that are able to rationally guide therapy. Circulating tumor cells (CTCs) have the potential to provide an assessment of tumor-specific biomarkers through a non-invasive, repeatable “liquid biopsy” of a patient’s cancer at a given point in time. CTCs have been extensively studied in men with mCRPC, where CTC enumeration using the Cellsearch® method has been validated and FDA approved to be used in conjunction with other clinical parameters as a prognostic biomarker in metastatic prostate cancer. In addition to enumeration, more sophisticated molecular profiling of CTCs is now feasible and may provide more clinical utility as it may reflect tumor evolution within an individual particularly under the pressure of systemic therapies. Here, we review technologies used to detect and characterize CTCs, and the potential biological and clinical utility of CTC molecular profiling in men with metastatic prostate cancer. PMID:26079252

Laboratory and clinical experience with neodymium:YAG laser prostatectomy

NASA Astrophysics Data System (ADS)

Kabalin, John N.

1996-05-01

Since 1991, we have undertaken extensive laboratory and clinical studies of the Neodymium:YAG (Nd:YAG) laser for surgical treatment of bladder outlet obstruction due to prostatic enlargement or benign prostatic hyperplasia (BPH). Side-firing optical fibers which emit a divergent, relatively low energy density Nd:YAG laser beam produce coagulation necrosis of obstructing periurethral prostate tissue, followed by gradual dissolution and slough in the urinary stream. Laser-tissue interactions and Nd:YAG laser dosimetry for prostatectomy have been studied in canine and human prostate model systems, enhancing clinical application. Ongoing studies examine comparative Nd:YAG laser dosimetry for various beam configurations produced by available side-firing optical fibers and continue to refine operative technique. We have documented clinical outcomes of Nd:YAG laser prostatectomy in 230 consecutive patients treated with the UrolaseTM side-firing optical fiber. Nd:YAG laser coagulation the prostate produces a remarkably low acute morbidity profile, with no significant bleeding or fluid absorption. No postoperative incontinence has been produced. Serial assessments of voiding outcomes over more than 3 years of followup show objective and symptomatic improvement following Nd:YAG laser prostatectomy which is comparable to older but more morbid electrosurgical approaches. Nd:YAG laser prostatectomy is a safe, efficacious, durable and cost-effective treatment for BPH.

High-sensitivity detection of PSA by time-resolved fluorometry with Europium chelate

NASA Astrophysics Data System (ADS)

Nahm, Kie B.; Jeong, Jin H.; Kim, Byoung C.; Kim, Jae H.; Kim, Young M.; Jeong, Dong S.; Oh, Sang W.; Choi, Eui Y.; Ko, Dong S.

2006-01-01

Prostate-specific antigen (PSA) is an androgen-dependent glycoprotein protease (M.W. 33 kDa) and a member of kallikrein super-family of serine protease, and has chymotrypsin-like enzymatic activity. It is synthesized by the prostate epithelial cells and found in the prostate gland and seminal plasma as a major protein. It is widely used as a clinical marker for diagnosis, screening, monitoring and prognosis of prostate cancer. In normal male adults, the concentration of PSA in the blood is below 4 ng/ml and this value increases in patients with the prostate cancer or the benign prostatic hyperplasia (BPH) due to its leakage into the circulatory system. As such, systematic monitoring of the PSA level in the blood can provide critical information about the progress of the prostatic disease. We have fabricated a bread-board time resolved fluorescence system that could detect a concentration of Prostate Specific Antigen t-PSA) at clinically meaningful level in plasma as well as in whole blood sample. We chose Europium chelates as the fluorescence markers to attach to the PSA for its long decay lifetime and relative photostability. We have simplified the electronic circuits considerably by employing a MCS. With this setup, we have successfully proved that PSA concentration of 4pg/mL can be detected with acceptable reliability.

Cyclin K dependent regulation of Aurora B affects apoptosis and proliferation by induction of mitotic catastrophe in prostate cancer.

PubMed

Schecher, Sabrina; Walter, Britta; Falkenstein, Michael; Macher-Goeppinger, Stephan; Stenzel, Philipp; Krümpelmann, Kristina; Hadaschik, Boris; Perner, Sven; Kristiansen, Glen; Duensing, Stefan; Roth, Wilfried; Tagscherer, Katrin E

2017-10-15

Cyclin K plays a critical role in transcriptional regulation as well as cell development. However, the role of Cyclin K in prostate cancer is unknown. Here, we describe the impact of Cyclin K on prostate cancer cells and examine the clinical relevance of Cyclin K as a biomarker for patients with prostate cancer. We show that Cyclin K depletion in prostate cancer cells induces apoptosis and inhibits proliferation accompanied by an accumulation of cells in the G2/M phase. Moreover, knockdown of Cyclin K causes mitotic catastrophe displayed by multinucleation and spindle multipolarity. Furthermore, we demonstrate a Cyclin K dependent regulation of the mitotic kinase Aurora B and provide evidence for an Aurora B dependent induction of mitotic catastrophe. In addition, we show that Cyclin K expression is associated with poor biochemical recurrence-free survival in patients with prostate cancer treated with an adjuvant therapy. In conclusion, targeting Cyclin K represents a novel, promising anti-cancer strategy to induce cell cycle arrest and apoptotic cell death through induction of mitotic catastrophe in prostate cancer cells. Moreover, our results indicate that Cyclin K is a putative predictive biomarker for clinical outcome and therapy response for patients with prostate cancer. © 2017 UICC.

Extraglandular and intraglandular vascularization of canine prostate.

PubMed

Stefanov, Miroslav

2004-03-01

The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism. Copyright 2004 Wiley-Liss, Inc.

Acute bacterial prostatitis after transrectal ultrasound-guided prostate biopsy: epidemiological, bacteria and treatment patterns from a 4-year prospective study.

PubMed

Campeggi, Alexandre; Ouzaid, Idir; Xylinas, Evanguelos; Lesprit, Philippe; Hoznek, Andras; Vordos, Dimitri; Abbou, Claude-Clément; Salomon, Laurent; de la Taille, Alexandre

2014-02-01

To evaluate the incidence, and clinical and bacterial features of iatrogenic prostatitis within 1 month after transrectal ultrasound-guided biopsy for detection of prostate cancer. From January 2006 to December 2009, 3000 patients underwent a 21-core transrectal ultrasound-guided prostate biopsy at Henri Mondor Hospital (Créteil, France) and were prospectively followed. All patients had a fluoroquinolone antimicrobial prophylaxis for 7 days. The primary study end-point was to evaluate the incidence of iatrogenic acute prostatitis within 1 month after the biopsy. The secondary end-point was to analyze the clinical and the bacterial features of the prostatitis. Overall, 20 patients of the entire study population (0.67%) had an acute bacterial prostatitis within 2.90 ± 1.77 days (range 1-7 days) after the transrectal ultrasound-guided biopsy. The groups of patients with (n = 20) and without (n = 2980) infection were similar in terms of age, prostate-specific antigen level and prostate volume. Escherichia coli was the only isolated bacteria. The subsequent tests for antibiotic susceptibility showed a 95% resistance for fluroquinolone and amoxicillin. Resistance to amoxiclav, trimethoprim-sulfamethoxazole, third generation cephalosporin and amikacin was 70%, 70%, 25% and 5% respectively. No resistance to imipenem was reported. They were all admitted for treatment without the need of intensive care unit referral. Complete recovery was achieved after 21.4 ± 7 days of antibiotic treatment. A fluroquinolone-based regimen still represents an appropriate prophylaxis protocol to minimize the risk of acute prostatitis secondary to prostate biopsy. Patients should be provided the appropriate care soon after the onset of the symptoms. An intravenous third generation cephalosporin or imipenem-based therapy seem to provide satisfying results. © 2013 The Japanese Urological Association.

Sonoelastographic evaluation with the determination of compressibility ratio for symmetrical prostatic regions in the diagnosis of clinically significant prostate cancer

PubMed Central

Słapa, Rafał Z.; Jakubowski, Wiesław S.; Migda, Bartosz; Dmowski, Tadeusz

2014-01-01

Aim Sonoelastography is a technique that assesses tissue hardness/compressibility. Utility and sensitivity of the method in prostate cancer diagnostics were assessed compared to the current gold standard in prostate cancer diagnostics i.e. systematic biopsy. Material and methods The study involved 84 patients suspected of prostate cancer based on elevated PSA levels or abnormal per rectal examination findings. Sonoelastography was used to evaluate the prostate gland. In the case of regions with hardness two-fold greater than that of symmetric prostate area (strain ratio >2), targeted biopsy was used; which was followed by an ultrasound-guided 8- or 10-core systematic biopsy (regardless of sonoelastography-indicated sites) as a reference point. Results The mean age of patients was 69 years. PSA serum levels ranged between 1.02 and 885 ng/dl. The mean prostate volume was 62 ml (19–149 ml). Prostate cancer was found in 39 out of 84 individuals. Statistically significant differences in strain ratios between cancers and benign lesions were shown. Sonoelastography guided biopsy revealed 30 lesions – overall sensitivity 77% (sensitivity of the method – 81%). Sonoelastographic sensitivity increased depending on cancer stage according to the Gleason grading system: 6–60%, 7–75%, 8–83%, 9/10–100%. The estimated sensitivity of systematic biopsy was 92%. Conclusions Sonoelastography shows higher diagnostic sensitivity in prostate cancer diagnostics compared to conventional imaging techniques, i.e. grey-scale TRUS, Doppler ultrasound. It allows to reduce the number of collected tissue cores, and thus limit the incidence of complications as well as the costs involved. Sonoelastography using the determination of compressibility ratio for symmetrical prostatic regions may prove useful in the detection of clinically significant prostate cancer. PMID:26674065

Singapore Urological Association Clinical Guidelines for Male Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia

PubMed Central

2017-01-01

The first clinical guidelines for male lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) were published in 2005. An update is urgently needed in view of BPH being recognised as one of ten chronic illnesses by the Ministry of Health, Singapore. This review summarises the definition of BPH and the epidemiology of male LUTS/BPH in Singapore. BPH can be phenotyped with noninvasive transabdominal ultrasonography, according to intravesical prostatic protrusion and prostate volume, and classified according to severity (staging) for individualised treatment. At the initial evaluation, the majority of patients (59%) can be managed with fluid adjustment, exercise and diet; 32% with medications, using alpha blockers and/or 5-alpha reductase inhibitors for prostates weighing more than 30 g; and 9% with surgical intervention for more advanced disease. The 2015 guidelines comprise updated evidence that will help family medicine practitioners and specialists manage this common ailment more cost-effectively. PMID:28848988

The role of epithelial plasticity in prostate cancer dissemination and treatment resistance

PubMed Central

Bitting, Rhonda L.; Schaeffer, Daneen; Somarelli, Jason A.; Garcia-Blanco, Mariano A.

2014-01-01

Nearly 30,000 men die annually in the USA of prostate cancer, nearly uniformly from metastatic dissemination. Despite recent advances in hormonal, immunologic, bone-targeted, and cytotoxic chemotherapies, treatment resistance and further dissemination are inevitable in men with metastatic disease. Emerging data suggests that the phenomenon of epithelial plasticity, encompassing both reversible mesenchymal transitions and acquisition of stemness traits, may underlie this lethal biology of dissemination and treatment resistance. Understanding the molecular underpinnings of this cellular plasticity from preclinical models of prostate cancer and from biomarker studies of human metastatic prostate cancer has provided clues to novel therapeutic approaches that may delay or prevent metastatic disease and lethality over time. This review will discuss the preclinical and clinical evidence for epithelial plasticity in this rapidly changing field and relate this to clinical phenotype and resistance in prostate cancer while suggesting novel therapeutic approaches. PMID:24414193

The epigenome as a therapeutic target in prostate cancer.

PubMed

Perry, Antoinette S; Watson, R William G; Lawler, Mark; Hollywood, Donal

2010-12-01

During cancer development and progression, tumor cells undergo abnormal epigenetic modifications, including DNA methylation, histone deacetylation and nucleosome remodeling. Collectively, these aberrations promote genomic instability and lead to silencing of tumor-suppressor genes and reactivation of oncogenic retroviruses. Epigenetic modifications, therefore, provide exciting new avenues for prostate cancer research. Promoter hypermethylation is widespread during neoplastic transformation of prostate cells, which suggests that restoration of a 'normal' epigenome through treatment with inhibitors of the enzymes involved could be clinically beneficial. Global patterns of histone modifications are also being defined and have been associated with clinical and pathologic predictors of prostate cancer outcome. Although treatment for localized prostate cancer can be curative, the development of successful therapies for the management of castration-resistant metastatic disease is urgently needed. Reactivation of tumor-suppressor genes by demethylating agents and histone deacetylase inhibitors could be a potential treatment option for patients with advanced disease.

About the Prostate and Urologic Cancer Research Group | Division of Cancer Prevention

Cancer.gov

The Prostate and Urologic Cancer Research Group conducts and supports research on prostate and bladder cancers, and new approaches to clinical prevention studies including cancer immunoprevention. The group develops, implements and monitors research efforts in chemoprevention, nutrition, genetic, and immunologic interventions, screening, early detection and other prevention

Prostate-specific antigen bounce after intensity-modulated radiotherapy for prostate cancer.

PubMed

Sheinbein, Courtney; Teh, Bin S; Mai, Wei Y; Grant, Walter; Paulino, Arnold; Butler, E Brian

2010-09-01

To report prostate-specific antigen (PSA) bounce in patients treated with intensity-modulated radiotherapy (IMRT) alone. Previous studies have reported PSA bounce in prostate cancer patients treated with conventional radiotherapy, 3D conformal radiotherapy, and permanent seed brachytherapy. From January 1997 to July 2002, 102 patients with clinically localized prostate cancer were treated with IMRT alone. No patients received androgen ablation. PSA bounce was defined as a PSA increase of at least 0.4 ng/mL, followed by any PSA decrease. Biochemical failure was defined by both the American Society for Therapeutic Radiology and Oncology 1996 and 2006 consensus definitions. The median follow-up was 76 months. The median length of time until the first PSA bounce was 13.6 months. Thirty-three patients (32.4%) had at least 1 PSA bounce, with 25 (24.5%) having 1 bounce; 6 (5.9%), 2 bounces; and 2 (2.0%), 4 bounces. PSA bounce was not significantly associated with biochemical no evidence of disease survival, clinical stage, pretreatment PSA, Gleason combined score, prostate planning target volume, PSA nadir, or mean dose to the prostate. The rate of PSA bounce in patients aged ≤ 70 and > 70 years was 44.4% and 22.8%, respectively (P = .032). Our patient series is the first report on PSA bounce in patients treated with IMRT. Our study confirms that the majority of patients with a bouncing PSA remain biochemically and clinically free of disease with extended follow-up. Copyright © 2010 Elsevier Inc. All rights reserved.

Differential Splicing of Oncogenes and Tumor Suppressor Genes in African- and Caucasian-American Populations: Contributing Factor in Prostate Cancer Disparities

DTIC Science & Technology

2016-10-01

Clinical cancer research : an official journal of the American Association for Cancer...kinase isoform p110delta impairs growth and survival in neuroblastoma cells. Clinical cancer research : an official journal of the American...Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer. Clinical cancer research : an official journal of the

Evaluation of atlas-based auto-segmentation software in prostate cancer patients

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

Greenham, Stuart, E-mail: stuart.greenham@ncahs.health.nsw.gov.au; Dean, Jenna; Fu, Cheuk Kuen Kenneth

2014-09-15

The performance and limitations of an atlas-based auto-segmentation software package (ABAS; Elekta Inc.) was evaluated using male pelvic anatomy as the area of interest. Contours from 10 prostate patients were selected to create atlases in ABAS. The contoured regions of interest were created manually to align with published guidelines and included the prostate, bladder, rectum, femoral heads and external patient contour. Twenty-four clinically treated prostate patients were auto-contoured using a randomised selection of two, four, six, eight or ten atlases. The concordance between the manually drawn and computer-generated contours were evaluated statistically using Pearson's product–moment correlation coefficient (r) and clinicallymore » in a validated qualitative evaluation. In the latter evaluation, six radiation therapists classified the degree of agreement for each structure using seven clinically appropriate categories. The ABAS software generated clinically acceptable contours for the bladder, rectum, femoral heads and external patient contour. For these structures, ABAS-generated volumes were highly correlated with ‘as treated’ volumes, manually drawn; for four atlases, for example, bladder r = 0.988 (P < 0.001), rectum r = 0.739 (P < 0.001) and left femoral head r = 0.560 (P < 0.001). Poorest results were seen for the prostate (r = 0.401, P < 0.05) (four atlases); however this was attributed to the comparison prostate volume being contoured on magnetic resonance imaging (MRI) rather than computed tomography (CT) data. For all structures, increasing the number of atlases did not consistently improve accuracy. ABAS-generated contours are clinically useful for a range of structures in the male pelvis. Clinically appropriate volumes were created, but editing of some contours was inevitably required. The ideal number of atlases to improve generated automatic contours is yet to be determined.« less

Long-term outcomes of open radical retropubic prostatectomy for clinically localized prostate cancer in the prostate-specific antigen era.

