Prediction of Erectile Function Following Treatment for Prostate Cancer

PubMed Central

Alemozaffar, Mehrdad; Regan, Meredith M.; Cooperberg, Matthew R.; Wei, John T.; Michalski, Jeff M.; Sandler, Howard M.; Hembroff, Larry; Sadetsky, Natalia; Saigal, Christopher S.; Litwin, Mark S.; Klein, Eric; Kibel, Adam S.; Hamstra, Daniel A.; Pisters, Louis L.; Kuban, Deborah A.; Kaplan, Irving D.; Wood, David P.; Ciezki, Jay; Dunn, Rodney L.; Carroll, Peter R.; Sanda, Martin G.

2013-01-01

Context Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking. Objective To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics. Design Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N = 1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years’ follow-up (n = 1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort. Main Outcome Measures Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment. Results Two years after prostate cancer treatment, 368 (37% [95% CI, 34%–40%]) of all patients and 335 (48% [95% CI, 45%–52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%–56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. Multivariable logistic regression models predicting erectile function estimated 2-year function probabilities from as low as 10% or less to as high as 70% or greater depending on the individual’s pretreatment patient characteristics and treatment details. The models performed well in predicting erections in external validation among CaPSURE cohort patients (areas under the receiver operating characteristic curve, 0.77 [95% CI, 0.74–0.80] for prostatectomy; 0.87 [95% CI, 0.80–0.94] for external radiotherapy; and 0.90 [95% CI, 0.85–0.95] for brachytherapy). Conclusion Stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. PMID:21934053

Elevated Prostate Health Index (phi) and Biopsy Reclassification During Active Surveillance of Prostate Cancer.

PubMed

Andreas, Darian; Tosoian, Jeffrey J; Landis, Patricia; Wolf, Sacha; Glavaris, Stephanie; Lotan, Tamara L; Schaeffer, Edward M; Sokoll, Lori J; Ross, Ashley E

2016-07-01

The Prostate Health Index (phi) has been FDA approved for decision-making regarding prostate biopsy. Phi has additionally been shown to positively correlate with tumor volume, extraprostatic disease and higher Gleason grade tumors. Here we describe a case in which an elevated phi encouraged biopsy of a gentleman undergoing active surveillance leading to reclassification of his disease as high risk prostate cancer.

Health-Related Quality of Life 2 Years After Treatment With Radical Prostatectomy, Prostate Brachytherapy, or External Beam Radiotherapy in Patients With Clinically Localized Prostate Cancer

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

Ferrer, Montserrat; CIBER en Epidemiologia y Salud Publica; Suarez, Jose Francisco

Purpose: To compare treatment impact on health-related quality of life (HRQL) in patients with localized prostate cancer, from before treatment to 2 years after the intervention. Methods and Materials: This was a longitudinal, prospective study of 614 patients with localized prostate cancer treated with radical prostatectomy (134), three-dimensional external conformal radiotherapy (205), and brachytherapy (275). The HRQL questionnaires administered before and after treatment (months 1, 3, 6, 12, and 24) were the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Associationmore » Symptom Index. Differences between groups were tested by analysis of variance and within-group changes by univariate repeated-measures analysis of variance. Generalized estimating equations (GEE) models were constructed to assess between-group differences in HRQL at 2 years of follow-up after adjusting for clinical variables. Results: In each treatment group, HRQL initially deteriorated after treatment with subsequent partial recovery. However, some dimension scores were still significantly lower after 2 years of treatment. The GEE models showed that, compared with the brachytherapy group, radical prostatectomy patients had worse EPIC sexual summary and urinary incontinence scores (-20.4 and -14.1; p < 0.001), and external radiotherapy patients had worse EPIC bowel, sexual, and hormonal summary scores (-3.55, -5.24, and -1.94; p < 0.05). Prostatectomy patients had significantly better EPIC urinary irritation scores than brachytherapy patients (+4.16; p < 0.001). Conclusions: Relevant differences between treatment groups persisted after 2 years of follow-up. Radical prostatectomy had a considerable negative effect on sexual functioning and urinary continence. Three-dimensional conformal radiotherapy had a moderate negative impact on bowel functioning, and brachytherapy caused moderate urinary irritation. These results provide relevant information for clinical decision making.« less

The Association of Long-term Treatment-related Side Effects With Cancer-specific and General Quality of Life Among Prostate Cancer Survivors

PubMed Central

Davis, Kimberly M.; Kelly, Scott P.; Luta, George; Tomko, Catherine; Miller, Anthony B.; Taylor, Kathryn L.

2018-01-01

OBJECTIVE To examine the association between treatment-related side effects and cancer-specific and general quality of life (QOL) among long-term prostate cancer survivors. MATERIALS AND METHODS Within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we conducted telephone interviews with prostate cancer survivors (N = 518) who were 5-10 years after diagnosis. We assessed demographic and clinical information, sexual, urinary, and bowel treatment-related side effects (Expanded Prostate Cancer Index Composite), cancer-specific QOL (Functional Assessment of Cancer Therapy—total score), and general QOL (the Medical Outcomes Study Short Form 12’s physical and mental subscales). RESULTS Participants were aged 74.6 years on average, primarily White (88.4%), and married (81.7%). Pearson correlation coefficients between the 3 treatment-related side effect domains (urinary, sexual, and bowel) and QOL ranged between 0.14 and 0.42 (P <.0001). Multivariable linear regression analyses revealed that poorer urinary and sexual functioning and greater bowel side effects were independently associated with poorer cancer-specific QOL (P <.0001). Bowel and urinary functions were also associated with poorer general QOL on the Medical Outcomes Study Short Form 12’s physical component summary and mental component summary (P <.05). Bowel side effects demonstrated the strongest association with all QOL outcomes. CONCLUSION Treatment-related side effects persisted for up to 10 years after diagnosis and continued to be associated with men’s QOL. These results suggest that each of the treatment-related side effects was independently associated with cancer-specific QOL. Compared with the other Expanded Prostate Cancer Index Composite domains, bowel side effects had the strongest association with cancer-specific and general QOL. These associations emphasize the tremendous impact that bowel side effects continue to have for men many years after their initial diagnosis. PMID:24975711

Health-related quality-of-life in low-income, uninsured men with prostate cancer.

PubMed

Krupski, Tracey L; Fink, Arlene; Kwan, Lorna; Maliski, Sally; Connor, Sarah E; Clerkin, Barbara; Litwin, Mark S

2005-05-01

The objective was to describe health-related quality-of-life (HRQOL) in low-income men with prostate cancer. Subjects were drawn from a statewide public assistance prostate cancer program. Telephone and mail surveys included the RAND 12-item Health Survey and UCLA Prostate Cancer Index Short Form and were compared with normative age-matched men without cancer from the general population reported on in the literature. Of 286 eligible men, 233 (81%) agreed to participate and completed the necessary items. The sample consisted of 51% Hispanics, 23% non-Hispanic whites, and 17% African Americans. The low-income men had worse scores in every domain of prostate-specific and general HRQOL than had the age-matched general population controls. The degree of disparity indicated substantial clinical differences in almost every domain of physical and emotional functioning between the sample group and the control group. Linear regression modeling determined that among the low-income men, Hispanic race, and income level were predictive of worse physical functioning, whereas only comorbidities predicted mental health. Low-income patients with prostate cancer appear to have quality-of-life profiles that are meaningfully worse than age-matched men from the general population without cancer reported on in the literature.

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.

Open radical prostatectomy after transurethral resection: perioperative, functional, oncologic outcomes.

PubMed

Fragkoulis, Charalampos; Pappas, Athanasios; Theocharis, Georgios; Papadopoulos, Georgios; Stathouros, Georgios; Ntoumas, Konstantinos

2018-04-01

To demonstrate any differences in the perioperative, functional and oncologic outcomes after radical retropubic prostatectomy (RRP) among those patients having previously performed transurethral resection of prostate (TURP) and those not. A total of 35 patients were diagnosed with prostate cancer (T1a and T1b) after TURP, underwent RRP and completed a 1 year follow up (group A). They were matched with a cohort of another 35 men (group B) in terms of age, body mass index (BMI), prostatic specific antigen (PSA), Gleason score, prostate volume (before surgery), pathological stage and neurovascular bundle-sparing technique. That was a retrospective study completed between September 2011 and March 2014. Not a significant difference was demonstrated among the two groups of patients concerning the functional and oncologic results. On the other hand, previous prostate surgery made the operation procedure more demanding. Besides, operative time and blood loss (though not translated in transfusion rates) were higher among patients in group A. Besides, catheter removal in group A patients was performed later than their counterparts of group B. RRP after TURP is a relatively safe procedure and in the hands of experienced surgeons, a previously performed TURP, does not seem to compromise oncologic outcomes of the operation. Continence is preserved, though erectile function seems to be compromised compared with patients undergoing RRP without prior TURP. Moreover, defining the prostate and bladder neck margins can be challenging and the surgeon has to be aware of the difficulties that might confront.

The Impact of Obesity on Patient Reported Outcomes Following Stereotactic Body Radiation Therapy for Prostate Cancer

PubMed Central

Cyr, Robyn; Feng, Li Rebekah; Bae, Edward; Danner, Malika T; Ayoob, Marilyn; Yung, Thomas M; Lei, Siyuan; Collins, Brian T; Saligan, Leorey; Simeng, Suy; Kumar, Deepak; Collins, Sean P

2016-01-01

Objectives The relationship between obesity (Body Mass Index ­>30 kg/m2) and quality of life (QoL) following prostate cancer (PCa) radiation therapy (RT) is unknown. Excess abdominal fat may compromise the precise delivery of radiation, putting surrounding organs at risk for greater radiation exposure. Stereotactic body radiation therapy (SBRT) utilizes a real-time tracking system that provides updated prostate position information and allows for correction of the therapeutic beam during treatment with high accuracy. In this study, we evaluate the impact of obesity on patient reported outcomes following SBRT for prostate cancer. Materials and methods Between February 2008 and April 2012, 88 obese and 178 non-obese patients with PCa were treated with SBRT at Georgetown University Hospital, Washington, DC. Health-related quality of life (HRQol) was assessed via the expanded prostate cancer index composite (EPIC)-26 at baseline, 6, 12, 18, and 24 months after 5-fraction delivery of 35-36.25 Gy with the CyberKnife. Patients who received androgen deprivation therapy (ADT) were excluded from this analysis due to its known negative impact on HRQoL. Results Pretreatment characteristics of obese and non-obese patient groups were similar except that obese patients had lower total testosterone levels. Urinary and bowel function and bother scores between the two patient cohorts were comparable at baseline and subsequent follow-ups. Sexual function and bother were also similar at baseline between both groups. Bother was defined by displeasure patients may experience from functional decline. At 24 months post-SBRT, obese men experienced borderline clinically significant decrease in sexual function and greater sexual bother compared to non-obese patients. Fatigue was significantly higher in obese patients compared to non-obese patients at 18 months post-SBRT. Conclusions Prostate SBRT affects obese and non-obese patients similarly in total HRQoL scores and majority of its domains. Obesity has been associated with cancer recurrence; therefore longer follow-up is required to determine the impact of obesity on cancer control. PMID:27551649

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.

Sexual function and bother after radical prostatectomy or radiation for prostate cancer: multivariate quality-of-life analysis from CaPSURE. Cancer of the Prostate Strategic Urologic Research Endeavor.

PubMed

Litwin, M S; Flanders, S C; Pasta, D J; Stoddard, M L; Lubeck, D P; Henning, J M

1999-09-01

To measure the effect of treatment choice (pelvic irradiation [XRT] versus radical prostatectomy [RP] with or without nerve sparing) on sexual function and sexual bother during the first 2 years after treatment. We studied sexual function and sexual bother in 438 men recently diagnosed with early-stage prostate cancer and treated with XRT or RP with or without nerve sparing. Outcomes were assessed with the University of California, Los Angeles Prostate Cancer Index, a validated health-related quality-of-life instrument that includes these two domains. To minimize the influence of other factors, we adjusted for age, comorbidity, general health, and previous treatment for erectile dysfunction. All subjects were drawn from CaPSURE, a national, longitudinal data base. Sexual function improved over time during the first year in all treatment groups; however, during the second year, sexual function began to decline in the XRT group. Older patients who received XRT showed substantial declines in sexual function throughout the 2 years, and older patients who underwent RP experienced a return of very low baseline sexual function. Sexual function was improved by the use of nerve-sparing procedures or erectile aids. Alterations in sexual bother were ameliorated by many factors, including age, general health perceptions, and sexual function. Patients undergoing XRT or RP with or without nerve sparing all showed comparable rates of improvement in sexual function during the first year after treatment for early-stage prostate cancer. However, in the second year after treatment, patients treated with XRT began to show declining sexual function; patients treated with RP did not.

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

PubMed Central

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

2015-01-01

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

Hypothermia and Rewarming Induce Gene Expression and Multiplication of Cells in Healthy Rat Prostate Tissue

PubMed Central

Kaija, Helena; Pakanen, Lasse; Kortelainen, Marja-Leena; Porvari, Katja

2015-01-01

Prostate cancer has been extensively studied, but cellular stress responses in healthy prostate tissue are rarely investigated. Hypothermia is known to cause alterations in mRNA and protein expressions and stability. The aim of this study was to use normal rat prostate as a model in order to find out consequences of cold exposure and rewarming on the expressions of genes which are either members or functionally/structurally related to erythroblastic leukemia viral oncogene B (ErbB) signaling pathway. Relative mRNA expressions of amphiregulin (AMR), cyclin D1 (CyD1), cyclin-dependent kinase inhibitor 1A (p21), transmembrane form of the prostatic acid phosphatase (PAcP), thrombomodulin (TM) and heat shock transcription factor 1 (HSF1) in rat ventral prostate were quantified in mild (2 or 4.5 h at room temperature) and severe (2 or 4.5 h at +10°C) hypothermia and in rewarming after cold exposure (2 h at +10°C followed by 2 h at room temperature or 3 h at +28°C). AMR protein level, apoptotic Bcl-2 associated X protein to B-cell CLL/lymphoma 2 (Bax/Bcl-2) mRNA ratio and proliferative index Ki-67 were determined. 4.5-h mild hypothermia, 2-h severe hypothermia and rewarming increased expression of all these genes. Elevated proliferation index Ki-67 could be seen in 2-h severe hypothermia, and the proliferation index had its highest value in longer rewarming with totally recovered normal body temperature. Pro-apoptotic tendency could be seen in 2-h mild hypothermia while anti-apoptosis was predominant in 4.5-h mild hypothermia and in shorter rewarming with only partly recovered body temperature. Hypothermia and following rewarming promote the proliferation of cells in healthy rat prostate tissue possibly via ErbB signaling pathway. PMID:25996932

Targeting Stromal Androgen Receptor Suppresses Prolactin-Driven Benign Prostatic Hyperplasia (BPH)

PubMed Central

Lai, Kuo-Pao; Huang, Chiung-Kuei; Fang, Lei-Ya; Izumi, Kouji; Lo, Chi-Wen; Wood, Ronald; Kindblom, Jon; Yeh, Shuyuan

2013-01-01

Stromal-epithelial interaction plays a pivotal role to mediate the normal prostate growth, the pathogenesis of benign prostatic hyperplasia (BPH), and prostate cancer development. Until now, the stromal androgen receptor (AR) functions in the BPH development, and the underlying mechanisms remain largely unknown. Here we used a genetic knockout approach to ablate stromal fibromuscular (fibroblasts and smooth muscle cells) AR in a probasin promoter-driven prolactin transgenic mouse model (Pb-PRL tg mice) that could spontaneously develop prostate hyperplasia to partially mimic human BPH development. We found Pb-PRL tg mice lacking stromal fibromuscular AR developed smaller prostates, with more marked changes in the dorsolateral prostate lobes with less proliferation index. Mechanistically, prolactin mediated hyperplastic prostate growth involved epithelial-stromal interaction through epithelial prolactin/prolactin receptor signals to regulate granulocyte macrophage-colony stimulating factor expression to facilitate stromal cell growth via sustaining signal transducer and activator of transcription-3 activity. Importantly, the stromal fibromuscular AR could modulate such epithelial-stromal interacting signals. Targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9®, led to the reduction of prostate size, which could be used in future therapy. PMID:23893956

A Longitudinal Study of Predictors of Sexual Dysfunction in Men on Active Surveillance for Prostate Cancer.

PubMed

Pearce, Shane M; Wang, Chi-Hsiung E; Victorson, David E; Helfand, Brian T; Novakovic, Kristian R; Brendler, Charles B; Albaugh, Jeffrey A

2015-09-01

The aim of this study was to examine the relationship between sexual dysfunction, repeat biopsies and other demographic and clinical factors in men on active surveillance (AS). Patient-reported outcomes (PROs) measures were administered at enrollment and every 6 months to assess quality of life (QOL), psychosocial and urological health outcomes. Using mixed-effects models, we examined the impact of repeat biopsies, total number of cores taken, anxiety, age, and comorbidity on sexual function over the first 24 months of enrolling in AS. PROs included the Expanded Prostate Cancer Index Composite-26 (EPIC-26) Sexual Function (SF) subscale, the American Urological Association-Symptom Index (AUA-SI), and the Memorial Anxiety Scale for Prostate Cancer (MAX-PC). At enrollment (n = 195), mean age was 66.5 ± 6.8 with a mean EPIC-26 SF score of 61.4 ± 30.4. EPIC-26 SF scores steadily decreased to 53.9 ± 30.7 at 24 months (P < 0.01). MAX-PC scores also progressively decreased over time (P = 0.03). Factors associated with lower EPIC-26 scores over time included age, unemployed status, diabetes, coronary artery disease, and hypertension (all P < 0.05). Higher prostate-specific antigen (PSA) was associated with a more rapid decline in EPIC-26 SF over time (P = 0.03). In multivariable analysis, age, diabetes, and PSA × time interaction remained significant predictors of diminished sexual function. Anxiety, number of biopsies, and total cores taken did not predict sexual dysfunction or change over time in our cohort. Men on AS experienced a gradual decline in sexual function during the first 24 months of enrollment. Older age, PSA × time, and diabetes were all independent predictors of diminished sexual function over time. Anxiety, AUA-SI, the number of cores and the number of biopsies were not predictors of reduced sexual function in men in AS.

The economic impact of chronic prostatitis.

PubMed

Calhoun, Elizabeth A; McNaughton Collins, Mary; Pontari, Michel A; O'Leary, Michael; Leiby, Benjamin E; Landis, J Richard; Kusek, John W; Litwin, Mark S

2004-06-14

Little information exists on the economic impact of chronic prostatitis. The objective of this study was to determine the direct and indirect costs associated with chronic prostatitis. Outcomes were assessed using a questionnaire designed to capture health care resource utilization. Resource estimates were converted into unit costs with direct medical cost estimates based on hospital cost-accounting data and indirect costs based on modified labor force, employment, and earnings data from the US Census Bureau. The total direct costs for the 3 months prior to entry into the cohort, excluding hospitalization, were $126 915 for the 167 study participants for an average of $954 per person among the 133 consumers. Of the men, 26% reported work loss valued at an average of $551. The average total costs (direct and indirect) for the 3 months was $1099 per person for those 137 men who had resource consumption with an expected annual total cost per person of $4397. For those study participants with any incurred costs, tests for association revealed that the National Institutes of Health Chronic Prostatitis Symptom Index (P<.001) and each of the 3 subcategories of pain (P =.003), urinary function (P =.03), and quality-of-life (P =.002) were significantly associated with resource use, although the quality-of-life subscale score from the National Institutes of Health Chronic Prostatitis Symptom Index was the only predictor of resource consumption. Chronic prostatitis is associated with substantial costs and lower quality-of-life scores, which predicted resource consumption. The economic impact of chronic prostatitis warrants increased medical attention and resources to identify and test effective treatment strategies.

Health-related quality of life, psychological well-being, and sexual function in patients with benign prostatic hyperplasia after prostatic surgery.

PubMed

Yim, Pierre W C; Wang, Wenru; Jiang, Ying; Zakir, Hussain Abdul Salam; Toh, Poh Choo; Lopez, Violeta; He, Hong-Gu

2015-11-01

Patients with benign prostatic hyperplasia (BPH) may receive prostatic surgery due to severe lower urinary tract symptoms (LUTS). This study aimed to investigate the health-related quality of life (HRQoL), psychological well-being, and sexual function of patients with BPH after prostatic surgery and identify the predictors of HRQoL among this group of patients. This was a cross-sectional, descriptive, correlational study. A convenience sample of 94 participants was recruited from a urology center in a tertiary public hospital in Singapore. The 12-item Short Form Health Survey version 2 (SF-12v2), International Prostate Symptom Score (IPSS), Hospital Anxiety and Depression Scale (HADS), and 5-item International Index of Erectile Function (IIEF-5) were used to measure the study variables. Compared to the general population norms and the findings of similar studies conducted in western countries, this group of patients reported poorer physical health but better mental health as assessed by SF-12v2. Despite the prostatic surgery, over a quarter of the patients experienced moderate LUTS, and 13.8% experienced severe erectile dysfunction. Multiple linear regression analysis identified that LUTS (B=-0.51, p=0.02) and maximum flow rate (B=-0.23, p=0.02) predicted poor physical health, accounting for 45.9% of variance, while HADS-Anxiety (B=-1.07, p<0.01) and LUTS (B=-0.32, p=0.03) predicted poor mental health, accounting for 57.2% of variance. The physical health of BPH patients with prostatic surgery was poor, with many suffering moderate LUTS and sexual dysfunction. Special attention should be given to those patients with severe LUTS who have a low maximum flow rate or have anxiety symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Interrelationships among angiogenesis, proliferation, and apoptosis in the tumor microenvironment during N-methyl-N-nitrosourea androgen-induced prostate carcinogenesis in rats.

PubMed

Liao, Zhiming; Boileau, Thomas W-M; Erdman, John W; Clinton, Steven K

2002-10-01

Proliferation, apoptosis and angiogenesis are critical biologic processes altered during carcinogenesis. Surrogate biomarkers of these processes represent potential intermediate endpoints for short-term intervention studies with preventive and therapeutic agents. We examined the interrelationships among these processes during prostate carcinogenesis induced by N-methyl-N-nitrosourea (MNU) in male Wistar-Unilever rats. Immunohistochemical and digital image analysis techniques were used to evaluate the proliferation index, the apoptotic index and microvessel density (MVD) in tissue representing stages of prostate carcinogenesis. The proliferation index in the normal glandular epithelium of the prostate is lower than that observed in hyperplastic foci and atypical hyperplasia (P < 0.01) and is further increased in carcinoma (P < 0.01). Apoptosis in the normal prostate epithelium or hyperplastic lesions is lower than in adenocarcinoma (P < 0.01). In parallel to proliferation index, MVD increases as prostate cancer progresses. As tumors enlarge, we observed a predictable change in biomarker expression within the tumor microenvironment. We examined prostate tumors vertical line 1 cm in diameter and biomarker expression was quantified within the peripheral (outer 1-2 mm), central (perinecrotic) and intermediate (remaining) areas of each tumor. The proliferation index is higher (P < 0.01) in the intermediate area than either in the peripheral area or central area. Similarly, the vascular density in the intermediate area is higher (P < 0.01) than either in the peripheral or central area. The apoptotic index is higher (P < 0.05) in the central perinecrotic core than that in either the intermediate or the peripheral area. In conclusion, we observe that angiogenesis, proliferation and apoptosis are linked biological processes predictably altered temporally and spatially during prostate carcinogenesis in the MNU model. These biomarker changes are similar to those reported in human prostate carcinogenesis and represent potential biomarkers for the assessment of dietary, chemopreventive and therapeutic agents.

Detection of prostate cancer index lesions with multiparametric magnetic resonance imaging (mp-MRI) using whole-mount histological sections as the reference standard.

PubMed

Russo, Filippo; Regge, Daniele; Armando, Enrico; Giannini, Valentina; Vignati, Anna; Mazzetti, Simone; Manfredi, Matteo; Bollito, Enrico; Correale, Loredana; Porpiglia, Francesco

2016-07-01

To evaluate the sensitivity of multiparametric magnetic resonance imaging (mp-MRI) for detecting prostate cancer foci, including the largest (index) lesions. In all, 115 patients with biopsy confirmed prostate cancer underwent mp-MRI before radical prostatectomy. A single expert radiologist recorded all prostate cancer foci including the index lesion 'blinded' to the pathologist's biopsy report. Stained whole-mount histological sections were used as the reference standard. All lesions were contoured by an experienced uropathologist who assessed their volume and pathological Gleason score. All lesions with a volume of >0.5 mL and/or pathological Gleason score of >6 were defined as clinically significant prostate cancer. Multivariate analysis was used to ascertain the characteristics of lesions identified by MRI. In all, 104 of 115 index lesions were correctly diagnosed by mp-MRI (sensitivity 90.4%; 95% confidence interval [CI] 83.5-95.1%), including 98/105 clinically significant index lesions (93.3%; 95% CI 86.8-97.3%), among which three of three lesions had a volume of <0.5 mL and Gleason score of >6. Overall, mp-MRI detected 131/206 lesions including 13 of 68 'insignificant' prostate cancers. The multivariate logistic regression modelling showed that pathological Gleason score (odds ratio [OR] 11.7, 95% CI 2.3-59.8; P = 0.003) and lesion volume (OR 4.24, 95% CI 1.3-14.7; P = 0.022) were independently associated with the detection of index lesions at MRI. This study shows that mp-MRI has a high sensitivity for detecting clinically significant prostate cancer index lesions, while having disappointing results for the detection of small-volume, low Gleason score prostate cancer foci. Thus, mp-MRI could be used to stratify patients according to risk, allowing better treatment selection. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Health-related quality of life in the first year after laparoscopic radical prostatectomy compared with open radical prostatectomy.