PubMed

Dorin, Ryan P; Daneshmand, Siamak; Lassoff, Mark A; Cai, Jie; Skinner, Donald G; Lieskovsky, Gary

2012-03-01

To determine long-term oncological outcomes and complication rates for patients with clinically organ confined prostate adenocarcinoma (PCa) treated with open radical retropubic prostatectomy and pelvic lymph node dissection (RRP/PLND) in the prostate-specific antigen (PSA) era. Outcomes data were obtained from a prospectively maintained prostate cancer database. Patients with cT1/cT2 PCa undergoing RRP/PLND without neoadjuvant therapy between July 1988 and June 2008 were included. Kaplan-Meier and Cox proportional regression models were used to evaluate factors influencing biochemical recurrence, clinical recurrence, and overall survival (OS). A total of 2487 patients met inclusion criteria, and median follow-up was 7.2 years (range 1-21 years). Of the patients, 49.7% were low risk, 33.2% intermediate risk, and 16.1% high risk by D'Amico criteria, and 6% were LN+. The 10-year biochemical recurrence-free survival (BCRFS) for low-, intermediate-, and high-risk patients was 92%, 83%, and 76%, respectively (P < .001), and 10 year OS was 91%, 83%, and 74%, respectively (P < .001). BCRFS at 10 years was 76% and 88% for patients with positive and negative margins, respectively (P < .001). Of the 2487 patients, 11% developed BCR, and 3.7% experienced CR, with 9 local recurrences. The overall complication rate was 2.3%, and the cancer specific mortality rate was 2%. D'Amico risk group, margin status, and LN status are significantly correlated with outcomes in patients undergoing RRP/PLND for clinically localized PCa. Local recurrence and death from prostate cancer are rare in patients undergoing open RRP/PLND for clinically organ confined disease in the PSA era. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Bilhim, Tiago, E-mail: tiagobilhim@hotmail.com; Pisco, Joao; Rio Tinto, Hugo

This study was designed to compare baseline data and clinical outcome between patients with prostate enlargement/benign prostatic hyperplasia (PE/BPH) who underwent unilateral and bilateral prostatic arterial embolization (PAE) for the relief of lower urinary tract symptoms (LUTS). This single-center, ambispective cohort study compared 122 consecutive patients (mean age 66.7 years) with unilateral versus bilateral PAE from March 2009 to December 2011. Selective PAE was performed with 100- and 200-{mu}m nonspherical polyvinyl alcohol (PVA) particles by a unilateral femoral approach. Bilateral PAE was performed in 103 (84.4 %) patients (group A). The remaining 19 (15.6 %) patients underwent unilateral PAE (groupmore » B). Mean follow-up time was 6.7 months in group A and 7.3 months in group B. Mean prostate volume, PSA, International prostate symptom score/quality of life (IPSS/QoL) and post-void residual volume (PVR) reduction, and peak flow rate (Qmax) improvement were 19.4 mL, 1.68 ng/mL, 11.8/2.0 points, 32.9 mL, and 3.9 mL/s in group A and 11.5 mL, 1.98 ng/mL, 8.9/1.4 points, 53.8 mL, and 4.58 mL/s in group B. Poor clinical outcome was observed in 24.3 % of patients from group A and 47.4 % from group B (p = 0.04). PAE is a safe and effective technique that can induce 48 % improvement in the IPSS score and a prostate volume reduction of 19 %, with good clinical outcome in up to 75 % of treated patients. Bilateral PAE seems to lead to better clinical results; however, up to 50 % of patients after unilateral PAE may have a good clinical outcome.« less

Clinical progression, acute urinary retention, prostate-related surgeries, and costs in patients with benign prostatic hyperplasia taking early versus delayed combination 5α-reductase inhibitor therapy and α-blocker therapy: a retrospective analysis.

PubMed

Morlock, Robert; Goodwin, Bridgett; Gomez Rey, Gabriel; Eaddy, Michael

2013-05-01

Two previous retrospective database analyses compared early combination therapy with an α-blocker (AB) and 5-α reductase inhibitor (5-ARI) to delayed combination therapy and found that patients receiving the delayed combination therapy were more likely to have clinical progression, acute urinary retention (AUR), and surgery. Although these studies indicate the clinical benefits of early treatment, both studies failed to take into account important baseline clinical measures, such as prostate-specific antigen (PSA) values. This study was designed to compare clinical and cost differences in men with benign prostatic hyperplasia (BPH) who initiated early versus delayed combination therapy with a 5-ARI + an AB, factoring in baseline PSA values. This retrospective claims data analysis assessed data from >14 million US men with linked medical data, pharmacy data, laboratory results, and enrollment information from January 1, 2000, to December 31, 2009. Men aged 50 or older and treated for BPH with a 5-ARI + an AB were identified. Patients were required to be eligible for services at least 6 months before and 12 months after the index medication date. Patients were assigned to 1 of 2 treatment groups based on therapy (early or delayed) and 3 cohorts based on availability of PSA laboratory values (patients with a PSA value, patients with a PSA value >1.5 and <10, and all patients). Using a logistic model, the likelihood of clinical progression (defined as the occurrence of AUR or prostate surgery) during the 12 months after the date of first prescription fill was compared between BPH patients receiving early versus delayed combination therapy. BPH-related medical costs (excluding pharmacy costs) were assessed using generalized linear models. Among the 13,551 patients identified for study inclusion, the highest risks for clinical progression, AUR, and prostate-related surgery were consistently demonstrated in patients with a PSA >1.5 and <10. Across all 3 cohorts, the delayed combination-treatment group was more likely to have clinical progression, AUR, and prostate-related surgeries versus the early combination-treatment group. The incremental difference in BPH-related costs between the delayed and early combination-treatment groups was $190 per patient overall; the greatest incremental difference ($397) was observed in patients with PSA >1.5 and <10. The results suggest that early initiation of combination therapy with 5-ARI + an AB, compared with delayed initiation, can reduce the risks for clinical progression, AUR, and prostate-related surgeries, as well as BPH-related medical costs, in patients with BPH. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Prostate contouring in MRI guided biopsy.

PubMed

Vikal, Siddharth; Haker, Steven; Tempany, Clare; Fichtinger, Gabor

2009-03-27

With MRI possibly becoming a modality of choice for detection and staging of prostate cancer, fast and accurate outlining of the prostate is required in the volume of clinical interest. We present a semi-automatic algorithm that uses a priori knowledge of prostate shape to arrive at the final prostate contour. The contour of one slice is then used as initial estimate in the neighboring slices. Thus we propagate the contour in 3D through steps of refinement in each slice. The algorithm makes only minimum assumptions about the prostate shape. A statistical shape model of prostate contour in polar transform space is employed to narrow search space. Further, shape guidance is implicitly imposed by allowing only plausible edge orientations using template matching. The algorithm does not require region-homogeneity, discriminative edge force, or any particular edge profile. Likewise, it makes no assumption on the imaging coils and pulse sequences used and it is robust to the patient's pose (supine, prone, etc.). The contour method was validated using expert segmentation on clinical MRI data. We recorded a mean absolute distance of 2.0 ± 0.6 mm and dice similarity coefficient of 0.93 ± 0.3 in midsection. The algorithm takes about 1 second per slice.

Prostate contouring in MRI guided biopsy

PubMed Central

Vikal, Siddharth; Haker, Steven; Tempany, Clare; Fichtinger, Gabor

2010-01-01

With MRI possibly becoming a modality of choice for detection and staging of prostate cancer, fast and accurate outlining of the prostate is required in the volume of clinical interest. We present a semi-automatic algorithm that uses a priori knowledge of prostate shape to arrive at the final prostate contour. The contour of one slice is then used as initial estimate in the neighboring slices. Thus we propagate the contour in 3D through steps of refinement in each slice. The algorithm makes only minimum assumptions about the prostate shape. A statistical shape model of prostate contour in polar transform space is employed to narrow search space. Further, shape guidance is implicitly imposed by allowing only plausible edge orientations using template matching. The algorithm does not require region-homogeneity, discriminative edge force, or any particular edge profile. Likewise, it makes no assumption on the imaging coils and pulse sequences used and it is robust to the patient's pose (supine, prone, etc.). The contour method was validated using expert segmentation on clinical MRI data. We recorded a mean absolute distance of 2.0 ± 0.6 mm and dice similarity coefficient of 0.93 ± 0.3 in midsection. The algorithm takes about 1 second per slice. PMID:21132083

Sensitivity study of an ultrasound coupled transrectal electrical Impedance Tomography system for prostate imaging

NASA Astrophysics Data System (ADS)

Wan, Y.; Halter, R.; Borsic, A.; Manwaring, P.; Hartov, A.; Paulsen, K.

2010-04-01

In 2009, prostate cancer ranks as the most common cancer and the second most fatal cancer in men in the United States. Unfortunately, the current clinical diagnostic methods (e.g. prostate-specific antigen (PSA), digital rectal examination, endorectal MRI, transrectal ultrasound, biopsy) used for detecting and staging prostate cancer are limited. It has been shown that cancerous prostate tissue has significantly different electrical properties when compared to benign tissues. Based on these electrical property findings, a TransRectal Electrical Impedance Tomography (TREIT) system is proposed as a novel prostate imaging modality. The TREIT system is comprised of an array of electrodes interfaced with a clinical TransRectal UltraSound (TRUS) probe. We evaluate this imaging system through series of phantom imaging experiments to assess the system's ability to image high and low contrast objects at various positions. We found that the TREIT system can easily discern high contrast inclusions of 1 cm in diameter at distances centered at 2 times the radius of the TREIT probe away from the probe surface. Furthermore, this technology's ability to detect low contrast inclusions suggests that it has the potential to successfully detect prostate cancer.

Resveratrol in prostate diseases – a short review

PubMed Central

Jasińska, Lidia; Ogrodowczyk, Marcin

2013-01-01

Introduction Resveratrol is a plant–derived polyphenol suggested to have many beneficial health effects, including antioxidant, anti–inflammatory, anti–proliferative, proapoptotic, and anti–angiogenic. It is even specu- lated that uptake of resveratrol by red wine consumption could be behind the so–called French paradox the lower incidence of cardiovascular diseases in the French population. These properties, together with good absorption and tolerance, would make it an attractive agent in prostatic diseases, especially in cancer prevention and treatment. Material and methods MEDLINE search (keywords “prostate res- veratrol”) resulted in 39 research papers published since 2007. It has been shown that resveratol down–regulate androgen receptor expression, inhibit proliferation, and promote apop- tosis in prostate cancer cell lines and enhance their sensitivity to ionizing radiation. Several studies on animal prostate cancer development also suggest that resveratrol is able do delay or prevent carcino- genesis in prostate. Despite these promising results, there is no proof of any therapeutic properties of resveratrol in prostate diseases from human clinical trials nor any information about ongoing trials in this field. Conclusions Resveratrol is produced and sold as a nutritional supplement, there is not enough clinical evidence to justify a recommendation for the administration of resveratrol in humans at present. PMID:24579014

[Causes of death among prostate cancer patients of different ages].

PubMed

Dariy, E V

2016-02-01

To date, there is no unified approach to evaluating and treating patients with suspected prostate cancer taking into account their age and comorbidities. That was the rationale for conducting this study. To assess the clinical course of prostate cancer in men of all ages with comorbidities. The study included 408 patients aged 50 to 92 years (mean age 74.3 years) with histologically verified prostate cancer. 30 (7.4%) patients had stage T1 disease, 273 (66.9%) - T2, 91 (22.3%) - T3 and 14 (3.4%) - T4. The maximum follow-up was 22 years, the minimum one - 6 months (on average 15.4 years). During the follow-up 159 patients died (39%), 51 of them (32%) of prostate cancer, 108 (68%) - from other diseases. Among the latter the causes of death were cancer (20.4%), cardiovascular and bronchopulmonary diseases (79.6%). Cancer-specific survival rate was 41.4 +/-12,4%, the survival rate for other diseases 23.4 +/-10,6% (p<0.05). We need a differentiated approach to selecting treatment for patients with prostate cancer, especially of old age, including the option for active surveillance of patients with clinically insignificant prostate cancer.

Feasibility of imaging epileptic seizure onset with EIT and depth electrodes.

PubMed

Witkowska-Wrobel, Anna; Aristovich, Kirill; Faulkner, Mayo; Avery, James; Holder, David

2018-06-01

Imaging ictal and interictal activity with Electrical Impedance Tomography (EIT) using intracranial electrode mats has been demonstrated in animal models of epilepsy. In human epilepsy subjects undergoing presurgical evaluation, depth electrodes are often preferred. The purpose of this work was to evaluate the feasibility of using EIT to localise epileptogenic areas with intracranial electrodes in humans. The accuracy of localisation of the ictal onset zone was evaluated in computer simulations using 9M element FEM models derived from three subjects. 5 mm radius perturbations imitating a single seizure onset event were placed in several locations forming two groups: under depth electrode coverage and in the contralateral hemisphere. Simulations were made for impedance changes of 1% expected for neuronal depolarisation over milliseconds and 10% for cell swelling over seconds. Reconstructions were compared with EEG source modelling for a radially orientated dipole with respect to the closest EEG recording contact. The best accuracy of EIT was obtained using all depth and 32 scalp electrodes, greater than the equivalent accuracy with EEG inverse source modelling. The localisation error was 5.2 ± 1.8, 4.3 ± 0 and 46.2 ± 25.8 mm for perturbations within the volume enclosed by depth electrodes and 29.6 ± 38.7, 26.1 ± 36.2, 54.0 ± 26.2 mm for those without (EIT 1%, 10% change, EEG source modelling, n = 15 in 3 subjects, p < 0.01). As EIT was insensitive to source dipole orientation, all 15 perturbations within the volume enclosed by depth electrodes were localised, whereas the standard clinical method of visual inspection of EEG voltages, only localised 8 out of 15 cases. This suggests that adding EIT to SEEG measurements could be beneficial in localising the onset of seizures. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Radiologic-pathologic findings of solitary fibrous tumor of the prostate presenting as a large mass with delayed filling-in on MRI.

PubMed

Bhargava, Puneet; Lee, Jean Hwa; Gupta, Saurabh; Seyal, Adeel Rahim; Vakar-Lopez, Funda; Moshiri, Mariam; Dighe, Manjiri Kiran

2012-01-01

We report a case of a solitary fibrous tumor of prostate presenting with urinary retention and a large prostate mass. We describe the clinical presentation, magnetic resonance imaging findings, and histopathology of this rare, benign tumor. Although clinical and radiologic appearances embrace various differential diagnoses including sarcoma, this mass was confirmed by histologic analysis following surgical resection. We report this rare, benign tumor to help the radiologist suggest the diagnosis when presented with a similar case.

Laser fluorescence spectrometers for medical diagnosis

NASA Astrophysics Data System (ADS)

Kwasny, Miroslaw; Mierczyk, Zygmunt

2000-11-01

The paper presents fibre fluorescence analysers for in vivo examined biological tissues. The systems devoted to clinical investigations are equipped with laser excitation sources; He-Cd (442 nm), Nd:YAG (II and III harmonic: 532 and 355 nm, respectively) and He-Ne (632.8 nm). They allow non-invasive determination of endogenous fluorophones level in any organs as well as monitoring of external sensitisers level when photodynamic method of diagnosis and treatment of tumors is used. Selection of various wavelengths within the range of porphyrines, excitation depends on different light penetration in various tissues. For the tumors localised under mucous membrane, UV, violet, and blue radiation was used for excitation and for deeply localised tumors, a radiation of longer wavelengths (green and red) was used. The carried out clinical examinations showed usefulness of fluorometric systems for diagnostics of skin diseases, gynaecological spheres, and pneumopathies. These analysers can be also applied for environmental protection, food control, and industrial processes monitoring.

Herniated Thoracic Spleen Mimicking Lung Metastasis on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT in a Patient With Prostate Cancer.

PubMed

Malik, Dharmender; Basher, Rajender K; Sood, Apurva; Devana, Sudheer Kumar; Bhattacharya, Anish; Mittal, Bhagwant Rai

2017-06-01

We report a case of clinically asymptomatic patient of prostate cancer who was previously subjected to radical prostatectomy presenting with a rising serum prostate-specific antigen level of 6.6 ng/mL. Whole-body PET/CT with Ga-labeled prostate-specific membrane antigen ligand was performed to assess for disease recurrence, which revealed an intense tracer uptake in a soft tissue mass in left hemithorax mimicking lung metastasis; which later turned out to be splenic tissue.

State of the art of prostatic arterial embolization for benign prostatic hyperplasia.

PubMed

Petrillo, Mario; Pesapane, Filippo; Fumarola, Enrico Maria; Emili, Ilaria; Acquasanta, Marzia; Patella, Francesca; Angileri, Salvatore Alessio; Rossi, Umberto G; Piacentini, Igor; Granata, Antonio Maria; Ierardi, Anna Maria; Carrafiello, Gianpaolo

2018-04-01

Prostatectomy via open surgery or transurethral resection of the prostate (TURP) is the standard treatment for benign prostatic hyperplasia (BPH). Several patients present contraindication for standard approach, individuals older than 60 years with urinary tract infection, strictures, post-operative pain, incontinence or urinary retention, sexual dysfunction, and blood loss are not good candidates for surgery. Prostatic artery embolization (PAE) is emerging as a viable method for patients unsuitable for surgery. In this article, we report results about technical and clinical success and safety of the procedure to define the current status.

Risk stratification of prostate cancer: integrating multiparametric MRI, nomograms and biomarkers

PubMed Central

Watson, Matthew J; George, Arvin K; Maruf, Mahir; Frye, Thomas P; Muthigi, Akhil; Kongnyuy, Michael; Valayil, Subin G; Pinto, Peter A

2016-01-01

Accurate risk stratification of prostate cancer is achieved with a number of existing tools to ensure the identification of at-risk patients, characterization of disease aggressiveness, prediction of cancer burden and extrapolation of treatment outcomes for appropriate management of the disease. Statistical tables and nomograms using classic clinicopathological variables have long been the standard of care. However, the introduction of multiparametric MRI, along with fusion-guided targeted prostate biopsy and novel biomarkers, are being assimilated into clinical practice. The majority of studies to date present the outcomes of each in isolation. The current review offers a critical and objective assessment regarding the integration of multiparametric MRI and fusion-guided prostate biopsy with novel biomarkers and predictive nomograms in contemporary clinical practice. PMID:27400645

SU-E-QI-19: Evaluation of a Clinical 1.5T MRI for Prostate Cancer MRS Imaging Using a In Vivo Tumor Model

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

Chen, X; Chen, L; Hensley, H

2014-06-15

Purpose: Magnetic resonance spectroscopic (MRS) imaging may provide important bio-markers to distinguish normal/cancerous prostate tissue. While MRS imaging requires a high uniform magnetic field, the ability of a clinical 1.5T MRI to achieve a comparable MRS signal is of interest for radiation treatment planning/assessment. This study is to evaluate the MRS imaging of a 1.5T clinical MRI for prostate cancers by comparing with a small animal 7T MRS scanner. Methods: A tumor model was developed by implanting LNCaP tumor cells in nude mice prostates. Tumor was monitored 3 weeks after implantation using MRI, and MRS imaging was performed on themore » tumor area when the tumor reached around 1cm in diameter. The 1.5T GE clinical MR scanner and the 7T Bruker small animal MR scanner were used for each mouse. MR spectrums acquired with these scanners were analyzed and compared. The signals of Choline and Citrate were considered. Results: The prostate tumor MR spectrum under the 1.5T clinical MRI showed a similar spectrum pattern to that acquired using the 7T animal MRI. The Choline signal (3.2ppm) is clear and there is no clear peak for Citrate (2.6ppm). However, the signal magnitude for Choline is not dominant compared to the background signal under 1.5T MRI. Typical cancerous prostate tissue MR spectrum with an increased Choline signal and a reduced Citrate signal was observed. In addition, signal variation is noticeable between repeated spectrum scans. The average of these scans showed a comparable and consistent spectrum to those under 7T MRI. Conclusion: The clinical 1.5T MRI is able to acquire a MR spectrum for prostate cancer comparable to those acquired using a dedicated 7T MRS scanner. However, to achieve a consistent and reliable spectrum, multiple repeated scans were necessary to get a statistical result and reduce the noise-induced artifact. This work was supported in part by the National Cancer Institute Grant R21 CA131979 and R01CA172638.« less

Prostate CT segmentation method based on nonrigid registration in ultrasound-guided CT-based HDR prostate brachytherapy

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

Yang, Xiaofeng, E-mail: xyang43@emory.edu; Rossi, Peter; Ogunleye, Tomi

2014-11-01

Purpose: The technological advances in real-time ultrasound image guidance for high-dose-rate (HDR) prostate brachytherapy have placed this treatment modality at the forefront of innovation in cancer radiotherapy. Prostate HDR treatment often involves placing the HDR catheters (needles) into the prostate gland under the transrectal ultrasound (TRUS) guidance, then generating a radiation treatment plan based on CT prostate images, and subsequently delivering high dose of radiation through these catheters. The main challenge for this HDR procedure is to accurately segment the prostate volume in the CT images for the radiation treatment planning. In this study, the authors propose a novel approachmore » that integrates the prostate volume from 3D TRUS images into the treatment planning CT images to provide an accurate prostate delineation for prostate HDR treatment. Methods: The authors’ approach requires acquisition of 3D TRUS prostate images in the operating room right after the HDR catheters are inserted, which takes 1–3 min. These TRUS images are used to create prostate contours. The HDR catheters are reconstructed from the intraoperative TRUS and postoperative CT images, and subsequently used as landmarks for the TRUS–CT image fusion. After TRUS–CT fusion, the TRUS-based prostate volume is deformed to the CT images for treatment planning. This method was first validated with a prostate-phantom study. In addition, a pilot study of ten patients undergoing HDR prostate brachytherapy was conducted to test its clinical feasibility. The accuracy of their approach was assessed through the locations of three implanted fiducial (gold) markers, as well as T2-weighted MR prostate images of patients. Results: For the phantom study, the target registration error (TRE) of gold-markers was 0.41 ± 0.11 mm. For the ten patients, the TRE of gold markers was 1.18 ± 0.26 mm; the prostate volume difference between the authors’ approach and the MRI-based volume was 7.28% ± 0.86%, and the prostate volume Dice overlap coefficient was 91.89% ± 1.19%. Conclusions: The authors have developed a novel approach to improve prostate contour utilizing intraoperative TRUS-based prostate volume in the CT-based prostate HDR treatment planning, demonstrated its clinical feasibility, and validated its accuracy with MRIs. The proposed segmentation method would improve prostate delineations, enable accurate dose planning and treatment delivery, and potentially enhance the treatment outcome of prostate HDR brachytherapy.« less

Prostate CT segmentation method based on nonrigid registration in ultrasound-guided CT-based HDR prostate brachytherapy

PubMed Central

Yang, Xiaofeng; Rossi, Peter; Ogunleye, Tomi; Marcus, David M.; Jani, Ashesh B.; Mao, Hui; Curran, Walter J.; Liu, Tian

2014-01-01

Purpose: The technological advances in real-time ultrasound image guidance for high-dose-rate (HDR) prostate brachytherapy have placed this treatment modality at the forefront of innovation in cancer radiotherapy. Prostate HDR treatment often involves placing the HDR catheters (needles) into the prostate gland under the transrectal ultrasound (TRUS) guidance, then generating a radiation treatment plan based on CT prostate images, and subsequently delivering high dose of radiation through these catheters. The main challenge for this HDR procedure is to accurately segment the prostate volume in the CT images for the radiation treatment planning. In this study, the authors propose a novel approach that integrates the prostate volume from 3D TRUS images into the treatment planning CT images to provide an accurate prostate delineation for prostate HDR treatment. Methods: The authors’ approach requires acquisition of 3D TRUS prostate images in the operating room right after the HDR catheters are inserted, which takes 1–3 min. These TRUS images are used to create prostate contours. The HDR catheters are reconstructed from the intraoperative TRUS and postoperative CT images, and subsequently used as landmarks for the TRUS–CT image fusion. After TRUS–CT fusion, the TRUS-based prostate volume is deformed to the CT images for treatment planning. This method was first validated with a prostate-phantom study. In addition, a pilot study of ten patients undergoing HDR prostate brachytherapy was conducted to test its clinical feasibility. The accuracy of their approach was assessed through the locations of three implanted fiducial (gold) markers, as well as T2-weighted MR prostate images of patients. Results: For the phantom study, the target registration error (TRE) of gold-markers was 0.41 ± 0.11 mm. For the ten patients, the TRE of gold markers was 1.18 ± 0.26 mm; the prostate volume difference between the authors’ approach and the MRI-based volume was 7.28% ± 0.86%, and the prostate volume Dice overlap coefficient was 91.89% ± 1.19%. Conclusions: The authors have developed a novel approach to improve prostate contour utilizing intraoperative TRUS-based prostate volume in the CT-based prostate HDR treatment planning, demonstrated its clinical feasibility, and validated its accuracy with MRIs. The proposed segmentation method would improve prostate delineations, enable accurate dose planning and treatment delivery, and potentially enhance the treatment outcome of prostate HDR brachytherapy. PMID:25370648

A randomised controlled trial to determine the clinical and cost effectiveness of thulium laser transurethral vaporesection of the prostate (ThuVARP) versus transurethral resection of the prostate (TURP) in the National Health Service (NHS) - the UNBLOCS trial: a study protocol for a randomised controlled trial.

PubMed

Worthington, Jo; Taylor, Hilary; Abrams, Paul; Brookes, Sara T; Cotterill, Nikki; Noble, Sian M; Page, Tobias; Swami, K Satchi; Lane, J Athene; Hashim, Hashim

2017-04-17

Transurethral resection of the prostate (TURP) has been the standard operation for benign prostatic obstruction (BPO) for 40 years, with approximately 25,000 procedures performed annually, and has remained largely unchanged. It is generally a successful operation, but has well-documented risks for the patient. Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a surgical technique similar to TURP. The small amount of study data currently available suggests that ThuVARP may have certain advantages over TURP, including reduced blood loss and shorter hospital stay, earlier return to normal activities, and shorter duration of catheterisation. A multicentre, pragmatic, randomised, controlled, parallel-group trial of ThuVARP versus standard TURP in men with BPO. Four hundred and ten men suitable for prostate surgery were randomised to receive either ThuVARP or TURP at four university teaching hospitals, and three district general hospitals. The key aim of the trial is to determine whether ThuVARP is equivalent to TURP judged on both the patient-reported International Prostate Symptom Score (IPSS) and the maximum urine flow rate (Qmax) at 12 months post-surgery. The general population has an increased life expectancy. As men get older their prostates enlarge, potentially causing BPO, which often requires surgery. Therefore, as the population ages, more prostate operations are needed to relieve obstruction. There is hence sustained interest in the condition and increasing need to find safer techniques than TURP. Various laser techniques have become available but none are widely used in the NHS because of lengthy training required for surgeons or inferior performance on clinical outcomes. Promising initial evidence from one RCT shows that ThuVARP has equivalent clinical effectiveness when compared to TURP, as well as other potential advantages. As ThuVARP uses a technique similar to that used in TURP, the learning curve is short, potentially making it also very quickly generalisable. This randomised study is designed to provide the high-quality evidence, in an NHS setting, with a range of patient-reported, clinical and cost-effectiveness outcomes, which will underpin and inform future NICE guidance. ISRCTN registry, ISRCTN00788389 . Registered on 20 September 2013.

The emerging role of obesity, diet and lipid metabolism in prostate cancer.

PubMed

Ferro, Matteo; Terracciano, Daniela; Buonerba, Carlo; Lucarelli, Giuseppe; Bottero, Danilo; Perdonà, Sisto; Autorino, Riccardo; Serino, Alessandro; Cantiello, Francesco; Damiano, Rocco; Andras, Iulia; De Placido, Sabino; Di Lorenzo, Giuseppe; Battaglia, Michele; Jereczek-Fossa, Barbara A; Mirone, Vincenzo; De Cobelli, Ottavio

2017-02-01

Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.

Influence of Antiflatulent Dietary Advice on Intrafraction Motion for Prostate Cancer Radiotherapy

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

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

Purpose: To evaluate the effect of an antiflatulent dietary advice on the intrafraction prostate motion in patients treated with intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Between February 2002 and December 2009, 977 patients received five-beam IMRT for prostate cancer to a dose of 76 Gy in 35 fractions combined with fiducial markers for position verification. In July 2008, the diet, consisting of dietary guidelines to obtain regular bowel movements and to reduce intestinal gas by avoiding certain foods and air swallowing, was introduced to reduce the prostate motion. The intrafraction prostate movement was determined from the portalmore » images of the first segment of all five beams. Clinically relevant intrafraction motion was defined as {>=}50% of the fractions with an intrafraction motion outside a range of 3 mm. Results: A total of 739 patients were treated without the diet and 105 patients were treated with radiotherapy after introduction of the diet. The median and interquartile range of the average intrafraction motion per patient was 2.53 mm (interquartile range, 2.2-3.0) without the diet and 3.00 mm (interquartile range, 2.4-3.5) with the diet (p < .0001). The percentage of patients with clinically relevant intrafraction motion increased statistically significant from 19.1% without diet to 42.9% with a diet (odds ratio, 3.18; 95% confidence interval, 2.07-4.88; p < .0001). Conclusions: The results of the present study suggest that antiflatulent dietary advice for patients undergoing IMRT for prostate cancer does not reduce the intrafraction movement of the prostate. Therefore, antiflatulent dietary advice is not recommended in clinical practice for this purpose.« less

Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms: systematic review.

PubMed

Sánchez-Gómez, L M; Polo-deSantos, M; Gómez-Sancha, F; Luengo-Matos, S

2015-06-01

Interest in having alternatives in the treatment of benign prostate hyperplasia. To assess the efficacy and safety of the Urolift® system for treating the symptoms of benign prostate hyperplasia. Systematic review of the literature through searches on PubMed, Cochrane Library, CRD, Clinical Trials and EuroScan, collecting indicators of efficacy and safety. We included 5 case series and one clinical trial. The patients' mean age ranged from 65-74.3 years, and the mean prostate volume was 41-55cm3. The mean number of Urolif® implants was 3.7-5.5. The maximum follow-up in months was 24, 12 (3 studies) and one (2 studies). Improvements were found in lower urinary tract symptoms, as measured with the International Prostate Symptom Score, Benign Prostatic Hyperplasia Impact Index (BPHII), maximum urinary flow (Qmax) and postvoid residual (PVR) volume. Improvements were in found sexual dysfunction symptoms, as measured with the Sexual Health Inventory for Men (SHIM) and the Male Sexual Health Questionnaire or Ejaculatory Dysfunction (MHSQ-EjD), and in quality of life (QoL). In the clinical trial, the differences were significant for International Prostate Symptom Score, BPHII, Qmax and QoL (p<.05). The adverse effects were mild. Although the quality of evidence is low, Urolift® constitutes a good therapeutic alternative for patients with benign prostate hyperplasia. The short to medium-term results show that the technique contributes to improving lower urinary tract symptoms, with no relevant side effects, does not affect sexual function and improves quality of life. Further research is required, especially on long-term results. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Plumbagin improves the efficacy of androgen deprivation therapy in prostate cancer: A pre-clinical study.

PubMed

Abedinpour, Parisa; Baron, Véronique T; Chrastina, Adrian; Rondeau, Gaelle; Pelayo, Jennifer; Welsh, John; Borgström, Per

2017-12-01

Plumbagin is a candidate drug for the treatment of prostate cancer. Previous observations indicated that it may improve the efficacy of androgen deprivation therapy (ADT). This study evaluates the effectiveness of treatment with combinations of plumbagin and alternative strategies for ADT in mouse models of prostate cancer to support its clinical use. Plumbagin was administered per oral in a new sesame oil formulation. Standard toxicology studies were performed in rats. For tumor growth studies, mouse prostate cancer cell spheroids were placed on top of grafted prostate tissue in a dorsal chamber and allowed to form tumors. Mice were separated in various treatment groups and tumor size was measured over time by intra-vital microscopy. Survival studies were done in mice after injection of prostate cancer cells in the prostate of male animals. Androgen receptor (AR) levels were analyzed by Western blot from prostate cancer cells treated with plumbagin. Plumbagin caused a decrease in AR levels in vitro. In mice, plumbagin at 1 mg/kg in sesame oil displayed low toxicity and caused a 50% tumor regression when combined with castration. The combination of plumbagin with various forms of chemical ADT including treatment with a GnRH receptor agonist, a GnRH receptor antagonist, or CYP17A1 inhibitors, outperformed ADT alone, increasing mouse survival compared to the standard regimen of castration alone. In contrast, the combination of plumbagin with AR antagonists, such as bicalutamide and enzalutamide, showed no improvement over AR antagonists alone. Thus, plumbagin is effective in combination with drugs that prevent the synthesis of testosterone or its conversion to dihydrotestosterone, but not with drugs that bind to AR. Plumbagin significantly improves the effect of ADT drugs currently used in the clinic, with few side effects in mice. © 2017 Wiley Periodicals, Inc.

Health-Related Quality of Life up to Six Years After {sup 125}I Brachytherapy for Early-Stage Prostate Cancer

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

Roeloffzen, Ellen M.A., E-mail: E.M.A.Roeloffzen@UMCUtrecht.n; Lips, Irene M.; Gellekom, Marion P.R. van

2010-03-15

Purpose: Health-related quality of life (HRQOL) after prostate brachytherapy has been extensively described in published reports but hardly any long-term data are available. The aim of the present study was to prospectively assess long-term HRQOL 6 years after {sup 125}I prostate brachytherapy. Methods and Materials: A total of 127 patients treated with {sup 125}I brachytherapy for early-stage prostate cancer between December 2000 and June 2003 completed a HRQOL questionnaire at five time-points: before treatment and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Researchmore » and Treatment of Cancer core questionnaire (EORTCQLQ-C30), and the tumor-specific EORTC prostate cancer module (EORTC-PR25). A change in a score of >=10 points was considered clinically relevant. Results: Overall, the HRQOL at 6 years after {sup 125}I prostate brachytherapy did not significantly differ from baseline. Although a statistically significant deterioration in HRQOL at 6 years was seen for urinary symptoms, bowel symptoms, pain, physical functioning, and sexual activity (p <.01), most changes were not clinically relevant. A statistically significant improvement at 6 years was seen for mental health, emotional functioning, and insomnia (p <.01). The only clinically relevant changes were seen for emotional functioning and sexual activity. Conclusion: This is the first study presenting prospective HRQOL data up to 6 years after {sup 125}I prostate brachytherapy. HRQOL scores returned to approximately baseline values at 1 year and remained stable up to 6 years after treatment. {sup 125}I prostate brachytherapy did not adversely affect patients' long-term HRQOL.« less

Notch Signaling in Prostate Cancer Cells Promotes Osteoblastic Metastasis

DTIC Science & Technology

2017-06-01

in the tumor- bone microenvironment. Conversely, inhibition of Notch3 in PC3, 22rv1 and C42B cells with shRNA, promoted prostate cancer–induced...metastasis and thus may be a therapeutic target for such metastatic lesions. 15. SUBJECT TERMS Prostate Cancer; Notch3; MMP3; Bone -Tumor microenvironment...9 4 1. Introduction: To address the clinical problem of disease progression in prostate cancer- induced bone metastasis, the

Durable remission of leptomeningeal metastases from hormone-responsive prostate cancer.

PubMed

Zhang, Meng; Mahta, Ali; Kim, Ryan Y; Akar, Serra; Kesari, Santosh

2012-06-01

Prostate cancer is rarely associated with leptomeningeal metastasis. An 87-year-old man with a history of prostate cancer presented with leptomeningeal metastasis. He received hormonal therapy with leuprolide. Subsequently, he achieved an impressive response, indicated by a constant fall in his PSA levels and by the stabilization of leptomeningeal disease and clinical improvement. Hormonal therapy may be effective in inducing remission in hormone-sensitive prostate cancer with leptomeningeal metastasis.

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

DTIC Science & Technology

2017-10-01

SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer (PCA) is a clinically and genetically heterogeneous and the development of a molecular classification is...AWARD NUMBER: W81XWH-16-1-0739 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH

Integrative clinical genomics of advanced prostate cancer.

PubMed

Robinson, Dan; Van Allen, Eliezer M; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim; Bradley, Robert K; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P; Hussain, Maha; Feng, Felix Y; Tomlins, Scott A; Cooney, Kathleen A; Smith, David C; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E; Morris, Michael J; Solomon, Stephen B; Durack, Jeremy C; Reuter, Victor E; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T; Bowden, Michaela; Balk, Stephen P; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y; Mostaghel, Elahe A; Cheng, Heather H; Mulcahy, Hyojeong; True, Lawrence D; Plymate, Stephen R; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Perez-Lopez, Raquel; Demichelis, Francesca; Robinson, Brian D; Schiffman, Marc; Nanus, David M; Tagawa, Scott T; Sigaras, Alexandros; Eng, Kenneth W; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I; Scher, Howard I; Pienta, Kenneth J; Kantoff, Philip; de Bono, Johann S; Rubin, Mark A; Nelson, Peter S; Garraway, Levi A; Sawyers, Charles L; Chinnaiyan, Arul M

2015-05-21

Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals. Copyright © 2015 Elsevier Inc. All rights reserved.

Integrative clinical genomics of advanced prostate cancer

PubMed Central

Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

2015-01-01

SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

ePCR: an R-package for survival and time-to-event prediction in advanced prostate cancer, applied to real-world patient cohorts.

PubMed

Laajala, Teemu D; Murtojärvi, Mika; Virkki, Arho; Aittokallio, Tero

2018-06-15

Prognostic models are widely used in clinical decision-making, such as risk stratification and tailoring treatment strategies, with the aim to improve patient outcomes while reducing overall healthcare costs. While prognostic models have been adopted into clinical use, benchmarking their performance has been difficult due to lack of open clinical datasets. The recent DREAM 9.5 Prostate Cancer Challenge carried out an extensive benchmarking of prognostic models for metastatic Castration-Resistant Prostate Cancer (mCRPC), based on multiple cohorts of open clinical trial data. We make available an open-source implementation of the top-performing model, ePCR, along with an extended toolbox for its further re-use and development, and demonstrate how to best apply the implemented model to real-world data cohorts of advanced prostate cancer patients. The open-source R-package ePCR and its reference documentation are available at the Central R Archive Network (CRAN): https://CRAN.R-project.org/package=ePCR. R-vignette provides step-by-step examples for the ePCR usage. Supplementary data are available at Bioinformatics online.

Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives.