PubMed

Hashine, Katsuyoshi; Nakashima, Takeshi; Iio, Hiroyuki; Ueno, Yoshiteru; Shimizu, Shinjiro; Ninomiya, Iku

2014-07-01

To assess health-related quality of life in the first year after laparoscopic radical prostatectomy compared with that after open radical prostatectomy. The subjects were 105 consecutive patients with localized prostate cancer treated with laparoscopic radical prostatectomy between January 2011 and June 2012. Health-related quality of life was evaluated using the International Prostate Symptom Score, Medical Outcome Study 8-Items Short Form Health Survey (SF-8) and Expanded Prostate Cancer Index Composite at baseline and 1, 3, 6 and 12 months after surgery. Comparisons were made with data for 107 consecutive patients treated with open radical prostatectomy between October 2005 and July 2007. The International Prostate Symptom Score change was similar in each group. The laparoscopic radical prostatectomy group had a better baseline Medical Outcome Study 8-Items Short Form Health Survey mental component summary score and a better Medical Outcome Study 8-Items Short Form Health Survey physical component summary score at 1 month after surgery. In Expanded Prostate Cancer Index Composite, obstructive/irritative symptoms did not differ between the groups, but urinary incontinence was worse until 12 months after surgery and particularly severe after 1 month in the laparoscopic radical prostatectomy group. The rate of severe urinary incontinence was much higher in the laparoscopic radical prostatectomy group in the early period. Urinary bother was worse in the laparoscopic radical prostatectomy group at 1 and 3 months, but did not differ between the groups thereafter. Urinary function and bother were good after nerve sparing procedures and did not differ between the groups. Bowel and sexual function and bother were similar in the two groups. Urinary function in the first year after laparoscopic radical prostatectomy is worse than that after open radical prostatectomy. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Changes in Adenosine Triphosphate and Nitric Oxide in the Urothelium of Patients with Benign Prostatic Hyperplasia and Detrusor Underactivity.

PubMed

Cho, Kang Jun; Koh, Jun Sung; Choi, Jinbong; Kim, Joon Chul

2017-12-01

We investigated changes in the levels of adenosine triphosphate and nitric oxide in the urothelium of men with detrusor underactivity and benign prostatic hyperplasia. We prospectively enrolled in study 30 men who planned to undergo surgical treatment for benign prostatic hyperplasia. The 15 patients with a bladder contractility index less than 100 were assigned to the detrusor underactivity group while the 15 with a bladder contractility index more than 100 were assigned to the no detrusor underactivity group. Bladder mucosal specimens were collected at surgical prostate resection, and adenosine triphosphate and endothelial nitric oxide synthase were analyzed in these specimens. The levels of adenosine triphosphate and endothelial nitric oxide synthase were compared between the 2 groups. The correlation of urodynamic parameters with adenosine triphosphate and endothelial nitric oxide synthase was assessed in all patients. Mean ± SEM endothelial nitric oxide synthase did not significantly differ between the detrusor underactivity and no underactivity groups (3.393 ± 0.969 vs 1.941 ± 0.377 IU/ml, p = 0.247). However, the mean level of adenosine triphosphate in the detrusor underactivity group was significantly lower than in the no detrusor underactivity group (1.289 ± 0.320 vs 9.262 ± 3.285 pmol, p = 0.011). In addition, in all patients adenosine triphosphate positively correlated with the bladder contractility index (r = 0.478, p = 0.018) and with detrusor pressure on maximal flow (r = 0.411, p = 0.046). Adenosine triphosphate was significantly decreased in the urothelium in men with detrusor underactivity and benign prostatic hyperplasia, reflecting the change in detrusor function. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

Engstroem, K; Casares-Magaz, O; Muren, L

Purpose: Multi-parametric MRI (mp-MRI) is being introduced in radiotherapy (RT) of prostate cancer, including for tumour delineation in focal boosting strategies. We recently developed an image-based tumour control probability model, based on cell density distributions derived from apparent diffusion coefficient (ADC) maps. Beyond tumour volume and cell densities, tumour hypoxia is also an important determinant of RT response. Since tissue perfusion from mp-MRI has been related to hypoxia we have explored the patterns of ADC and perfusion maps, and the relations between them, inside and outside prostate index lesions. Methods: ADC and perfusion maps from 20 prostate cancer patients weremore » used, with the prostate and index lesion delineated by a dedicated uro-radiologist. To reduce noise, the maps were averaged over a 3×3×3 voxel cube. Associations between different ADC and perfusion histogram parameters within the prostate, inside and outside the index lesion, were evaluated with the Pearson’s correlation coefficient. In the voxel-wise analysis, scatter plots of ADC vs perfusion were analysed for voxels in the prostate, inside and outside of the index lesion, again with the associations quantified with the Pearson’s correlation coefficient. Results: Overall ADC was lower inside the index lesion than in the normal prostate as opposed to ktrans that was higher inside the index lesion than outside. In the histogram analysis, the minimum ktrans was significantly correlated with the maximum ADC (Pearson=0.47; p=0.03). At the voxel level, 15 of the 20 cases had a statistically significant inverse correlation between ADC and perfusion inside the index lesion; ten of the cases had a Pearson < −0.4. Conclusion: The minimum value of ktrans across the tumour was correlated to the maximum ADC. However, on the voxel level, the ‘local’ ktrans in the index lesion is inversely (i.e. negatively) correlated to the ‘local’ ADC in most patients. Research agreement with Varian Medical Systems, not related to the work presented in this abstract.« less

Heat shock protein 9-mediated inflammation reaction in patients with chronic prostatitis with erectile dysfunction.

PubMed

Zhao, H-F; Li, X; Jiang, X-Z

2016-10-01

To investigate the role of heat shock protein (HSP)-9 on the inflammation reaction present in patients with chronic prostatitis with erectile dysfunction (ED). A total of 160 participants in the study were assigned to one of four groups of the same size. Group A had patients with chronic prostatitis and ED. Group B had patients with simple chronic prostatitis. Group C had patients with ED. And group D had healthy volunteers. The serum levels of HSP-9, CRP, TNF-a, IL-6 and CD3 in each individual's serum were tested by ELISA. Additionally, the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Index of Erectile Function-5 (IIEF-5) scores were recorded for each case. The serum levels of HSP-9, CRP, TNF-a, IL-6 and CD3 in the serum of groups A and B were distinctly higher than those of groups C and D (p<0.05). While comparisons between groups A and B, or between groups C and D yielded no significant differences. Nevertheless, the NIH-CPSI scores in the group A were significantly higher (mostly moderately severe) than in the group B (mild to moderate). Furthermore, the IIEF-5 scores in the group A were also significantly higher than those in the group C. The serum levels of HSP-9, CRP, TNF-a, IL-6 and CD3 in the sera of patients with chronic prostatitis with ED were clearly increased, reflecting a high degree of inflammation which may be related to the clinical manifestations in patients with chronic prostatitis and ED.

Evaluation of the resistive index of prostatic blood flow in benign prostatic hyperplasia.

PubMed

Abdelwahab, Osama; El-Barky, Ehab; Khalil, Mostafa Mahmoud; Kamar, Ahmad

2012-01-01

The aim of this work is to study the resistive index (RI) of prostatic blood flow by transrectal power Doppler sonography in benign prostatic hyperplasia (BPH) to determine its correlation with other parameters of BPH. Eighty-two male patients aged 52-86 years with lower urinary tract symptoms (LUTS) due to BPH were included in the study. Patients with prostate cancer, neurogenic bladder, or with other pathology (e.g. prostatitis, bladder stone) were excluded from the study. All patients were evaluated by full history including Internatinoal Prostate Symptoms Score (IPSS), general and local examination (DRE), neurologic examination, uroflowmetry, laboratory investigations including urine analysis, routine laboratory tests and serum prostate specific antigen (PSA). Transrectal ultrasonography was used to calculate the total prostatic volume. Transrectal Power Doppler Ultrasound (PUD) was used to identify the capsular and urethral arteries of the prostate and to measures the RI value. The mean prostate volume was 75.1 ± 44.7 g. The mean RI of the right and left capsular arteries were 0.76 ± 0.06 and 0.76 ± 0.07, respectively. The mean RI of the urethral arteries was 0.76 ± 0.08. There was a high significative correlation between the increase of the RI of the right and left capsular and urethral arteries and the degree of obstruction (P value < 0.001), severity of symptoms (P value < 0.001) and also the prostatic volume (P value < 0.001). Resistive index of the prostatic blood flow can be applied as an easy and non-invasive tool to evaluate the lower urinary tract obstruction due to BPH.

Ki-67 expression in early prostate cancer and associated pathological lesions.

PubMed Central

Feneley, M R; Young, M P; Chinyama, C; Kirby, R S; Parkinson, M C

1996-01-01

AIM: To assess cell proliferation in early prostate cancer and associated pathological lesions. METHODS: Using the Ki-67 antibody, the cell proliferation index was measured in early stage prostatic carcinoma in 37 incidental tumours diagnosed at transurethral prostatectomy (TURP) and in 20 low volume cancers treated by radical prostatectomy. Proliferation indexes have also been measured in areas of normal peripheral zone, transition zone hyperplasia, atrophic appearing lobules, and high grade prostatic intraepithelial neoplasia in the radical prostatectomy cases. RESULTS: In the TURP series the proliferation index correlated with grade and stage. Logistic regression analysis, however, showed that Gleason grade was the most reliable predictor of biopsy proven residual disease and clinical progression. In the radical series transition zone carcinoma the proliferation index was half that of peripheral zone carcinoma. The atrophic lobules also showed a high proliferation index of the same order as seen in the peripheral zone carcinoma. Normal peripheral zone showed the lowest proliferation index and in hyperplastic transition zone it was also less than the other areas. CONCLUSIONS: There is only limited support for the correlation of proliferation index with grade in early stage prostatic carcinoma. The findings do not suggest that proliferation index adds to the prognostic information given by grade and stage in pT1 disease. The significant difference in proliferation index in transition zone and peripheral zone carcinomas supports the morphological distinction of these tumour types and is consistent with differences in biological behaviour. The high proliferation index in lobules considered morphologically atrophic is reminiscent of previous observations in which carcinoma was spatially associated with atrophy. Images PMID:9038759

Sedentary behavior and prostate cancer risk in the NIH-AARP Diet and Health Study

PubMed Central

Lynch, Brigid M.; Friedenreich, Christine M.; Kopciuk, Karen A.; Hollenbeck, Albert R.; Moore, Steven C.; Matthews, Charles E.

2014-01-01

Sedentary behavior (sitting time) has been proposed as an independent risk factor for some cancers; however, its role in the development of prostate cancer has not been determined. We examined the prospective associations of self-reported daily sitting time and daily television/video viewing time with risk of developing or dying from prostate cancer among 170,481 men in the NIH-AARP Diet and Health Study. We estimated hazard ratios and 95% confidence intervals using Cox Proportional Hazards regression. Between 1996 and 2006 there were 13,751 incident (including 1,365 advanced) prostate cancer cases identified; prostate cancer mortality (through 2008) was 669. No strong or significant association with prostate cancer risk was seen in fully adjusted models for either daily sitting or television/video time. There was some suggestion of effect modification by body mass index (interaction for television/video time and body mass index, p = 0.02). For total prostate cancer risk, television/video time was associated with a slightly elevated, but non-significant increased amongst obese men (HR=1.28, 95%CI: 0.98, 1.69); a null association was observed amongst overweight men (HR=1.04, 0.89, 1.22); and, for men with a normal body mass index, television/video time was associated with a non-significant risk decrease (HR=0.82, 95%CI: 0.66, 1.01). Similar patterns were observed for total daily sitting and television/video time in advanced prostate cancer and prostate cancer mortality. Sedentary behavior appears to play a limited role in the development of prostate cancer, however we cannot rule out potential effect modification by body mass index or the impact of measurement error on results. PMID:24526287

The prevalence of and risk factors for prostatitis-like symptoms and its relation to erectile dysfunction in Chinese men.

PubMed

Zhang, Z; Li, Z; Yu, Q; Wu, C; Lu, Z; Zhu, F; Zhang, H; Liao, M; Li, T; Chen, W; Xian, X; Tan, A; Mo, Z

2015-11-01

The aim of this study was to describe the prevalence of and risk factors for prostatitis-like symptoms and its relation to erectile dysfunction (ED) among southern Chinese men. Data were collected from 2790 men attending the Fangchenggang Area Male Healthy and Examination Survey from September 2009 to December 2009. The prostatitis-like symptoms were assessed by the NIH Chronic Prostatitis Symptom Index and ED was assessed using the 5-item International Index of Erectile Function. Lifestyle and demographic characteristics were obtained through a questionnaire. Prevalence of prostatitis-like symptoms was 12.4% among 2790 Chinese men aged 20-84 years. In smokers who smoked ≥20 cigarettes per day (age-adjusted OR = 1.29; 95% CI = 1.00-1.66; p = 0.04), physical inactivity (age-adjusted OR = 1.31; 95% CI = 1.03-1.66; p = 0.02) was a significant risk factor for prostatitis-like symptoms. Alcohol consumption (daily drinking) also was a risk factor for prostatitis-like symptoms, although the differences were not statistically significant (age-adjusted OR = 1.36; 95% CI = 0.96-1.92; p = 0.07). Those with diabetes may also be at higher risk for prostatitis-like symptoms (age-adjusted OR = 1.37; 95% CI = 0.85-2.21; p = 0.19). In addition, men with ED were more likely to have had prostatitis-like symptoms (age-adjusted OR = 1.86; 95% CI = 0.47-2.36; p < 0.0001), and the ORs increased with increasing severity of ED status (mild ED, mild to moderate ED, and moderate to severe ED were 1.57, 2.62, and 3.24, respectively. Test for trend, p = 0.0001). Our results show that prostatitis-like symptoms are prevalent in Southern China affecting men of all ages. Smoking, drinking, lack of physical activity, and elevated plasma glucose level were associated with an increased risk of prostatitis-like symptoms. In addition, our results reveal that ED accounted for a large proportion (61.5%) among men with prostatitis-like symptoms; we also confirm the magnitude of ED associated with prostatitis-like symptoms. Thus, interventions to evaluate and improve ED might help ameliorate prostatitis-like symptoms and vice versa. © 2015 American Society of Andrology and European Academy of Andrology.

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: the Pros-IT CNR study.

PubMed

Porreca, Angelo; Noale, Marianna; Artibani, Walter; Bassi, Pier Francesco; Bertoni, Filippo; Bracarda, Sergio; Conti, Giario Natale; Corvò, Renzo; Gacci, Mauro; Graziotti, Pierpaolo; Magrini, Stefano Maria; Mirone, Vincenzo; Montironi, Rodolfo; Muto, Giovanni; Pecoraro, Stefano; Ricardi, Umberto; Russi, Elvio; Tubaro, Andrea; Zagonel, Vittorina; Crepaldi, Gaetano; Maggi, Stefania

2018-06-13

The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

The role of BPH, lower urinary tract symptoms, and PSA levels on erectile function of Brazilian men who undergo prostate cancer screening.

PubMed

Antunes, Alberto A; Srougi, Miguel; Dall'oglio, Marcos F; Vicentini, Fabio; Paranhos, Mario; Freire, Geraldo C

2008-07-01

Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are common problems in middle-aged and older men. Recently, epidemiologic studies have shown significant associations between severity of LUTS and male sexual dysfunction. We analyzed the role of prostate enlargement, LUTS, and prostate specific antigen (PSA) levels in the erectile function of Brazilian men who underwent prostate cancer (PCa) screening. We analyzed data from 1,008 consecutive patients enrolled in a PCa screening program. Benign prostatic hyperplasia (BPH) was defined as a prostate weight greater than 30 g as defined by digital rectal examination. For statistical analysis, we used the chi-squared and analysis of variance tests. The odds ratios (OR) for correlation of ED with prostate volume LUTS and PSA were estimated using logistic regression models. The American Urological Association (AUA) symptom score for LUTS and the International Index of Erectile Function. Mean patient age was 61.2 years (45-87) and median PSA value was 1.9 ng/mL. BPH was identified in 48.5% of patients. Mild, moderate, and severe LUTS were found in 52.3%, 30.9%, and 16.8% of cases, respectively. ED was classified as absent, mild, mild to moderate, moderate, and severe in 18.6%, 23.1%, 18.6%, 15.2%, and 24.5%, respectively. While only 5.4% of the patients with no ED presented severe LUTS, this finding was observed in 27.1% of patients with severe ED (P < 0.001). Univariate logistic regression analysis demonstrated that age, prostate volume, AUA symptom score, and PSA levels were significant predictors of ED. However, when controlled for patient age, only LUTS remained as an independent predictor of ED. Controlling for patient age, LUTS are independent risk factors for the development of ED among Brazilian men who undergo PCa screening. Antunes AA, Srougi M, Dall'Oglio MF, Vicentini F, Paranhos M, and Freire GC. The role of BPH, lower urinary tract symptoms, and PSA levels on erectile function of Brazilian men who undergo prostate cancer screening.

Investigation of scattering coefficients and anisotropy factors of human cancerous and normal prostate tissues using Mie theory

NASA Astrophysics Data System (ADS)

Pu, Yang; Chen, Jun; Wang, Wubao

2014-02-01

The scattering coefficient, μs, the anisotropy factor, g, the scattering phase function, p(θ), and the angular dependence of scattering intensity distributions of human cancerous and normal prostate tissues were systematically investigated as a function of wavelength, scattering angle and scattering particle size using Mie theory and experimental parameters. The Matlab-based codes using Mie theory for both spherical and cylindrical models were developed and applied for studying the light propagation and the key scattering properties of the prostate tissues. The optical and structural parameters of tissue such as the index of refraction of cytoplasm, size of nuclei, and the diameter of the nucleoli for cancerous and normal human prostate tissues obtained from the previous biological, biomedical and bio-optic studies were used for Mie theory simulation and calculation. The wavelength dependence of scattering coefficient and anisotropy factor were investigated in the wide spectral range from 300 nm to 1200 nm. The scattering particle size dependence of μs, g, and scattering angular distributions were studied for cancerous and normal prostate tissues. The results show that cancerous prostate tissue containing larger size scattering particles has more contribution to the forward scattering in comparison with the normal prostate tissue. In addition to the conventional simulation model that approximately considers the scattering particle as sphere, the cylinder model which is more suitable for fiber-like tissue frame components such as collagen and elastin was used for developing a computation code to study angular dependence of scattering in prostate tissues. To the best of our knowledge, this is the first study to deal with both spherical and cylindrical scattering particles in prostate tissues.

Comprehensive quality-of-life outcomes in the setting of a multidisciplinary, equal access prostate cancer clinic.

PubMed

Rice, Kevin; Hudak, Jane; Peay, Kimberly; Elsamanoudi, Sally; Travis, Judith; Lockhart, Robbin; Cullen, Jennifer; Black, Libby; Houge, Susan; Brassell, Stephen

2010-11-01

To identify racial and demographic factors that influence treatment choice and its resulting impact on health-related quality of life (HRQoL) for prostate cancer patients. Patients presenting to an equal access, military, multidisciplinary prostate cancer clinic composed the study group. The Expanded Prostate Cancer Index Composite (EPIC), EPIC Demographic, and Medical Outcomes Study Short Form 36 were the instruments used. Evaluation was performed before treatment and every 3 months after treatment. The study group comprised 665 patients. Caucasians were 3-fold more likely to choose surgery (radical prostatectomy [RP]) over external beam radiation therapy (EBRT). Patients who earned more than $100,000 annually disproportionately chose RP (P < .0001). Similarly, those having a graduate school degree disproportionally chose RP (P < .0001). Patients undergoing RP had the greatest risk of urinary function decline (P < .0001) and sexual bother (P = .0003). African Americans (AA) had a greater risk of urinary function decline irrespective of treatment choice. Patients undergoing EBRT had equivalent urinary function to expectant management (EM) at 12 months (P < .0001). Brachytherapy was the only treatment that posed an increased risk of urinary bother decline when compared with EM (P = .0217). EBRT alone did not show significant decrement in sexual function when compared with EM. RP was chosen by patients of Caucasian ethnicity and patients with higher income and education level, despite providing the greatest risk of HRQoL decline. EBRT had no significant impact on urinary function, sexual function, or sexual bother scores at 12 months. EBRT may be offered to older patients with minimal HRQoL impact. Pretreatment counseling of HRQoL outcomes is essential to overall prostate cancer management. Published by Elsevier Inc.

[Use of [-2] pro PSA and phi index for early detection of prostate cancer: a prospective of 452 patients].

PubMed

Houlgatte, A; Vincendeau, S; Desfemmes, F; Ramirez, J; Benoist, N; Bensalah, K; Durand, X

2012-05-01

Early detection of prostate cancer (Pca) is a real challenge to reduce morbidity and mortality while avoiding over-diagnosis and over-treatment. The prostate specific antigen (PSA) is characterized by its imperfections justifying the evaluation of new serum or urinary specific markers allowing a better selection of patients at risk of developing aggressive Pca. To compare the value of -2pro PSA and phi index to total and free PSA. Serum sampled from 452 patients from two university centers were used to determine levels of PSA before performing biopsies. The patients were included in this study based on the PSA serum concentration between 1.6 ng/mL and 8 ng/mL according to the WHO international standard. All biopsies were performed according to a standardized protocol consisting of 12 cores or more. Sera were analyzed centrally in one of the two institutions with on a single analyzer. Sera from 243 prostate cancer and 208 negative biopsies patients have been taken into account. Sera were analyzed blinded for total PSA, free PSA and [-2] proPSA using Access(®) immunoassay method from Beckman Coulter. The Prostate Health Index (phi) was calculated using the formula phi=([-2] proPSA/fPSA)×sqrt (PSA). The median value of the phi index is significantly (P>0.0001) higher for patients with cancer (phi=65.8) compared to patients with negative biopsies (phi=40.6). At a given sensitivity, the phi index significantly increases the specificity of detection of prostate cancer compared to other markers. The phi index currently appears as the best predictor of prostate cancer for patients with a total PSA between 1.6 and 8 ng/mL according to the WHO standard. The improvement in specificity of the phi index over tPSA could reduce significantly the numbers of unnecessary biopsies. Whether this new biomarker could be an indicator of aggressive prostate cancer remains to be confirmed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Long-term efficacy of Serenoa repens treatment in patients with mild and moderate symptomatic benign prostatic hyperplasia.

PubMed

Sinescu, Ioanel; Geavlete, Petrisor; Multescu, Razvan; Gangu, Constantin; Miclea, Florin; Coman, Ioan; Ioiart, Ioan; Ambert, Valentin; Constantin, Traian; Petrut, Bogdan; Feciche, Bogdan

2011-01-01

The study aimed to evaluate the long-term efficacy of treatment with extract of Serenoa repens (Prostamol Uno) in patients with lower urinary tract symptoms (LUTS) induced by benign prostatic hyperplasia (BPH). We studied 120 patients with mild or moderate LUTS induced by BPH, maximal urinary flow (Q(max)) <15 ml with a voided volume ≥150 ml, prostate-specific antigen <4 ng/ml, and residual urinary volume <150 ml, treated daily for 24 months with one capsule of 320 mg ethanolic extract of Serenoa repens. Statistically significant improvements in the International Prostate Symptom Score (5.5 points), quality of life (QoL; 1.8 points), Q(max) (5.6 ml/s), International Index of Erectile Function (IIEF; 6.4 points) and reduction in residual urinary volume were observed during the study period. The mean prostate volume at 24 months was 36 ml, compared to 39.8 ml at baseline. Long-term treatment with 320 mg ethanolic extract of Serenoa repens proved to be efficient in reducing urinary obstruction, improving symptomatology and QoL of BPH patients. It also had a positive effect on sexual function, demonstrated by the statistically significant increase in the IIEF. Copyright © 2011 S. Karger AG, Basel.

Relationship among diet habit and lower urinary tract symptoms and sexual function in outpatient-based males with LUTS/BPH: a multiregional and cross-sectional study in China

PubMed Central

Chen, Yuke; Yu, Wei; Zhou, Liqun; Wu, Shiliang; Yang, Yang; Wang, Jianye; Tian, Ye; He, Dalin; Xu, Yong; Huang, Jian; Wang, Xiaofeng; Gao, Xin; Li, Hanzhong; Ma, Lulin; Zhang, Ning; Zhao, Shengtian; Jin, Xunbo

2016-01-01

Objectives This study assessed the effect of diet habits on lower urinary tract symptoms (LUTS) and sexual function in Chinese men with LUTS/benign prostatic hypertrophy (LUTS/BPH). Setting Multicentre study conducted between July 2013 and December 2013 in 11 hospitals in 3 geographic regions in China. Participants Overall, participants with LUTS/BPH accounted for 61.4% (2584/4208) of the respondents, whose data were processed in the following statistical analysis. Primary and secondary outcome measures LUTS and sexual function were assessed based on the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function 5 (IIEF-5) score. Prostate volume (PV) was determined by ultrasound. Results A total of 4208 participants met the inclusion criteria. The average age of the whole participants was 65.8±7.7 years. Overall, participants with LUTS/BPH accounted for 61.4% (2584/4208) of the respondents, whose data were processed in the following statistical analysis. Generally, prostate enlargement was greatest in south China. LUTS and male sexual dysfunction (MSD) were most severe in northwest China. Based on multivariable analysis, PV enlarged as the age (p<0.001), body mass index (BMI; p<0.001) and vegetable intake (p<0.001) increased. Age (p<0.001) and BMI (p<0.05) independently increased the IPSS. A higher level of education (p<0.001) and more frequent meat, fish and egg intake (p<0.05) decreased the IPSS. Age (p<0.001), BMI (p<0.001), low education level (p<0.05), vegetable intake (p=0.001), and milk and dairy product intake (p=0.001) decreased the IIEF-5 score. Conclusions In addition to factors including age, obesity and level of education, dietary habits and geographic difference might also play an important role in the variation of PV, LUTS and MSD for Chinese men with LUTS/BPH. PMID:27580828

Sociodemographic disparities in the utilization of proton therapy for prostate cancer at an urban academic center.

PubMed

Woodhouse, Kristina D; Hwang, Wei-Ting; Vapiwala, Neha; Jain, Akansha; Wang, Xingmei; Both, Stefan; Shah, Meera; Frazier, Marquise; Gabriel, Peter; Christodouleas, John P; Tochner, Zelig; Deville, Curtiland

2017-01-01

Despite increasing use, proton therapy (PT) remains a relatively limited resource. The purpose of this study was to assess clinical and demographic differences in PT use for prostate cancer compared to intensity modulated radiation therapy (IMRT) at a single institution. All patients with low- and intermediate-risk prostate cancer (N = 633) who underwent definitive radiation therapy between 2010 and 2015 were divided into PT (n = 508) and IMRT (n = 125) comparison groups and compared using χ 2 and independent sample t tests. Univariable and multivariable logistic regression analyses were conducted to assess the associations between PT use and demographic, clinical, and treatment characteristics. The PT and IMRT cohorts varied by age, race, poverty, distance, treatment year, and treating physician. Patients who underwent IMRT were more likely to be older (mean age, 66 vs. 68 years), black (51% vs. 75%), and living in poverty or close to the facility (mean distance between residence and facility, 90 vs. 21 miles; P < .05). Prostate-specific antigen, prostate volume, and International Index of Erectile Function were significantly higher in the IMRT cohort ( P < .05), but insurance type, risk group, tumor stage, Gleason score, and patient-reported urinary and bowel scores did not differ significantly ( P > .05). Patients who underwent PT were more likely to receive hypofractionated therapy and less likely to receive androgen deprivation therapy ( P < .01). On multivariable analysis, black (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.15-0.57) and other race (OR, 0.42; 95% CI, 0.20-0.90); distance (OR, 1.14; 95% CI, 1.06-1.24); treatment years 2011 (OR, 4.87; 95% CI, 2.23-10.6), 2012 (OR, 8.27; 95% CI, 3.43-19.9), and 2014 (OR, 4.44; 95% CI, 1.94-10.2) relative to 2010; and a single treating physician (OR, 0.38; 95% CI, 0.18-0.81) relative to the reference physician with the highest rate of use were associated with PT use, whereas clinical factors such as prostate-specific antigen, prostate volume, International Index of Erectile Function, and androgen deprivation therapy were not. Sociodemographic disparities exist in PT use for prostate cancer at an urban academic institution. Further investigation of potential barriers to access is warranted to ensure equitable distribution across all demographic groups.