PubMed

Backhaus, Philipp; Noto, Benjamin; Avramovic, Nemanja; Grubert, Lena Sophie; Huss, Sebastian; Bögemann, Martin; Stegger, Lars; Weckesser, Matthias; Schäfers, Michael; Rahbar, Kambiz

2018-05-01

Prostate-specific membrane antigen (PSMA) is the up-and-coming target for molecular imaging of prostate cancer. Despite its name, non-prostate-related PSMA expression in physiologic tissue as well as in benign and malignant disease has been reported in various publications. Unlike in prostate cancer, PSMA expression is only rarely observed in non-prostate tumor cells. Instead, expression occurs in endothelial cells of tumor-associated neovasculature, although no endothelial expression is observed under physiologic conditions. The resulting potential for tumor staging in non-prostate malignant tumors has been demonstrated in first patient studies. This review summarizes the first clinical studies and deduces future perspectives in staging, molecular characterization, and PSMA-targeted radionuclide therapy based on histopathologic examinations of PSMA expression. The non-exclusivity of PSMA in prostate cancer opens a window to utilize the spectrum of available radioactive PSMA ligands for imaging and molecular characterization and maybe even therapy of non-prostate disease.

Long-Term Outcomes of Alternative Brachytherapy Techniques for Early Prostate Cancer

DTIC Science & Technology

2007-01-01

Oncol 2003;21:3979-86. 15. Whitmore WF, Jr., Hilaris B, Grabstald H. Retropubic implantation to iodine 125 in the treatment of prostatic cancer. J...brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma. Int J Radiat Oncol Biol Phys 1996;35:875-9. 29. Stock RG

Long-Term Outcomes of Alternative Brachytherapy Techniques for Early Prostate Cancer

DTIC Science & Technology

2008-01-01

course and predictors of symptoms after primary prostate cancer therapy. J Clin Oncol 2003;21:3979-86. 15. Whitmore WF, Jr., Hilaris B, Grabstald H...clinically localized, high-risk prostatic carcinoma. Int J Radiat Oncol Biol Phys 1996;35:875-9. 29. Stock RG , Stone NN, De Wyngaert JK, Lavagnini P

Next generation patient-derived prostate cancer xenograft models

PubMed Central

Lin, Dong; Xue, Hui; Wang, Yuwei; Wu, Rebecca; Watahiki, Akira; Dong, Xin; Cheng, Hongwei; Wyatt, Alexander W; Collins, Colin C; Gout, Peter W; Wang, Yuzhuo

2014-01-01

There is a critical need for more effective therapeutic approaches for prostate cancer. Research in this area, however, has been seriously hampered by a lack of clinically relevant, experimental in vivo models of the disease. This review particularly focuses on the development of prostate cancer xenograft models based on subrenal capsule grafting of patients’ tumor tissue into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. This technique allows successful development of transplantable, patient-derived cancer tissue xenograft lines not only from aggressive metastatic, but also from localized prostate cancer tissues. The xenografts have been found to retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, response to androgen ablation and metastatic ability. As such, they are highly clinically relevant and provide valuable tools for studies of prostate cancer progression at cellular and molecular levels, drug screening for personalized cancer therapy and preclinical drug efficacy testing; especially when a panel of models is used to cover a broader spectrum of the disease. These xenograft models could therefore be viewed as next-generation models of prostate cancer. PMID:24589467

The AISPEP (Associazione Italiana Sindromi Pelvico Prostatiche) chronic prostatitis questionnaire (AISPEP-Q). focus on the disease: anamnestic data, life activities, symptoms, sexual habits, quality of life and knowledge about prostatitis from 93 questions answered on the Internet.

PubMed

Mazzoli, Sandra; Magri, Vittorio; Guercini, Federico; Simone, Alberto; Paolicchi, Fabio; Cai, Tommaso

2007-06-01

Chronic prostatitis (CP) has been described as one of the most common illnesses men aged < or = 50, showing a significant impact on patients' quality of life comparable with other chronic diseases, such as unstable angina or Crohn's disease. CP also is a social and economic problem due to its high incidence in the young male population and to the absence of evidence for the effectiveness of treatment. Today, however, although validated outcome questionnaires are available to follow prostatitis patients, diagnostic and treatment options are based on experience, expert opinion and poor clinical trial data. More extensive and better-designed epidemiological studies are needed to evaluate and describe prostatitis patient clinical characteristics, in order to carry out correct and useful treatment. The aim of this report is to present the new Associazione Italiana Sindromi Pelvico Prostatiche questionnaire (AISPEP-Q) in order to provide a tool for increasing knowledge in prostatitis patient characteristics and design future epidemiological studies.

DNA Repair in Prostate Cancer: Biology and Clinical Implications.

PubMed

Mateo, Joaquin; Boysen, Gunther; Barbieri, Christopher E; Bryant, Helen E; Castro, Elena; Nelson, Pete S; Olmos, David; Pritchard, Colin C; Rubin, Mark A; de Bono, Johann S

2017-03-01

For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification. To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease. A literature search up to July 2016 was conducted, including clinical trials and preclinical basic research studies. Keywords included DNA repair, BRCA, ATM, CRPC, prostate cancer, PARP, platinum, predictive biomarkers, and hereditary cancer. We review how the DNA repair pathway is relevant to prostate carcinogenesis and progression. Data on how this may be relevant to hereditary cancer and genetic counseling are included, as well as data from clinical trials of PARP inhibitors and platinum therapeutics in PC. Relevant studies have identified genomic defects in DNA repair in PCs in 20-30% of advanced castration-resistant PC cases, a proportion of which are germline aberrations and heritable. Phase 1/2 clinical trial data, and other supporting clinical data, support the development of PARP inhibitors and DNA-damaging agents in this molecularly defined subgroup of PC following success in other cancer types. These studies may be an opportunity to improve patient care with personalized therapeutic strategies. Key literature on how genomic defects in the DNA damage repair pathway are relevant for prostate cancer biology and clinical management is reviewed. Potential implications for future changes in patient care are discussed. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The Relationship of Baseline Prostate Specific Antigen and Risk of Future Prostate Cancer and Its Variance by Race.

PubMed

Verges, Daniel P; Dani, Hasan; Sterling, William A; Weedon, Jeremy; Atallah, William; Mehta, Komal; Schreiber, David; Weiss, Jeffrey P; Karanikolas, Nicholas T

2017-01-01

Several studies suggest that a baseline prostate specific antigen (PSA) measured in young men predicts future risk of prostate cancer. Considering recent recommendations against PSA screening, high-risk populations (e.g. black men, men with a high baseline PSA) may be particularly vulnerable in the coming years. Thus, we investigated the relationship between baseline PSA and future prostate cancer in a black majority-minority urban population. A retrospective analysis was performed of the prostate biopsy database (n = 994) at the Brooklyn Veterans Affairs Hospital. These men were referred to urology clinic for elevated PSA and biopsied between 2007 and 2014. Multivariate logistic regression was used to predict positive prostate biopsy from log-transformed baseline PSA, race (black, white, or other), and several other variables. The majority of men identified as black (50.2%). Median age at time of baseline PSA and biopsy was 58.6 and 64.8, respectively. Median baseline PSA was similar among black men and white men (2.70 vs 2.91 for black men vs white men, p = 0.232). Even so, black men were more likely than white men to be diagnosed with prostate cancer (OR 1.62, p < 0.0001). Black men less than age 70 were at particularly greater risk than their white counterparts. Baseline PSA was not a statistically significant predictor of future prostate cancer (p = 0.101). Black men were more likely to be diagnosed with prostate cancer than were white men, despite comparable baseline PSA. In our pre-screened population at the urology clinic, a retrospective examination of baseline PSA did not predict future prostate cancer. Copyright © 2016 National Medical Association. Published by Elsevier Inc. All rights reserved.

Graminex Pollen: Phenolic Pattern, Colorimetric Analysis and Protective Effects in Immortalized Prostate Cells (PC3) and Rat Prostate Challenged with LPS.

PubMed

Locatelli, Marcello; Macchione, Nicola; Ferrante, Claudio; Chiavaroli, Annalisa; Recinella, Lucia; Carradori, Simone; Zengin, Gokhan; Cesa, Stefania; Leporini, Lidia; Leone, Sheila; Brunetti, Luigi; Menghini, Luigi; Orlando, Giustino

2018-05-11

Prostatitis, a general term describing prostate inflammation, is a common disease that could be sustained by bacterial or non-bacterial infectious agents. The efficacy of herbal extracts with antioxidant and anti-inflammatory effects for blunting the burden of inflammation and oxidative stress, with possible improvements in clinical symptoms, is under investigation. Pollen extracts have been previously reported as promising agents in managing clinical symptoms related to prostatitis. The aim of the present work was to evaluate the protective effects of Graminex pollen (Graminex TM , Deshler, OH, USA), a commercially available product based on standardized pollen extracts, in rat prostate specimens, ex vivo. In this context, we studied the putative mechanism of action of pollen on multiple inflammatory pathways, including the reduction of prostaglandin E₂ (PGE₂), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and malondialdehyde (MDA), whose activities were significantly increased by inflammatory stimuli. We characterized by means of chromatographic and colorimetric studies the composition of Graminex pollen to better correlate the activity of pollen on immortalized prostate cells (PC3), and in rat prostate specimens challenged with Escherichia coli lipopolysaccharide (LPS). We found that Graminex pollen was able to reduce radical oxygen species (ROS) production by PC3 cells and MDA, NFκB mRNA, and PGE₂ levels, in rat prostate specimens. According to our experimental evidence, Graminex pollen appears to be a promising natural product for the management of the inflammatory components in the prostate.

Analysis of the spatial distribution of prostate cancer obtained from histopathological images

NASA Astrophysics Data System (ADS)

Diaz, Kristians; Castaneda, Benjamin; Montero, Maria Luisa; Yao, Jorge; Joseph, Jean; Rubens, Deborah; Parker, Kevin J.

2013-03-01

Understanding the spatial distribution of prostate cancer and how it changes according to prostate specific antigen (PSA) values, Gleason score, and other clinical parameters may help comprehend the disease and increase the overall success rate of biopsies. This work aims to build 3D spatial distributions of prostate cancer and examine the extent and location of cancer as a function of independent clinical parameters. The border of the gland and cancerous regions from wholemount histopathological images are used to reconstruct 3D models showing the localization of tumor. This process utilizes color segmentation and interpolation based on mathematical morphological distance. 58 glands are deformed into one prostate atlas using a combination of rigid, affine, and b-spline deformable registration techniques. Spatial distribution is developed by counting the number of occurrences in a given position in 3D space from each registered prostate cancer. Finally a difference between proportions is used to compare different spatial distributions. Results show that prostate cancer has a significant difference (SD) in the right zone of the prostate between populations with PSA greater and less than 5ng/ml. Age does not have any impact in the spatial distribution of the disease. Positive and negative capsule-penetrated cases show a SD in the right posterior zone. There is SD in almost all the glands between cases with tumors larger and smaller than 10% of the whole prostate. A larger database is needed to improve the statistical validity of the test. Finally, information from whole-mount histopathological images may provide better insight into prostate cancer.

[Ultrasound physiotherapy treatment of prostatitis].

PubMed

Talberg, P I; Andryukhin, M I; Mazina, S E; Nikolaev, A L

2016-12-01

Develop a method of treatment of prostatitis based on the use of a standard antibiotic, immunomodulatory therapy, and transrectal ultrasound physiotherapy. The dynamics of the accumulation of the antibiotic was investigated in male rats. Sonication was performed immediately before the administration of the antibiotic and its accumulation in the process at 10, 20, 40, 60, 80, 100 min after dosing. The clinical study included 138 patients with chronic prostatitis. Patients of the experimental group, in addition to standard therapy, 10 sessions of transrectal ultrasound physical therapy was performed. The efficacy of treatment was assessed after 14 and 28 days after initiation. and its discussion. Experiments on laboratory animals have shown that the highest concentration and the residence time of antibiotic in the prostate tissue is noted ultrasonic treatment in the period of maximum blood concentration of the test drug. The data obtained allow to determine that the ultrasonic treatment must be performed considering the pharmacokinetics of the antibiotic. In conducting clinical trials on day 14 of treatment and clinical manifestations of prostatitis bacterial microflora in prostatic secretions were no patients in both groups. In 15% of patients of the experimental group the number of leukocytes decreased to the normal range. After 28 days the amount of leukocytes was normal in 51% of patients in the control and 85% in the experimental group. In animal experiments defined the optimal time interval separating the moment of injection of the antibiotic from the beginning of sonication. Clinical studies have shown that the transrectal ultrasound exposure during the period of maximum concentration of the antibiotic in the blood, improves patient outcomes by 33.8%.

A software tool for advanced MRgFUS prostate therapy planning and follow up

NASA Astrophysics Data System (ADS)

van Straaten, Dörte; Hoogenboom, Martijn; van Amerongen, Martinus J.; Weiler, Florian; Issawi, Jumana Al; Günther, Matthias; Fütterer, Jurgen; Jenne, Jürgen W.

2017-03-01

US guided HIFU/FUS ablation for the therapy of prostate cancer is a clinical established method, while MR guided HIFU/FUS applications for prostate recently started clinical evaluation. Even if MRI examination is an excellent diagnostic tool for prostate cancer, it is a time consuming procedure and not practicable within an MRgFUS therapy session. The aim of our ongoing work is to develop software to support therapy planning and post-therapy follow-up for MRgFUS on localized prostate cancer, based on multi-parametric MR protocols. The clinical workflow of diagnosis, therapy and follow-up of MR guided FUS on prostate cancer was deeply analyzed. Based on this, the image processing workflow was designed and all necessary components, e.g. GUI, viewer, registration tools etc. were defined and implemented. The software bases on MeVisLab with several implemented C++ modules for the image processing tasks. The developed software, called LTC (Local Therapy Control) will register and visualize automatically all images (T1w, T2w, DWI etc.) and ADC or perfusion maps gained from the diagnostic MRI session. This maximum of diagnostic information helps to segment all necessary ROIs, e.g. the tumor, for therapy planning. Final therapy planning will be performed based on these segmentation data in the following MRgFUS therapy session. In addition, the developed software should help to evaluate the therapy success, by synchronization and display of pre-therapeutic, therapy and follow-up image data including the therapy plan and thermal dose information. In this ongoing project, the first stand-alone prototype was completed and will be clinically evaluated.

Development and Evaluation of a Tumor Marker for Prostate Cancer — EDRN Public Portal

Cancer.gov

Major strides in the early detection, staging, monitoring, and risk stratification of men with prostate cancer have been realized over the last few decades. We have recently witnessed a reduction in the death rate for prostate cancer, stage migration with increased numbers of men with local/regional disease, and a greater understanding of the natural history of progression following recurrence. These advances, while not solely dependant on biomarkers, can be attributed to the discovery of Prostate Specific Antigen (PSA) in the late 1970's. In the wake of these discoveries, we still continue to unnecessarily biopsy men at risk for having prostate cancer to identify the 1:4 with the disease, understage men with presumed local disease, continue to lack an accurate method for staging which can direct treatment options for the individual patient and continue to poorly understand the tumor biology and kinetics of disease progression. Clearly, discovery of a new tumor marker and validation/clinical investigation of the markers are mandatory to advance our knowledge and direct the care of men with prostate cancer. With this research, we intend to evaluate the clinical, diagnostic, and prognostic accuracy of new and existing biomarkers on a prospective serum bank collected from men either participating in early detection programs or engaging in pre or post treatment situations. By increasing our clinical research and specimen collections we hope to further advance the staging and direction for treatment in men with prostate cancer. This study approaches patients scheduled for a prostate biopsy, patients visiting the Urology Outpatient Clinic with PSA elevation, patients scheduled for radical prostatectomy, prostate cancer patients with scheduled appointments in Radiation Oncology and men participating in early prostate cancer detection screenings. Subjects will be excluded from the study if: 1) Subjects have any mental impairment that would hinder the ability to provide informed consent. 2) The subject has undergone a radical prostatectomy and is visiting the urology clinic for a follow up appointment. We can not evaluate the protein profiles in the serum/urine for this group of patients because of prostate removal. 3) Subjects have had previous chemotherapy treatment. Such treatments often induce oxidative damage that could affect protein expression. Therefore, such patients are excluded as their exposure histories may be confounded with respect to exposures relevant to prostate cancer. 4) The patient has had previous prostate surgery. These procedures will affect protein expression. 5) Subjects have had previous cancer other than non-melanoma skin cancer. Systemic oxidative DNA damage is suspected as a potential etiologic factor in a number of other cancers. Therefore, such patients are excluded as their exposure histories maybe confounded with respect to exposures relevant to prostate cancer. Upon receiving consent, urine and blood specimens are collected from the subjects. The urine and blood are then processed and stored in our freezer bank. This study represents little to no risk to the patient. Risks include mild pain and bruising which may result from the needle stick. There is a very small chance of infection. There is also a very small chance that the patient may feel faint or pass out from the needle stick. These are the usual risks associated with phlebotomy. Collection of the urine introduces no increased risk to the patient. Adverse experiences that are both serious and unexpected will be immediately reported by telephone to the Primary Investigator, Alan. W. Partin M.D., Ph.D., (410) 614-4876.

Fiducial marker guided prostate radiotherapy: a review

PubMed Central

Jain, Suneil; Hounsell, Alan R; O'Sullivan, Joe M

2016-01-01

Image-guided radiotherapy (IGRT) is an essential tool in the accurate delivery of modern radiotherapy techniques. Prostate radiotherapy positioned using skin marks or bony anatomy may be adequate for delivering a relatively homogeneous whole-pelvic radiotherapy dose, but these surrogates are not reliable when using reduced margins, dose escalation or hypofractionated stereotactic radiotherapy. Fiducial markers (FMs) for prostate IGRT have been in use since the 1990s. They require surgical implantation and provide a surrogate for the position of the prostate gland. A variety of FMs are available and they can be used in a number of ways. This review aimed to establish the evidence for using prostate FMs in terms of feasibility, implantation procedures, types of FMs used, FM migration, imaging modalities used and the clinical impact of FMs. A search strategy was defined and a literature search was carried out in Medline. Inclusion and exclusion criteria were applied, which resulted in 50 articles being included in this review. The evidence demonstrates that FMs provide a more accurate surrogate for the position of the prostate than either external skin marks or bony anatomy. A combination of FM alignment and soft-tissue analysis is currently the most effective and widely available approach to ensuring accuracy in prostate IGRT. FM implantation is safe and well tolerated. FM migration is possible but minimal. Standardization of all techniques and procedures in relation to the use of prostate FMs is required. Finally, a clinical trial investigating a non-surgical alternative to prostate FMs is introduced. PMID:27585736

The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

PubMed

Whitaker, Hayley C; Kote-Jarai, Zsofia; Ross-Adams, Helen; Warren, Anne Y; Burge, Johanna; George, Anne; Bancroft, Elizabeth; Jhavar, Sameer; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Saunders, Edward; Page, Elizabeth; Mitra, Anita; Mitchell, Gillian; Lindeman, Geoffrey J; Evans, D Gareth; Blanco, Ignacio; Mercer, Catherine; Rubinstein, Wendy S; Clowes, Virginia; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Donaldson, Alan; Izatt, Louise; Dorkins, Huw; Male, Alison; Tucker, Kathy; Stapleton, Alan; Lam, Jimmy; Kirk, Judy; Lilja, Hans; Easton, Douglas; Cooper, Colin; Eeles, Rosalind; Neal, David E

2010-10-13

Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

The rs10993994 Risk Allele for Prostate Cancer Results in Clinically Relevant Changes in Microseminoprotein-Beta Expression in Tissue and Urine

PubMed Central

Whitaker, Hayley C.; Warren, Anne Y.; Burge, Johanna; George, Anne; Bancroft, Elizabeth; Jhavar, Sameer; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Saunders, Edward; Page, Elizabeth; Mitra, Anita; Mitchell, Gillian; Lindeman, Geoffrey J.; Evans, D. Gareth; Blanco, Ignacio; Mercer, Catherine; Rubinstein, Wendy S.; Clowes, Virginia; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Donaldson, Alan; Izatt, Louise; Dorkins, Huw; Male, Alison; Tucker, Kathy; Stapleton, Alan; Lam, Jimmy; Kirk, Judy; Lilja, Hans; Easton, Douglas; Cooper, Colin; Eeles, Rosalind; Neal, David E.