Health-related quality of life after robot-assisted radical prostatectomy compared with laparoscopic radical prostatectomy.

PubMed

Koike, Hiroyuki; Kohjimoto, Yasuo; Iba, Akinori; Kikkawa, Kazuro; Yamashita, Shimpei; Iguchi, Takashi; Matsumura, Nagahide; Hara, Isao

2017-09-01

The objective of this study is to compare the quality of life (QOL) outcomes between laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). Between July 2007 and July 2013, 229 patients with localized prostate cancer underwent LRP while 105 patients with localized prostate cancer underwent RARP between December 2012 and August 2014. We evaluated their QOL using the 8-item Short-Form Health Survey (SF-8) and Expanded Prostate Cancer Index of Prostate (EPIC) questionnaires at preoperative and at postoperative 3, 6 and 12 months. In the LRP and RARP groups, over 80 and 90% of patients answered questionnaires at each follow-up time, respectively. At baseline QOL of EPIC and SF-8, there was no significant difference between LRP and RARP groups. At postoperative 3 months, Physical and Mental Components of SF-8 and Urinary Summary (U), all Urinary Subscales, Sexual Function and Bowel Function of EPIC showed significantly better scores in RARP group than in LRP group. At postoperative 6 and 12 months, there were no differences between LRP and RARP groups in terms of all QOL scores. RARP group showed better scores in SF-8 as well as urinary and sexual function of EPIC at postoperative-3 months. These differences disappeared at postoperative 6 and 12 months.

Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy.

PubMed

Perdonà, Sisto; Bruzzese, Dario; Ferro, Matteo; Autorino, Riccardo; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; Longo, Michele; Spinelli, Rosa; Di Lorenzo, Giuseppe; Oliva, Andrea; De Sio, Marco; Damiano, Rocco; Altieri, Vincenzo; Terracciano, Daniela

2013-02-15

Prostate health index (phi) and prostate cancer antigen 3 (PCA3) have been recently proposed as novel biomarkers for prostate cancer (PCa). We assessed the diagnostic performance of these biomarkers, alone or in combination, in men undergoing first prostate biopsy for suspicion of PCa. One hundred sixty male subjects were enrolled in this prospective observational study. PSA molecular forms, phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay), and other established biomarkers (tPSA, fPSA, and %fPSA) were assessed before patients underwent a 18-core first prostate biopsy. The discriminating ability between PCa-negative and PCa-positive biopsies of Beckman coulter phi and PCA3 score and other used biomarkers were determined. One hundred sixty patients met inclusion criteria. %p2PSA (p2PSA/fPSA × 100), phi and PCA3 were significantly higher in patients with PCa compared to PCa-negative group (median values: 1.92 vs. 1.55, 49.97 vs. 36.84, and 50 vs. 32, respectively, P ≤ 0.001). ROC curve analysis showed that %p2PSA, phi, and PCA3 are good indicator of malignancy (AUCs = 0.68, 0.71, and 0.66, respectively). A multivariable logistic regression model consisting of both the phi index and PCA3 score allowed to reach an overall diagnostic accuracy of 0.77. Decision curve analysis revealed that this "combined" marker achieved the highest net benefit over the examined range of the threshold probability. phi and PCA3 showed no significant difference in the ability to predict PCa diagnosis in men undergoing first prostate biopsy. However, diagnostic performance is significantly improved by combining phi and PCA3. Copyright © 2012 Wiley Periodicals, Inc.

A Longitudinal Study of Predictors of Sexual Dysfunction in Men on Active Surveillance for Prostate Cancer

PubMed Central

Pearce, Shane M; Wang, Chi-Hsiung E; Victorson, David E; Helfand, Brian T; Novakovic, Kristian R; Brendler, Charles B; Albaugh, Jeffrey A

2015-01-01

Aim The aim of this study was to examine the relationship between sexual dysfunction, repeat biopsies and other demographic and clinical factors in men on active surveillance (AS). Methods Patient-reported outcomes (PROs) measures were administered at enrollment and every 6 months to assess quality of life (QOL), psychosocial and urological health outcomes. Using mixed-effects models, we examined the impact of repeat biopsies, total number of cores taken, anxiety, age, and comorbidity on sexual function over the first 24 months of enrolling in AS. Main Outcome Measures PROs included the Expanded Prostate Cancer Index Composite-26 (EPIC-26) Sexual Function (SF) subscale, the American Urological Association-Symptom Index (AUA-SI), and the Memorial Anxiety Scale for Prostate Cancer (MAX-PC). Results At enrollment (n = 195), mean age was 66.5 ± 6.8 with a mean EPIC-26 SF score of 61.4 ± 30.4. EPIC-26 SF scores steadily decreased to 53.9 ± 30.7 at 24 months (P < 0.01). MAX-PC scores also progressively decreased over time (P = 0.03). Factors associated with lower EPIC-26 scores over time included age, unemployed status, diabetes, coronary artery disease, and hypertension (all P < 0.05). Higher prostate-specific antigen (PSA) was associated with a more rapid decline in EPIC-26 SF over time (P = 0.03). In multivariable analysis, age, diabetes, and PSA × time interaction remained significant predictors of diminished sexual function. Anxiety, number of biopsies, and total cores taken did not predict sexual dysfunction or change over time in our cohort. Conclusions Men on AS experienced a gradual decline in sexual function during the first 24 months of enrollment. Older age, PSA × time, and diabetes were all independent predictors of diminished sexual function over time. Anxiety, AUA-SI, the number of cores and the number of biopsies were not predictors of reduced sexual function in men in AS. PMID:26468379

Prevalence of prostatitis-like symptoms in a managed care population.

PubMed

Clemens, J Quentin; Meenan, Richard T; O'Keeffe-Rosetti, Maureen C; Gao, Sara Y; Brown, Sheila O; Calhoun, Elizabeth A

2006-08-01

We calculated the prevalence of symptoms typically associated with chronic prostatitis/chronic pelvic pain syndrome in men in a managed care population in the Pacific Northwest. A questionnaire mailing to 5,000 male enrollees 25 to 80 years old in the Kaiser Permanente Northwest (Portland, Oregon) health plan was performed. The questionnaires included screening questions about the presence, duration and severity of pelvic pain, and the National Institutes of Health Chronic Prostatitis Symptom Index. Chronic prostatitis/chronic pelvic pain syndrome symptoms were defined in 2 ways: 1) presence of any of the following for a duration of 3 or more months: pain in the perineum, testicles, tip of penis, pubic or bladder area, dysuria, ejaculatory pain; and 2) perineal and/or ejaculatory pain, and a National Institutes of Health Chronic Prostatitis Symptom Index total pain score of 4 or more. Prevalence estimates were age adjusted to the total Kaiser Permanente Northwest male population. A total of 1,550 questionnaires were returned. The prevalence of chronic prostatitis/chronic pelvic pain syndrome symptoms was 7.5% for definition 1 and 5.9% for definition 2. Mean National Institutes of Health Chronic Prostatitis Symptom Index scores were 17 for definitions 1 and 2. Of those with prostatitis-like symptoms, 30% met criteria for having both definitions present. The prevalence of prostatitis-like symptoms using either of the 2 diagnoses was 11.2%. This population based study indicates that approximately 1 in 9 men have prostatitis-like symptoms. Application of 2 different definitions for prostatitis-like symptoms identified unique groups of men, with limited overlap in the groups.

New and Emerging Technologies in Treatment of Lower Urinary Tract Symptoms From Benign Prostatic Hyperplasia.

PubMed

Gupta, Nikhil K; Gange, Steven N; McVary, Kevin T

2018-03-29

Lower urinary tract symptoms (LUTS) from bladder outlet obstruction from benign prostatic hyperplasia (BPH) occur in a large percentage of urologic patients. Treatment of this condition with medical and surgical therapy provides symptom relief but has serious adverse effects and causes sexual dysfunction. New technologies to treat BPH-associated LUTS aim to effectively treat urinary symptoms and minimize side effects and sexual dysfunction. To review the efficacy of new and emerging therapies for treatment of LUTS from BPH. A literature search was performed to identify therapies for LUTS from BPH with early outcomes data within the past 5 years. Improvement in International Prostate Symptom Score (IPSS) and effect on sexual functions such as erectile and ejaculatory functions as measured on the International Index of Erectile Function and the Male Sexual Health Questionnaire. Technologies introduced within the past 5 years include techniques using intraprostatic injectables, mechanical devices, and prostatic tissue ablation. Most technologies remain in the development phase and have only phase I and II studies available that show promising alleviation of urinary symptoms. Injectables have not typically surpassed placebo or sham effects, although special cohorts could be exceptions. Thus far, convective water vapor ablation therapy and prostatic urethral lift have shown the most promise, with short- and medium-term data available on phase III studies demonstrating significant improvement in IPSS with minimal impact on sexual function. Many of these technologies are limited in their potential treatment population by prostate size and conformation, whereas other therapies might be more generalizable. Many new technologies aim to treat LUTS from BPH and minimize sexual side effects. Most therapies remain experimental, although prostatic urethral lift and water vapor ablation therapy have been brought to market and show promise. Long-term durability of symptom relief remains to be demonstrated. Gupta NK, Gange SN, McVary KT. New and Emerging Technologies in Treatment of Lower Urinary Tract Symptoms From Benign Prostatic Hyperplasia. Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2018. Published by Elsevier Inc.

Relief of BPO or improvement in quality of life?

PubMed

Teillac, P

1998-01-01

Benign prostatic hyperplasia (BPH) can cause benign prostatic enlargement with subsequent benign prostatic obstruction (BPO) and lower urinary tract symptoms (LUTS). A reduction in the size of the prostate has long been considered one of the most important treatment goals. However, there is a poor correlation between prostate size and both LUTS and BPO, and between BPO and symptoms. Today, the urologist's primary objectives are to minimize symptoms, relieve BPO and decrease the morbidity associated with BPO. From the patient's point of view, rapid relief of LUTS and immediate improvement in associated quality of life (QOL) are the most important factors. Although there is a good correlation between relief of symptoms (as measured by the International Prostate Symptom Score [I-PSS], for example) and associated improvement in bothersomeness and QOL, particularly that associated with filling ('irritative') symptoms, it is still important to quantify LUTS-related bothersomeness and QOL. Various questionnaires have been developed to measure bothersomeness (e.g. Symptom Problem Index [SPI], Danish PSS [DAN-PSS], International Continence Society BPH Study Group [ICSmale] questionnaire) and QOL (e.g. I-PSS-QOL, BPH Impact Index [BII] and QOL9 BPH-specific questionnaire). In addition, the impact of treatment on sexual function should also be taken into account when judging the overall well being or QOL of the patient. A grading system to evaluate the global improvement in patients following treatment has been established. Patients are either graded as showing 'slight', 'moderate' or 'marked' improvement, with the reduction in I-PSS or BII scores required for each classification dependent on baseline symptom severity. Medical treatment strategies designed to alleviate the symptoms of BPH and consequently improve the patient's QOL are now becoming increasingly important.

SU-E-T-76: A Software System to Monitor VMAT Plan Complexity in a Large Radiotherapy Centre

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

Arumugam, S; Xing, A; Ingham Institute, Sydney, NSW

2015-06-15

Purpose: To develop a system that analyses and reports the complexity of Volumetric Modulated Arc Therapy (VMAT) plans to aid in the decision making for streamlining patient specific dosimetric quality assurance (QA) tests. Methods: A software system, Delcheck, was developed in-house to calculate VMAT plan and delivery complexity using the treatment delivery file. Delcheck has the functionality to calculate multiple plan complexity metrics including the Li-Xing Modulation Index (LI-MI), multiplicative combination of Leaf Travel and Modulation Complexity Score (LTMCSv), Monitor Units per prescribed dose (MU/D) and the delivery complexity index (MIt) that incorporates the modulation of dose rate, leaf speedmore » and gantry speed. Delcheck includes database functionality to store and compare plan metrics for a specified treatment site. The overall plan and delivery complexity is assessed based on the 95% conformance limit of the complexity metrics as Similar, More or Less complex. The functionality of the software was tested using 42 prostate conventional, 10 prostate SBRT and 15 prostate bed VMAT plans generated for an Elekta linear accelerator. Results: The mean(σ) of LI-MI for conventional, SBRT and prostate bed plans were 1690(486), 3215.4(1294) and 3258(982) respectively. The LTMCSv of the studied categories were 0.334(0.05), 0.325(0.07) and 0.3112(0.09). The MU/D of the studied categories were 2.4(0.4), 2.7(0.7) and 2.5(0.5). The MIt of the studied categories were 21.6(3.4), 18.2(3.0) and 35.9(6.6). The values of the complexity metrics show that LI-MI appeared to resolve the plan complexity better than LTMCSv and MU/D. The MIt value increased as the delivery complexity increased. Conclusion: The developed software was shown to be working as expected. In studied treatment categories Prostate bed plans are more complex in both plan and delivery and SBRT is more complex in plan and less complex in delivery as demonstrated by LI-MI and MIt. This project was funded through a Cancer Council NSW Project Grant (RG14-11)« less

Health related quality of life patterns in patients treated with interstitial prostate brachytherapy for localized prostate cancer--data from CaPSURE.

PubMed

Downs, Tracy M; Sadetsky, Natalia; Pasta, David J; Grossfeld, Gary D; Kane, Christopher J; Mehta, Shilpa S; Carroll, Peter R; Lubeck, Deborah P

2003-11-01

We measured the impact brachytherapy monotherapy (BMT) has on general and disease specific health related quality of life (HRQOL) compared to patients treated with radical prostatectomy (RP). We studied 419 men with newly diagnosed prostate cancer who enrolled in CaPSURE (Cancer of the Prostate Strategic Urological Research Endeavor) data base whose primary treatment was brachytherapy monotherapy (92) or radical prostatectomy (327). The validated RAND 36-Item Health Survey and the UCLA Prostate Cancer Index were used to measure HRQOL before treatment and at 6-month intervals during the first 2 years after treatment. Patients treated with BMT or RP did not differ greatly in general HRQOL after treatment. Both treatment groups showed early functional impairment in most general domains with scores returning to or approaching baseline in most domains 18 to 24 months after treatment. Patients treated with BMT had significantly higher urinary function scores at 0 to 6 months after treatment (84.5, SD 18.7) than patients treated with RP (63.3, SD 26.6). Urinary bother scores at 0 to 6 months after treatment were not significantly different between patients treated with BMT (67.7, SD 31.2) and those treated with RP (67.4, SD 29.1). Both treatment groups had decreases in sexual function that did not return to pretreatment levels. Overall BMT and RP are well tolerated procedures that cause mild changes in general HRQOL. Disease specific HRQOL patterns are different in patients treated with BMT or RP. Baseline and serial HRQOL measurements after treatment can provide valuable information regarding expected quality of life outcome after treatment for localized prostate cancer.

Sexual self-schema and depressive symptoms after prostate cancer.

PubMed

Hoyt, Michael A; Carpenter, Kristen M

2015-04-01

The years following prostate cancer treatment are characterized by changes in sexual functioning and risk for depressive symptoms. Sexual self-schema (SSS) is a cognitive generalization about sexual aspects of the self that are associated with sexual behavior, affect, and the processing of sexually relevant information. This study tested if men's SSS moderates the impact of sexual morbidity on depressive symptoms. Men (N = 66) treated for localized prostate cancer in the preceding 2 years were assessed at T1 and 4 months later (T2). Questionnaires included the Center for Epidemiologic Studies Depression Scale, Sexual Self-schema Scale for Men, Sexual Experience Scale, and Expanded Prostate Cancer Index Composite. Regressions controlled for age, sexual activity, and T1 depressive symptoms revealed no significant effect of SSS on depressive symptoms; however, better sexual functioning was related to fewer depressive symptoms (B = -0.25, p < 0.05). Results showed significant interactions between SSS and sexual outcomes. Among men with high SSS, poor sexual functioning was associated with increased depressive symptoms; loss of sexual function was particularly distressing. There was no significant effect of sexual functioning. Among men with high SSS, there was an inverse relationship between sexual engagement and depressive symptoms. Among men with lower SSS, greater frequency of sexual behavior was associated with increased depressive symptoms. SSS may be an important individual difference in determining the impact of sexual morbidity on psychological adjustment. Men high on SSS are more vulnerable to psychological consequences of lower sexual functioning and less engagement in sexual activities. Copyright © 2014 John Wiley & Sons, Ltd.

The relationship of TMPRSS2-ERG gene fusion between primary and metastatic prostate cancers.

PubMed

Guo, Charles C; Wang, Yan; Xiao, Li; Troncoso, Patricia; Czerniak, Bogdan A

2012-05-01

Recent studies have revealed the presence of TMPRSS2-ERG gene fusion in both primary and metastatic prostate cancers. However, the relationship between primary and corresponding metastatic prostate cancers with respect to the status of this gene fusion remains unclear. Using fluorescence in situ hybridization, we evaluated the rearrangement of the ERG gene in the radical prostatectomy specimens and corresponding lymph node metastases from 19 patients with prostate cancer. The mean age of the patients was 61 years, and the median Gleason score in the radical prostatectomy specimens was 7 (4 + 3). Prostate cancer was unifocal in 6 cases and multifocal in 13 cases, including 10 with 2 foci and 3 with 3 foci. In the primary prostate cancers, rearrangement of the ERG gene was observed in 13 cases and associated with deletion of the 5' ERG gene in 8 cases. In the metastases, the ERG rearrangement was present in 10 cases and associated with deletion of the 5' ERG gene in 6 cases. In unifocal prostate cancers, the status of the ERG rearrangement was concordant between the primary prostate cancer and metastasis in 5 of 6 cases. In multifocal prostate cancer, despite a significant interfocal discordance, the status of the ERG rearrangement was concordant between the index (largest) primary tumor focus and metastasis in all 13 cases. Our study demonstrates a close relationship of the TMPRSS2-ERG gene fusion status between primary and metastatic prostate cancer. The concordance of the ERG gene rearrangement status between the index primary tumor focus and metastasis suggests that metastasis most likely arises from the index tumor focus in multifocal prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of 120-W 2-μm continuous wave laser vapoenucleation of the prostate on sexual function.

PubMed

Wang, Yubin; Shao, Jinkai; Lu, Yongning; Lü, Yongan; Li, Xiaodong

2014-03-01

The objective of this work is to evaluate the impact of 120-W 2-μm continuous wave (cw) laser vapoenucleation of the prostate in patients with benign prostatic hyperplasia (BPH) on sexual function. One hundred twenty-two consecutive patients with BPH were retrospectively collected in this study and were classified into two groups for surgical treatment with 2-μm cw laser vapoenucleation or transurethral resection of the prostate (TURP). International Index of Erectile Function (IIEF) and general assessment questions were completed before and 12 months after treatment to determine the impact on sexual function. A total of 33 patients (52.4%) in group 1 and 31 (52.5%) in group 2 reported various degrees of erectile dysfunction before surgery. Interestingly, an increase in IIEF-EF score by 2 points was reported by 16 (25.4%) and 14 (23.7%) patients, respectively, and mean EF score did show a marginal but not significant increase postoperatively in both group. Differences about orgasmic intercourse satisfaction, sexual desire domain, and overall satisfaction scores in each group were not significant between preoperative and postoperative, but there was a significant decrease in the orgasmic function domain score at 12 months postoperation in both groups (p < 0.001). The prevalence of postoperative retrograde ejaculation was significantly higher than at baseline assessment in two groups. This study demonstrates that there is no difference between 2 μm laser vapoenucleation and TURP in terms of impact on sexual function. No significant erectile function improvement was observed after surgery, but these two techniques significantly lowered the IIEF orgasmic function domain and this was mainly caused by retrograde ejaculation.

Relationships among participant international prostate symptom score, benign prostatic hyperplasia impact index changes and global ratings of change in a trial of phytotherapy in men with lower urinary tract symptoms.

PubMed

Barry, Michael J; Cantor, Alan; Roehrborn, Claus G

2013-03-01

We related changes in American Urological Association symptom index scores with bother measures and global ratings of change in men with lower urinary tract symptoms who were enrolled in a saw palmetto trial. To be eligible for study men were 45 years old or older, and had a peak uroflow of 4 ml per second or greater and an American Urological Association symptom index score of 8 to 24. Participants self-administered the American Urological Association symptom index, International Prostate Symptom Score quality of life item, Benign Prostatic Hyperplasia Impact Index and 2 global change questions at baseline, and at 24, 48 and 72 weeks. In 357 participants global ratings of a little better were associated with a mean decrease in American Urological Association symptom index scores from 2.8 to 4.1 points across 3 time points. The analogous range for mean decreases in Benign Prostatic Hyperplasia Impact Index scores was 1.0 to 1.7 points and for the International Prostate Symptom Score quality of life item it was 0.5 to 0.8 points. At 72 weeks for the first global change question each change measure discriminated between participants who rated themselves at least a little better vs unchanged or worse 70% to 72% of the time. A multivariate model increased discrimination to 77%. For the second global change question each change measure correctly discriminated ratings of at least a little better vs unchanged or worse 69% to 74% of the time and a multivariate model increased discrimination to 79%. Changes in American Urological Association symptom index scores could discriminate between participants rating themselves at least a little better vs unchanged or worse. Our findings support the practice of powering studies to detect group mean differences in American Urological Association symptom index scores of at least 3 points. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Urinary Microbiome Differs Significantly Between Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls as Well as Between Patients With Different Clinical Phenotypes.

PubMed

Shoskes, Daniel A; Altemus, Jessica; Polackwich, Alan S; Tucky, Barbara; Wang, Hannah; Eng, Charis

2016-06-01

To study the urinary microbiome of patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) compared with controls. We identified 25 patients with CP/CPPS and 25 men who were either asymptomatic or only had urinary symptoms. Midstream urine was collected. Symptom severity was measured with the National Institutes of Health Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the urine pellet and bacterial-specific 16Sr-DNA-capture identified by MiSeq sequencing. Taxonomic and functional bioinformatic analyses used principal coordinate analysis (PCoA)/MacQIIME, LEfSe, and PiCRUSt algorithms. Patients and controls were similar ages (52.3 vs 57.0 years, P = .27). For patients, median duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0, and mean UPOINT domains was 3.6. Weighted 3D UniFrac PCoA revealed tighter clustering of controls distinct from the wider clustering of cases (P = .001; α-diversity P = .005). Seventeen clades were overrepresented in patients, for example, Clostridia, and 5 were underrepresented, eg, Bacilli, resulting in predicted perturbations in functional pathways. PiCRUSt inferred differentially regulated pathways between cases and controls that may be of relevance including sporulation, chemotaxis, and pyruvate metabolism. PCoA-derived microbiomic differences were noted for neurologic/systemic domains (P = .06), whereas LEfSe identified differences associated with each of the 6 clinical features. Urinary microbiomes from patients with CP/CPPS have significantly higher alpha(phylogenetic) diversity which cluster differently from controls, and higher counts of Clostridia compared with controls, resulting in predicted perturbations of functional pathways which could suggest metabolite-specific targeted treatment. Several measures of severity and clinical phenotype have significant microbiome differences. Copyright © 2016 Elsevier Inc. All rights reserved.

CD-163 correlated with symptoms (pain or discomfort) of prostatic inflammation.

PubMed

Yamamichi, Fukashi; Shigemura, Katsumi; Arakawa, Soichi; Tanaka, Kazushi; Fujisawa, Masato

2015-01-01

The purpose of this study is to identify significant immune-system related for symptom of patients with prostatic inflammation in order to investigate the etiology of prostatic inflammation which may relate to potentially chronic prostatitis (CP). We investigated the expression of immune system-related biomarkers such as Interleukin (IL) -6 (humoral immunity), CD-3 (T-lymphocyte), and CD-163 (macrophage) in prostate biopsy (PBx) specimens from patients with prostatic inflammation (without cancer) which had been neither clinically diagnosed benign prostatic hyperplasia nor chronic prostatitis. We examined the correlation between these markers' expressions and the symptom scores using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS)/quality of life (QOL) which are the index for lower urinary tract symptoms (LUTS). Our results showed CD-163 (macrophage) reflected pain or discomfort on NIH-CPSI scores (P=0.0389 and r=0.3307) in the patients with prostatic inflammation; however, the control patients had no significant correlation between symptom scores and those immune-related markers' expression. These results suggest that pain or discomfort related to macrophages in the relationship between immune-system and the symptom of prostatic inflammation. In conclusion, CD-163, related to immune-system (macrophage), correlated with symptoms (pain or discomfort) of prostatic inflammation and might represent a significant immune-system related biomarker for pain or LUTS score in potentially CP.

Risk assessment models to evaluate the necessity of prostate biopsies in North Chinese patients with 4-50 ng/mL PSA.

PubMed

Zhao, Jing; Liu, Shuai; Gao, Dexuan; Ding, Sentai; Niu, Zhihong; Zhang, Hui; Huang, Zhilong; Qiu, Juhui; Li, Qing; Li, Ning; Xie, Fang; Cui, Jilei; Lu, Jiaju

2017-02-07

Prostate-specific antigen (PSA) is widely used for prostate cancer screening, but low specificity results in high false positive rates of prostate biopsies. To develop new risk assessment models to overcome the diagnostic limitation of PSA and reduce unnecessary prostate biopsies in North Chinese patients with 4-50 ng/mL PSA. A total of 702 patients in seven hospitals with 4-10 and 10-50 ng/mL PSA, respectively, who had undergone transrectal ultrasound-guided prostate biopsies, were assessed. Analysis-modeling stage for several clinical indexes related to prostate cancer and renal function was carried out. Multiple logistic regression analyses were used to develop new risk assessment models of prostate cancer for both PSA level ranges 4-10 and 10-50 ng/mL. External validation stage of the new models was performed to assess the necessity of biopsy. The new models for both PSA ranges performed significantly better than PSA for detecting prostate cancers. Both models showed higher areas under the curves (0.937 and 0.873, respectively) compared with PSA alone (0.624 and 0.595), at pre-determined cut-off values of 0.1067 and 0.6183, respectively. Patients above the cut-off values were recommended for immediate biopsy, while the others were actively observed. External validation of the models showed significantly increased detection rates for prostate cancer (4-10 ng/mL group, 39.29% vs 17.79%, p=0.006; 10-50 ng/mL group, 71.83% vs 50.0%, p=0.015). We developed risk assessment models for North Chinese patients with 4-50 ng/mL PSA to reduce unnecessary prostate biopsies and increase the detection rate of prostate cancer.

Study of quality of life in patients with benign prostatic hyperplasia under treatment with silodosin.

PubMed

Castro-Díaz, D; Callejo, D; Cortés, X; Pérez, M

2014-01-01

To assess the impact of urinary symptoms associated with benign prostatic hyperplasia and its treatment with silodosin, on quality of life (QoL) and sexual function, depending on age, severity of symptoms, time on treatment and prostate size. A cross-sectional, observational study was conducted in 305 urology practices all around Spain. Socio-demographic and clinical data were collected and patients filled the following questionnaires: EQ-5D, Sexual Function Index (SFI) and International Prostate Symptom Score (IPSS). Multiple regression models were used to determine factors independently associated with patients' QoL. A total of 1,019 patients were enrolled, mean (SD) for: age 62.7 (5.7), EQ-5D 89.9 (13.9), sexual drive-SFI 3.71 (1.67), erection-SFI 6.11 (3.08), ejaculation-SFI 4.50 (2.06) problems-SFI 6.85 (3.37) and overall satisfaction-SFI 2.00 (0.99). The EQ-5D and SFI score were statistically lower with: older age, severe LUTS and greater prostate size (P<.01), but no differences were found related to time on treatment with silodosin. The EQ-5D score was positively associated with sexual satisfaction and desire size of SFI and the EQ-5D VAS score, and negatively with disability, semi-urban residence and comorbidities in the multiple regression analyses. Severe LUTS and older age are associated to a greater deterioration in sexual function and quality of life. However time on treatment with silodosin does not produce deterioration in the quality of life. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

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.

Metabolic syndrome and prostate abnormalities in male subjects of infertile couples

PubMed Central

Lotti, Francesco; Corona, Giovanni; Vignozzi, Linda; Rossi, Matteo; Maseroli, Elisa; Cipriani, Sarah; Gacci, Mauro; Forti, Gianni; Maggi, Mario

2014-01-01

No previous study has evaluated systematically the relationship between metabolic syndrome (MetS) and prostate-related symptoms and signs in young infertile men. We studied 171 (36.5 ± 8.3-years-old) males of infertile couples. MetS was defined based on the National Cholesterol Education Program Third Adult Treatment Panel. All men underwent hormonal (including total testosterone (TT) and insulin), seminal (including interleukin-8 (IL-8), seminal plasma IL-8 (sIL-8)), scrotal and transrectal ultrasound evaluations. Because we have previously assessed correlations between MetS and scrotal parameters in a larger cohort of infertile men, here, we focused on transrectal features. Prostate-related symptoms were assessed using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (IPSS). Twenty-two subjects fulfilled MetS criteria. In an age-adjusted logistic ordinal model, insulin levels increased as a function of MetS components (Wald = 29.5, P < 0.0001) and showed an inverse correlation with TT (adjusted r = -0.359, P< 0.0001). No association between MetS and NIH-CPSI or IPSS scores was observed. In an age-, TT-, insulin-adjusted logistic ordinal model, an increase in number of MetS components correlated negatively with normal sperm morphology (Wald = 5.59, P< 0.02) and positively with sIL-8 levels (Wald = 4.32, P < 0.05), which is a marker of prostate inflammation, with prostate total and transitional zone volume assessed using ultrasound (Wald = 17.6 and 12.5, both P < 0.0001), with arterial peak systolic velocity (Wald = 9.57, P = 0.002), with texture nonhomogeneity (hazard ratio (HR) = 1.87 (1.05–3.33), P < 0.05), with calcification size (Wald = 3.11, P < 0.05), but not with parameters of seminal vesicle size or function. In conclusion, in males of infertile couples, MetS is positively associated with prostate enlargement, biochemical (sIL8) and ultrasound-derived signs of prostate inflammation but not with prostate-related symptoms, which suggests that MetS is a trigger for a subclinical, early-onset form of benign prostatic hyperplasia. PMID:24435050

Relationship among diet habit and lower urinary tract symptoms and sexual function in outpatient-based males with LUTS/BPH: a multiregional and cross-sectional study in China.

PubMed

Chen, Yuke; Yu, Wei; Zhou, Liqun; Wu, Shiliang; Yang, Yang; Wang, Jianye; Tian, Ye; He, Dalin; Xu, Yong; Huang, Jian; Wang, Xiaofeng; Gao, Xin; Li, Hanzhong; Ma, Lulin; Zhang, Ning; Zhao, Shengtian; Jin, Xunbo

2016-08-31

This study assessed the effect of diet habits on lower urinary tract symptoms (LUTS) and sexual function in Chinese men with LUTS/benign prostatic hypertrophy (LUTS/BPH). Multicentre study conducted between July 2013 and December 2013 in 11 hospitals in 3 geographic regions in China. Overall, participants with LUTS/BPH accounted for 61.4% (2584/4208) of the respondents, whose data were processed in the following statistical analysis. LUTS and sexual function were assessed based on the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function 5 (IIEF-5) score. Prostate volume (PV) was determined by ultrasound. A total of 4208 participants met the inclusion criteria. The average age of the whole participants was 65.8±7.7 years. Overall, participants with LUTS/BPH accounted for 61.4% (2584/4208) of the respondents, whose data were processed in the following statistical analysis. Generally, prostate enlargement was greatest in south China. LUTS and male sexual dysfunction (MSD) were most severe in northwest China. Based on multivariable analysis, PV enlarged as the age (p<0.001), body mass index (BMI; p<0.001) and vegetable intake (p<0.001) increased. Age (p<0.001) and BMI (p<0.05) independently increased the IPSS. A higher level of education (p<0.001) and more frequent meat, fish and egg intake (p<0.05) decreased the IPSS. Age (p<0.001), BMI (p<0.001), low education level (p<0.05), vegetable intake (p=0.001), and milk and dairy product intake (p=0.001) decreased the IIEF-5 score. In addition to factors including age, obesity and level of education, dietary habits and geographic difference might also play an important role in the variation of PV, LUTS and MSD for Chinese men with LUTS/BPH. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Erectile Function Durability Following Permanent Prostate Brachytherapy

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

Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.or; Galbreath, Robert W.

2009-11-01

Purpose: To evaluate long-term changes in erectile function following prostate brachytherapy. Methods and Materials: This study included 226 patients with prostate cancer and preimplant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) who underwent brachytherapy in two prospective randomized trials between February 2001 and January 2003. Median follow-up was 6.4 years. Pre- and postbrachytherapy potency was defined as IIEF-6 >= 13 without pharmacologic or mechanical support. The relationship among clinical, treatment, and dosimetric parameters and erectile function was examined. Results: The 7-year actuarial rate of potency preservation was 55.6% with median postimplant IIEF of 22 in potentmore » patients. Potent patients were statistically younger (p = 0.014), had a higher preimplant IIEF (p < 0.001), were less likely to be diabetic (p = 0.002), and were more likely to report nocturnal erections (p = 0.008). Potency preservation in men with baseline IIEF scores of 29-30, 24-28, 18-23, and 13-17 were 75.5% vs. 73.6%, 51.7% vs. 44.8%, 48.0% vs. 40.0%, and 23.5% vs. 23.5% in 2004 vs. 2008. In multivariate Cox regression analysis, preimplant IIEF, hypertension, diabetes, prostate size, and brachytherapy dose to proximal penis strongly predicted for potency preservation. Impact of proximal penile dose was most pronounced for men with IIEF of 18-23 and aged 60-69. A significant minority of men who developed postimplant impotence ultimately regained erectile function. Conclusion: Potency preservation and median IIEF scores following brachytherapy are durable. Thoughtful dose sparing of proximal penile structures and early penile rehabilitation may further improve these results.« less

Prostate Cancer Predictive Simulation Modelling, Assessing the Risk Technique (PCP-SMART): Introduction and Initial Clinical Efficacy Evaluation Data Presentation of a Simple Novel Mathematical Simulation Modelling Method, Devised to Predict the Outcome of Prostate Biopsy on an Individual Basis.

PubMed

Spyropoulos, Evangelos; Kotsiris, Dimitrios; Spyropoulos, Katherine; Panagopoulos, Aggelos; Galanakis, Ioannis; Mavrikos, Stamatios

2017-02-01

We developed a mathematical "prostate cancer (PCa) conditions simulating" predictive model (PCP-SMART), from which we derived a novel PCa predictor (prostate cancer risk determinator [PCRD] index) and a PCa risk equation. We used these to estimate the probability of finding PCa on prostate biopsy, on an individual basis. A total of 371 men who had undergone transrectal ultrasound-guided prostate biopsy were enrolled in the present study. Given that PCa risk relates to the total prostate-specific antigen (tPSA) level, age, prostate volume, free PSA (fPSA), fPSA/tPSA ratio, and PSA density and that tPSA ≥ 50 ng/mL has a 98.5% positive predictive value for a PCa diagnosis, we hypothesized that correlating 2 variables composed of 3 ratios (1, tPSA/age; 2, tPSA/prostate volume; and 3, fPSA/tPSA; 1 variable including the patient's tPSA and the other, a tPSA value of 50 ng/mL) could operate as a PCa conditions imitating/simulating model. Linear regression analysis was used to derive the coefficient of determination (R 2 ), termed the PCRD index. To estimate the PCRD index's predictive validity, we used the χ 2 test, multiple logistic regression analysis with PCa risk equation formation, calculation of test performance characteristics, and area under the receiver operating characteristic curve analysis using SPSS, version 22 (P < .05). The biopsy findings were positive for PCa in 167 patients (45.1%) and negative in 164 (44.2%). The PCRD index was positively signed in 89.82% positive PCa cases and negative in 91.46% negative PCa cases (χ 2 test; P < .001; relative risk, 8.98). The sensitivity was 89.8%, specificity was 91.5%, positive predictive value was 91.5%, negative predictive value was 89.8%, positive likelihood ratio was 10.5, negative likelihood ratio was 0.11, and accuracy was 90.6%. Multiple logistic regression revealed the PCRD index as an independent PCa predictor, and the formulated risk equation was 91% accurate in predicting the probability of finding PCa. On the receiver operating characteristic analysis, the PCRD index (area under the curve, 0.926) significantly (P < .001) outperformed other, established PCa predictors. The PCRD index effectively predicted the prostate biopsy outcome, correctly identifying 9 of 10 men who were eventually diagnosed with PCa and correctly ruling out PCa for 9 of 10 men who did not have PCa. Its predictive power significantly outperformed established PCa predictors, and the formulated risk equation accurately calculated the probability of finding cancer on biopsy, on an individual patient basis. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Bollito, Enrico; Manfredi, Matteo; Scarpa, Roberto Mario; Sottile, Antonino; Randone, Donato Franco; Porpiglia, Francesco

2014-12-01

To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE). in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals). The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97). The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

PubMed

Loeb, Stacy; Shin, Sanghyuk S; Broyles, Dennis L; Wei, John T; Sanda, Martin; Klee, George; Partin, Alan W; Sokoll, Lori; Chan, Daniel W; Bangma, Chris H; van Schaik, Ron H N; Slawin, Kevin M; Marks, Leonard S; Catalona, William J

2017-07-01

To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study. The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram. Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis. Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Adenomatous-Dominant Benign Prostatic Hyperplasia (AdBPH) as a Predictor for Clinical Success Following Prostate Artery Embolization: An Age-Matched Case–Control Study

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

Little, M. W., E-mail: m.little@doctors.org.uk; Boardman, P.; Macdonald, A. C.

PurposeTo investigate the clinical impact of performing prostate artery embolization (PAE) on patients with adenomatous-dominant benign prostatic hyperplasia (AdBPH).Materials and MethodsTwelve patients from the ongoing proSTatic aRtery EmbolizAtion for the treatMent of benign prostatic hyperplasia (STREAM) trial were identified as having AdBPH; defined as two or more adenomas within the central gland of ≥1 cm diameter on multi-parametric MRI (MP-MRI). These patients were age-matched with patients from the STREAM cohort, without AdBPH. Patients were followed up with repeat MP-MRI at 3 months and 1 year. International prostate symptom score (IPSS), international index for erectile function (IIEF), and quality of life assessment from themore » IPSS and EQ-5D-5S questionnaires were recorded pre-PAE and at 6 weeks, 3 months, and 1 year.ResultsThe mean age of patients was 68 (61–76). All patients had PAE as a day-case procedure. The technical success in the cohort was 23/24 (96%). There was a significant reduction in prostate volume following embolization with a median reduction of 34% (30–55) in the AdBPH group, compared to a mean volume reduction of 22% (9–44) in the non-AdBPH group (p = 0.04). There was a significant reduction in IPSS in the AdBPH group following PAE when compared with the control group [AdBPH median IPSS 8 (3–15) vs. non-AdBPH median IPSS 13 (8–18), p = 0.01]. IPSS QOL scores significantly improved in the AdBPH group (p = 0.007). There was no deterioration in sexual function in either group post-PAE.ConclusionsThis is the first time that AdBPH has been identified as being a predictor of clinical success following PAE.« less

ERG Expression Levels in Prostate Tumors Reflect Functional Status of the Androgen Receptor (AR) as a Consequence of Fusion of ERG with AR Regulated Gene Promoters

DTIC Science & Technology

2010-01-01

mathematically defined in the following formulas. ARGI = Σ (I PMEPA1 + IPSA +INKX3.1+IODC1+IAMD1) ARFI=CI=ARGI+IERG Detection of TMPRSS2-ERG Fusion Junctions...ERG expression into the Androgen Receptor Function Index, ARFI. ARGI = Σ (I PMEPA1 + IPSA +INKX3.1+IODC1+IAMD1) ARFI=CI=ARGI+IERG In the high ERG

Causes of death among cancer patients.

PubMed

Zaorsky, N G; Churilla, T M; Egleston, B L; Fisher, S G; Ridge, J A; Horwitz, E M; Meyer, J E

2017-02-01

The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. The greatest relative decrease in index-cancer death (generally from > 60% to < 30%) was among those with cancers of the testis, kidney, bladder, endometrium, breast, cervix, prostate, ovary, anus, colorectum, melanoma, and lymphoma. Index-cancer deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among <50-year olds (e.g. SMR >1,000 for lymphomas, P < 0.001). The highest SMRs were typically within the first year after cancer diagnosis (SMRs 10-10,000, P < 0.001). Prostate cancer patients had increasing SMRs from Alzheimer's disease, as did testicular patients from suicide. The risk of death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis. © 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.

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.

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

PubMed

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

2017-08-15

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

The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study.

PubMed

Gnanapragasam, V J; Bratt, O; Muir, K; Lee, L S; Huang, H H; Stattin, P; Lophatananon, A

2018-02-28

The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer. We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality. The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n = 20,586), C-index 0.77 vs. 074; radiotherapy (n = 11,872), C-index 0.73 vs. 0.69; and conservative management (n = 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001). This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

Carr-Purcell-Meiboom-Gill imaging of prostate cancer: quantitative T2 values for cancer discrimination.

PubMed

Roebuck, Joseph R; Haker, Steven J; Mitsouras, Dimitris; Rybicki, Frank J; Tempany, Clare M; Mulkern, Robert V

2009-05-01

Quantitative, apparent T(2) values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T(2) values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy-proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 x 1.1 x 4 mm(3) was obtained in 10.7 min, resulting in data sets suitable for generating high-quality images with variable T(2)-weighting and for evaluating quantitative T(2) values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T(1)- and T(2)-weighted signal intensities and available histopathology reports, yielded significantly (P<.0001) longer apparent T(2) values in suspected healthy tissue (193+/-49 ms) vs. suspected cancer (100+/-26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T(2)-weighted fast spin echo (FSE) imaging alone, including quantitative T(2) values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time FSE sequences.

Carr-Purcell-Meiboom-Gill (CPMG) Imaging of Prostate Cancer: Quantitative T2 Values for Cancer Discrimination

PubMed Central

Roebuck, Joseph R.; Haker, Steven J.; Mitsouras, Dimitris; Rybicki, Frank J.; Tempany, Clare M.; Mulkern, Robert V.

2009-01-01

Quantitative, apparent T2 values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T2 values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 × 1.1 × 4 mm3 was obtained in 10.7 minutes, resulting in data sets suitable for generating high quality images with variable T2-weighting and for evaluating quantitative T2 values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T1- and T2-weighted signal intensities and available histopathology reports, yielded significantly (p < 0.0001) longer apparent T2 values in suspected healthy tissue (193 ± 49 ms) vs. suspected cancer (100 ± 26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T2-weighted fast spin echo imaging alone, including quantitative T2 values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time fast spin echo (FSE) sequences. PMID:18823731

The effectiveness of dried cranberries ( Vaccinium macrocarpon) in men with lower urinary tract symptoms.

PubMed

Vidlar, Ales; Vostalova, Jitka; Ulrichova, Jitka; Student, Vladimir; Stejskal, David; Reichenbach, Richard; Vrbkova, Jana; Ruzicka, Filip; Simanek, Vilim

2010-10-01

Lower urinary tract symptoms (LUTS) are a common condition in older men. The objective of the present study was to evaluate the efficacy and tolerability of cranberry (Vaccinium macrocarpon) powder in men at risk of prostate disease with LUTS, elevated prostate-specific antigen (PSA), negative prostate biopsy and clinically confirmed chronic non-bacterial prostatitis. Forty-two participants received either 1500 mg of the dried powdered cranberries per d for 6 months (cranberry group; n 21) or no cranberry treatment (control group; n 21). Physical examination, International Prostate Symptom Score, quality of life (QoL), five-item version of the International Index of Erectile Function (IIEF-5), basic clinical chemistry parameters, haematology, Se, testosterone, PSA (free and total), C-reactive protein (CRP), antioxidant status, transrectal ultrasound prostate volume, urinary flow rate, ultrasound-estimated post-void residual urine volume at baseline, and at 3 and 6 months, and urine ex vivo anti-adherence activity were determined in all subjects. In contrast to the control group, patients in the cranberry group had statistically significant improvement in International Prostate Symptom Score, QoL, urination parameters including voiding parameters (rate of urine flow, average flow, total volume and post-void residual urine volume), and lower total PSA level on day 180 of the study. There was no influence on blood testosterone or serum CRP levels. There was no statistically significant improvement in the control group. The results of the present trial are the first firm evidence that cranberries may ameliorate LUTS, independent of benign prostatic hyperplasia or C-reactive protein level.

Phase 1 and 2 studies demonstrate the safety and efficacy of intraprostatic injection of PRX302 for the targeted treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

PubMed

Denmeade, Samuel R; Egerdie, Blair; Steinhoff, Gary; Merchant, Rosemina; Abi-Habib, Ralph; Pommerville, Peter

2011-05-01

PRX302 is a prostate specific antigen (PSA)-activated pore-forming protein toxin under development as a targeted approach for improving lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) without affecting sexual function. To evaluate the safety and efficacy of PRX302 in men with moderate to severe BPH. Eligible subjects were refractory, intolerant, or unwilling to undergo medical therapies for BPH and had International Prostate Symptom Score (IPSS) ≥12, a quality of life (QoL) score ≥3, and prostate volumes between 30 and 80 g. Fifteen patients were enrolled in phase 1 studies, and 18 patients entered phase 2 studies. Subjects received intraprostatic injection of PRX302 into the right and left transition zone via a transperineal approach in an office-based setting. Phase 1 subjects received increasing concentrations of PRX302 at a fixed volume; phase 2 subjects received increasing volumes per deposit at a fixed concentration. IPSS, QoL, prostate volume, maximum flow rate (Q(max)), International Index of Erectile Function, serum PSA levels, pharmacokinetics, and adverse events were recorded at 30, 60, 90, 180, 270, and 360 d after treatment with PRX302. Sixty percent of men in the phase 1 study and 64% of men in the phase 2 study treated with PRX302 had ≥30% improvement compared to baseline in IPSS out to day 360. Patients also experienced improvement in QoL and reduction in prostate volume out to day 360. Patients receiving ≥1 ml of PRX302 per deposit had the best response overall. PRX302 had no deleterious effect on erectile function. Adverse events were mild to moderate and transient in nature. The major study limitation was the small sample size. The promising safety profile and evidence of efficacy in the majority of treated subjects in these phase 1 and 2 studies supports further development of PRX302 as a minimally invasive, targeted treatment for BPH. Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Molecular Markers of Estrogen Metabolism and Progression From High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) to Prostate Cancer

DTIC Science & Technology

2006-02-01

recruitment. Adipocytes (i.e., fat cells) regulate insulin sensitivity , steroid hormone metabolism, inflammatory responses , and release leptin and other...diabetes and insulin sensitivity on prostate cancer risk. • Less tangible, but no less significant, this study initiated a prostate cancer...proliferator-activated receptr alpha (PPARalpha) gene is associated with lower body mass index in patients with non- insulin -dependent diabetes mellitus

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

PubMed

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

2018-04-01

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

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.

Comparison of intravesical prostatic protrusion, prostate volume and serum prostatic-specific antigen in the evaluation of bladder outlet obstruction.

PubMed

Lim, Kok Bin; Ho, Henry; Foo, Keong Tatt; Wong, Michael Yuet Chen; Fook-Chong, Stephanie

2006-12-01

The aims of this study were to define the relationship between intravesical prostatic protrusion (IPP), prostate-specific antigen (PSA) and prostate volume (PV) and to determine which one of them is the best predictor of bladder outlet obstruction (BOO) due to benign prostatic enlargement. A prospective study of 114 male patients older than 50 years examined between November 2001 and 2002 was performed. They were evaluated with digital rectal examination, International Prostate Symptoms Score, PSA, uroflowmetry, postvoid residual urine measurement, IPP and PV using transabdominal ultrasound scan. Statistical analysis included scatter plot with Spearman's correlation coefficients and nominal logistic regression Prostate volume, IPP and PSA showed parallel correlation. Although all three indices had good correlation with BOO index, IPP was the best. The Spearman rho correlation coefficients were 0.314, 0.408 and 0.507 for PV, PSA and IPP, respectively. Using receiver-operator characteristic curves, the areas under the curve for PV, PSA and IPP were 0.637, 0.703 and 0.772, respectively. The positive predictive values of PV, PSA and IPP were 65%, 68% and 72%, respectively. Using a nominal regression model, IPP remained the most significant independent index to determine BOO. All three non-invasive indices correlate with one another. The study showed that IPP is a better predictor for BOO than PSA or PV.

Effects of 8-Year Treatment of Long-Acting Testosterone Undecanoate on Metabolic Parameters, Urinary Symptoms, Bone Mineral Density, and Sexual Function in Men With Late-Onset Hypogonadism.

PubMed

Permpongkosol, Sompol; Khupulsup, Kalayanee; Leelaphiwat, Supatra; Pavavattananusorn, Sarawan; Thongpradit, Supranee; Petchthong, Thanom

2016-08-01

The long-term effects of long-acting testosterone undecanoate (TU) and androgen receptor CAG repeat lengths in Thai men with late-onset hypogonadism (LOH) have not been reported. To analyze the 8-year follow-up effects of intramuscular TU therapy on metabolic parameters, urinary symptoms, bone mineral density, and sexual function and investigate CAG repeat lengths in men with LOH. We reviewed the medical records of 428 men with LOH who had been treated with TU and 5 patients were diagnosed with prostate cancer during TU therapy. There were 120 patients (mean age = 65.6 ± 8.9 years) who had 5 to 8 years of continuous TU supplementation and sufficiently completed records for analysis. Genomic DNA was extracted from peripheral blood and the CAG repeat region was amplified by polymerase chain reaction. Fragment analysis, sequencing, electropherography, and chromatography were performed. The main outcome measure was dynamic parameter changes during testosterone supplementation. TU did not improve all obesity parameters. A statistically significant decrease was found in waist circumference, percentage of body fat, glycated hemoglobin, cholesterol, low-density lipoprotein, and International Prostate Symptom Score (P < .05). TU did not produce differences in body mass index, high-density lipoprotein, triglyceride, or the Aging Male Symptoms score from baseline. However, a statistically significant increase was found in the level of testosterone, prostate-specific antigen, hematocrit, International Index of Erectile Function score, and vertebral and femoral bone mineral density (P < .05). No major adverse cardiovascular events or prostate cancer occurred during this study. The CAG repeat length was 14 to 28 and the median CAG length was 22. There was no association between CAG repeat length and any of the anthropometric measurements. Long-term TU treatment in men with LOH for up to 8 years appears to be safe, tolerable, and effective in correcting obesity parameters. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Putative Prostate Cancer Risk SNP in an Androgen Receptor‐Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites

PubMed Central

Bu, Huajie; Narisu, Narisu; Schlick, Bettina; Rainer, Johannes; Manke, Thomas; Schäfer, Georg; Pasqualini, Lorenza; Chines, Peter; Schweiger, Michal R.; Fuchsberger, Christian

2015-01-01

ABSTRACT Genome‐wide association studies have identified genomic loci, whose single‐nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin‐immunoprecipitation‐coupled sequencing and microarray expression profiling in TMPRSS2‐ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor‐binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T>G in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR‐binding motif, which is enriched in the neighborhood of canonical androgen‐responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor‐suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH. PMID:26411452

Long-term side-effects of intermittent androgen suppression therapy in prostate cancer: results of a phase II study.