2010-01-01

Background Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. Methodology/Principal Findings MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. Conclusions These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring. PMID:20967219

The androgen receptor malignancy shift in prostate cancer.

PubMed

Copeland, Ben T; Pal, Sumanta K; Bolton, Eric C; Jones, Jeremy O

2018-05-01

Androgens and the androgen receptor (AR) are necessary for the development, function, and homeostatic growth regulation of the prostate gland. However, once prostate cells are transformed, the AR is necessary for the proliferation and survival of the malignant cells. This change in AR function appears to occur in nearly every prostate cancer. We have termed this the AR malignancy shift. In this review, we summarize the current knowledge of the AR malignancy shift, including the DNA-binding patterns that define the shift, the transcriptome changes associated with the shift, the putative drivers of the shift, and its clinical implications. In benign prostate epithelial cells, the AR primarily binds consensus AR binding sites. In carcinoma cells, the AR cistrome is dramatically altered, as the AR associates with FOXA1 and HOXB13 motifs, among others. This shift leads to the transcription of genes associated with a malignant phenotype. In model systems, some mutations commonly found in localized prostate cancer can alter the AR cistrome, consistent with the AR malignancy shift. Current evidence suggests that the AR malignancy shift is necessary but not sufficient for transformation of prostate epithelial cells. Reinterpretation of prostate cancer genomic classification systems in light of the AR malignancy shift may improve our ability to predict clinical outcomes and treat patients appropriately. Identifying and targeting the molecular factors that contribute to the AR malignancy shift is not trivial but by doing so, we may be able to develop new strategies for the treatment or prevention of prostate cancer. © 2018 Wiley Periodicals, Inc.

Recent advances in circulating tumor cells and cell-free DNA in metastatic prostate cancer: a review.

PubMed

Parimi, Sunil; Ko, Jenny J

2017-10-01

The treatment landscape of metastatic prostate cancer has changed dramatically over the past five years. As new discoveries are made and further novel therapies become available, there is a heightened urgency to develop biomarkers that can guide prognoses and predict therapy responses. Circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) in the blood have emerged as potential promising tumor avatars. Areas covered: In this review, we describe technological breakthroughs and clinical implementation of the CTCs and ctDNA. We also discuss the key challenges that must be overcome before circulating blood-based biomarkers can be universally adopted into the management of patients with metastatic prostate cancer. Expert commentary: Both CTCs and ctDNA have the potential to be incorporated into routine patient care, with increasing numbers of prospective trials incorporating them into clinical designs. CTCs and ctDNA will thus have an increasingly valuable role in augmenting our understanding of prostate cancer at a molecular level, aiding in prognostication of prostate cancer patients, acting as a surrogate for OS in clinical trials, and helping us prioritize our treatment selections by elucidating resistance mechanisms.

BET inhibitors in metastatic prostate cancer: therapeutic implications and rational drug combinations.

PubMed

Markowski, Mark C; De Marzo, Angelo M; Antonarakis, Emmanuel S

2017-12-01

The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas covered: We speculate that a combination approach using inhibitors of BET proteins (BETi) with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer. Preclinical data has identified several molecular targets that may enhance the effect of BET inhibition in the clinic. This review will summarize the known preclinical data implicating BET as an important therapeutic target in advanced prostate cancer, highlight the ongoing clinical trials targeting this protein family, and speculate on rationale combination strategies using BETi together with other agents in prostate cancer. A literature search using Pubmed was performed for this review. Expert opinion: Use of BETi in the treatment of mCRPC patients may require the addition of a second novel agent.

Clinical Significance of Prostatic Calculi: A Review

PubMed Central

2018-01-01

Prostatic calculi often occur in middle-aged and old men. Prostatic calculi are usually classified as primary/endogenous stones or secondary/extrinsic stones. Endogenous stones are commonly caused by obstruction of the prostatic ducts around the enlarged prostate by benign prostatic hyperplasia (BPH) or by chronic inflammation. Extrinsic stones occur mainly around the urethra, because they are caused by urine reflux. The exact prevalence of prostatic calculi is not known, and it has been reported to vary widely, from 7% to 70%. Most cases of prostatic calculi are not accompanied by symptoms. Therefore, most cases are found incidentally during the diagnosis of BPH using transrectal ultrasonography (TRUS). However, prostatic calculi associated with chronic prostatitis may be accompanied by chronic pelvic pain. Rare cases have been reported in which extrinsic prostatic calculi caused by urine reflux have led to voiding difficulty due to their size. More than 80% of prostatic calculi are composed of calcium phosphate. Prostatic calculi can be easily diagnosed using TRUS or computed tomography. Treatment is often unnecessary, but if an individual experiences difficulty in urination or chronic pain, prostatic calculi can be easily removed using a transurethral electroresection loop or holmium laser. PMID:29076299

Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome.

PubMed

Sökeland, J

2000-09-01

To test the hypothesis that in patients with benign prostatic hyperplasia (BPH), the outcome of drug therapy with finasteride may be predictable from the baseline prostate volume and that positive clinical effects might be expected only in patients with prostate volumes of > 40 mL, using a subgroup analysis of results from a previously reported clinical trial of finasteride and phytotherapy. A subgroup of 431 patients was analysed from a randomized, multicentre, double-blind clinical trial involving 543 patients with the early stages of BPH. Patients received a fixed combination of extracts of saw palmetto fruit (Serenoa repens) and nettle root (Urtica dioica) (PRO 160/120) or the synthetic 5alpha-reductase inhibitor finasteride. The patients assessed had valid ultrasonographic measurements and baseline prostate volumes of either 40 mL. All 516 patients were included in the safety analysis. The results of the original trial showed equivalent efficacy for both treatments. The mean (SD) maximum urinary flow (the main outcome variable) increased (from baseline values) after 24 weeks by 1.9 (5.6) mL/s with PRO 160/120 and by 2.4 (6.3) mL/s with finasteride. There were no statistically significant group differences (P = 0.52). The subgroups with small prostates ( 40 mL were similar, at 2.3 (6.1) and 2. 2 (5.3) mL/s, respectively. There were improvements in the International Prostate Symptom Score in both treatment groups, with no statistically significant differences. The subgroup analysis showed slightly better results for voiding symptoms in the patients with prostates of > 40 mL, but there were also improvements in the subgroup with smaller prostates. The safety analysis showed that more patients in the finasteride group reported adverse events and also there were more adverse events in this group than in patients treated with PRO 160/120. The present analysis showed that the efficacy of both PRO 160/120 and finasteride was equivalent and unrelated to prostate volume. However, PRO 160/120 had better tolerability than finasteride.

Three-dimensional nonrigid landmark-based magnetic resonance to transrectal ultrasound registration for image-guided prostate biopsy.

PubMed

Sun, Yue; Qiu, Wu; Yuan, Jing; Romagnoli, Cesare; Fenster, Aaron

2015-04-01

Registration of three-dimensional (3-D) magnetic resonance (MR) to 3-D transrectal ultrasound (TRUS) prostate images is an important step in the planning and guidance of 3-D TRUS guided prostate biopsy. In order to accurately and efficiently perform the registration, a nonrigid landmark-based registration method is required to account for the different deformations of the prostate when using these two modalities. We describe a nonrigid landmark-based method for registration of 3-D TRUS to MR prostate images. The landmark-based registration method first makes use of an initial rigid registration of 3-D MR to 3-D TRUS images using six manually placed approximately corresponding landmarks in each image. Following manual initialization, the two prostate surfaces are segmented from 3-D MR and TRUS images and then nonrigidly registered using the following steps: (1) rotationally reslicing corresponding segmented prostate surfaces from both 3-D MR and TRUS images around a specified axis, (2) an approach to find point correspondences on the surfaces of the segmented surfaces, and (3) deformation of the surface of the prostate in the MR image to match the surface of the prostate in the 3-D TRUS image and the interior using a thin-plate spline algorithm. The registration accuracy was evaluated using 17 patient prostate MR and 3-D TRUS images by measuring the target registration error (TRE). Experimental results showed that the proposed method yielded an overall mean TRE of [Formula: see text] for the rigid registration and [Formula: see text] for the nonrigid registration, which is favorably comparable to a clinical requirement for an error of less than 2.5 mm. A landmark-based nonrigid 3-D MR-TRUS registration approach is proposed, which takes into account the correspondences on the prostate surface, inside the prostate, as well as the centroid of the prostate. Experimental results indicate that the proposed method yields clinically sufficient accuracy.

Does [-2]Pro-Prostate Specific Antigen Meet the Criteria to Justify Its Inclusion in the Clinical Decision-Making Process?

PubMed

Sanchis-Bonet, Angeles; Barrionuevo-González, Marta; Bajo-Chueca, Ana; Morales-Palacios, Nelson; Sanchez-Chapado, Manuel

2018-01-01

To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets the criteria to justify its inclusion in a predictive model of prostate cancer (PCa) diagnosis and in the clinical decision-making process. A total 172 men with total prostate-specific antigen of 2-10 ng/mL underwent measurement of free PSA and p2PSA before prostate biopsy in an observational and prospective study. From these measurements, the Prostate Health Index (PHI) was calculated. Clinical and analytical predictive models were created incorporating PHI. Of 172 men, 72 (42%) were diagnosed with PCa, 33 (46%) of whom were found to be with high-grade disease. PHI score was the most predictive of biopsy outcomes in terms of discriminative ability (area under the curve = 0.79), with an added gain in predictive accuracy of 17%. All the models that incorporated PHI worked better in terms of calibration close to 45° on the slope. In the decision curve analysis, at a threshold probability of 40% we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors. PHI score is a more discriminant biomarker, has superior calibration and superior net benefit, and provides a higher rate of avoided biopsies; thus, it can be useful for aiding in making a more informed decision for each patient. © 2018 S. Karger AG, Basel.

Incidental Prostate Adenocarcinoma in Cystoprostatectomy Specimens: Partial Versus Complete Prostate Sampling.

PubMed

Filter, Emily R; Gabril, Manal Y; Gomez, Jose A; Wang, Peter Z T; Chin, Joseph L; Izawa, Jonathan; Moussa, Madeleine

2017-08-01

The rate of incidental prostate adenocarcinoma (PCa) detection in radical cystoprostatectomy (RCP) varies widely, ranging from 15% to 54%. Such variability may be explained by institutional differences in prostate grossing protocols. Either partial or complete submission of the prostate gland in RCP may result in detection of clinically insignificant or significant incidental PCa. The aim of the study was to compare the clinical significance of PCa in RCP specimens in partial versus complete sampling. Seventy-two out of 158 RCP cases showed incidental PCa. The pathologic features, including Gleason score, margin status, extraprostatic extension (EPE), seminal vesicle invasion (SVI), PCa stage, and tumor volume, were assessed. The 72 cases were divided into partial (n = 21, 29.1%) and complete sampling (n = 51, 70.8%) groups. EPE was detected in 13/72 (18.1%) with 11/13 (84.6%) cases in the complete group. Positive margins were present in 11/72 (15.3%) with 9/11 (81.8%) in the complete group. SVI was detected in 4/72 (5.6%) with 3/4 (75.0%) in the complete group. Overall, 4/72 (5.6%) had a Gleason score >7, all of which were in the complete group. Our data suggest that complete sampling of the prostate may be the ideal approach to grossing RCP specimens, allowing for greater detection of clinically significant incidental PCa.

A Comprehensive Review of Contemporary Role of Local Treatment of the Primary Tumor and/or the Metastases in Metastatic Prostate Cancer

PubMed Central

Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

2014-01-01

To provide an overview of the currently available literature regarding local control of primary tumor and oligometastases in metastatic prostate cancer and salvage lymph node dissection of clinical lymph node relapse after curative treatment of prostate cancer. Evidence Acquisition. A systematic literature search was conducted in 2014 to identify abstracts, original articles, review articles, research articles, and editorials relevant to the local control in metastatic prostate cancer. Evidence Synthesis. Local control of primary tumor in metastatic prostate cancer remains experimental with low level of evidence. The concept is supported by a growing body of genetic and molecular research as well as analogy with other cancers. There is only one retrospective observational population based study showing prolonged survival. To eradicate oligometastases, several options exist with excellent local control rates. Stereotactic body radiotherapy is safe, well tolerated, and efficacious treatment for lymph node and bone lesions. Both biochemical and clinical progression are slowed down with a median time to initiate ADT of 2 years. Salvage lymph node dissection is feasible in patients with clinical lymph node relapse after local curable treatment. Conclusion. Despite encouraging oncologic midterm results, a complete cure remains elusive in metastatic prostate cancer patients. Further advances in imaging are crucial in order to rapidly evolve beyond the proof of concept. PMID:25485280

Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers

PubMed Central

Zhong, Yali; Li, Xiaoli; Ji, Yasai; Li, Xiaoran; Li, Yaqing; Yu, Dandan; Yuan, Yuan; Liu, Jian; Li, Huixiang; Zhang, Mingzhi; Ji, Zhenyu; Fan, Dandan; Wen, Jianguo; Goscinski, Mariusz Adam; Yuan, Long; Hao, Bin; Nesland, Jahn M; Suo, Zhenhe

2017-01-01

Cells generate adenosine-5′-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the “Warburg Effect”, in which cancer cells rely preferentially on glycolysis instead of mitochondrial OXPHOS as the main energy source even in the presence of high oxygen tension. One of the main players in controlling OXPHOS is the mitochondrial gatekeeperpyruvate dehydrogenase complex (PDHc) and its major subunit is E1α (PDHA1). To further analyze the function of PDHA1 in cancer cells, it was knock out (KO) in the human prostate cancer cell line LnCap and a stable KO cell line was established. We demonstrated that PDHA1 gene KO significantly decreased mitochondrial OXPHOS and promoted anaerobic glycolysis, accompanied with higher stemness phenotype including resistance to chemotherapy, enhanced migration ability and increased expression of cancer stem cell markers. We also examined PDHA1 protein expression in prostate cancer tissues by immunohistochemistry and observed that reduced PDHA1 protein expression in clinical prostate carcinomas was significantly correlated with poor prognosis. Collectively, our results show that negative PDHA1 gene expressionis associated with significantly higher cell stemness in prostate cancer cells and reduced protein expression of this gene is associated with shorter clinical outcome in prostate cancers. PMID:28076853

Clinical correlates of enlarged prostate size in subjects with sexual dysfunction

PubMed Central

Corona, Giovanni; Gacci, Mauro; Maseroli, Elisa; Rastrelli, Giulia; Vignozzi, Linda; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2014-01-01

Digito-rectal examination (DRE) of the prostate provides useful information on the state of prostate growth and on the presence of suspected peripheral nodules. The aim of this study is to describe the clinical and biochemical correlates of finding an enlarged prostate size at DRE in subjects with sexual dysfunction (SD). A consecutive series of 2379 patients was retrospectively studied. The analysis was focused on a subset of subjects (n = 1823; mean age 54.7 ± 11.4) selected for being free from overt prostatic diseases. Several parameters were investigated. After adjusting for confounders, the presence of an enlarged prostate size at DRE was associated with a higher risk of metabolic syndrome (HR = 1.346 (1.129–1.759); P = 0.030), type 2 diabetes mellitus (HR = 1.489 (1.120–1.980); P = 0.006), increased LDL cholesterol (>100 mg dl−1; HR = 1.354 (1.018–1.801); P = 0.037) and increased mean blood pressure (BP) values (HR = 1.017 (1.007–1.027) for each mmHg increment; P = 0.001). Accordingly, enlarged prostate size was also associated with a higher risk of arteriogenic erectile dysfunction (ED), as well as with other andrological conditions, such as varicocele and premature ejaculation (PE). PSA levels were significantly higher in subjects with enlarged prostate size when compared to the rest of the sample (HR = 3.318 (2.304; 4.799) for each log unit increment in PSA levels; P < 0.0001). Arteriogenic ED, according to different criteria, was also associated with increased PSA levels. In conclusion, our data support the need to examine prostate size either by clinical (DRE) or biochemical (PSA) inspection in subjects with SD, in order to have insights into the nature of the SD and the metabolic and cardiovascular (CV) background of the patient. PMID:24830688

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.

Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer.

PubMed

Nordström, Tobias; Akre, Olof; Aly, Markus; Grönberg, Henrik; Eklund, Martin

2018-04-01

Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines. We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7. The median PSA-density was 0.10 ng/ml 2 (IQR 0.075-0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05-1.07 and OR 1.07, 95% CI 1.06-1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml 2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml 2 and 0.15 ng/ml 2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors. PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

Clinical outcomes of prostate cancer patients in Yokosuka City, Japan: A comparative study between cases detected by prostate-specific antigen-based screening in Yokosuka and those detected by other means.

PubMed

Sakai, Naoki; Taguri, Masataka; Kobayashi, Kazuki; Noguchi, Sumio; Ikeda, Shigeru; Koh, Hideshige; Satomi, Yoshiaki; Furuhata, Akihiko

2015-08-01

To investigate whether prostate-specific antigen-based screening reduced the prostate cancer mortality rate in Yokosuka, Japan. We carried out a cohort study, in which we compared clinical outcomes between patients detected by prostate-specific antigen-based screening (S group n = 524) versus those detected by other means (NS group n = 1044). Clinical and pathological factors were evaluated using Cox regression analyses and the Kaplan-Meier method. A total of 1.5% (8/524) of patients in the S group and 6.7% (70/1044) of those in the NS group died from prostate cancer during follow up. A total of 8.0% (42/524) of patients in the S group and 11.4% (119/1044) in the NS group died from other causes. The 10-year cancer specific survival rates of the S and NS groups were 97% and 86%, respectively (P < 0.001). The median age was significantly lower in the S group than the NS group: 71 and 73 years, respectively (P < 0.001). The rate of Gleason score 8-10 was significantly lower in the S group than the NS group: 9.7% and 16.7%, respectively (P < 0.001). The rate of patients with metastasis or prostate-specific antigen 100 ng/mL or more was significantly lower in the S group than the NS group: 7.8% and 23.0%, respectively (P < 0.001). On multivariate analysis, Gleason score 8-10 compared with Gleason score 6 was independently associated with cancer-specific survival (hazard ratio 4.808, 95% confidence interval 1.044-22.14, P = 0.044). Prostate-specific antigen-based population screening in Yokosuka City might help to reduce the prostate cancer mortality rate. © 2015 The Japanese Urological Association.