PubMed

Malone, Shawn; Perry, Gad; Segal, Roanne; Dahrouge, Simone; Crook, Juanita

2005-09-01

To assess the feasibility and tolerability of intermittent androgen suppression therapy (IAS) in prostate cancer. Patients with recurrent or metastic prostate cancer received cyclical periods of treatment with leuprolide acetate and nilutamide for 8 months, and rest periods. Cycles were repeated at progression until the treatment failed to achieve normal prostate-specific antigen (PSA) levels. Patients were followed with PSA level, testosterone level, haemoglobin level, weight and bone mineral density evaluations. The median time to treatment failure, recovery from anaemia, or normalization of testosterone level was estimated by the Kaplan-Meier method. In all, 95 patients received 245 cycles; the median duration of rest periods was 8 months and median time to treatment failure 47 months. Testosterone recovery during rest periods was documented in 117 (61%) of cycles. Anaemia was mild and reported in 33%, 44% and 67% of cycles 1, 2 and 3, respectively. Sexual function recovered during the rest periods in 47% of cycles. There was no significant overall change in body mass index at the end of the treatment period. Osteoporosis was documented in at least one site evaluated in 41 patients (37%). IAS has the potential to reduce side-effects, including recovery of haemoglobin level, return of sexual function and absence of weight gain at the end of the study period.

Changes in lower urinary tract symptoms and quality of life after salvage radiotherapy for biochemical recurrence of prostate cancer.

PubMed

Miyake, Makito; Tanaka, Nobumichi; Asakawa, Isao; Tatsumi, Yoshihiro; Nakai, Yasushi; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Hasegawa, Masatoshi; Konishi, Noboru; Fujimoto, Kiyohide

2015-06-01

The aim of this study was to evaluate chronologic changes in lower urinary tract symptoms (LUTS), health-related (HR) quality of life (QOL), and disease-specific QOL during the first 12 months after salvage radiotherapy (SRT) for biochemical recurrence of prostate cancer in patients who underwent radical prostatectomy. In 81 patients who received SRT (70 Gy/35fr/7 weeks), International Prostate Symptom Score (IPSS), 36-Item Short Form scores, and UCLA-Prostate Cancer Index (UCLA-PCI) were recorded before, during, and immediately after SRT, and 1-12 months after the completion of SRT. The total IPSS and storage symptom-related sum were significantly increased following initiation of SRT, and returned to the baseline 6 months after SRT. For three of eight domains of HRQOL, and the physical component summary score showed transient deterioration in the period between completion of SRT and 1 month following SRT. The UCLA-PCI for urinary function/bother and bowel function/bother was affected until 1-6 months after SRT. This is the first report to concurrently evaluate detailed chronologic changes in LUTS and QOL in patients who received SRT. Knowledge of changes in LUTS and QOL outcomes associated with SRT may influence treatment recommendations and enable patients to make better-informed decisions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chlamydia trachomatis versus common uropathogens as a cause of chronic bacterial prostatitis: Is there any difference? Results of a prospective parallel-cohort study

PubMed Central

Pisano, Francesca; Nesi, Gabriella; Magri, Vittorio; Verze, Paolo; Perletti, Gianpaolo; Gontero, Paolo; Mirone, Vincenzo; Bartoletti, Riccardo

2017-01-01

Purpose The role of Chlamydia trachomatis (CT) infection in chronic bacterial prostatitis (CBP) is well known. What is unclear is whether there are any differences in the course or clinical outcome of the disease when the cause is CT or other uropathogens. Materials and Methods A series of 311 patients affected by CBP due to CT (cohort A) was compared with a group of 524 patients affected by CBP caused by common uropathogen bacteria (cohort B). All participants completed the following questionnaires: National Institutes of Health Chronic Prostatitis Symptom Index, International Prostate Symptom Score, International Index of Erectile Function-15 erectile function domain (IIEF-15-EFD), Premature Ejaculation Diagnostic Tool (PEDT), and the Short Form 36 (SF-36) Health Survey. All patients were followed with clinical and microbiological evaluations. Results After a mean follow-up time of 42.3 months, the number of symptomatic episodes was significantly higher in patients in cohort A than in cohort B (4.1±1.1 vs. 2.8±0.8, p<0.001), and the mean time to first symptomatic recurrence was shorter in cohort A than in cohort B (3.3±2.3 months vs. 5.7±1.9 months, p<0.001). Moreover, scores on the SF-36 tool were significantly lower in cohort A (96.5±1.0 vs. 99.7±1.9, p<0.001) at the first symptomatic recurrence. Cohort A also showed significantly lower scores on the IIEF-15-EFD and PEDT questionnaires at the end of the follow-up period (26.8±2.9 vs. 27.3±3.3, p=0.02 and 11.5±2.3 vs. 4.5±2.8, p<0.001, respectively). Conclusions Patients affected by CBP due to CT infection have a higher number of symptomatic recurrences with a more severe impact on quality of life. PMID:29124247

Relationship of chronic histologic prostatic inflammation in biopsy specimens with serum isoform [-2]proPSA (p2PSA), %p2PSA, and prostate health index in men with a total prostate-specific antigen of 4-10 ng/ml and normal digital rectal examination.

PubMed

Lazzeri, Massimo; Abrate, Alberto; Lughezzani, Giovanni; Gadda, Giulio Maria; Freschi, Massimo; Mistretta, Francesco; Lista, Giuliana; Fossati, Nicola; Larcher, Alessandro; Kinzikeeva, Ella; Buffi, Nicolòmaria; Dell'Acqua, Vincenzo; Bini, Vittorio; Montorsi, Francesco; Guazzoni, Giorgio

2014-03-01

To investigate the relationship between serum [-2]proPSA (p2PSA) and derivatives with chronic histologic prostatic inflammation (CHPI) in men undergoing prostate biopsy for suspected prostate cancer (PCa). This nested case-control study resulted from an observational prospective trial for the definition of sensibility, specificity, and accuracy of p2PSA, %p2PSA, and Beckman Coulter Prostate Health Index (PHI), in men undergoing prostate biopsy, with a total prostate-specific antigen (PSA) of 4-10 ng/mL and normal digital rectal examination. CHPI was the outcome of interest and defined as the presence of moderate to large infiltration of lymphomononuclear cells with interstitial and/or glandular disruption in absence of PCa. p2PSA, %p2PSA, and PHI were considered the index tests and compared with the established biomarker reference standard tests: tPSA, fPSA, %fPSA. Of 267 patients subjected to prostate biopsy, 73 (27.3%) patients were diagnosed with CHPI. Comparing CHPI with PCa patients, %p2PSA and PHI were found to be significantly lower, whereas fPSA and %fPSA were significantly higher. %p2PSA and PHI were the most accurate predictors of CHPI at biopsy, significantly outperforming tPSA, fPSA, and %fPSA. On the contrary, no significant differences were found in PSA, p2PSA, and derivatives between CHPI and benign prostatic hyperplasia (BPH) patients. Our findings showed that p2PSA, %p2PSA, and PHI values might discriminate PCa from CHPI or BPH, but not CHPI from BPH, in men with a total PSA 4-10 ng/mL and normal digital rectal examination. p2PSA isoform and its derivatives could be useful in clinical decision making to avoid unnecessary biopsies in patients with CHPI and elevated tPSA value. Copyright © 2014 Elsevier Inc. All rights reserved.

Predicting prostate biopsy outcome: prostate health index (phi) and prostate cancer antigen 3 (PCA3) are useful biomarkers.

PubMed

Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Marino, Ada; Sorrentino, Alessandra; Di Carlo, Angelina; Autorino, Riccardo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Altieri, Vincenzo; Mariano, Angela; Macchia, Vincenzo; Terracciano, Daniela

2012-08-16

Indication for prostate biopsy is presently mainly based on prostate-specific antigen (PSA) serum levels and digital-rectal examination (DRE). In view of the unsatisfactory accuracy of these two diagnostic exams, research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as phi and PCA3. The purpose of this prospective study was to assess the diagnostic accuracy of phi and PCA3 for prostate cancer using biopsy as gold standard. Phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay) and other established biomarkers (tPSA, fPSA and %fPSA) were assessed before a 18-core prostate biopsy in a group of 251 subjects at their first biopsy. Values of %p2PSA and phi were significantly higher in patients with PCa compared with PCa-negative group (p<0.001) and also compared with high grade prostatic intraepithelial neoplasia (HGPIN) (p<0.001). PCA3 score values were significantly higher in PCa compared with PCa-negative subjects (p<0.001) and in HGPIN vs PCa-negative patients (p<0.001). ROC curve analysis showed that %p2PSA, phi and PCA3 are predictive of malignancy. In conclusion, %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men undergoing their first prostate biopsy. PCA3 score is more useful in discriminating between HGPIN and non-cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

Body mass index as a classifier to predict biochemical recurrence after radical prostatectomy in patients with lower prostate-specific antigen levels

PubMed Central

Goto, Keisuke; Nagamatsu, Hirotaka; Teishima, Jun; Kohada, Yuki; Fujii, Shinsuke; Kurimura, Yoshimasa; Mita, Koji; Shigeta, Masanobu; Maruyama, Satoshi; Inoue, Yoji; Nakahara, Mitsuru; Matsubara, Akio

2017-01-01

Prostate cancer, one of the most common malignant tumors among men, is closely associated with obesity and, thus far, several studies have suggested the association between obesity and aggressive pathological characteristics in the United States. However, the effect of obesity on prostate cancer mortality is controversial, and it remains unclear whether obesity contributes to the aggressiveness of prostate cancer in Asian patients. The aim of the present study was to investigate the association between body mass index (BMI) and the clinicopathological characteristics of prostate cancer in 2,003 Japanese patients who underwent radical prostatectomy. There was a significant association between higher BMI and higher Gleason score (GS). The multivariate analysis also revealed that BMI was an independent indicator for GS ≥8 at surgery. Moreover, among patients with lower prostate-specific antigen levels, biochemical recurrence-free survival was significantly worse in those with higher BMI. These results suggest that BMI may be a classifier for predicting adverse pathological findings and biochemical recurrence after radical prostatectomy in Japanese patients. PMID:28515927

Gonorrhea infection increases the risk of prostate cancer in Asian population: a nationwide population-based cohort study.

PubMed

Wang, Y-C; Chung, C-H; Chen, J-H; Chiang, M-H; Ti-Yin; Tsao, C-H; Lin, F-H; Chien, W-C; Shang, S-T; Chang, F-Y

2017-05-01

This nationwide population-based retrospective cohort study evaluated the risk of developing prostate cancer among patients with gonorrhea. We identified cases of newly diagnosed gonorrhea in men between 2000 and 2010 from the Taiwan National Health Insurance Research Database. Each patient with gonorrhea was matched to four controls, based on age and index year. All subjects were followed up from the index date to December 31, 2010. The Cox proportional hazards regression model was used to assess the risk of prostate cancer. A total of 355 men were included in the study group, and 1,420 age-matched subjects without gonorrhea were included in the control group. After adjusting for age, comorbidities, urbanization level, hospital level, and monthly income, gonorrhea was significantly associated with an increased risk of prostate cancer (adjusted hazard ratio = 5.66, 95% confidence interval = 1.36-23.52). Men aged 45-70 years and those with lower monthly income were more strongly associated with prostate cancer in the study group than the control group. The higher risk for developing prostate cancer were also found in those without syphilis, without genital warts, without diabetes mellitus, without chronic obstructive pulmonary disease, without benign prostatic hypertrophy, without chronic prostatitis, and without alcoholism. The Kaplan-Meier analysis showed the risk of prostate cancer was significantly higher in the study group than in the control group. Gonorrhea may be involved in the development of prostate cancer. More intensive screening and prevention interventions for prostate cancer should be recommended in men with gonorrhea.

Sexual Function After Stereotactic Body Radiotherapy for Prostate Cancer: Results of a Prospective Clinical Trial

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

Wiegner, Ellen A.; King, Christopher R., E-mail: crking@stanford.ed

Purpose: To study the sexual quality of life for prostate cancer patients after stereotactic body radiotherapy (SBRT). Methods and Materials: Using the Expanded Prostate Cancer Index Composite (EPIC)-validated quality-of-life questionnaire, the sexual function of 32 consecutive patients who received prostate SBRT in a prospective Phase II clinical trial were analyzed at baseline, and at median times of 4, 12, 20, and 50 months after treatment. SBRT consisted of 36.25 Gy in five fractions of 7.25 Gy using the Cyberknife. No androgen deprivation therapy was given. The use of erectile dysfunction (ED) medications was monitored. A comprehensive literature review for radiotherapy-alonemore » modalities based on patient self-reported questionnaires served as historical comparison. Results: Median age at treatment was 67.5 years, and median follow-up was 35.5 months (minimum 12 months). The mean EPIC sexual domain summary score, sexual function score, and sexual bother score decreased by 45%, 49%, and 25% respectively at 50 months follow-up. These differences reached clinical relevance by 20 months after treatment. Baseline ED rate was 38% and increased to 71% after treatment (p = 0.024). Use of ED medications was 3% at baseline and progressed to 25%. For patients aged <70 years at follow-up, 60% maintained satisfactory erectile function after treatment compared with only 12% aged {>=}70 years (p = 0.008). Penile bulb dose was not associated with ED. Conclusions: The rates of ED after treatment appear comparable to those reported for other modalities of radiotherapy. Given the modest size of this study and the uncertainties in the physiology of radiotherapy-related ED, these results merit further investigations.« less

Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases.

PubMed

Wassberg, Cecilia; Lubberink, Mark; Sörensen, Jens; Johansson, Silvia

2017-12-01

18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point. Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV 50% ). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP. A total of 47 index lesions and a range of 2-122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV 50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

Health-related quality of life using SF-8 and EPIC questionnaires after treatment with radical retropubic prostatectomy and permanent prostate brachytherapy.

PubMed

Hashine, Katsuyoshi; Kusuhara, Yoshito; Miura, Noriyoshi; Shirato, Akitomi; Sumiyoshi, Yoshiteru; Kataoka, Masaaki

2009-08-01

The health-related quality of life (HRQOL) after treatment of prostate cancer is examined using a new HRQOL tool. HRQOL, based on the expanded prostate cancer index composite (EPIC) and SF-8 questionnaires, was prospectively compared after either a radical retropubic prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) at a single institute. Between October 2005 and June 2007, 96 patients were treated by an RRP and 88 patients were treated by a PPB. A HRQOL survey was completed at baseline, and at 1, 3, 6 and 12 months after treatment, prospectively. The general HRQOL in the RRP and PPB groups was not different after 3 months. However, at baseline and 1 month after treatment, the mental component summary was significantly better in the PPB group than in the RRP group. Moreover, the disease-specific HRQOL was worse regarding urinary and sexual functions in the RRP group. Urinary irritative/obstructive was worse in the PPB group, but urinary incontinence was worse in the RRP group and had not recovered to baseline after 12 months. The bowel function and bother were worse in the PPB group than in the RRP group after 3 months. In the RRP group, the patients with nerve sparing demonstrated the same scores in sexual function as the PPB group. This prospective study revealed the differences in the HRQOL after an RRP and PPB. Disease-specific HRQOL is clarified by using EPIC survey. These results will be helpful for making treatment decisions.

Health-related Quality of Life using SF-8 and EPIC Questionnaires after Treatment with Radical Retropubic Prostatectomy and Permanent Prostate Brachytherapy

PubMed Central

Hashine, Katsuyoshi; Kusuhara, Yoshito; Miura, Noriyoshi; Shirato, Akitomi; Sumiyoshi, Yoshiteru; Kataoka, Masaaki

2009-01-01

Objective The health-related quality of life (HRQOL) after treatment of prostate cancer is examined using a new HRQOL tool. HRQOL, based on the expanded prostate cancer index composite (EPIC) and SF-8 questionnaires, was prospectively compared after either a radical retropubic prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) at a single institute. Methods Between October 2005 and June 2007, 96 patients were treated by an RRP and 88 patients were treated by a PPB. A HRQOL survey was completed at baseline, and at 1, 3, 6 and 12 months after treatment, prospectively. Results The general HRQOL in the RRP and PPB groups was not different after 3 months. However, at baseline and 1 month after treatment, the mental component summary was significantly better in the PPB group than in the RRP group. Moreover, the disease-specific HRQOL was worse regarding urinary and sexual functions in the RRP group. Urinary irritative/obstructive was worse in the PPB group, but urinary incontinence was worse in the RRP group and had not recovered to baseline after 12 months. The bowel function and bother were worse in the PPB group than in the RRP group after 3 months. In the RRP group, the patients with nerve sparing demonstrated the same scores in sexual function as the PPB group. Conclusions This prospective study revealed the differences in the HRQOL after an RRP and PPB. Disease-specific HRQOL is clarified by using EPIC survey. These results will be helpful for making treatment decisions. PMID:19477898

Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo

NASA Astrophysics Data System (ADS)

Huland, David M.; Jain, Manu; Ouzounov, Dimitre G.; Robinson, Brian D.; Harya, Diana S.; Shevchuk, Maria M.; Singhal, Paras; Xu, Chris; Tewari, Ashutosh K.

2014-11-01

Multiphoton microscopy can instantly visualize cellular details in unstained tissues. Multiphoton probes with clinical potential have been developed. This study evaluates the suitability of multiphoton gradient index (GRIN) endoscopy as a diagnostic tool for prostatic tissue. A portable and compact multiphoton endoscope based on a 1-mm diameter, 8-cm length GRIN lens system probe was used. Fresh ex vivo samples were obtained from 14 radical prostatectomy patients and benign and malignant areas were imaged and correlated with subsequent H&E sections. Multiphoton GRIN endoscopy images of unfixed and unprocessed prostate tissue at a subcellular resolution are presented. We note several differences and identifying features of benign versus low-grade versus high-grade tumors and are able to identify periprostatic tissues such as adipocytes, periprostatic nerves, and blood vessels. Multiphoton GRIN endoscopy can be used to identify both benign and malignant lesions in ex vivo human prostate tissue and may be a valuable diagnostic tool for real-time visualization of suspicious areas of the prostate.

What couples say about their recovery of sexual intimacy after prostatectomy: toward the development of a conceptual model of couples' sexual recovery after surgery for prostate cancer.

PubMed

Wittmann, Daniela; Carolan, Marsha; Given, Barbara; Skolarus, Ted A; Crossley, Heather; An, Lawrence; Palapattu, Ganesh; Clark, Patricia; Montie, James E

2015-02-01

Interventions designed to help couples recover sexual intimacy after prostatectomy have not been guided by a comprehensive conceptual model. We examined a proposed biopsychosocial conceptual model of couples' sexual recovery that included functional, psychological, and relational aspects of sexuality, surgery-related sexual losses, and grief and mourning as recovery process. We interviewed 20 couples preoperatively and 3 months postoperatively. between 2010 and 2012. Interviews were analyzed with Analytic Induction qualitative methodology, using NVivo software. Paired t-tests described functional assessment data. Study findings led to a revised conceptual model. Couples' experiences were assessed through semi-structured interviews; male participants' sexual function was assessed with the Expanded Prostate Cancer Index Composite and female participants' sexual function with the Female Sexual Function Index. Preoperatively, 30% of men had erectile dysfunction (ED) and 84% of partners were postmenopausal. All valued sexual recovery, but worried about cancer spread and surgery side effects. Faith in themselves and their surgeons led 90% of couples to overestimate erectile recovery. Postoperatively, most men had ED and lost confidence. Couples' sexual activity decreased. Couples reported feeling loss and grief: cancer diagnosis was the first loss, followed by surgery-related sexual losses. Couples' engagement in intentional sex, patients' acceptance of erectile aids, and partners' interest in sex aided the recovery of couples' sexual intimacy recovery. Unselfconscious sex, not returning to erectile function baseline, was seen as the end point. Survey findings documented participants' sexual function losses, confirming qualitative findings. Couples' sexual recovery requires addressing sexual function, feelings about losses, and relationship simultaneously. Perioperative education should emphasize the roles of nerve damage in ED and grief and mourning in sexual recovery. © 2014 International Society for Sexual Medicine.

What couples say about their recovery of sexual intimacy after prostatectomy: toward the development of a conceptual model of couples’ sexual recovery after surgery for prostate cancer

PubMed Central

Wittmann, Daniela; Carolan, Marsha; Given, Barbara; Skolarus, Ted A.; Crossley, Heather; An, Lawrence; Palapattu, Ganesh; Clark, Patricia; Montie, James E.

2015-01-01

Introduction Interventions designed to help couples recover sexual intimacy after prostatectomy have not been guided by a comprehensive conceptual model. Aim We examined a proposed biopsychosocial conceptual model of couples’ sexual recovery that included functional, psychological and relational aspects of sexuality, surgery-related sexual losses, and grief and mourning as recovery process. Methods We interviewed twenty couples pre-operatively and 3-months post-operatively. between 2010 and 2012. Interviews were analyzed with Analytic Induction qualitative methodology, using NVivo software. Paired t-tests described functional assessment data. Study findings led to a revised conceptual model. Main Outcome Measures Couples’ experiences were assessed through semi-structured interviews; male participants’ sexual function was assessed with the Expanded Prostate Cancer Index Composite and female participants’ sexual function with the Female Sexual Function Index. Results Pre-operatively, 30% of men had erectile dysfunction (ED), 84% of partners were post-menopausal. All valued sexual recovery, but worried about cancer spread and surgery side-effects. Faith in themselves and their surgeons led 90% of couples to overestimate erectile recovery. Post-operatively, most men had ED and lost confidence. Couples’ sexual activity decreased. Couples reported feeling loss and grief: cancer diagnosis was the first loss, followed by surgery-related sexual losses. Couples’ engagement in intentional sex, patients’ acceptance of erectile aids and partners’ interest in sex aided the recovery of couples’ sexual intimacy recovery. Unselfconscious sex, not return to erectile function baseline, was seen as the endpoint. Survey findings documented participants’ sexual function losses, confirming qualitative findings. Conclusions Couples’ sexual recovery requires addressing sexual function, feelings about losses and relationship simultaneously. Peri-operative education should emphasize the roles of nerve damage in ED and grief and mourning in sexual recovery. PMID:25358901

[Extracorporeal shock wave therapy in chronic prostatitis].

PubMed

Kul'chavenya, E V; Shevchenko, S Yu; Brizhatyuk, E V

2016-04-01

Chronic prostatitis is a prevalent urologic disease, but treatment outcomes are not always satisfactory. As a rule, chronic prostatitis results in chronic pelvic pain syndrome, significantly reducing the patient's quality of life. Open pilot prospective non-comparative study was conducted to test the effectiveness of extracorporeal shock wave therapy (ESWT) using Aries (Dornier) machine in patients with chronic prostatitis (CP) of IIIb category. A total of 27 patients underwent ESWL as monotherapy, 2 times a week for a course of 6 sessions. Exposure settings: 5-6 energy level (by sensation), the frequency of 5 Hz, 2000 pulses per session; each patient received a total energy up to 12000 mJ. per procedure. Treatment results were evaluated using NIH-CPSI (National Institute of Health Chronic Prostatitis Symptom Index) upon completing the 3 week course of 6 treatments and at 1 month after ESWT. Immediately after the ESWT course positive trend was not significant: pain index decreased from 9.1 to 7.9, urinary symptom score remained almost unchanged (4.2 at baseline, 4.1 after treatment), quality of life index also showed a slight improvement, dropping from 7.2 points to 6.0. Total NIH-CPSI score decreased from 20.5 to 18.0. One month post-treatment pain significantly decreased to 3.2 points, the urinary symptom score fell to 2.7 points, the average quality of life score was 3.9 points. ESWT, performed on Aries (Dornier) machine, is highly effective as monotherapy in patients with category IIIb chronic prostatitis.

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2–10 ng/ml

PubMed Central

Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D’Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K.; Terracciano, Daniela

2013-01-01

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2–10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2–10 ng/ml at initial biopsy, outperforming currently used %fPSA. PMID:23861782

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) significantly improve prostate cancer detection at initial biopsy in a total PSA range of 2-10 ng/ml.

PubMed

Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D'Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K; Terracciano, Daniela

2013-01-01

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA.

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.

Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis.

PubMed

Filella, Xavier; Giménez, Nuria

2013-04-01

The usefulness of %[-2] proPSA and Prostate Health Index (phi) in the detection of prostate cancer are currently unknown. It has been suggested that these tests can distinguish prostate cancer from benign prostatic diseases better than PSA or %fPSA. We performed a systematic review and meta-analysis of the available scientific evidence to evaluate the clinical usefulness of %[-2] proPSA and phi. Relevant published papers were identified by searching computerized bibliographic systems. Data on sensitivity and specificity were extracted from 12 studies: 10 studies about %[-2] proPSA (3928 patients in total, including 1762 with confirmed prostate cancer) and eight studies about phi (2919 patients in total, including 1515 with confirmed prostate cancer). The sensitivity for the detection of prostate cancer was 90% for %[-2] proPSA and phi, while the pooled specificity was 32.5% (95% CI 30.6-34.5) and 31.6% (95% CI 29.2-34.0) for %[-2] proPSA and phi, respectively. The measurement of %[-2] proPSA improves the accuracy of prostate cancer detection in comparison with PSA or %fPSA, particularly in the group of patients with PSA between 2 μg/L and 10 μg/L. Similar results were obtained measuring phi. Using these tests, it is possible to reduce the number of unnecessary biopsies, maintaining a high cancer detection rate. Published results also showed that %[-2] proPSA and phi are related to the aggressiveness of the tumor.

Effects of home-based diet and exercise on functional outcomes among older, overweight long-term cancer survivors: RENEW: a randomized controlled trial.

PubMed

Morey, Miriam C; Snyder, Denise C; Sloane, Richard; Cohen, Harvey Jay; Peterson, Bercedis; Hartman, Terryl J; Miller, Paige; Mitchell, Diane C; Demark-Wahnefried, Wendy

2009-05-13

Five-year survival rates for early stage colorectal, breast, and prostate cancer currently exceed 90% and are increasing. Cancer survivors are at greater risk for second malignancies, other comorbidities, and accelerated functional decline. Lifestyle interventions may provide benefit, but it is unknown whether long-term cancer survivors can modify their lifestyle behaviors sufficiently to improve functional status. To determine whether a telephone counseling and mailed print material-based diet and exercise intervention is effective in reorienting functional decline in older, overweight cancer survivors. Randomized controlled trial of 641 overweight (body mass index > or = 25 and < 40), long-term (> or = 5 years) survivors (aged 65-91 years) of colorectal, breast, and prostate cancer, who were randomly assigned to an intervention group (n = 319) or delayed intervention (control) group (n = 322) in Canada, the United Kingdom, and 21 US states. Individuals were recruited for the Reach out to Enhance Wellness (RENEW) trial from July 1, 2005, through May 17, 2007. A 12-month, home-based tailored program of telephone counseling and mailed materials promoting exercise, improved diet quality, and modest weight loss. The control group was wait-listed for 12 months. Change in self-reported physical function on the Short-Form 36 physical function subscale (score range, 0-100; a high score indicates better functioning) from baseline to 12 months was the primary end point. Secondary outcomes included changes in function on the basic and advanced lower extremity function subscales of the Late Life Function and Disability Index (score range, 0-100), physical activity, body mass index, and overall health-related quality of life. The mean baseline Short-Form 36 physical function score was 75.7. At the 12-month follow-up, the mean function scores declined less rapidly in the intervention group (-2.15; 95% confidence interval [CI], -0.36 to -3.93) compared with the control group (-4.84; 95% CI, -3.04 to -6.63) (P = .03). The mean baseline basic lower extremity function score was 78.2. The mean changes in basic lower extremity function were 0.34 (95% CI, -0.84 to 1.52) in the intervention group compared with -1.89 (95% CI, -0.70 to -3.09) in the control group (P = .005). Physical activity, dietary behaviors, and overall quality of life increased significantly in the intervention group compared with the control group, and weight loss also was greater (2.06 kg [95% CI, 1.69 to 2.43 kg] vs 0.92 kg [95% CI, 0.51 to 1.33 kg], respectively; P < .001). Among older, long-term survivors of colorectal, breast, and prostate cancer, a diet and exercise intervention reduced the rate of self-reported functional decline compared with no intervention. clinicaltrials.gov Identifier: NCT00303875.

Biases in Recommendations for and Acceptance of Prostate Biopsy Significantly Affect Assessment of Prostate Cancer Risk Factors: Results From Two Large Randomized Clinical Trials

PubMed Central

Goodman, Phyllis J.; Till, Cathee; Schenk, Jeannette M.; Lucia, M. Scott; Thompson, Ian M.

2016-01-01

Purpose To identify factors related to who undergoes a prostate biopsy in a screened population and to estimate the impact of biopsy verification on risk factor–prostate cancer associations. Patients and Methods Men who were screened regularly from the placebo arms of two large prostate cancer prevention trials (Prostate Cancer Prevention Trial [PCPT] and Selenium and Vitamin E Cancer Prevention Trial [SELECT]) were examined to define incident prostate cancer cohorts. Because PCPT had an end-of-study biopsy, prostate cancer cases were categorized by a preceding prostate-specific antigen/digital rectal examination prompt (yes/no) and noncases by biopsy-proven negative status (yes v no). We estimated the association of risk factors (age, ethnicity, family history, body mass index, medication use) with prostate cancer and quantified differences in risk associations across cohorts. Results Men 60 to 69 years of age, those with benign prostatic hyperplasia, and those with a family history of prostate cancer were more likely, and those with a higher body mass index (≥ 25), diabetes, or a smoking history were less likely, to undergo biopsy, adjusting for age and longitudinal prostate-specific antigen and digital rectal examination. Medication use, education, and marital status also influenced who underwent biopsy. Some risk factor estimates for prostate cancer varied substantially across cohorts. Black (v other ethnicities) had odds ratios (ORs) that varied from 1.20 for SELECT (community screening standards, epidemiologic-like cohort) to 1.83 for PCPT (end-of-study biopsy supplemented with imputed end points). Statin use in SELECT provided an OR of 0.65 and statin use in in PCPT provided an OR of 0.99, a relative difference of 34%. Conclusion Among screened men enrolled in prostate cancer prevention trials, differences in risk factor estimates for prostate cancer likely underestimate the magnitude of bias found in other cohorts with varying screening and biopsy recommendations and acceptance. Risk factors for prostate cancer derived from epidemiologic studies not only may be erroneous but may lead to misdirected research efforts. PMID:27998216

The Prostate Health Index in predicting initial prostate biopsy outcomes in Asian men with prostate-specific antigen levels of 4-10 ng/mL.

PubMed

Ng, C F; Chiu, Peter K F; Lam, N Y; Lam, H C; Lee, Kim W M; Hou, Simon S M

2014-04-01

To investigate the role of the Prostate Health Index (phi) in prostate cancer (PCa) detection in patients with a prostate-specific antigen (PSA) level of 4-10 ng/mL receiving their first prostatic biopsy in an Asian population. This was a retrospective study of archived serum samples from patients enlisted in our tissue bank. Patients over 50 years old, with PSA level of 4-10 ng/mL, a negative digital rectal examination, and received their first prostatic biopsy between April 2008 and April 2013, were recruited. The serum sample collected before biopsy was retrieved for the measurement of various PSA derivatives and the phi value was calculated for each patient. The performance of these parameters in predicting the prostatic biopsy results was assessed. Two hundred and thirty consecutive patients, with 21 (9.13 %) diagnosed with PCa, were recruited for this study. Statistically significant differences between PCa patients and non-PCa patients were found for total PSA, PSA density, [-2]proPSA (p2PSA), free-to-total PSA ratio (%fPSA), p2PSA-to-free PSA ratio (%p2PSA), and phi. The areas under the curve of the receiver operating characteristic curve for total PSA, PSA density, %fPSA, %p2PSA, and phi were 0.547, 0.634, 0.654, 0.768, and 0.781, respectively. The phi was the best predictor of the prostatic biopsies results. At a sensitivity of 90 %, the use of the phi could have avoided unnecessary biopsies in 104 (45.2 %) patients. Use of the phi could improve the accuracy of PCa detection in patients with an elevated PSA level and thus avoid unnecessary prostatic biopsies.

Effect of Pulsed Electromagnetic Field Therapy on Prostate Volume and Vascularity in the Treatment of Benign Prostatic Hyperplasia: A Pilot Study in a Canine Model

PubMed Central

Leoci, Raffaella; Aiudi, Giulio; Silvestre, Fabio; Lissner, Elaine; Lacalandra, Giovanni Michele

2014-01-01

BACKGROUND Benign prostatic hyperplasia (BPH) is a result of urogenital aging. Recent studies suggest that an age-related impairment of the blood supply to the lower urinary tract plays a role in the development of BPH and thus may be a contributing factor in the pathogenesis of BPH. The canine prostate is a model for understanding abnormal growth of the human prostate gland. We studied the efficacy of pulsed electromagnetic field therapy (PEMF) in dogs to modify prostate blood flow and evaluated its effect on BPH. METHODS PEMF (5 min, twice a day for 3 weeks) was performed on 20 dogs affected by BPH. Prostatic volume, Doppler assessment by ultrasonography, libido, semen quality, testosterone levels, and seminal plasma volume, composition and pH were evaluated before and after treatment. RESULTS The 3 weeks of PEMF produced a significant reduction in prostatic volume (average 57%) without any interference with semen quality, testosterone levels or libido. Doppler parameters showed a reduction of peripheral resistances and a progressive reduction throughout the trial of the systolic peak velocity, end-diastolic velocity, mean velocity, mean, and peak gradient of the blood flow in the dorsal branch of the prostatic artery. The pulsatility index and the resistance index did not vary significantly over time. CONCLUSIONS The efficacy of PEMF on BPH in dogs, with no side effects, suggests the suitability of this treatment in humans and supports the hypothesis that impairment of blood supply to the lower urinary tract may be a causative factor in the development of BPH. Prostate 74:1132–1141, 2014. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:24913937

Is it necessary to cure prostate cancer when it is possible? (Understanding the role of prostate inflammation resolution to prostate cancer evolution)

PubMed Central

Wheeler, Ronald E

2007-01-01

Objective: Definitive therapy with radical prostatectomy, cryotherapy, or radiation therapy generally follows the initial diagnosis of prostate cancer, particularly when men have at least 10 additional years of life expectancy. There is growing concern regarding the optimal conservative treatment for patients who decline or do not otherwise qualify for such definitive curative treatment. For those patients who choose a watchful waiting approach, it would be beneficial to know what specific dietary and nutritional methods could potentially slow the progression of their disease. In this prospective study, it was our goal to analyze the efficacy and safety of treating prostate cancer conservatively using the principles of a Mediterranean diet in association with a specific prostate nutritional supplement. Method: Twenty-three men aged 43–74 (median age: 64) with biopsy proven, organ-confined prostate cancer who had already declined immediate hormonal therapy and attempts at a curative cancer treatment agreed to participate in a Chronic Disease Management (CDM) protocol highlighted by diet with a specific prostate nutritional supplement. The diet recommended was a modified Mediterranean diet while a patented nutritional prostatitis formula (Peenuts®) was the supplement common to all patients. Prostate specific antigen (PSA), a recognized marker of prostate disease and prostate cancer activity, was the primary indicator to validate exacerbation or suppression of disease. All men were followed with serial PSA testing, a digital rectal exam, an International Prostate Symptom Score index (IPSS-Index) and an expressed prostatic secretion (EPS) examination. The primary Gleason sum/score represented in this study was 6 (n = 11), while Gleason sum patterns 5, 5/6, 6/7, and 7 were also evaluated. Referencing the Partin Tables, organ confinement was predicted to be 66%. Results: Eighty-seven percent of men (n = 20) noted a 58% reduction (range of improvement: 13%–90%) in PSA over an average of 38.5 months (range: 13–84 months). The remaining 13% of men included three men who experienced a mild elevation in PSA of 0.3 ng/ml, 0.7 ng/ml, and 0.9 ng/ml over 14 months, 42 months, and 34 months, respectively. Fifteen men had completed an initial and secondary IPSS-Index while 14 men had undergone an initial and secondary EPS. The mean percentage reduction in IPSS-Index was 61% (range: 20%–100% with a median of 55%), while men evaluated with EPS examinations noted a mean percentage reduction in white blood cells of 77.5% (range: 33%–99% with a median of 82%). These results were evaluated using the t-test, Wilcoxon Analysis and the Null Hypothesis and found to be statistically significant. Conclusion: Clearly there is a need to develop effective alternative conservative therapies for the increasing numbers of prostate cancer patients who will not tolerate definitive curative measures or simply choose a conservative approach. Although this prospective study had no control arm, was of limited duration and included only 23 participants, it did appear to show significant benefit to the majority of prostate cancer patients treated with selective nutritional and dietary therapy alone. Such treatments may provide a safe and effective long-term treatment alternative for some patients. Further study is encouraged. PMID:18044088

[Efficacy and safety of Longjintonglin Capsule for the treatment of type III prostatitis].

PubMed

Shang, Xue-Jun; Geng, Qiang; Duan, Jian-Min; Zheng, De-Quan; Xie, Lei; Guo, Jun

2014-12-01

To study the therapeutic effect and safety of Longjintonglin Capsule in the treatment of type III prostatitis (chronic prostatitis/chronic pelvic pain syndrome, CP/CPPS). We selected 240 patients with type III prostatitis according to the diagnostic standards of the American National Institute of Health (NIH) and treated them with Longjintonglin Capsule orally 3 capsules once tid for 12 weeks. Based on the NIH chronic prostatitis symptom index (NIH-CPSI), traditional Chinese medicine (TCM) syndrome score, and leukocyte count in the expressed prostatic secretion (EPS), we evaluated the results of treatment. Totally 238 patients completed the treatment, including 108 IIIA and 120 III B prostatitis cases. Before and after 4, 8, and 12 weeks of treatment, the total NIH-CPSI scores were 23.12 ± 6.99, 18.22 ± 6.39, 14.12 ± 5.88, and 12.36 ± 6.04 (P < 0.01) in the IIIA prostatitis patients and 22.01 ± 6.28, 17.56 ± 5.89, 13.67 ± 5.18, and 11.45 ± 5.22 in the III prostatitis patients (P < 0.01), the TCM syndrome scores were 52.12 ± 13.08, 48.13 ± 12.11, 43.05 ± 11.19, and 40.78 ± 10. 59 in the former (P < 0.01) and 53.02 ± 12.12, 49.32 ± 12.78, 44.01 ± 11.79, and 39.67 ± 10.26 in the latter (P < 0.01), and the leukocyte counts were 26.09 ± 21.55, 23.02 ± 18.61, 18.25 ± 17.79, and 15.36 ± 16.38 in the IIIA cases (P < 0.01). Neither abnormalities in liver and renal function nor obvious adverse events were observed during the experiment. Longjintonglin Capsule, with its advantages of safety, effectiveness, and no obvious adverse reactions in the treatment of type III prostatitis, deserves to be recommended for clinical application.

Recovery of Baseline Erectile Function in Men Following Radical Prostatectomy for High-Risk Prostate Cancer: A Prospective Analysis Using Validated Measures.

PubMed

Sridhar, Ashwin N; Cathcart, Paul J; Yap, Tet; Hines, John; Nathan, Senthil; Briggs, Timothy P; Kelly, John D; Minhas, Suks

2016-03-01

Recovery of baseline erectile function (EF) after robotic radical prostatectomy in men with high-risk prostate cancer is under-reported. Published studies have selectively reported on low-risk disease using non-validated and poorly defined thresholds for EF recovery. To assess return to baseline EF in men after robotic radical prostatectomy for high-risk prostate cancer. Five hundred thirty-one men underwent robotic radical prostatectomy for high-risk prostate cancer from February 2010 through July 2014. Pre- and postoperative EF was prospectively assessed using the International Index of Erectile Dysfunction (IIEF-5) questionnaire. Multivariate logistic regression analysis determined the effect of age, preoperative function, comorbidities, body mass index, prostate-specific antigen level, cancer stage or grade, nerve-sparing status, adjuvant therapy, and continence on EF return (defined as postoperative return to baseline EF with or without use of phosphodiesterase type 5 inhibitors). Kaplan-Meier analysis and log-rank test were used to analyze return over time. Mann-Whitney U-test was used to compare IIEF-5 scores. Pre- and postoperative EF was assessed using the IIEF-5 Sexual Health Inventory for Men at 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years postoperatively. Overall, return of EF was seen in 23.5% of patients at 18 months. This was significantly increased in men no older than 60 years (P = .024), with a preoperative IIEF-5 score of at least 22 (P = .042), and after undergoing neurovascular bundle preservation (34.9% of patients, P < .001). There was no significant change in IIEF-5 scores from 3 to 36 months in patients who were treated with phosphodiesterase type 5 inhibitors in the non-neurovascular bundle preservation group (P = .87), although there was significant improvement in those receiving second- or third-line therapies (P = .042). Other than preoperative hypertension (P = .03), none of the other comorbidities predicted return of EF. In this study, 23.5% of men recovered to baseline EF. Of those who underwent bilateral neurovascular bundle preservation robotic radical prostatectomy, 70% recovered baseline EF; however, this accounted for only 9.6% of all patients. Only 4% of men who underwent non-neurovascular bundle preservation had baseline recovery with phosphodiesterase type 5 inhibitors up to 36 months. There was significant improvement after use of second- or third-line therapies, indicating the need for earlier institution of these treatment modalities. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Are 10-, 10-12-, or > 12-mm prostate biopsy core quality control cutoffs reasonable?

PubMed

Sanches, Brunno C F; Lalli, Ana Luiza; Azal Neto, Wilmar; Billis, Athanase; Reis, Leonardo Oliveira

2018-07-01

To explore the role of prostate biopsy core length on prediction of index tumor clinical significance and localization on radical prostatectomy (RP) and time to recurrence, hypothesizing 10-, 10-12-, or > 12-mm minimum core as potential biopsy quality control. Assessed 2424 prostate biopsy cores and corresponding RP of 202 patients submitted to the first set of 12 cores prostate biopsy between 2010 and 2015. Analyzed biopsy core length, age, prostate volume (PV), free and total PSA ratio, PSA density, RP index tumor clinical significance, extension, localization, surgical margins, and cancer control. Prostate biopsy confronted to surgical specimens defined Gleason grade-grouping system (1-5) agreement. Median age was 63.7 years, PSA 10.1 ng/dl, PSA density 28%, and mean follow-up 5 years. Recurrence was identified in 64 (31.7%) patients and predicted by PSA > 10 at time of diagnosis (p = 0.008), seminal vesicle invasion (p = 0.0019), core tumor percentage (p = 0.033), and tumor localization predominantly in the prostate base (p = 0017). The mean core length was longer in index tumor positive cores (p = 0.043) and in tumors classified as clinically insignificant (p = 0.011), without impact on tumor localization (basal vs apical p = 0.592; left vs. right p = 0.320). Biopsy core length categories (≤ 10, 10-12 and > 12 mm) did not significantly impact Gleason grade-grouping agreement or time to recurrence (p > 0.05). Core length was not significantly different in all Gleason grade-groupings 1-5 (p = 0.312). Prostate biopsy core length impacts tumor characterization; however, 10 mm minimum core length and even 10-12- and > 12-mm categories failed as a biopsy quality control in our data.

PCA3-based nomogram for predicting prostate cancer and high grade cancer on initial transrectal guided biopsy.

PubMed

Elshafei, Ahmed; Chevli, K Kent; Moussa, Ayman S; Kara, Onder; Chueh, Shih-Chieh; Walter, Peter; Hatem, Asmaa; Gao, Tianming; Jones, J Stephen; Duff, Michael

2015-12-01

To develop a validated prostate cancer antigen 3 (PCA3) based nomogram that predicts likelihood of overall prostate cancer (PCa) and intermediate/high grade prostate cancer (HGPCa) in men pursuing initial transrectal prostate biopsy (TRUS-PBx). Data were collected on 3,675 men with serum prostate specific antigen level (PSA) ≤ 20 ng/ml who underwent initial prostate biopsy with at least 10 cores sampling at time of the biopsy. Two logistic regression models were constructed to predict overall PCa and HGPCa incorporating age, race, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and digital rectal exam (DRE). One thousand six hundred twenty (44%) patients had biopsy confirmed PCa with 701 men (19.1%) showing HGPCa. Statistically significant predictors of overall PCa were age (P < 0.0001, OR. 1.51), PSA at diagnosis (P < 0.0001, OR.1.95), PCA3 (P < 0.0001, OR.3.06), TPV (P < 0.0001, OR.0.47), FH (P = 0.003, OR.1.32), and abnormal DRE (P = 0.001, OR. 1.32). While for HGPCa, predictors were age (P < 0.0001, OR.1.77), PSA (P < 0.0001, OR.2.73), PCA3 (P < 0.0001, OR.2.26), TPV (P < 0.0001, OR.0.4), and DRE (P < 0.0001, OR.1.53). Two nomograms were reconstructed for predicted overall PCa probability at time of initial biopsy with a concordance index of 0.742 (Fig. 1), and HGPCa with a concordance index of 0.768 (Fig. 2). Our internally validated initial biopsy PCA3 based nomogram is reconstructed based on a large dataset. The c-index indicates high predictive accuracy, especially for high grade PCa and improves the ability to predict biopsy outcomes. © 2015 Wiley Periodicals, Inc.

Dosimetric and radiobiological characterizations of prostate intensity-modulated radiotherapy and volumetric-modulated arc therapy: A single-institution review of ninety cases

PubMed Central

Khan, Muhammad Isa; Jiang, Runqing; Kiciak, Alexander; ur Rehman, Jalil; Afzal, Muhammad; Chow, James C. L.

2016-01-01

This study reviewed prostate volumetric-modulated arc therapy (VMAT) plans with intensity-modulated radiotherapy (IMRT) plans after prostate IMRT technique was replaced by VMAT in an institution. Characterizations of dosimetry and radiobiological variation in prostate were determined based on treatment plans of 40 prostate IMRT patients (planning target volume = 77.8–335 cm3) and 50 VMAT patients (planning target volume = 120–351 cm3) treated before and after 2013, respectively. Both IMRT and VMAT plans used the same dose-volume criteria in the inverse planning optimization. Dose-volume histogram, mean doses of target and normal tissues (rectum, bladder and femoral heads), dose-volume points (D99% of planning target volume; D30%, D50%, V30 Gy and V35 Gy of rectum and bladder; D5%, V14 Gy, V22 Gy of femoral heads), conformity index (CI), homogeneity index (HI), gradient index (GI), prostate tumor control probability (TCP), and rectal normal tissue complication probability (NTCP) based on the Lyman-Burman-Kutcher algorithm were calculated for each IMRT and VMAT plan. From our results, VMAT plan was found better due to its higher (1.05%) CI, lower (0.83%) HI and (0.75%) GI than IMRT. Comparing doses in normal tissues between IMRT and VMAT, it was found that IMRT mostly delivered higher doses of about 1.05% to the normal tissues than VMAT. Prostate TCP and rectal NTCP were found increased (1%) for VMAT than IMRT. It is seen that VMAT technique can decrease the dose-volume evaluation criteria for the normal tissues. Based on our dosimetric and radiobiological results in treatment plans, it is concluded that our VMAT implementation could produce comparable or slightly better target coverage and normal tissue sparing with a faster treatment time in prostate radiotherapy. PMID:27651562

Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

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

Pugh, Thomas J.; Munsell, Mark F.; Choi, Seungtaek

Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence ofmore » modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a larger patient cohort are warranted.« less

Effect of Body Mass Index on Intrafraction Prostate Displacement Monitored by Real-Time Electromagnetic Tracking

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

Butler, Wayne M., E-mail: wbutler@wheelinghospital.org; Wheeling Jesuit University, Wheeling, West Virginia; Morris, Mallory N.

2012-10-01

Purpose: To evaluate, using real-time monitoring of implanted radiofrequency transponders, the intrafraction prostate displacement of patients as a function of body mass index (BMI). Methods and Materials: The motions of Beacon radiofrequency transponders (Calypso Medical Technologies, Seattle, WA) implanted in the prostate glands of 66 men were monitored throughout the course of intensity modulated radiation therapy. Data were acquired at 10 Hz from setup to the end of treatment, but only the 1.7 million data points with a 'beam on' tag were used in the analysis. There were 21 obese patients, with BMI {>=}30 and 45 nonobese patients in themore » study. Results: Mean displacements were least in the left-right lateral direction (0.56 {+-} 0.24 mm) and approximately twice that magnitude in the superior-inferior and anterior-posterior directions. The net vector displacement was larger still, 1.95 {+-} 0.47 mm. Stratified by BMI cohort, the mean displacements per patient in the 3 Cartesian axes as well as the net vector for patients with BMI {>=}30 were slightly less (<0.2 mm) but not significantly different than the corresponding values for patients with lower BMIs. As a surrogate for the magnitude of oscillatory noise, the standard deviation for displacements in all measured planes showed no significant differences in the prostate positional variability between the lower and higher BMI groups. Histograms of prostate displacements showed a lower frequency of large displacements in obese patients, and there were no significant differences in short-term and long-term velocity distributions. Conclusions: After patients were positioned accurately using implanted radiofrequency transponders, the intrafractional displacements in the lateral, superior-inferior, and anterior-posterior directions as well as the net vector displacements were smaller, but not significantly so, for obese men than for those with lower BMI.« less

Prostate health index and prostate cancer gene 3 score but not percent-free Prostate Specific Antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Fiori, Cristian; Bollito, Enrico; Cappia, Susanna; Mario Scarpa, Roberto; Sottile, Antonino; Franco Randone, Donato; Porpiglia, Francesco

2015-10-01

To determine if prostate health index (PHI), prostate cancer antigen gene 3 (PCA3) score, and percentage of free prostate-specific antigen (%fPSA) may be used to differentiate asymptomatic acute and chronic prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA levels and negative findings on digital rectal examination at repeat biopsy (re-Bx). In this prospective study, 252 patients were enrolled, undergoing PHI, PCA3 score, and %fPSA assessments before re-Bx. We used 3 multivariate logistic regression models to test the PHI, PCA3 score, and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the "gray zone" of PSA (4-10ng/ml) cohort (171 individuals). Of the 252 patients, 43 (17.1%) had diagnosis of PCa. The median PHI was significantly different between men with a negative biopsy and those with a positive biopsy (34.9 vs. 48.1, P<0.001), as for the PCA3 score (24 vs. 54, P<0.001) and %fPSA (11.8% vs. 15.8%, P = 0.012). The net benefit of using PCA3 and PHI to differentiate prostatitis and PCa was moderate, although it extended to a good range of threshold probabilities (40%-100%), whereas that from using %fPSA was negligible: this pattern was reported for the whole population as for the "gray zone" PSA cohort. In front of a good diagnostic performance of all the 3 biomarkers in distinguishing negative biopsy vs. positive biopsy, the clinical benefit of using the PCA3 score and PHI to estimate prostatitis vs. PCa was comparable. PHI was the only determinant for prostatitis vs. BPH, whereas no biomarkers could differentiate prostate inflammation from HG-PIN. Copyright © 2015 Elsevier Inc. All rights reserved.

Association between radiation therapy, surgery, or observation for localized prostate cancer and patient-reported outcomes after 3 years

PubMed Central

Barocas, Daniel A.; Alvarez, JoAnn; Resnick, Matthew J.; Koyama, Tatsuki; Hoffman, Karen E.; Tyson, Mark D.; Conwill, Ralph; McCollum, Dan; Cooperberg, Matthew R.; Goodman, Michael; Greenfield, Sheldon; Hamilton, Ann S.; Hashibe, Mia; Kaplan, Sherrie H.; Paddock, Lisa E.; Stroup, Antoinette M.; Wu, Xiao-Cheng; Penson, David F.

2017-01-01

Importance Prostate cancer treatments are associated with side effects. Understanding the side effects of contemporary approaches to management of localized prostate could inform shared decision-making. Objective To compare the harms of radical prostatectomy (RP), radiation (EBRT) and active surveillance (AS). Design The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, cohort study of men diagnosed with localized prostate cancer in 2011–2012. This study reports follow up through August 2015. Setting Patients accrued from five Surveillance Epidemiology, and End Results registry sites and the Cancer of the Prostate Strategic Urologic Research Endeavor. Participants Men < 80 years old with clinical stage cT1-2 disease, prostate specific antigen < 50 ng/mL, enrolled within six months of diagnosis, who completed a baseline survey and at least 1 follow-up survey. Exposure Treatment with RP, EBRT or AS was ascertained within one year of diagnosis. Main Outcome and Measures Patient-reported function in sexual, urinary incontinence, urinary irritative, bowel, and hormonal domains on the 26-item Expanded Prostate Cancer Index Composite (EPIC) 36 months after enrollment. Domain scores range from 0–100. Higher score indicates better function. Minimum clinically important difference defined as 10–12, 6, 5, 5, and 4, respectively. Results The cohort included 2550 men (mean age 63.8 years, 74% white, 55% intermediate or high risk), of whom 1523 (59.7%) underwent RP, 598 (23.5%) EBRT, and 429 (16.8%) AS. Men undergoing EBRT were older (mean age 68.1 vs. 61.5, p<0.001), and had worse baseline sexual function (mean EPIC domain score 52.3 vs. 65.2, p<0.001) than men undergoing RP. At 3 years, adjusted mean sexual domain score for men undergoing RP had declined more than for men undergoing EBRT (mean difference −11.9 points, 95% CI [−15.1, −8.7]). The difference in decline in sexual domain scores between EBRT and AS was not clinically significant (−4.3 points, 95% CI [−9.2, 0.7]). RP was associated with worse urinary incontinence than EBRT (−18.0 points, 95% CI [−20.5, −15.4]) or AS (−12.7 points, 95% CI [−16.0, −9.3]) and better urinary irritative symptoms compared to AS (5.2 points, 95% CI [3.2, 7.2]). No clinically significant differences for bowel or hormone function were noted beyond 12 months. No differences in global quality of life or disease-specific survival (3 deaths) were noted (99.7–100%). Conclusion and Relevance In this cohort of men with localized prostate cancer, RP was associated with a larger decline in sexual function and urinary incontinence than EBRT or AS after 3 years, and lesser urinary irritative symptoms compared to AS; however, there were no meaningful differences in bowel or hormonal function beyond 12 months and no meaningful differences in global quality of life measures. These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer. PMID:28324093

Health-related quality of life after salvage high-intensity focused ultrasound (HIFU) treatment for locally radiorecurrent prostate cancer.