A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.

PubMed

Klein, Eric A; Cooperberg, Matthew R; Magi-Galluzzi, Cristina; Simko, Jeffry P; Falzarano, Sara M; Maddala, Tara; Chan, June M; Li, Jianbo; Cowan, Janet E; Tsiatis, Athanasios C; Cherbavaz, Diana B; Pelham, Robert J; Tenggara-Hunter, Imelda; Baehner, Frederick L; Knezevic, Dejan; Febbo, Phillip G; Shak, Steven; Kattan, Michael W; Lee, Mark; Carroll, Peter R

2014-09-01

Prostate tumor heterogeneity and biopsy undersampling pose challenges to accurate, individualized risk assessment for men with localized disease. To identify and validate a biopsy-based gene expression signature that predicts clinical recurrence, prostate cancer (PCa) death, and adverse pathology. Gene expression was quantified by reverse transcription-polymerase chain reaction for three studies-a discovery prostatectomy study (n=441), a biopsy study (n=167), and a prospectively designed, independent clinical validation study (n=395)-testing retrospectively collected needle biopsies from contemporary (1997-2011) patients with low to intermediate clinical risk who were candidates for active surveillance (AS). The main outcome measures defining aggressive PCa were clinical recurrence, PCa death, and adverse pathology at prostatectomy. Cox proportional hazards regression models were used to evaluate the association between gene expression and time to event end points. Results from the prostatectomy and biopsy studies were used to develop and lock a multigene-expression-based signature, called the Genomic Prostate Score (GPS); in the validation study, logistic regression was used to test the association between the GPS and pathologic stage and grade at prostatectomy. Decision-curve analysis and risk profiles were used together with clinical and pathologic characteristics to evaluate clinical utility. Of the 732 candidate genes analyzed, 288 (39%) were found to predict clinical recurrence despite heterogeneity and multifocality, and 198 (27%) were predictive of aggressive disease after adjustment for prostate-specific antigen, Gleason score, and clinical stage. Further analysis identified 17 genes representing multiple biological pathways that were combined into the GPS algorithm. In the validation study, GPS predicted high-grade (odds ratio [OR] per 20 GPS units: 2.3; 95% confidence interval [CI], 1.5-3.7; p<0.001) and high-stage (OR per 20 GPS units: 1.9; 95% CI, 1.3-3.0; p=0.003) at surgical pathology. GPS predicted high-grade and/or high-stage disease after controlling for established clinical factors (p<0.005) such as an OR of 2.1 (95% CI, 1.4-3.2) when adjusting for Cancer of the Prostate Risk Assessment score. A limitation of the validation study was the inclusion of men with low-volume intermediate-risk PCa (Gleason score 3+4), for whom some providers would not consider AS. Genes representing multiple biological pathways discriminate PCa aggressiveness in biopsy tissue despite tumor heterogeneity, multifocality, and limited sampling at time of biopsy. The biopsy-based 17-gene GPS improves prediction of the presence or absence of adverse pathology and may help men with PCa make more informed decisions between AS and immediate treatment. Prostate cancer (PCa) is often present in multiple locations within the prostate and has variable characteristics. We identified genes with expression associated with aggressive PCa to develop a biopsy-based, multigene signature, the Genomic Prostate Score (GPS). GPS was validated for its ability to predict men who have high-grade or high-stage PCa at diagnosis and may help men diagnosed with PCa decide between active surveillance and immediate definitive treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Monte Carlo investigation of I-125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET.

PubMed

Mason, J; Al-Qaisieh, B; Bownes, P; Henry, A; Thwaites, D

2013-03-01

In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.

Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

DTIC Science & Technology

2016-10-01

prostate cancer through sequencing xenografts and tissue samples. Qualify novel drivers of AR- prostate cancer through in vitro models. Develop novel...ability of RNASEH2A to modulate radio-sensitivity in prostate cancer cell lines and xenograft models. 3: Investigate RNASEH2A as a marker of radio...lung cancer clinical management. List of the Specific Aims: Aim 1: To establish patient-derived xenografts (PDX) models of pre-neoplastic lesions

hsa-miR-135a-1 inhibits prostate cancer cell growth and migration by targeting EGFR.

PubMed

Xu, Bin; Tao, Tao; Wang, Yiduo; Fang, Fang; Huang, Yeqing; Chen, Shuqiu; Zhu, Weidong; Chen, Ming

2016-10-01

Prostate cancer is one of the leading causes of death in men worldwide. Differentially expressed microRNAs (miRNAs) are associated with metastatic prostate cancer. However, their potential roles for affecting prostate cancer initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs in human metastatic prostate cancer tissues. We further validated our miRNA expression data using two large, independent clinical prostate cancer datasets from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA). Our data support a model in which hsa-miR-135-1 acts as a potential tumor suppressor in metastatic prostate cancer. First, its downregulation was positively correlated with late TNM stage, high Gleason score, and adverse prognosis. Second, cell growth, cell cycle progression, cell migration and invasion, and xenograft tumor formation were dramatically inhibited by miR-135a overexpression. Third, in the microarray gene expression data analysis using Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, Ingenuity Pathway Analysis (IPA), and Oncomine concept analysis, we showed that miR-135a targets multiple oncogenic pathways including epidermal growth factor receptor (EGFR), which we verified using functional experimental assays. These results help advance our understanding of the function of miRNAs in metastatic prostate cancer and provide a basis for further clinical investigation.

Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

PubMed Central

Hsiao, Wayland; Anastasia, Katrina; Hall, John; Goodman, Michael; Rimland, David; Ritenour, Chad W. M.; Issa, Muta M.

2009-01-01

HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5). In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients. PMID:19219374

Male Oncology Research and Education program for men at high risk for prostate cancer.

PubMed

Lorentz, J; Liu, S K; Vesprini, D

2018-04-01

Three groups of men are at high risk of developing prostate cancer: men with a strong family history of prostate cancer, men of West African or Caribbean ancestry, and men with a germline pathogenic variant in a prostate cancer-associated gene. Despite the fact that those men constitute a significant portion of the male population in North America, few recommendations for prostate cancer screening specific to them have been developed. For men at general population risk for prostate cancer, screening based on prostate-specific antigen (psa) has remained controversial despite the abundance of literature on the topic. As a result, recommendations made by major screening authorities are inconsistent (ranging from no psa screening to baseline psa screening at age 45), allowing physicians to pick and choose how to screen their patients. The Male Oncology Research and Education (more) program is an observational research program that serves as an academic platform for multiple research foci. For its participants, serum and dna are biobanked, medical information is collected, and contact for relevant research-related opportunities is maintained. This research program is paired with a specialized clinic called the more clinic, where men at high risk are regularly screened for prostate cancer in a standard approach that includes physical examination and serum psa measurement. In this article, we describe the goals, participant accrual to date, and projects specific to this unique program.

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.

[Prostate cancer screening using prostate-specific antigen: The views of general and laboratory physicians].

PubMed

Giménez, N; Filella, X; Gavagnach, M; Allué, J A; Pedrazas, D; Ferrer, F

2018-03-21

It is currently recommended to provide individualised information on benefit-risk balance and shared decision-making in prostate cancer screening using prostate-specific antigen (PSA). To determine the usual practice and the views of general and laboratory practitioners in the screening of prostate cancer using PSA. A cross-sectional study based on a questionnaire and on PSA screening requests from Primary Health Care (PHC) in men older than 49 years with no prostatic symptoms. In 2015, PHC in Catalonia requested PSA on 15.2% of males. A total of 114 general practitioners and 227 laboratory practitioners participated in the questionnaire. The mean age of those who responded was 43 years with a mean of 17 years' experience, and included 64% women. According to general practitioners, 61% of PSA was performed at the patient's request. The uncertainty score when requesting PSA was 5 points for general practitioners and 5.7 for laboratory professionals. Interest in having clinical recommendations received 7.2 points in PHC, and 8.8 in the laboratory. Knowledge about the different clinical practice guidelines received was less than 5 points overall. General practitioners requested PSA screening in almost one-sixth of men over the age of 49 without prostate disease, often at the patient's request, and after informing them of the benefits and risks. PHC and laboratory physicians were interested in having recommendations and information, although they did not usually consult clinical practice guidelines immediately. Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Three-Dimensional Magnetic Resonance Spectroscopic Imaging of Brain and Prostate Cancer1

PubMed Central

Kurhanewicz, John; Vigneron, Daniel B; Nelson, Sarah J

2000-01-01

Abstract Clinical applications of magnetic resonance spectroscopic imaging (MRSI) for the study of brain and prostate cancer have expanded significantly over the past 10 years. Proton MRSI studies of the brain and prostate have demonstrated the feasibility of noninvasively assessing human cancers based on metabolite levels before and after therapy in a clinically reasonable amount of time. MRSI provides a unique biochemical “window” to study cellular metabolism noninvasively. MRSI studies have demonstrated dramatic spectral differences between normal brain tissue (low choline and high N-acetyl aspartate, NAA) and prostate (low choline and high citrate) compared to brain (low NAA, high choline) and prostate (low citrate, high choline) tumors. The presence of edema and necrosis in both the prostate and brain was reflected by a reduction of the intensity of all resonances due to reduced cell density. MRSI was able to discriminate necrosis (absence of all metabolites, except lipids and lactate) from viable normal tissue and cancer following therapy. The results of current MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy as well as the magnitude and time course of metabolic changes after therapy can improve our understanding of cancer aggressiveness and mechanisms of therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the potential for improved diagnosis, staging and treatment planning of brain and prostate cancer. Additionally, studies are under way to determine the accuracy of anatomic and metabolic parameters in providing an objective quantitative basis for assessing disease progression and response to therapy. PMID:10933075

Epidemiology of prostatitis

PubMed Central

Krieger, John N.; Lee, Shaun Wen Huey; Jeon, Jeonseong; Cheah, Phaik Yeong; Liong, Men Long; Riley, Donald E.

2008-01-01

Background Prostatitis describes a combination of infectious diseases (acute and chronic bacterial prostatitis), chronic pelvic pain syndrome, and asymptomatic inflammation. Materials and methods We employed evidence-based methods to review the epidemiology of prostatitis syndromes. Results The prevalence of prostatitis symptoms could be compared in five studies surveying 10 617 men. Overall, 873 participants met various criteria for prostatitis, representing an overall rate of 8.2%, with prevalence ranging from 2.2 to 9.7%. A history of sexually transmitted diseases was associated with an increased risk for prostatitis symptoms. Men reporting a history of prostatitis symptoms had a substantially increased rate of benign prostatic hyperplasia, lower urinary tract symptoms and prostate cancer. In one study, the incidence of physician-diagnosed prostatitis was 4.9 cases per 1000 person-years. Two studies suggest that about one-third of men reporting prostatitis symptoms had resolution after 1 year. Patients with previous episodes and more severe symptoms are at higher risk for chronic pelvic pain. Discussion The prevalence of prostatitis symptoms is high, comparable to rates of ischamic heart disease and diabetes. Clinical evaluation appears necessary to verify that prostatitis is responsible for patients’ symptoms. Prostatitis symptoms may increase a man’s risk for benign prostate hypertrophy, lower urinary tract symptoms and prostate cancer. We need to define natural history and consequences of prostatitis, develop better algorithms for diagnosis and treatment, and develop strategies for prevention. PMID:18164907

Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2017-06-01

Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality. This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality. Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value < 0.005). The presence of IDC-P on diagnostic needle biopsy remained an independent predictor of prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis. IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association between IDC-P and reactive stroma provides evidence in support of the idea that stromal factors facilitate carcinoma invasion to the prostatic acini and ducts. Prostate 77:859-865, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Diffusion anisotropy in fresh and fixed prostate tissue ex vivo.

PubMed

Bourne, Roger M; Bongers, Andre; Chatterjee, Aritrick; Sved, Paul; Watson, Geoffrey

2016-08-01

To investigate diffusion anisotropy in whole human prostate specimens Seven whole radical prostatectomy specimens were obtained with informed patient consent and institutional ethics approval. Diffusion tensor imaging was performed at 9.4 Tesla. Diffusion tensors were calculated from the native acquired data and after progressive downsampling Fractional anisotropy (FA) decreased as voxel volume increased, and differed widely between prostates. Fixation decreased mean FA by ∼0.05-0.08 at all voxel volumes but did not alter principle eigenvector orientation. In unfixed tissue high FA (> 0.6) was found only in voxels of volume <0.5 mm(3) , and then only in a small fraction of all voxels. At typical clinical voxel volumes (4-16 mm(3) ) less than 50% of voxels had FA > 0.25. FA decreased at longer diffusion times (Δ = 60 or 80 ms compared with 20 ms), but only by ∼0.02 at typical clinical voxel volume. Peripheral zone FA was significantly lower than transition zone FA in five of the seven prostates FA varies widely between prostates. The very small proportion of clinical size voxels with high FA suggests that in clinical DWI studies ADC based on three-direction measurements will be minimally affected by anisotropy. Magn Reson Med 76:626-634, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Abiraterone for Hormone-Sensitive Prostate Cancers

Cancer.gov

An NCI Cancer Currents blog post on results from two clinical trials that showed adding abiraterone to androgen-deprivation therapy improved survival for men with metastatic hormone-sensitive prostate cancer.

An MRI-Compatible Robotic System With Hybrid Tracking for MRI-Guided Prostate Intervention

PubMed Central

Krieger, Axel; Iordachita, Iulian I.; Guion, Peter; Singh, Anurag K.; Kaushal, Aradhana; Ménard, Cynthia; Pinto, Peter A.; Camphausen, Kevin; Fichtinger, Gabor

2012-01-01

This paper reports the development, evaluation, and first clinical trials of the access to the prostate tissue (APT) II system—a scanner independent system for magnetic resonance imaging (MRI)-guided transrectal prostate interventions. The system utilizes novel manipulator mechanics employing a steerable needle channel and a novel six degree-of-freedom hybrid tracking method, comprising passive fiducial tracking for initial registration and subsequent incremental motion measurements. Targeting accuracy of the system in prostate phantom experiments and two clinical human-subject procedures is shown to compare favorably with existing systems using passive and active tracking methods. The portable design of the APT II system, using only standard MRI image sequences and minimal custom scanner interfacing, allows the system to be easily used on different MRI scanners. PMID:22009867

MRI-guided brachytherapy

PubMed Central

Tanderup, Kari; Viswanathan, Akila; Kirisits, Christian; Frank, Steven J.

2014-01-01

The application of MRI-guided brachytherapy has demonstrated significant growth during the last two decades. Clinical improvements in cervix cancer outcomes have been linked to the application of repeated MRI for identification of residual tumor volumes during radiotherapy. This has changed clinical practice in the direction of individualized dose administration, and mounting evidence of improved clinical outcome with regard to local control, overall survival as well as morbidity. MRI-guided prostate HDR and LDR brachytherapy has improved the accuracy of target and organs-at-risk (OAR) delineation, and the potential exists for improved dose prescription and reporting for the prostate gland and organs at risk. Furthermore, MRI-guided prostate brachytherapy has significant potential to identify prostate subvolumes and dominant lesions to allow for dose administration reflecting the differential risk of recurrence. MRI-guided brachytherapy involves advanced imaging, target concepts, and dose planning. The key issue for safe dissemination and implementation of high quality MRI-guided brachytherapy is establishment of qualified multidisciplinary teams and strategies for training and education. PMID:24931089

A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer.

PubMed

Lunardi, Andrea; Ala, Ugo; Epping, Mirjam T; Salmena, Leonardo; Clohessy, John G; Webster, Kaitlyn A; Wang, Guocan; Mazzucchelli, Roberta; Bianconi, Maristella; Stack, Edward C; Lis, Rosina; Patnaik, Akash; Cantley, Lewis C; Bubley, Glenn; Cordon-Cardo, Carlos; Gerald, William L; Montironi, Rodolfo; Signoretti, Sabina; Loda, Massimo; Nardella, Caterina; Pandolfi, Pier Paolo

2013-07-01

Here we report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. We show that castration counteracts tumor progression in a Pten loss-driven mouse model of prostate cancer through the induction of apoptosis and proliferation block. Conversely, this response is bypassed with deletion of either Trp53 or Zbtb7a together with Pten, leading to the development of castration-resistant prostate cancer (CRPC). Mechanistically, the integrated acquisition of data from mouse models and patients identifies the expression patterns of XAF1, XIAP and SRD5A1 as a predictive and actionable signature for CRPC. Notably, we show that combined inhibition of XIAP, SRD5A1 and AR pathways overcomes castration resistance. Thus, our co-clinical approach facilitates the stratification of patients and the development of tailored and innovative therapeutic treatments.

18F-FDG PET and PET/CT in the Localization and Characterization of Lesions in Patients with Ovarian Cancer.

PubMed

Caprio, M G; Capacchione, D; Mainolfi, C; Spera, A M; Salvatore, B; Cella, L; Salvatore, M; Pace, L

2012-01-01

The aim was to compare the imaging findings of (18)F-fluorodeoxyglucose ((18)F-FDG) PET and integrated PET/CT in patients with primary, recurrent or metastatic ovarian cancer. 21 women with ovarian cancer were evaluated. All patients had a integrated PET/CT scan. Localization, infiltration and uptake intensity of [(18)F]FDG were evaluated on PET and PET/CT. The certainty of localisation and characterisation was scored on a 3 point scale (L1 definite localisation; L2 probable localisation; L3 uncertain localisation; C1 benign; C2 equivocal; C3 malignant). PET scored as L1 54 lesions (44%), as L2 51 (42%), and as L3 17 (14%). On the other hand, PET/CT scored as L1 120 lesions (98%), as L2 2 (2%), and none as L3. Thus PET/CT allowed a better localization in 54% of lesions. Moreover, PET scored as C1 25 lesions (20%), as C2 62 (51%), and as C3 35 (29%). On the other hand, PET/CT scored as C1 57 lesions (47%), as C2 13 (11%), and as C3 52 (42%). Thus PET/CT allowed a sensible reduction in the number of equivocal lesions (40%). Even when patients were subgrouped on the basis of clinical stage of the disease, PET/CT was capable of better definition of the lesions either for localization and for characterization. In patients with ovarian cancer, PET/CT allows better anatomical localisation of pathologic uptake providing high accuracy for staging and restaging of ovarian cancer when compared with PET alone.