PubMed

Berge, Viktor; Baco, Eduard; Dahl, Alv A; Karlsen, Steinar Johan

2011-09-01

To evaluate health-related quality of life (HRQOL) after salvage high-intensity focused ultrasound (HIFU) for locally radiorecurrent prostate cancer (PCa). Since June 2006 we have treated 61 patients consecutively by salvage HIFU. All patients were offered the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI) questionnaire at baseline and at follow-up. Scores ranged from 0 (worst) to 100 (best). Clinically significant changes were defined as a minimum difference of 10 points between the baseline score and the score at follow-up.   Fifty-seven patients (93%) had evaluable data at baseline, compared with 46 (75%) after treatment. The mean time lapse between HIFU treatment and questionnaire response was 17.5 months (range 6-29 months). The mean score for urinary function decreased from 79.7 ± 12.1 prior to HIFU to 67.4 ± 17.8 after HIFU (P < 0.001). The mean score for sexual function decreased from 32.1 ± 24.1 prior to HIFU to 17.2 ± 17.0 after HIFU (P < 0.001). There were no significant effects on bowel function. There was a significant reduction in the mean score for Physical HRQOL, but the mean score for Mental HRQOL was did not change significantly. Treatment of localized radiorecurrent PCa by salvage HIFU is associated with clinically significant reductions in urinary and sexual function domains after a mean follow-up of 17.5 months. © 2011 The Japanese Urological Association.

Health-related quality-of-life effects of radical prostatectomy and primary radiotherapy for screen-detected or clinically diagnosed localized prostate cancer.

PubMed

Madalinska, J B; Essink-Bot, M L; de Koning, H J; Kirkels, W J; van der Maas, P J; Schröder, F H

2001-03-15

The current study was undertaken within the framework of a screening trial to compare the health-related quality-of-life (HRQOL) outcomes of two primary treatment modalities for localized prostate cancer: radical prostatectomy and external-beam radiotherapy. We conducted a prospective longitudinal cohort study among 278 patients with early screen-detected (59%) or clinically diagnosed (41%) prostate cancer using both generic and disease-specific HRQOL measures (SF-36, UCLA Prostate Cancer Index [urinary and bowel modules] and items relating to sexual functioning) at three points in time: t1 (baseline), t2 (6 months later), and t3 (12 months after t1). Questionnaires were completed by 88% to 93% of all initially enrolled patients. Patients referred for primary radiotherapy were significantly older than prostatectomy patients (63 v 68 years, P <.01). Analyses (adjusted for age and pretreatment level of functioning) revealed poorer levels of generic HRQOL after radiotherapy. Prostatectomy patients reported significantly higher (P <.01) posttreatment incidences of urinary incontinence (39% to 49%) and erectile dysfunction (80% to 91%) than radiotherapy patients (respectively, 6% to 7% and 41% to 55%). Bowel problems (urgency) affected 30% to 35% of the radiotherapy group versus 6% to 7% of the prostatectomy group (P <.01). Patients with screen-detected and clinically diagnosed cancer reported similar posttreatment HRQOL. Prostatectomy and radiotherapy differed in the type of HRQOL impairment. Because the HRQOL effects may be valued differently at the individual level, patients should be made fully aware of the potential benefits and adverse consequences of therapies for early prostate cancer. Differences in posttreatment HRQOL were not related to the method of cancer detection.

Ejaculation profiles of men following radiation therapy for prostate cancer.

PubMed

Sullivan, John F; Stember, Doron S; Deveci, Serkan; Akin-Olugbade, Yemi; Mulhall, John P

2013-05-01

Radical prostatectomy (RP) is associated with anejaculation, which for some men is a source of bother and sexual dissatisfaction. Clinical experience has shown us some men after pelvic radiation therapy (RT) also experience anejaculation. This analysis was conducted to define the ejaculation profiles of men after RT for prostate cancer (PCa). As a routine part of the sexual health evaluation for post-RT patients, men provided information regarding their ejaculatory function and orgasm. Analysis was conducted of a sexual medicine database reviewing demographic data, PCa factors, erectile, ejaculatory, and orgasmic function. Men with prior history of RP, cryotherapy, focal therapies, and androgen deprivation therapy (ADT) were excluded. Patients completed the International Index of Erectile Function (IIEF) questionnaire at follow-up visits commencing with the first posttreatment visit and specific attention was paid to the IIEF orgasm domain. Three hundred and sixty-four consecutive patients were included. Two hundred and fifty-two patients had external beam, and 112 patients had brachytherapy (BT). Mean age was 64 ± 11 (42-78) years and mean follow-up after RT was 6 ± 4.5 years. Mean prostate size at time of RT was 42 ± 21 g. Of the entire population, 72% lost the ability to ejaculate in an antegrade fashion after prostate RT by their last visit. The proportion experiencing anejaculation at 1, 3, and 5 years after RT was 16%, 69%, and 89%, respectively. For men with at least two IIEF questionnaires completed, the orgasm domain scores decreased dramatically over the follow-up period; orgasm domain scores (0-10): <12 months post-RT 7.4, 13-24 months 5.4, 25-36 months 3.2, >36 months 2.8 (P < 0.01). Multivariable analysis identified several factors predictive of failure to ejaculate: older age, ADT, RT dose > 100 Gy, and smaller prostates at the time of RT. The vast majority of men after prostate RT will experience anejaculation and should be counseled accordingly prior to undergoing therapy. We have identified predictive factors. © 2013 International Society for Sexual Medicine.

A randomized trial of internet-based versus traditional sexual counseling for couples after localized prostate cancer treatment.

PubMed

Schover, Leslie R; Canada, Andrea L; Yuan, Ying; Sui, Dawen; Neese, Leah; Jenkins, Rosell; Rhodes, Michelle M

2012-01-15

After treatment for prostate cancer, multidisciplinary sexual rehabilitation involving couples appears more promising than traditional urologic treatment for erectile dysfunction (ED). The authors of this report conducted a randomized trial comparing traditional or internet-based sexual counseling with waitlist (WL) control. Couples were randomized adaptively to a 3-month WL, a 3-session face-to-face format (FF), or an internet-based format (WEB1). A second internet-based group (WEB2) was added to examine the relation between web site use and outcomes. At baseline, post-WL, post-treatment, and 6-month, and 12-month follow-up assessments, participants completed the International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI), the Brief Symptom Inventory-18 to measure emotional distress, and the abbreviated Dyadic Adjustment Scale. Outcomes did not change during the WL period. Of 115 couples that were randomized to FF or WEB1 and 71 couples in the WEB2 group, 34% dropped out. Neither drop-outs nor improvements in outcomes differed significantly between the 3 treatment groups. In a linear mixed-model analysis that included all participants, mean ± standard deviation IIEF scores improved significantly across time (baseline, 29.7 ± 17.9; 12 months, 36.2 ± 22.4; P < .001). FSFI scores also improved significantly (baseline, 15.4 ± 8.5; 12 months, 18.2 ± 10.7; P = .034). Better IIEF scores were associated with finding an effective medical treatment for ED and normal female sexual function at baseline. In the WEB2 group, IIEF scores improved significantly more in men who completed >75% of the intervention. An internet-based sexual counseling program for couples was as effective as a brief, traditional sex therapy format in producing enduring improvements in sexual outcomes after prostate cancer. Copyright © 2011 American Cancer Society.

Health-Related Quality of Life After Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Prostate Cancer

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

Morton, Gerard C., E-mail: gerard.morton@sunnybrook.ca; Loblaw, D. Andrew; Chung, Hans

Purpose: To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change. Methods and Materials: Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received high-dose-rate brachytherapy as a single 15-Gy implant, followed by external beam radiotherapy to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]). The proportion of patients developing a clinically significant difference in the EPIC domainmore » score (minimally important difference of >0.5 standard deviation) was determined and correlated with the baseline clinical and dosimetric factors. The study accrued 125 patients, with a median follow-up of 24 months. Results: By 24 months, 23% had Grade 2 urinary toxicity and only 5% had Grade 2 bowel toxicity, with no Grade 3 toxicity. The proportion of patients reporting a significant decrease in EPIC urinary, bowel, sexual, and hormonal domain scores was 53%, 51%, 45%, and 40% at 12 months and 57%, 65%, 51%, and 30% at 24 months, respectively. The proportion with a >1 standard deviation decrease in the EPIC urinary, bowel, sexual, and hormonal domain scores was 38%, 36%, 24%, and 20% at 12 months and 46%, 48%, 19%, and 8% at 24 months, respectively. On multivariate analysis, the dose to 10% of the urethra was associated with a decreasing EPIC urinary domain score (p = .0089) and, less strongly (p = .0312) with a decreasing hormonal domain score. No association was found between the prostate volume, bladder dose, or high-dose volume and urinary health-related quality of life. A high baseline International Index of Erectile Function score was associated (p = .0019) with a decreasing sexual domain score. The optimal maximal dose to 10% of the urethra cutpoint for urinary health-related quality of life was 120% of the prescription dose. Conclusion: EPIC was a more sensitive tool for detecting the effects on function and bother than were the generic toxicity scales. The urethral dose had the strongest association with a deteriorating urinary quality of life.« less

Apparent Diffusion Coefficient Values of the Benign Central Zone of the Prostate: Comparison With Low- and High-Grade Prostate Cancer.

PubMed

Gupta, Rajan T; Kauffman, Christopher R; Garcia-Reyes, Kirema; Palmeri, Mark L; Madden, John F; Polascik, Thomas J; Rosenkrantz, Andrew B

2015-08-01

The apparent diffusion coefficient (ADC) values for benign central zone (CZ) of the prostate were compared with ADC values of benign peripheral zone (PZ), benign transition zone (TZ), and prostate cancer, using histopathologic findings from radical prostatectomy as the reference standard. The study included 27 patients with prostate cancer (mean [± SD] age, 60.0 ± 7.6 years) who had 3-T endorectal coil MRI of the prostate performed before undergoing prostatectomy with whole-mount histopathologic assessment. Mean ADC values were recorded from the ROI within the index tumor and within benign CZ, PZ, and TZ, with the use of histopathologic findings as the reference standard. ADC values of the groups were compared using paired t tests and ROC curve analysis. The ADC of benign CZ in the right (1138 ± 123 × 10(-6) mm(2)/s) and left (1166 ± 141 × 10(-6) mm(2)/s) lobes was not significantly different (p = 0.217). However, the ADC of benign CZ (1154 ± 129 × 10(-6) mm(2)/s) was significantly lower (p < 0.001) than the ADCs of benign PZ (1579 ± 197 × 10(-6) mm(2)/s) and benign TZ (1429 ± 180 × 10(-6) mm(2)/s). Although the ADC of index tumors (1042 ± 134 × 10(-6) mm(2)/s) was significantly lower (p = 0.002) than the ADC of benign CZ there was no significant difference (p = 0.225) between benign CZ and tumors with a Gleason score of 6 (1119 ± 87 × 10(-6) mm(2)/s). In 22.2% of patients (6/27), including five patients who had tumors with a Gleason score greater than 6, the ADC was lower in benign CZ than in the index tumor. The AUC of ADC for the differentiation of benign CZ from index tumors was 72.4% (sensitivity, 70.4%; specificity, 51.9%), and the AUC of ADC for differentiation from tumors with a Gleason score greater than 6 was 76.7% (sensitivity, 75.0%; specificity, 65.0%). The ADC of benign CZ is lower than the ADC of other zones of the prostate and overlaps with the ADC of prostate cancer tissue, including high-grade tumors. Awareness of this potential diagnostic pitfall is important to avoid misinterpreting the normal CZ as suspicious for tumor.

Cross-cultural adaptation and validation of the French version of the Expanded Prostate cancer Index Composite questionnaire for health-related quality of life in prostate cancer patients.

PubMed

Anota, Amélie; Mariet, Anne-Sophie; Maingon, Philippe; Joly, Florence; Bosset, Jean-François; Guizard, Anne-Valérie; Bittard, Hugues; Velten, Michel; Mercier, Mariette

2016-12-06

Health-related quality of life (HRQoL) has been positioned as one of the major endpoints in oncology. Thus, there is a need to validate cancer-site specific survey instruments. This study aimed to perform a transcultural adaptation of the 50-item Expanded Prostate cancer Index Composite (EPIC) questionnaire for HRQoL in prostate cancer patients and to validate the psychometric properties of the French-language version. The EPIC questionnaire measures urinary, bowel, sexual and hormonal domains. The first step, corresponding to transcultural adaptation of the original English version of the EPIC was performed according to the back translation technique. The second step, comprising the validation of the psychometric properties of the EPIC questionnaire, was performed in patients under treatment for localized prostate cancer (treatment group) and in patients cured of prostate cancer (cured group). The EORTC QLQ-C30 and QLQ-PR25 prostate cancer module were also completed by patients to assess criterion validity. Two assessments were performed, i.e., before and at the end of treatment for the Treatment group, to assess sensitivity to change; and at 2 weeks' interval in the Cured group to assess test-retest reliability. Psychometric properties were explored according to classical test theory. The first step showed overall good acceptability and understanding of the questionnaire. In the second step, 215 patients were included from January 2012 to June 2014: 125 in the Treatment group, and 90 in the Cured group. All domains exhibited good internal consistency, except the bowel domain (Cronbach's α = 0.61). No floor effect was observed. Test-retest reliability assessed in the cured group was acceptable, expect for bowel function (intraclass coefficient = 0.68). Criterion validity was good for each domain and subscale. Construct validity was not demonstrated for the hormonal and bowel domains. Sensitivity to change was exhibited for 5/8 subscales and 2/4 summary scores for patients who experienced toxicities during treatment. The French EPIC questionnaire seems to have adequate psychometric properties, comparable to those exhibited by the original English-language version, except for the construct validity, which was not available in original version.

External validation of a PCA-3-based nomogram for predicting prostate cancer and high-grade cancer on initial prostate biopsy.

PubMed

Greene, Daniel J; Elshafei, Ahmed; Nyame, Yaw A; Kara, Onder; Malkoc, Ercan; Gao, Tianming; Jones, J Stephen

2016-08-01

The aim of this study was to externally validate a previously developed PCA3-based nomogram for the prediction of prostate cancer (PCa) and high-grade (intermediate and/or high-grade) prostate cancer (HGPCa) at the time of initial prostate biopsy. A retrospective review was performed on a cohort of 336 men from a large urban academic medical center. All men had serum PSA <20 ng/ml and underwent initial transrectal ultrasound-guided prostate biopsy with at least 10 cores sampling for suspicious exam and/or elevated PSA. Covariates were collected for the nomogram and included age, ethnicity, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and abnormal finding on digital rectal exam (DRE). These variables were used to test the accuracy (concordance index) and calibration of a previously published PCA3 nomogram. Biopsy confirms PCa and HGPCa in 51.0% and 30.4% of validation patients, respectively. This differed from the original cohort in that it had significantly more PCa and HGPCA (51% vs. 44%, P = 0.019; and 30.4% vs. 19.1%, P < 0.001). Despite the differences in PCa detection the concordance index was 75% and 77% for overall PCa and HGPCa, respectively. Calibration for overall PCa was good. This represents the first external validation of a PCA3-based prostate cancer predictive nomogram in a North American population. Prostate 76:1019-1023, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

Estrogen Metabolism and Prostate Cancer Risk: A Prospective Study

DTIC Science & Technology

2005-05-01

growth hormone concentrations in blood and the risk for prostate cancer: A case- control study. Prostate. 2005- Jan 21 ( Electronic publication ahead... cigarette smoking status, education, body mass index (BMI), and waist to hip ratio (WHRATIO). The beverage specific analyses were further mutually adjusted...affecting the metabolism of detoxification enzymes, impairment of immune system and depression of DNA repair enzymes (31). It remains unclear to what

Positive Response to Thermobalancing Therapy Enabled by Therapeutic Device in Men with Non-Malignant Prostate Diseases: BPH and Chronic Prostatitis.

PubMed

Aghajanyan, Ivan Gerasimovich; Allen, Simon

2016-04-18

The most common types of non-malignant prostate diseases are benign prostatic hyperplasia (BPH) and chronic prostatitis (CP). The aim of this study was to find out whether thermobalancing therapy with a physiotherapeutic device is effective for BPH and CP. During a 2.5-year period, 124 men with BPH over the age of 55 were investigated. Clinical parameters were tested twice: via the International Prostate Symptom Score (IPSS) and via ultrasound measurement of prostate volume (PV) and uroflowmetry maximum flow rate (Q max ), before and after six months of therapy. In 45 men with CP under the age of 55, the dynamics of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) were studied. The results of the investigated index tests in men with BPH confirmed a decrease in IPSS ( p < 0.001), a reduction in PV ( p < 0.001), an increase in Q max ( p < 0.001), and an improvement of quality of life (QoL) ( p < 0.001). NIH-CPSI scores in men with CP indicated positive dynamics. The observed positive changes in IPSS, PV, and Q max in men with BPH and the improvement in NIH-CPSI-QoL in patients with CP after using a physiotherapeutic device for six months as mono-therapy, support the view that thermobalancing therapy with the device can be recommended for these patients. Furthermore, the therapeutic device is free of side effects.

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

PubMed

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

2016-12-01

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

Impact of resistance training on body composition and metabolic syndrome variables during androgen deprivation therapy for prostate cancer: a pilot randomized controlled trial.

PubMed

Dawson, Jacqueline K; Dorff, Tanya B; Todd Schroeder, E; Lane, Christianne J; Gross, Mitchell E; Dieli-Conwright, Christina M

2018-04-03

Prostate cancer patients on androgen deprivation therapy (ADT) experience adverse effects such as lean mass loss, known as sarcopenia, fat gain, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance training can increase lean mass, reduce body fat, and improve physical function and quality of life, but no exercise interventions in prostate cancer patients on ADT have concomitantly improved body composition and MetS. This pilot trial investigated 12 weeks of resistance training on body composition and MetS changes in prostate cancer patients on ADT. An exploratory aim examined if a combined approach of training and protein supplementation would elicit greater changes in body composition. Prostate cancer patients on ADT were randomized to resistance training and protein supplementation (TRAINPRO), resistance training (TRAIN), protein supplementation (PRO), or control stretching (STRETCH). Exercise groups (EXE = TRAINPRO, TRAIN) performed supervised exercise 3 days per week for 12 weeks, while non-exercise groups (NoEXE = PRO, STRETCH) performed a home-based stretching program. TRAINPRO and PRO received 50 g⋅day - 1 of whey protein. The primary outcome was change in lean mass assessed through dual energy x-ray absorptiometry. Secondary outcomes examined changes in sarcopenia, assessed through appendicular skeletal mass (ASM) index (kg/m 2 ), body fat %, strength, physical function, quality of life, MetS score and the MetS components of waist circumference, blood pressure, glucose, high-density lipoprotein-cholesterol, and triglyceride levels. A total of 37 participants were randomized; 32 participated in the intervention (EXE n = 13; NoEXE n = 19). At baseline, 43.8% of participants were sarcopenic and 40.6% met the criteria for MetS. Post-intervention, EXE significantly improved lean mass (d = 0.9), sarcopenia prevalence (d = 0.8), body fat % (d = 1.1), strength (d = 0.8-3.0), and prostate cancer-specific quality of life (d = 0.9) compared to NoEXE (p < 0.05). No significant differences were observed between groups for physical function or MetS-related variables except waist circumference (d = 0.8). A 12-week resistance training intervention effectively improved sarcopenia, body fat %, strength and quality of life in hypogonadal prostate cancer patients, but did not change MetS or physical function. PRO did not offer additional benefit in improving body composition. ClinicalTrials.gov: NCT01909440 . Registered 24 July 2013.

Prospective validation of %p2PSA and the Prostate Health Index, in prostate cancer detection in initial prostate biopsies of Asian men, with total PSA 4-10 ng ml-1.

PubMed

Tan, Lincoln Gl; Tan, Yung Khan; Tai, Bee Choo; Tan, Karen Ml; Gauhar, Vineet; Tiong, Ho Yee; Hawkins, Robert Cw; Thamboo, Thomas P; Hong, Felicia Sk; Chiong, Edmund

2017-01-01

Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic "gray zone" of 4-10 ng ml-1 . False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index (PHI) in Asian men presenting with a total PSA between 4.0 and 10 ng ml-1 . We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng ml-1 . Thirty (19.1%) were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHI. The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity (95% CI) of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 (49%) unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHI levels also correspond to increasing the risk of detecting GS ≥7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 ng ml-1 .

Lifestyle and Risk of Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Cohort of United States Male Health Professionals

PubMed Central

Zhang, Ran; Sutcliffe, Siobhan; Giovannucci, Edward; Willett, Walter C.; Platz, Elizabeth A.; Rosner, Bernard A.; Dimitrakoff, Jordan D.; Wu, Kana

2015-01-01

Purpose Although chronic prostatitis/chronic pelvic pain syndrome is a prevalent urological disorder among men of all ages, its etiology remains unknown. Only a few previous studies have examined associations between lifestyle factors and chronic prostatitis/chronic pelvic pain syndrome, of which most were limited by the cross-sectional study design and lack of control for possible confounders. To address these limitations we performed a cohort study of major lifestyle factors (obesity, smoking and hypertension) and chronic prostatitis/chronic pelvic pain syndrome risk in the HPFS (Health Professionals Follow-up Study), a large ongoing cohort of United States based male health professionals. Materials and Methods The HPFS includes 51,529 men who were 40 to 75 years old at baseline in 1986. At enrollment and every 2 years thereafter participants have completed questionnaires on lifestyle and health conditions. In 2008 participants completed an additional set of questions on recent chronic prostatitis/chronic pelvic pain syndrome pain symptoms modified from the NIH (National Institutes of Health)-CPSI (Chronic Prostatitis Symptom Index) as well as questions on approximate date of symptom onset. The 653 participants with NIH-CPSI pain scores 8 or greater who first experienced symptoms after 1986 were considered incident chronic prostatitis/chronic pelvic pain syndrome cases and the 19,138 who completed chronic prostatitis/chronic pelvic pain syndrome questions but did not report chronic prostatitis/chronic pelvic pain syndrome related pain were considered noncases. Results No associations were observed for baseline body mass index, waist circumference, waist-to-hip ratio, cigarette smoking and hypertension with chronic prostatitis/chronic pelvic pain syndrome risk (each OR ≤1.34). Conclusions In this large cohort study none of the lifestyle factors examined was associated with chronic prostatitis/chronic pelvic pain syndrome risk. As the etiology of chronic prostatitis/chronic pelvic pain syndrome remains unknown, additional prospective studies are needed to elucidate modifiable risk factors for this common condition. PMID:26070893

Transrectal real-time tissue elastography targeted biopsy coupled with peak strain index improves the detection of clinically important prostate cancer.

PubMed

Ma, Qi; Yang, Dong-Rong; Xue, Bo-Xin; Wang, Cheng; Chen, Han-Bin; Dong, Yun; Wang, Cai-Shan; Shan, Yu-Xi

2017-07-01

The focus of the present study was to evaluate transrectal real-time tissue elastography (RTE)-targeted two-core biopsy coupled with peak strain index for the detection of prostate cancer (PCa) and to compare this method with 10-core systematic biopsy. A total of 141 patients were enrolled for evaluation. The diagnostic value of peak strain index was assessed using a receiver operating characteristic curve. The cancer detection rates of the two approaches and corresponding positive cores and Gleason score were compared. The cancer detection rate per core in the RTE-targeted biopsy (44%) was higher compared with that in systematic biopsy (30%). The peak strain index value of PCa was higher compared with that of the benign lesion. PCa was detected with the highest sensitivity (87.5%) and specificity (85.5%) using the threshold value of a peak strain index of ≥5.97 with an area under the curve value of 0.95. When the Gleason score was ≥7, RTE-targeted biopsy coupled with peak strain index detected 95.6% of PCa cases, but 84.4% were detected using systematic biopsy. Peak strain index as a quantitative parameter may improve the differentiation of PCa from benign lesions in the prostate peripheral zone. Transrectal RTE-targeted biopsy coupled with peak strain index may enhance the detection of clinically significant PCa, particularly when combined with systematic biopsy.

Alterations in regional homogeneity of resting-state cerebral activity in patients with chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Lin, Yusong; Bai, Yan; Liu, Peng; Yang, Xuejuan; Qin, Wei; Gu, Jianqin; Ding, Degang; Tian, Jie; Wang, Meiyun

2017-01-01

The purpose of this study was to explore the neural mechanism in Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) using resting-state functional magnetic resonance imaging. The functional magnetic resonance imaging was performed on 31 male CP/CPPS-patients and 31 age and education matched male healthy controls on a 3-T magnetic resonance imaging unit. A two-sample t-test was adopted to reveal the regional homogeneity between the patients and healthy controls. The mean regional homogeneity values in the alerted brain regions of patients were correlated with the clinical measurements by using Pearson's correlation analyses. The CP/CPPS-patients had significantly decreased regional homogeneity in the bilateral anterior cingulate cortices, insular cortices and right medial prefrontal cortex, while significantly increased regional homogeneity in the brainstem and right thalamus compared with the healthy controls. In the CP/CPPS-patients, the mean regional homogeneity value in the left anterior cingulate cortex, bilateral insular cortices and brainstem were respectively correlated with the National Institutes of Health Chronic Prostatitis Symptom Index total score and pain subscale. These brain regions are important in the pain modulation process. Therefore, an impaired pain modulatory system, either by decreased descending pain inhibition or enhanced pain facilitation, may explain the pain symptoms in CP/CPPS.