Hearing aid fitting for visual and hearing impaired patients with Usher syndrome type IIa.

PubMed

Hartel, B P; Agterberg, M J H; Snik, A F; Kunst, H P M; van Opstal, A J; Bosman, A J; Pennings, R J E

2017-08-01

Usher syndrome is the leading cause of hereditary deaf-blindness. Most patients with Usher syndrome type IIa start using hearing aids from a young age. A serious complaint refers to interference between sound localisation abilities and adaptive sound processing (compression), as present in today's hearing aids. The aim of this study was to investigate the effect of advanced signal processing on binaural hearing, including sound localisation. In this prospective study, patients were fitted with hearing aids with a nonlinear (compression) and linear amplification programs. Data logging was used to objectively evaluate the use of either program. Performance was evaluated with a speech-in-noise test, a sound localisation test and two questionnaires focussing on self-reported benefit. Data logging confirmed that the reported use of hearing aids was high. The linear program was used significantly more often (average use: 77%) than the nonlinear program (average use: 17%). The results for speech intelligibility in noise and sound localisation did not show a significant difference between type of amplification. However, the self-reported outcomes showed higher scores on 'ease of communication' and overall benefit, and significant lower scores on disability for the new hearing aids when compared to their previous hearing aids with compression amplification. Patients with Usher syndrome type IIa prefer a linear amplification over nonlinear amplification when fitted with novel hearing aids. Apart from a significantly higher logged use, no difference in speech in noise and sound localisation was observed between linear and nonlinear amplification with the currently used tests. Further research is needed to evaluate the reasons behind the preference for the linear settings. © 2016 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd.

Tissue polypeptide-specific antigen (TPS) determinations before and during intermittent maximal androgen blockade in patients with metastatic prostatic carcinoma.

PubMed

Kil, P J M; Goldschmidt, H M J; Wieggers, B J A; Kariakine, O B; Studer, U E; Whelan, P; Hetherington, J; de Reijke, Th M; Hoekstra, J W; Collette, L

2003-01-01

To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to clinical progression. Finally to compare TPS with prostate-specific antigen (PSA) measurements in terms of prognostic impact in patients with metastatic prostatic carcinoma. TPS and PSA measurements were performed before start of and monthly during intermittent MAB in 68 patients participating in EORTC protocol 30954. Both TPS and PSA were measured in serum. Fifty-six patients from eight centers were included in the final analysis because at least three TPS values were available. TPS and PSA values were correlated with clinical course of the disease. Median follow-up was 21.3 months. Three patient groups were defined on clinical grounds: (a) clinically progressive disease (n=18); (b) clinically stable disease (n=33); and (c) patients who did not reach a predefined nadir PSA value following 9 months of treatment (n=5). Pretreatment TPS was significantly higher in the clinically progressive patients than in the other patient groups (p=0.0041). When grouping patients according to their pretreatment TPS values (cut-off value of 100 U/l) the pretreatment TPS value (>100 U/l) proved to be a statistically significant prognostic factor with respect to time to progression: elevated TPS was associated with a 3.8 increased risk for progressive disease (p=0.0055). Pretreatment PSA (>100 ng/ml) was of no prognostic value for time to progression. In five patients increase of TPS coincided with or preceded clinical progression during treatment, whereas PSA remained normal. Additional value of pretreatment TPS measurements in metastatic prostate cancer patients is found in defining the patients with rapid clinical progression. Following MAB an increase in TPS signifies clinical progression even if PSA is found to remain normal.

Castration-resistant Prostate Cancer: Preservation of Quality of Life and Well-being.

PubMed

Rosario, Derek J; Greasley, Rosa; Bourke, Liam

2016-12-01

Managing optimal health in castrate-resistant prostate cancer is a complex clinical challenge. Quality of life should be assessed with disease-specific validated tools and can be used in clinical practice to assist in considering management options. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy

DTIC Science & Technology

2010-03-01

clinical effectiveness of chemotherapy. MAOA influences chemotherapy resistance 3 INTRODUCTION Despite numerous clinical trials conducted...therapy resistance. Although residual viable tumor cells were identified in each case, chemotherapy effects were evident. We previously reported the...found that MAOA expression was upregulated in prostate cancers in association with higher Gleason grades (11), but effects on modulating cytotoxic drug

Prostate Active Surveillance Study — EDRN Public Portal

Cancer.gov

Primary Objective: To discover and confirm biomarkers that predict aggressive disease as defined by pre-specified histological, PSA, clinical criteria, or outcomes based on these variables. Secondary Objectives: To determine the proportion of patients on active surveillance who progress based on the above criteria. To determine the clinical predictors of disease progression. To measure the recurrence-free, disease-specific, and overall survival of men on active surveillance for clinically localized prostate cancer.

PCA3 Reference Set Application: T2-Erg-Martin Sanda-Emory (2014) — EDRN Public Portal

Cancer.gov

We hypothesize that combining T2:erg (T2:erg) fusion and PCA3 detection in urine collected after digital rectal exam can improve the specificity of identifying clinically significant prostate cancer presence over the standard PSA and DRE. To address this hypothesis we propose to validate the performance of the urinary T2:erg in a multiplex model predicting the diagnosis of clinically significant prostate cancer on subsequent prostate biopsy using post-DRE pre biopsy urine specimens from a cohort of 900 men on the EDRN’s PCA3 trial.

Integrating multiparametric prostate MRI into clinical practice

PubMed Central

2011-01-01

Abstract Multifunctional magnetic resonance imaging (MRI) techniques are increasingly being used to address bottlenecks in prostate cancer patient management. These techniques yield qualitative, semi-quantitative and fully quantitative biomarkers that reflect on the underlying biological status of a tumour. If these techniques are to have a role in patient management, then standard methods of data acquisition, analysis and reporting have to be developed. Effective communication by the use of scoring systems, structured reporting and a graphical interface that matches prostate anatomy are key elements. Practical guidelines for integrating multiparametric MRI into clinical practice are presented. PMID:22187067

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

STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors

PubMed Central

Hubert, Rene S.; Vivanco, Igor; Chen, Emily; Rastegar, Shiva; Leong, Kahan; Mitchell, Steve C.; Madraswala, Rashida; Zhou, Yanhong; Kuo, James; Raitano, Arthur B.; Jakobovits, Aya; Saffran, Douglas C.; Afar, Daniel E. H.

1999-01-01

In search of novel genes expressed in metastatic prostate cancer, we subtracted cDNA isolated from benign prostatic hypertrophic tissue from cDNA isolated from a prostate cancer xenograft model that mimics advanced disease. One novel gene that is highly expressed in advanced prostate cancer encodes a 339-amino acid protein with six potential membrane-spanning regions flanked by hydrophilic amino- and carboxyl-terminal domains. This structure suggests a potential function as a channel or transporter protein. This gene, named STEAP for six-transmembrane epithelial antigen of the prostate, is expressed predominantly in human prostate tissue and is up-regulated in multiple cancer cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma. Immunohistochemical analysis of clinical specimens demonstrates significant STEAP expression at the cell–cell junctions of the secretory epithelium of prostate and prostate cancer cells. Little to no staining was detected at the plasma membranes of normal, nonprostate human tissues, except for bladder tissue, which expressed low levels of STEAP at the cell membrane. Protein analysis located STEAP at the cell surface of prostate-cancer cell lines. Our results support STEAP as a cell-surface tumor-antigen target for prostate cancer therapy and diagnostic imaging. PMID:10588738

Comprehensive overview of prostatitis.

PubMed

Khan, Farhan Ullah; Ihsan, Awais Ullah; Khan, Hidayat Ullah; Jana, Ruby; Wazir, Junaid; Khongorzul, Puregmaa; Waqar, Muhammad; Zhou, Xiaohui

2017-10-01

Prostatitis is a common urinary tract syndrome that many doctors find problematic to treat effectively. It is the third most commonly found urinary tract disease in men after prostate cancer and Benign Prostate Hyperplasia (BPH). Prostatitis may account for 25% of all office visits made to the urological clinics complaining about the genital and urinary systems all over the world. In the present study, we classified prostatitis and comprehensively elaborated the etiology, pathogenesis, diagnosis, and treatment of acute bacterial prostatitis (category I), chronic bacterial prostatitis (category II), chronic pelvic pain syndrome (CPPS) (category III), and asymptomatic prostatitis (category IV). In addition, we also tried to get some insights about other types of prostatitis-like fungal, viral and gonococcal prostatitis. The aim of this review is to present the detail current perspective of prostatitis in a single review. To the best of our knowledge currently, there is not a single comprehensive review, which can completely elaborate this important topic in an effective way. Furthermore, this review will provide a solid platform to conduct future studies on different aspects such as risk factors, mechanism of pathogenesis, proper diagnosis, and rational treatment plans for fungal, viral, and gonococcal prostatitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Strain-specific induction of experimental autoimmune prostatitis (EAP) in mice.

PubMed

Jackson, Christopher M; Flies, Dallas B; Mosse, Claudio A; Parwani, Anil; Hipkiss, Edward L; Drake, Charles G

2013-05-01

Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. Copyright © 2012 Wiley Periodicals, Inc.

Strain-Specific Induction of Experimental Autoimmune Prostatitis (EAP) in Mice

PubMed Central

Jackson, Christopher M.; Flies, Dallas B.; Mosse, Claudio A.; Parwani, Anil; Hipkiss, Edward L.; Drake, Charles G.

2013-01-01

BACKGROUND Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. METHODS Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. RESULTS In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. CONCLUSIONS These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. PMID:23129407

Patient-derived Hormone-naive Prostate Cancer Xenograft Models Reveal Growth Factor Receptor Bound Protein 10 as an Androgen Receptor-repressed Gene Driving the Development of Castration-resistant Prostate Cancer.

PubMed

Hao, Jun; Ci, Xinpei; Xue, Hui; Wu, Rebecca; Dong, Xin; Choi, Stephen Yiu Chuen; He, Haiqing; Wang, Yu; Zhang, Fang; Qu, Sifeng; Zhang, Fan; Haegert, Anne M; Gout, Peter W; Zoubeidi, Amina; Collins, Colin; Gleave, Martin E; Lin, Dong; Wang, Yuzhuo

2018-06-01

Although androgen deprivation therapy is initially effective in controlling growth of hormone-naive prostate cancers (HNPCs) in patients, currently incurable castration-resistant prostate cancer (CRPC) inevitably develops. To identify CRPC driver genes that may provide new targets to enhance CRPC therapy. Patient-derived xenografts (PDXs) of HNPCs that develop CRPC following host castration were examined for changes in expression of genes at various time points after castration using transcriptome profiling analysis; particular attention was given to pre-CRPC changes in expression indicative of genes acting as potential CRPC drivers. The functionality of a potential CRPC driver was validated via its knockdown in cultured prostate cancer cells; its clinical relevance was established using data from prostate cancer patient databases. Eighty genes were found to be significantly upregulated at the CRPC stage, while seven of them also showed elevated expression prior to CRPC development. Among the latter, growth factor receptor bound protein 10 (GRB10) was the most significantly and consistently upregulated gene. Moreover, elevated GRB10 expression in clinical prostate cancer samples correlated with more aggressive tumor types and poorer patient treatment outcome. GRB10 knockdown markedly reduced prostate cancer cell proliferation and activity of AKT, a well-established CRPC mediator. A positive correlation between AKT activity and GRB10 expression was also found in clinical cohorts. GRB10 acts as a driver of CRPC and sensitizes androgen receptor pathway inhibitors, and hence GRB10 targeting provides a novel therapeutic strategy for the disease. Development of castration-resistant prostate cancer (CRPC) is a major problem in the management of the disease. Using state-of-the-art patient-derived hormone-naive prostate cancer xenograft models, we found and validated the growth factor receptor bound protein 10 gene as a driver of CRPC, indicating that it may be used as a new molecular target to enhance current CRPC therapy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Prostate cancer - treatment

MedlinePlus

... usually painless. Treatment is done in a radiation oncology center that is usually connected to a hospital. ... Cancer Network website. NCCN clinical practice guidelines in oncology (NCCN guidelines): prostate cancer. Version 2.2017. www. ...

Adjuvant Chemotherapy Improves Prostate Cancer Survival

Cancer.gov

Giving some men with prostate cancer chemotherapy after standard treatment with radiation and hormone therapy modestly improves how long they live, according to results from a new NCI-funded clinical trial.

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.

Lesion volume predicts prostate cancer risk and aggressiveness: validation of its value alone and matched with prostate imaging reporting and data system score.

PubMed

Martorana, Eugenio; Pirola, Giacomo Maria; Scialpi, Michele; Micali, Salvatore; Iseppi, Andrea; Bonetti, Luca Reggiani; Kaleci, Shaniko; Torricelli, Pietro; Bianchi, Giampaolo

2017-07-01

To demonstrate the association between magnetic resonance imaging (MRI) estimated lesion volume (LV), prostate cancer detection and tumour clinical significance, evaluating this variable alone and matched with Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score. We retrospectively analysed 157 consecutive patients, with at least one prior negative systematic prostatic biopsy, who underwent transperineal prostate MRI/ultrasonography fusion-targeted biopsy between January 2014 and February 2016. Suspicious lesions were delineated using a 'region of interest' and the system calculated prostate volume and LV. Patients were divided in groups considering LV (≤0.5, 0.5-1, ≥1 mL) and PI-RADS score (1-5). We considered clinically significant prostate cancer as all cancers with a Gleason score of ≥3 + 4 as suggested by PI-RADS v2. A direct comparison between MRI estimated LV (MRI LV) and histological tumour volume (HTV) was done in 23 patients who underwent radical prostatectomy during the study period. Differences between MRI LV and HTV were assessed using the paired sample t-test. MRI LV and HTV concordance was verified using a Bland-Altman plot. The chi-squared test and logistic and ordinal regression models were used to evaluate difference in frequencies. The MRI LV and PI-RADS score were associated both with prostate cancer detection (both P < 0.001) and with significant prostate cancer detection (P < 0.001 and P = 0.008, respectively). When the two variables were matched, increasing LV increased the risk within each PI-RADS group. Prostate cancer detection was 1.4-times higher for LVs of 0.5-1 mL and 1.8-times higher for LVs of ≥1 mL; significant prostate cancer detection was 2.6-times for LVs of 0.5-1 mL and 4-times for LVs of ≥1 mL. There was a positive correlation between MRI LV and HTV (r = 0.9876, P < 0.001). Finally, Bland-Altman analysis showed that MRI LV was underestimated by 4.2% compared to HTV. Study limitations include its monocentric and retrospective design and the limited cohort. This study demonstrates that PI-RADS score and the MRI LV, independently and in combination, are associated with prostate cancer detection and with tumour clinical significance. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

PubMed

Lokant, M T; Naz, R K

2015-04-01

Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P < 0.01) compared with PC and prostatitis. All others were nonsignificant (P < 0.05). Men (33%) with BPH had PSA antibodies by ELISA and Western blot. These discoveries may find clinical application in differential diagnosis among prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis. © 2014 Blackwell Verlag GmbH.

[Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

PubMed

Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

2016-01-01

To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (P<0.05). The patients with prostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (P<0.001). Multiple linear regression analysis showed that IL-8 and IL-6 levels and white blood cell count in the prostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

Real World Evidence: A Quantitative and Qualitative Glance at Participant Feedback from a Free-Response Survey Investigating Experiences of a Structured Exercise Intervention for Men with Prostate Cancer

PubMed Central

Cahill, F.; Burgess, C.; Peat, N.; Rudman, S.; Kinsella, J.; Cahill, D.; George, G.; Santaolalla, A.; Van Hemelrijck, M.

2017-01-01

Aim To explore patient experiences of a structured exercise intervention for men with prostate cancer (PCa). Sample 41 men with either localised or advanced PCa who had been referred for a structured exercise programme by their physician and then subsequently consented to a telephone survey. Method Participants underwent a 10-week supervised exercise programme within a large cancer centre hospital consisting of 8 sessions. They then completed a short multiple choice telephone survey, elaborating on their responses where appropriate. Views expressed by participants were analysed using an affinity diagram and common themes were identified. Results Feedback from our telephone surveys was consistently positive and suggests that the structured exercise intervention provides exercise confidence, motivation to exercise, and social support and promotes positive health behaviour change in the context of exercise. Individual differences arose amongst participants in their perceived utility of the intervention, with 73.3% expressing a preference for structured exercise classes and 19.5% expressing a preference for exercising independently. Conclusion Design of a structured exercise intervention for patients with PCa should embrace the positive aspects outlined here but consider patients' individual differences. Ongoing feedback from patients should be utilised alongside traditional study designs to inform intervention design in this area. PMID:28758113

Factors associated with current and severe physical side-effects after prostate cancer treatment: What men report.

PubMed

Steentjes, L; Siesling, S; Drummond, F J; van Manen, J G; Sharp, L; Gavin, A

2018-01-01

We identified patient and disease characteristics associated with (1) "current" physical side-effects of any severity; and (2) "severe" physical side-effects "ever" experienced by 3,348 (54%) prostate cancer (PCa) survivors in Ireland diagnosed 2-18 years previously. Postal questionnaires collected symptoms at diagnosis, post-biopsy complications, comorbidities, primary treatments and physical side-effects post-treatment (urinary incontinence, erectile dysfunction, libido loss, bowel problems, breast changes, hot flushes, and fatigue, "ever" and "current" at time of questionnaire completion). Men were grouped by "early" (localised) and "late" (locally advanced/advanced) disease at diagnosis. Multivariable logistic regression analysis identified patient and disease-related factors associated with post-treatment side-effects. Complications post-biopsy were associated with higher risk of "current" libido loss and impotence. Radical prostatectomy was associated with higher risk of "current" and "severe" incontinence, libido loss and impotence in both early and late disease. In early disease, brachytherapy was associated with lower risk of "current" fatigue and "severe" impotence. Comorbidities were associated with higher risk of "current" experience of four side-effects (incontinence, libido loss, bowel problems, fatigue). Men on active surveillance/watchful-waiting reported lower risk of sexual dysfunction. These findings could inform development of tailored information on side-effects, which, in turn, could inform treatment decision-making and post-treatment monitoring. © 2016 John Wiley & Sons Ltd.

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.

Singapore Urological Association Clinical Guidelines for Male Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia.

PubMed

2017-08-01

The first clinical guidelines for male lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) were published in 2005. An update is urgently needed in view of BPH being recognised as one of ten chronic illnesses by the Ministry of Health, Singapore. This review summarises the definition of BPH and the epidemiology of male LUTS/BPH in Singapore. BPH can be phenotyped with noninvasive transabdominal ultrasonography, according to intravesical prostatic protrusion and prostate volume, and classified according to severity (staging) for individualised treatment. At the initial evaluation, the majority of patients (59%) can be managed with fluid adjustment, exercise and diet; 32% with medications, using alpha blockers and/or 5-alpha reductase inhibitors for prostates weighing more than 30 g; and 9% with surgical intervention for more advanced disease. The 2015 guidelines comprise updated evidence that will help family medicine practitioners and specialists manage this common ailment more cost-effectively. Copyright: © Singapore Medical Association.

Serum pro-gastrin-releasing peptide (31-98) in benign prostatic hyperplasia and prostatic carcinoma.

PubMed

Nagakawa, Osamu; Furuya, Yuzo; Fujiuchi, Yasuyoshi; Fuse, Hideki

2002-09-01

To clarify whether serum levels of pro-gastrin-releasing peptide (ProGRP) (31-98) could be a useful marker in patients with prostatic carcinoma. GRP is produced and secreted by prostatic neuroendocrine cells. Serum levels of ProGRP(31-98) were measured by enzyme-linked immunosorbent assay in 20 patients with benign prostatic hyperplasia and 107 patients with prostatic carcinoma. The mean serum levels of ProGRP(31-98) in patients with distant metastasis and hormone-resistant prostate cancer were significantly elevated compared with those in patients with organ-confined disease. Significantly elevated levels of ProGRP(31-98) were detected in 9 patients with prostatic carcinoma before any treatment. During hormone-resistant prostate cancer progression, ProGRP(31-98) levels were elevated in 9 patients (23%). Of the 9 patients with Stage D3 and elevated serum ProGRP, 4 had a normal serum prostate-specific antigen level. ProGRP may be a potential tumor marker for prostate cancer. Additional studies in large groups of patients are needed to define the clinical value of ProGRP.

Prostatic Adenocarcinoma with Concurrent Sertoli Cell Tumor in a Dog

PubMed Central

Gill, C. W.

1981-01-01

A case of metastatic prostatic adenocarcinoma with concurrent Sertoli cell tumor is presented in an old, miniature Schnauzer dog. The prostatic neoplasm was highly anaplastic and had metastasized widely. Clinical signs were compatible with increased estrogen production. It is interesting to note that the prostatic carcinoma, usually considered to be androgen dependent, developed and metastasized, despite the presence of apparently increased estrogen levels. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:7340923

Magnetic resonance imaging in prostate brachytherapy: Evidence, clinical end points to data, and direction forward.

PubMed

Pugh, Thomas J; Pokharel, Sajal S

The integration of multiparametric MRI into prostate brachytherapy has become a subject of interest over the past 2 decades. MRI directed high-dose-rate and low-dose-rate prostate brachytherapy offers the potential to improve treatment accuracy and standardize postprocedure quality. This article reviews the evidence to date on MRI utilization in prostate brachytherapy and postulates future pathways for MRI integration. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Triptorelin Injection

MedlinePlus

... used to treat the symptoms associated with advanced prostate cancer. Triptorelin injection (Triptodur) is used to treat central ... a medical office or clinic. When used for prostate cancer, an injection of 3.75 mg of triptorelin ( ...

Applying strategies from libertarian paternalism to decision making for prostate specific antigen (PSA) screening

PubMed Central

2011-01-01

Background Despite the recent publication of results from two randomized clinical trials, prostate specific antigen (PSA) screening for prostate cancer remains a controversial issue. There is lack of agreement across studies that PSA screening significantly reduces prostate cancer mortality. In spite of these facts, the widespread use of PSA testing in the United States leads to overdetection and overtreatment of clinically indolent prostate cancer, and its associated harms of incontinence and impotence. Discussion Given the inconclusive results from clinical trials and incongruent PSA screening guidelines, the decision to screen for prostate cancer with PSA testing is an uncertain one for patients and health care providers. Screening guidelines from some health organizations recommend an informed decision making (IDM) or shared decision making (SDM) approach for deciding on PSA screening. These approaches aim to empower patients to choose among the available options by making them active participants in the decision making process. By increasing involvement of patients in the clinical decision-making process, IDM/SDM places more of the responsibility for a complex decision on the patient. Research suggests, however, that patients are not well-informed of the harms and benefits associated with prostate cancer screening and are also subject to an assortment of biases, emotion, fears, and irrational thought that interferes with making an informed decision. In response, the IDM/SDM approaches can be augmented with strategies from the philosophy of libertarian paternalism (LP) to improve decision making. LP uses the insights of behavioural economics to help people better make better choices. Some of the main strategies of LP applicable to PSA decision making are a default decision rule, framing of decision aids, and timing of the decision. In this paper, we propose that applying strategies from libertarian paternalism can help with PSA screening decision-making. Summary Our proposal to augment IDM and SDM approaches with libertarian paternalism strategies is intended to guide patients toward a better decision about testing while maintaining personal freedom of choice. While PSA screening remains controversial and evidence conflicting, a libertarian-paternalism influenced approach to decision making can help prevent the overdiagnosis and overtreatment of prostate cancer. PMID:21510865

Applying strategies from libertarian paternalism to decision making for prostate specific antigen (PSA) screening.

PubMed

Wheeler, David C; Szymanski, Konrad M; Black, Amanda; Nelson, David E

2011-04-21

Despite the recent publication of results from two randomized clinical trials, prostate specific antigen (PSA) screening for prostate cancer remains a controversial issue. There is lack of agreement across studies that PSA screening significantly reduces prostate cancer mortality. In spite of these facts, the widespread use of PSA testing in the United States leads to overdetection and overtreatment of clinically indolent prostate cancer, and its associated harms of incontinence and impotence. Given the inconclusive results from clinical trials and incongruent PSA screening guidelines, the decision to screen for prostate cancer with PSA testing is an uncertain one for patients and health care providers. Screening guidelines from some health organizations recommend an informed decision making (IDM) or shared decision making (SDM) approach for deciding on PSA screening. These approaches aim to empower patients to choose among the available options by making them active participants in the decision making process. By increasing involvement of patients in the clinical decision-making process, IDM/SDM places more of the responsibility for a complex decision on the patient. Research suggests, however, that patients are not well-informed of the harms and benefits associated with prostate cancer screening and are also subject to an assortment of biases, emotion, fears, and irrational thought that interferes with making an informed decision. In response, the IDM/SDM approaches can be augmented with strategies from the philosophy of libertarian paternalism (LP) to improve decision making. LP uses the insights of behavioural economics to help people better make better choices. Some of the main strategies of LP applicable to PSA decision making are a default decision rule, framing of decision aids, and timing of the decision. In this paper, we propose that applying strategies from libertarian paternalism can help with PSA screening decision-making. Our proposal to augment IDM and SDM approaches with libertarian paternalism strategies is intended to guide patients toward a better decision about testing while maintaining personal freedom of choice. While PSA screening remains controversial and evidence conflicting, a libertarian-paternalism influenced approach to decision making can help prevent the overdiagnosis and overtreatment of prostate cancer.

An integrated view of the role of miR-130b/301b miRNA cluster in prostate cancer.

PubMed

Fort, Rafael Sebastián; Mathó, Cecilia; Oliveira-Rizzo, Carolina; Garat, Beatriz; Sotelo-Silveira, José Roberto; Duhagon, María Ana

2018-01-01

Prostate cancer is a major health problem worldwide due to its high incidence morbidity and mortality. There is currently a need of improved biomarkers, capable to distinguish mild versus aggressive forms of the disease, and thus guide therapeutic decisions. Although miRNAs deregulated in cancer represent exciting candidates as biomarkers, its scientific literature is frequently fragmented in dispersed studies. This problem is aggravated for miRNAs belonging to miRNA gene clusters with shared target genes. The miRNA cluster composed by hsa-mir-130b and hsa-mir-301b precursors was recently involved in prostate cancer pathogenesis, yet different studies assigned it opposite effects on the disease. We sought to elucidate the role of the human miR-130b/301b miRNA cluster in prostate cancer through a comprehensive data analysis of most published clinical cohorts. We interrogated methylomes, transcriptomes and patient clinical data, unifying previous reports and adding original analysis using the largest available cohort (TCGA-PRAD). We found that hsa-miR-130b-3p and hsa-miR-301b-3p are upregulated in neoplastic vs normal prostate tissue, as well as in metastatic vs primary sites. However, this increase in expression is not due to a decrease of the global DNA methylation of the genes in prostate tissues, as the promoter of the gene remains lowly methylated in normal and neoplastic tissue. A comparison of the levels of human miR-130b/301b and all the clinical variables reported for the major available cohorts, yielded positive correlations with malignance, specifically significant for T-stage, residual tumor status and primary therapy outcome. The assessment of the correlations between the hsa-miR-130b-3p and hsa-miR-301b-3p and candidate target genes in clinical samples, supports their repression of tumor suppressor genes in prostate cancer. Altogether, these results favor an oncogenic role of miR-130b/301b cluster in prostate cancer.

Disparities in staging prostate magnetic resonance imaging utilization for nonmetastatic prostate cancer patients undergoing definitive radiation therapy.

PubMed

Ajayi, Ayobami; Hwang, Wei-Ting; Vapiwala, Neha; Rosen, Mark; Chapman, Christina H; Both, Stefan; Shah, Meera; Wang, Xingmei; Agawu, Atu; Gabriel, Peter; Christodouleas, John; Tochner, Zelig; Deville, Curtiland

2016-01-01

There is growing evidence supporting incorporating multiparametric (mp) magnetic resonance imaging (MRI) scans into risk stratification, active surveillance, and treatment paradigms for prostate cancer. The purpose of our study was to determine whether demographic disparities exist in staging MRI utilization for prostate cancer patients. An institutional database of 705 nonmetastatic prostate cancer patients treated with radiation therapy from 2005 through 2013 was used to identify patients undergoing versus not undergoing pretreatment diagnostic prostate mpMRI. Uni- and multivariable logistic regression evaluated the relationship of clinical and demographic characteristics with MRI utilization. All demographic variables assessed, except the other race category, were significantly associated with MRI utilization (all P < .05), including age (odds ratio [OR], 0.92), black race (OR, 0.51), poverty (OR, 0.53), closer distance to radiation facility (OR, 1.79), and nonprivate primary insurance (OR, 0.57) on univariable analysis, while clinical stage T3 (OR, 3.37) was the only clinical characteristic. On multivariable analysis stratified by D'Amico risk group, age remained significant across all risk groups, whereas the black versus white racial (OR, 0.21; 95% confidence interval, 0.08-0.55) and nonprivate versus private insurance type (OR, 0.37; 95% confidence interval, 0.16-0.86) disparities persisted in the low-risk group. Clinical stage T3 remained associated in the high-risk group. For race specifically, the percentages of whites, blacks, and others undergoing MRI in the overall cohort and by risk group were, respectively: overall, 80% (343/427), 68% (156/231), and 85% (40/47); low risk, 86%, 56%, and 63%; intermediate risk, 79%, 72%, and 95%; and high risk, 72%, 72%, and 100%. In this urban, academic center cohort, older patients across all risk groups and black or nonprivate insurance patients in the low risk group were less likely to undergo staging prostate MRI scans. Further research should investigate these differences to ensure equitable utilization across all demographic groups considering the burden of prostate cancer disparities.

Prostate Specific Membrane Antigen Positron Emission Tomography May Improve the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging in Localized Prostate Cancer.

PubMed

Rhee, H; Thomas, P; Shepherd, B; Gustafson, S; Vela, I; Russell, P J; Nelson, C; Chung, E; Wood, G; Malone, G; Wood, S; Heathcote, P

2016-10-01

Positron emission tomography using ligands targeting prostate specific membrane antigen has recently been introduced. Positron emission tomography imaging with (68)Ga-PSMA-HBED-CC has been shown to detect metastatic prostate cancer lesions at a high rate. In this study we compare multiparametric magnetic resonance imaging and prostate specific membrane antigen positron emission tomography of the prostate with whole mount ex vivo prostate histopathology to determine the true sensitivity and specificity of these imaging modalities for detecting and locating tumor foci within the prostate. In a prospective clinical trial setting 20 patients with localized prostate cancer and a planned radical prostatectomy were recruited. All patients underwent multiparametric magnetic resonance imaging and positron emission tomography before surgery, and whole mount histopathology slides were directly compared to the images. European Society of Urogenital Radiology guidelines for reporting magnetic resonance imaging were used as a template for regional units of analysis. The uropathologist and radiologists were blinded to individual components of the study, and the final correlation was performed by visual and deformable registration analysis. A total of 50 clinically significant lesions were identified from the whole mount histopathological analysis. Based on regional analysis the sensitivity, specificity, positive predictive value and negative predictive value for multiparametric magnetic resonance imaging were 44%, 94%, 81% and 76%, respectively. With prostate specific membrane antigen positron emission tomography the sensitivity, specificity, positive predictive value and negative predictive value were 49%, 95%, 85% and 88%, respectively. Prostate specific membrane antigen positron emission tomography yielded a higher specificity and positive predictive value. A significant proportion of cancers are potentially missed and underestimated by both imaging modalities. Prostate specific membrane antigen positron emission tomography may be used in addition to multiparametric magnetic resonance imaging to help improve local staging in those patients undergoing retropubic radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Hemato-biochemical alterations and urinalysis in dogs suffering from benign prostatic hyperplasia

PubMed Central

Das, M. R.; Patra, R. C.; Das, R. K.; Rath, P. K.; Mishra, B. P.

2017-01-01

Aim: The study was designed to evaluate the hemato-biochemical alterations, urinalysis along with histomorphological and histological changes of prostate glands in dogs affected with benign prostatic hyperplasia (BPH) in and around Bhubaneswar, Odisha, India. Materials and Methods: In toto, 445 dogs presented to the Teaching Veterinary Clinical Complex of the College of Veterinary Sciences and Animal Husbandry, one Government Veterinary Hospital and two pet clinics in and around Bhubaneswar screened for the presence of BPH. Most of the 57 dogs were 6 years and above as reported by the owners. Only 57 dogs found positive for BPH basing on the presence of typical clinical signs subjected for a detailed hemato-biochemical study. Most of the 57 dogs were 6 years and above as reported by the owners. Routine and microscopic urinalyses were done as per the routine procedure. Histomorphological evaluations of prostate glands were done through manual rectal palpation. Histological examinations of prostate tissue sections of two dead dogs were conducted with routine hematoxylin and eosin stain. Results: The study revealed about 12.8% (57/445) of dogs was suffering from BPH. Typical clinical signs - such as passing small thin tape-shaped feces, holding tail away from backward, tenesmus, and straining during urination and defecation - were seen in most of the cases. Urine samples of affected dogs were positive for glucose, occult blood, and protein. A significant decrease in lymphocytes and increase in eosinophil counts in dogs with BPH was recorded. Serum biochemical analysis showed a nonsignificant increase in creatinine and blood urea nitrogen with a significant decrease in total protein, albumin, globulin, A:G ratio. Histology of prostate glands collected during postmortem was characterized by fibrosis of prostate gland, and hyperplasia of the acinar epithelium. Conclusions: High rate of the prevalence of BPH in dogs poses an alarming condition which if diagnosed at an early stage can certainly prolong the longevity of the dogs. PMID:28435196

Clinical results from first use of prostate stent as fiducial for radiotherapy of prostate cancer.

PubMed

Carl, Jesper; Nielsen, Jane; Holmberg, Mats; Larsen, Erik Hoejkjaer; Fabrin, Knud; Fisker, Rune V

2011-05-01

A clinical feasibility study using a removable prostate stent as fiducial for image-guided radiotherapy (IGRT) of localized prostate cancer (PC). The study included patients with local or locally advanced PC. The clinical target volume (CTV) was outlined on magnetic resonance (MR) images co-registered to planning computer tomography (CT) images. Daily online IGRT was delivered using the stent as fiducial. Risk of migration was estimated using multiple MR. Acute urinary toxicity was scored using the international prostate symptom score (IPSS). Late gastro-intestinal (GI) and genito-urinary (GU) toxicity was scored using the Radio Therapy Oncology Group (RTOG) score, biochemical failure (BF) was defined as an elevation of prostate specific antigen (PSA) above nadir plus 2 ng/ml after radiotherapy. One hundred men were enrolled in the study. Ninety completed radiotherapy with the stent as fiducial. No migration of the stent was seen, but three cases of dislocation of the stent to the bladder were observed. Acute urinary toxicity based on IPSS was comparable to toxicity in patients who had gold markers (GM) as fiducials. Removal of the stent was associated with a high frequency of urinary retention. Late GI and GU toxicity and BF were comparable to those of other studies, but longer observation time is needed. This study reports the first clinical results of using a prostate stent as fiducial. No migration of the stent observed. Dislocation of the stent to the urinary bladder was observed in three cases, requiring removal of the stent and insertion of a new fiducial. Acute toxicity during radiotherapy evaluated from IPSS was comparable to toxicity in patients with GM. Removal of the stent was associated with a high frequency of post procedural urinary retention. Late toxicity and BF were comparable to those of other studies, though longer observation time is needed.

Kilovoltage Intrafraction Monitoring for Prostate Intensity Modulated Arc Therapy: First Clinical Results

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

Ng, Jin Aun; Institute of Medical Physics, School of Physics, University of Sydney, New South Wales; Booth, Jeremy T.

2012-12-01

Purpose: Most linear accelerators purchased today are equipped with a gantry-mounted kilovoltage X-ray imager which is typically used for patient imaging prior to therapy. A novel application of the X-ray system is kilovoltage intrafraction monitoring (KIM), in which the 3-dimensional (3D) tumor position is determined during treatment. In this paper, we report on the first use of KIM in a prospective clinical study of prostate cancer patients undergoing intensity modulated arc therapy (IMAT). Methods and Materials: Ten prostate cancer patients with implanted fiducial markers undergoing conventionally fractionated IMAT (RapidArc) were enrolled in an ethics-approved study of KIM. KIM involves acquiringmore » kV images as the gantry rotates around the patient during treatment. Post-treatment, markers in these images were segmented to obtain 2D positions. From the 2D positions, a maximum likelihood estimation of a probability density function was used to obtain 3D prostate trajectories. The trajectories were analyzed to determine the motion type and the percentage of time the prostate was displaced {>=}3, 5, 7, and 10 mm. Independent verification of KIM positional accuracy was performed using kV/MV triangulation. Results: KIM was performed for 268 fractions. Various prostate trajectories were observed (ie, continuous target drift, transient excursion, stable target position, persistent excursion, high-frequency excursions, and erratic behavior). For all patients, 3D displacements of {>=}3, 5, 7, and 10 mm were observed 5.6%, 2.2%, 0.7% and 0.4% of the time, respectively. The average systematic accuracy of KIM was measured at 0.46 mm. Conclusions: KIM for prostate IMAT was successfully implemented clinically for the first time. Key advantages of this method are (1) submillimeter accuracy, (2) widespread applicability, and (3) a low barrier to clinical implementation. A disadvantage is that KIM delivers additional imaging dose to the patient.« less