Intra-vesical Prostatic Protrusion (IPP) Can Be Reduced by Prostatic Artery Embolization

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

Lin, Yen-Ting, E-mail: ymerically@gmail.com; Amouyal, Grégory, E-mail: gregamouyal@hotmail.com; Thiounn, Nicolas, E-mail: nicolas.thiounn@egp.aphp.fr

BackgroundProstate artery embolization (PAE) is a new approach to improve lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia. PAE results in global reduction of prostate volume (PV). There are no data available on the efficacy of PAE in reducing intra-vesical prostatic protrusion (IPP), an anatomic feature that is clinically related with bladder outlet obstruction and LUTS.ObjectiveTo assess the results of PAE in patients with significant IPP due to median lobe hyperplasia and to compare the IPSS decrease and IPP change.Material and MethodsProspective analysis of 18 consecutive patients with significant IPP (>5 mm) related to median lobe hyperplasia undergoing PAEmore » using 30–500-μm-calibrated trisacryl microspheres. We measured IPP on sagittal T2-weighted images before and 3 months after PAE. IPSS and clinical results were also evaluated at 3 months.ResultsPAE resulted in significant IPP reduction (1.57 cm ± 0.55 before PAE and 1.30 cm ± 0.46 after PAE, p = 0.0005) (Fig. 1) with no complication. IPSS, quality of life (QoL), total prostate-specific antigen (PSA) level, and PV showed significant reduction after PAE, and maximum urinary flow rate (Q{sub max}) showed significant increase after PAE. No significant change of International Index of Erectile Function (IIEF) for clinical evaluation after PAE. A significant correlation was found between the IPP change and the IPSS change (r = 0.636, p = 0.0045).ConclusionPatients had significant IPP reduction as well as significant symptomatic improvement after PAE, and these improvements were positively correlated.« less

Comparative Study Using 100-300 Versus 300-500 μm Microspheres for Symptomatic Patients Due to Enlarged-BPH Prostates.

PubMed

Gonçalves, Octavio Meneghelli; Carnevale, Francisco Cesar; Moreira, Airton Mota; Antunes, Alberto Azoubel; Rodrigues, Vanessa Cristina; Srougi, Miguel

2016-10-01

The purpose of the study was to compare safety and efficacy outcomes following prostate artery embolization (PAE) for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) with 100-300 versus 300-500 μm tris-acryl gelatin microspheres. Patients were prospectively treated between August 2011 and June 2013 to receive PAE with 100-300 μm (group A) or 300-500 μm (group B) tris-acryl gelatin microspheres. Patients were followed for a minimum of 12 months and were assessed for changes in International Prostate Symptom Score (IPSS), quality of life (QoL) index, prostate volume determined by magnetic resonance imaging, serum prostate specific antigen (PSA), and maximum urine flow rate (Qmax), as well as any treatment-related adverse events. Fifteen patients were included in each group, and PAE was technically successful in all cases. Both groups experienced significant improvement in mean IPSS, QoL, prostate volume, PSA, and Qmax (p < 0.05 for all). The differences observed between the two groups included a marginally insignificant more adverse events (p = 0.066) and greater mean serum PSA reduction at 3 months of follow-up (p = 0.056) in group A. Both 100-300 and 300-500 μm microspheres are safe and effective embolic agents for PAE to treat LUTS-related to BPH. Although functional and imaging outcomes did not differ significantly following use of the two embolic sizes, the greater incidence of adverse events with 100-300 μm microspheres suggests that 300-500 μm embolic materials may be more appropriate.

[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.

A Comparison of Radical Perineal, Radical Retropubic, and Robot-Assisted Laparoscopic Prostatectomies in a Single Surgeon Series

PubMed Central

Mirza, Moben; Art, Kevin; Wineland, Logan; Tawfik, Ossama; Thrasher, J. Brantley

2011-01-01

Objective. We sought to compare positive surgical margin rates (PSM), estimated blood loss (EBL), and quality of life outcomes (QOL) among perineal (RPP), retropubic (RRP), and robot-assisted laparoscopic (RALP) prostatectomies. Methods. Records from 463 consecutive men undergoing RPP (92), RRP (180), or RALP (191) for clinically localized prostate cancer were retrospectively reviewed. Age, percent tumor volume, Gleason score, stage, EBL, PSM, and QOL using the expanded prostate cancer index composite (EPIC) were compared. Results. PSM were similar when adjusted for stage, grade, and volume. EBL was significantly less in the RALP (189 ml) group compared to both RPP (475 ml) and RRP (999 ml) groups. When corrected for nerve sparing, there were no differences in erectile function and sexual function amongst the three groups. Urinary summary and pad usage scores showed no significant differences. Conclusion. RPP, RRP, and RALP offer similar surgical and QOL outcomes. RALP and RPP demonstrate less EBL compared to RRP. PMID:22111001

Direct effects of tadalafil on lower urinary tract symptoms versus indirect effects mediated through erectile dysfunction symptom improvement: integrated data analyses from 4 placebo controlled clinical studies.

PubMed

Brock, Gerald B; McVary, Kevin T; Roehrborn, Claus G; Watts, Steven; Ni, Xiao; Viktrup, Lars; Wong, David G; Donatucci, Craig

2014-02-01

Tadalafil has regulatory approval for the treatment of men with signs/symptoms of benign prostatic hyperplasia with and without erectile dysfunction. We assessed whether the effects of treatment with tadalafil for lower urinary tract symptoms/benign prostatic hyperplasia are independent of improvements in erectile dysfunction. Four separate analyses used integrated data from 4 randomized, double-blind, placebo controlled studies in men with lower urinary tract symptoms/benign prostatic hyperplasia with and without erectile dysfunction to test whether total I-PSS (International Prostate Symptom Score) improvement was due to improvement in IIEF-EF (International Index of Erectile Function-Erectile Function domain score). Unidirectional and bidirectional path analysis models determined direct and indirect treatment effects mediated by improvements in lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction symptoms. A total of 1,496 men, of whom 77% had erectile dysfunction, received at least 1 dose of tadalafil 5 mg once daily or placebo. The placebo adjusted treatment effect for men with erectile dysfunction was represented by a mean decrease of -2.3 (p <0.0001) in total I-PSS vs -2.2 (p = 0.0007) for men without erectile dysfunction. The correlation between change from baseline in total I-PSS and IIEF-EF was weak (r(2) = 0.08, p <0.0001). The unidirectional path analysis model suggested that the total treatment effect on total I-PSS score improvement (2.25) was derived from a direct treatment effect of 1.57 (70%, p <0.001) and an indirect treatment effect of 0.67 (30% via IIEF-EF improvement, p <0.001). Bidirectional path analysis showed that total I-PSS improvement was largely attributed to direct (92.5%, p <0.001) vs indirect (7.5%, p = 0.32) treatment effects via IIEF-EF improvement. Regardless of the analytical approach, self-reported erectile dysfunction status did not appreciably influence tadalafil treatment response in men with lower urinary tract symptoms/benign prostatic hyperplasia, supporting the dual action of tadalafil on lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction. Copyright © 2014. Published by Elsevier Inc.

Health-related quality of life in Japanese men with localized prostate cancer: assessment with the SF-8.

PubMed

Sugimoto, Mikio; Takegami, Misa; Suzukamo, Yoshimi; Fukuhara, Shunichi; Kakehi, Yoshiyuki

2008-06-01

To evaluate health related quality of life (HRQOL) using the Medical Outcomes Study 8-items Short Form Health Survey (SF-8) questionnaire in Japanese patients with early prostate cancer. A cross-sectional analysis was done in 457 patients with prostate cancer treated with radical prostatectomy, external beam radiotherapy, brachytherapy, androgen deprivation therapy, and watchful waiting or a combination these therapies. General HRQOL was measured using the Japanese version of the SF-8 questionnaire and disease-specific HRQOL was assessed using the Japanese version of the Extended Prostate Cancer Index Composite. The external beam radiotherapy group reported significantly lower values for the physical health component summary score (PCS) in comparison to the radical prostatectomy and brachytherapy groups (P < 0.05). In the analysis of both the PCS and the mental health component summary score (MCS) over time after treatment, higher scores with time were found in the radical prostatectomy group. No significant change over time after androgen deprivation therapy in the PCS was found. In contrast, the MCS was found to deteriorate in the early period, showing a significant increase over time. SF-8 in combination with the Extended Prostate Cancer Index Composite has shown to be a helpful tool in the HRQOL assessment of Japanese patients treated for localized prostate cancer.

Prostate health index (PHI) and prostate-specific antigen (PSA) predictive models for prostate cancer in the Chinese population and the role of digital rectal examination-estimated prostate volume.

PubMed

Chiu, Peter K F; Roobol, Monique J; Teoh, Jeremy Y; Lee, Wai-Man; Yip, Siu-Ying; Hou, See-Ming; Bangma, Chris H; Ng, Chi-Fai

2016-10-01

To investigate PSA- and PHI (prostate health index)-based models for prediction of prostate cancer (PCa) and the feasibility of using DRE-estimated prostate volume (DRE-PV) in the models. This study included 569 Chinese men with PSA 4-10 ng/mL and non-suspicious DRE with transrectal ultrasound (TRUS) 10-core prostate biopsies performed between April 2008 and July 2015. DRE-PV was estimated using 3 pre-defined classes: 25, 40, or 60 ml. The performance of PSA-based and PHI-based predictive models including age, DRE-PV, and TRUS prostate volume (TRUS-PV) was analyzed using logistic regression and area under the receiver operating curves (AUC), in both the whole cohort and the screening age group of 55-75. PCa and high-grade PCa (HGPCa) was diagnosed in 10.9 % (62/569) and 2.8 % (16/569) men, respectively. The performance of DRE-PV-based models was similar to TRUS-PV-based models. In the age group 55-75, the AUCs for PCa of PSA alone, PSA with DRE-PV and age, PHI alone, PHI with DRE-PV and age, and PHI with TRUS-PV and age were 0.54, 0.71, 0.76, 0.78, and 0.78, respectively. The corresponding AUCs for HGPCa were higher (0.60, 0.70, 0.85, 0.83, and 0.83). At 10 and 20 % risk threshold for PCa, 38.4 and 55.4 % biopsies could be avoided in the PHI-based model, respectively. PHI had better performance over PSA-based models and could reduce unnecessary biopsies. A DRE-assessed PV can replace TRUS-assessed PV in multivariate prediction models to facilitate clinical use.

Protective effects of seahorse extracts in a rat castration and testosterone-induced benign prostatic hyperplasia model and mouse oligospermatism model.

PubMed

Xu, Dong-Hui; Wang, Li-Hong; Mei, Xue-Ting; Li, Bing-Ji; Lv, Jun-Li; Xu, Shi-Bo

2014-03-01

This study investigated the effects of seahorse (Hippocampus spp.) extracts in a rat model of benign prostatic hyperplasia (BPH) and mouse model of oligospermatism. Compared to the sham operated group, castration and testosterone induced BPH, indicated by increased penile erection latency; decreased penis nitric oxide synthase (NOS) activity; reduced serum acid phosphatase (ACP) activity; increased prostate index; and epithelial thickening, increased glandular perimeter, increased proliferating cell nuclear antigen (PCNA) index and upregulation of basic fibroblast growth factor (bFGF) in the prostate. Seahorse extracts significantly ameliorated the histopathological changes associated with BPH, reduced the latency of penile erection and increased penile NOS activity. Administration of seahorse extracts also reversed epididymal sperm viability and motility in mice treated with cyclophosphamide (CP). Seahorse extracts have potential as a candidate marine drug for treating BPH without inducing the side effects of erectile dysfunction (ED) or oligospermatism associated with the BPH drug finasteride. Copyright © 2014 Elsevier B.V. All rights reserved.

Focal therapy for localized unifocal and multifocal prostate cancer: A prospective development study using real time MR guided focused ultrasound

NASA Astrophysics Data System (ADS)

Napoli, A.; Caliolo, G.; Boni, F.; Anzidei, M.; Catalano, C.

2017-03-01

To assess safety and feasibility of non-invasive high intensity 3T MR guided focused ultrasound (MRgFUS) treatment of localized prostate cancer in an exploratory designed study. Men aged 45-80 years were eligible for this prospective study if they had low-risk localized prostate cancer (prostate specific antigen [PSA] ≤10 ng/mL, Gleason score ≤ 3 + 3), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI (Discovery 750, GE; Gd-Bopta, Bracco) and have a spinal anesthetic. Patients underwent focal therapy using real time MR guided high intensity focused ultrasound (MRgFUS), delivered to all known cancer lesions, with a margin of normal tissue. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. 8 men were recruited between June 2011 and June 2012. After treatment, one man was admitted to hospital for acute urinary retention. Another patient had self-resolving, mild, intermittent dysuria (median duration 5.0 days). Urinary tract infection was not reported. Urinary debris occurred in 6 men (75%), with a median duration of 12 days. Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 6 to 12 months (p=0.060), as were median IIEF-15 scores for intercourse satisfaction (p=0.433), sexual desire (p=0.622), and overall satisfaction (p=0.256). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 6 to 12 months (p=0.026). All 8 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. No histological evidence of cancer was identified in 7 of 8 men biopsied at 6 months (87,5%); overall, the entire population (8 patients) was free of clinically significant cancer and had no evidence of disease on multi-parametric MRI at 6 to 12 months. MR guided Focused Ultrasound focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinically significant prostate cancer.

Targeting the Kinase-Independent Pro-survival Function of EGFR in Prostate Cancer

DTIC Science & Technology

2013-06-01

AD AWARD NUMBER: W81XWH-09-1-0343 TITLE: Targeting the Kinase-Independent Pro -survival Function of EGFR in Prostate Cancer...SUBTITLE Targeting the Kinase-Independent, Pro -survival Function of EGFR in Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-09-1...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The proposed study, targeting the kinase independent pro -survival function of EGFR in prostate

Prediction of non-biochemical recurrence rate after radical prostatectomy in a Japanese cohort: development of a postoperative nomogram.

PubMed

Okubo, Hidenori; Ohori, Makoto; Ohno, Yoshio; Nakashima, Jun; Inoue, Rie; Nagao, Toshitaka; Tachibana, Masaaki

2014-05-01

To develop a nomogram based on postoperative factors and prostate-specific antigen levels to predict the non-biochemical recurrence rate after radical prostatectomy ina Japanese cohort. A total of 606 Japanese patients with T1-3N0M0 prostate cancer who underwent radical prostatectomy and pelvic lymph node dissection at Tokyo Medical University hospital from 2000 to 2010 were studied. A nomogram was constructed based on Cox hazard regression analysis evaluating the prognostic significance of serum prostate-specific antigen and pathological factors in the radical prostatectomy specimens. The discriminating ability of the nomogram was assessed by the concordance index (C-index), and the predicted and actual outcomes were compared with a bootstrapped calibration plot. With a mean follow up of 60.0 months, a total of 187 patients (30.9%) experienced biochemical recurrence, with a 5-year non-biochemical recurrence rate of 72.3%. Based on a Cox hazard regression model, a nomogram was constructed to predict non-biochemical recurrence using serum prostate-specific antigen level and pathological features in radical prostatectomy specimens. The concordance index was 0.77, and the calibration plots appeared to be accurate. The postoperative nomogram described here can provide valuable information regarding the need for adjuvant/salvage radiation or hormonal therapy in patients after radical prostatectomy.

Dosimetric differences between intraoperative and postoperative plans using Cs-131 in transrectal ultrasound–guided brachytherapy for prostatic carcinoma

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

Jones, Andrew, E-mail: aojones@geisinger.edu; Treas, Jared; Yavoich, Brian

2014-01-01

The aim of the study was to investigate the differences between intraoperative and postoperative dosimetry for transrectal ultrasound–guided transperineal prostate implants using cesium-131 ({sup 131}Cs). Between 2006 and 2010, 166 patients implanted with {sup 131}Cs had both intraoperative and postoperative dosimetry studies. All cases were monotherapy and doses of 115 were prescribed to the prostate. The dosimetric properties (D{sub 90}, V{sub 150}, and V{sub 100} for the prostate) of the studies were compared. Two conformity indices were also calculated and compared. Finally, the prostate was automatically sectioned into 6 sectors (anterior and posterior sectors at the base, midgland, and apex)more » and the intraoperative and postoperative dosimetry was compared in each individual sector. Postoperative dosimetry showed statistically significant changes (p < 0.01) in every dosimetric value except V{sub 150}. In each significant case, the postoperative plans showed lower dose coverage. The conformity indexes also showed a bimodal frequency distribution with the index indicating poorer dose conformity in the postoperative plans. Sector analysis revealed less dose coverage postoperatively in the base and apex sectors with an increase in dose to the posterior midgland sector. Postoperative dosimetry overall and in specific sectors of the prostate differs significantly from intraoperative planning. Care must be taken during the intraoperative planning stage to ensure complete dose coverage of the prostate with the understanding that the final postoperative dosimetry will show less dose coverage.« less

Treatment plan comparison of linac step and shoot, tomotherapy, rapidarc, and proton therapy for prostate cancer by using the dosimetrical and the biological indices

NASA Astrophysics Data System (ADS)

Lee, Suk; Cao, Yuan Jie; Chang, Kyung Hwan; Shim, Jang Bo; Kim, Kwang Hyeon; Lee, Nam Kwon; Park, Young Je; Kim, Chul Yong; Cho, Sam Ju; Lee, Sang Hoon; Min, Chul Kee; Kim, Woo Chul; Cho, Kwang Hwan; Huh, Hyun Do; Lim, Sangwook; Shin, Dongho

2015-07-01

The purpose of this study was to use various dosimetrical indices to determine the best intensitymodulated radiation therapy (IMRT) modality - for treating patients with prostate cancer. Ten patients with prostate cancer were included in this study. IMRT plans were designed to include different modalities, including the linac step and shoot, tomotherapy, RapidArc, and proton systems. Various dosimetrical indices, like the prescription isodose to target volume (PITV) ratio, conformity index (CI), homogeneity index (HI), target coverage index (TCI), modified dose homogeneity index (MHI), conformation number (CN), critical organ scoring index (COSI), and quality factor (QF), were determined to compare the different treatment plans. Biological indices, such as the generalized equivalent uniform dose (gEUD) based the tumor control probability (TCP), and the normal tissue complication probability (NTCP), were also calculated and used to compare the treatment plans. The RapidArc plan attained better PTV coverage, as evidenced by its superior PITV, CI, TCI, MHI, and CN values. Regarding organ at risks (OARs), proton therapy exhibited superior dose sparing for the rectum and the bowel in low dose volumes, whereas the tomotherapy and RapidArc plans achieved better dose sparing in high dose volumes. The QF scores showed no significant difference among these plans (p = 0.701). The average TCPs for prostate tumors in the RapidArc, linac and proton plans were higher than the average TCP for Tomotherapy (98.79%, 98.76%, and 98.75% vs. 98.70%, respectively). Regarding the rectum NTCP, RapidArc showed the most favorable result (0.09%) whereas linac resulted in the best bladder NTCP (0.08%).

Cellular prostatic acid phosphatase, a PTEN-functional homologue in prostate epithelia, functions as a prostate-specific tumor suppressor

PubMed Central

Muniyan, Sakthivel; Ingersoll, Matthew A.; Batra, Surinder K.; Lin, Ming-Fong

2014-01-01

The inactivation of tumor suppressor genes (TSGs) plays a vital role in the progression of human cancers. Nevertheless, those ubiquitous TSGs have been shown with limited roles in various stages of diverse carcinogenesis. Investigation on identifying unique TSG, especially for early stage of carcinogenesis, is imperative. As such, the search for organ-specific TSGs has emerged as a major strategy in cancer research. Prostate cancer (PCa) has the highest incidence in solid tumors in US males. Cellular prostatic acid phosphatase (cPAcP) is a prostate-specific differentiation antigen. Despite intensive studies over the past several decades on PAcP as a PCa biomarker, the role of cPAcP as a PCa-specific tumor suppressor has only recently been emerged and validated. The mechanism underlying the pivotal role of cPAcP as a prostate-specific TSG is, in part, due to its function as a protein tyrosine phosphatase (PTP) as well as a phosphoinositide phosphatase (PIP), an apparent functional homologue to Phosphatase and tensin homolog (PTEN) in PCa cells. This review is focused on discussing the function of this authentic prostate-specific tumor suppressor and the mechanism behind the loss of cPAcP expression leading to prostate carcinogenesis. We review other phosphatases’ roles as TSGs which regulate oncogenic PI3K signaling in PCa and discuss the functional similarity between cPAcP and PTEN in prostate carcinogenesis. PMID:24747769

Comparison Between the Four-kallikrein Panel and Prostate Health Index for Predicting Prostate Cancer.

PubMed

Nordström, Tobias; Vickers, Andrew; Assel, Melissa; Lilja, Hans; Grönberg, Henrik; Eklund, Martin

2015-07-01

The four-kallikrein panel and the Prostate Health Index (PHI) have been shown to improve prediction of prostate cancer (PCa) compared with prostate-specific antigen (PSA). No comparison of the four-kallikrein panel and PHI has been presented. To compare the four-kallikrein panel and PHI for predicting PCa in an independent cohort. Participants were from a population-based cohort of PSA-tested men in Stockholm County. We included 531 men with PSA levels between 3 and 15 ng/ml undergoing first-time prostate biopsy during 2010-2012. Models were fitted to case status. We computed calibration curves, the area under the receiver-operating characteristics curve (AUC), decision curves, and percentage of saved biopsies. The four-kallikrein panel showed AUCs of 69.0 when predicting any-grade PCa and 71.8 when predicting high-grade cancer (Gleason score ≥7). Similar values were found for PHI: 70.4 and 71.1, respectively. Both models had higher AUCs than a base model with PSA value and age (p<0.0001 for both); differences between models were not significant. Sensitivity analyses including men with any PSA level or a previous biopsy did not materially affect our findings. Using 10% predicted risk of high-grade PCa by the four-kallikrein panel or PHI of 39 as cut-off for biopsy saved 29% of performed biopsies at a cost of delayed diagnosis for 10% of the men with high-grade cancers. Both models showed limited net benefit in decision analysis. The main study limitation was lack of digital rectal examination data and biopsy decision being based on PSA information. The four-kallikrein panel and PHI similarly improved discrimination when predicting PCa and high-grade PCa. Both are simple blood tests that can reduce the number of unnecessary biopsies compared with screening with total PSA, representing an important new option to reduce harm. Prostate-specific antigen screening is controversial due to limitations of the test. We found that two blood tests, the Prostate Health Index and the four-kallikrein panel, performed similarly and could both aid in decision making among Swedish men undergoing a prostate biopsy. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

How Precisely Can Prostate Cancer Be Managed?

PubMed Central

2016-01-01

Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2-ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy. Oncotype DX, Prolaris, the biopsy-based Decipher prostate cancer test, and ProMark may improve predictive risk stratification in addition to the traditional Gleason score and tumor stage. Decipher and Prolaris may predict biochemical recurrence and metastasis after radical prostatectomy and possibly help identify patients who need adjuvant therapy. Androgen receptor splice variant 7 appears effective in guiding the selection of second hormonal manipulation with abiraterone or enzalutamide versus chemotherapy when treating metastatic castration-resistant prostate cancer. PMID:27915475

Repeat prostate biopsies prior to radical prostatectomy do not impact erectile function recovery and mid- to long-term continence.

PubMed

Furrer, Marc A; Vilaseca, Antoni; Corradi, Renato B; Boxler, Silvan; Thalmann, George N; Nguyen, Daniel P

2018-06-01

A growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long-term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy. From 1996 to 2015, 1015 consecutive patients underwent radical prostatectomy, and subsequently had urinary continence and erectile function assessed for >2 years follow-up. One-fourth of patients (275; 27%) had ≥2 biopsies before prostatectomy. Logistic regression models tested whether repeat biopsy before prostatectomy predicted continence or erectile function recovery. For the overall cohort, continence rates were 84%, 92%, 96%, and 98% at 3, 6, 12, and 24 months, respectively. Repeat biopsy before prostatectomy was associated with lower continence rate at 3 months compared to single biopsy (P = 0.03); however, no significant differences were observed at 6, 12, or 24 months. In multivariable analyses adjusting for age, body mass index and diabetes/cardiovascular disease/smoking, the association between repeat biopsy and lower likelihood of continence at 3 months remained (odds ratio 0.67, 95% confidence interval 0.47-0.97; P = 0.03). Overall erectile function recovery rates were 16%, 33%, 51%, and 55% at 3, 6, 12, and 24 months, respectively. No difference in erectile function recovery rates was seen at any time point for single biopsy versus repeat biopsy. In multivariable analyses, repeat biopsy was not predictive of erectile function recovery at any time point. Repeat biopsy before radical prostatectomy impairs early continence after surgery. However, erectile function recovery and mid-term to long-term continence are not affected. These data support the current trend towards active surveillance and delayed local treatment in patients with low- to intermediate-risk prostate cancer. © 2018 Wiley Periodicals, Inc.

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

Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

PubMed

Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

2016-07-01

High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 < 30, 30 < 35 and ≥35 kg/m(2), respectively, compared to the reference (18.5 < 25 kg/m(2)). No statistically significant associations were seen between BMI and prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels. © 2016 UICC.

Lifestyle and Risk of Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Cohort of United States Male Health Professionals.

PubMed

Zhang, Ran; Sutcliffe, Siobhan; Giovannucci, Edward; Willett, Walter C; Platz, Elizabeth A; Rosner, Bernard A; Dimitrakoff, Jordan D; Wu, Kana

2015-11-01

Although chronic prostatitis/chronic pelvic pain syndrome is a prevalent urological disorder among men of all ages, its etiology remains unknown. Only a few previous studies have examined associations between lifestyle factors and chronic prostatitis/chronic pelvic pain syndrome, of which most were limited by the cross-sectional study design and lack of control for possible confounders. To address these limitations we performed a cohort study of major lifestyle factors (obesity, smoking and hypertension) and chronic prostatitis/chronic pelvic pain syndrome risk in the HPFS (Health Professionals Follow-up Study), a large ongoing cohort of United States based male health professionals. The HPFS includes 51,529 men who were 40 to 75 years old at baseline in 1986. At enrollment and every 2 years thereafter participants have completed questionnaires on lifestyle and health conditions. In 2008 participants completed an additional set of questions on recent chronic prostatitis/chronic pelvic pain syndrome pain symptoms modified from the NIH (National Institutes of Health)-CPSI (Chronic Prostatitis Symptom Index) as well as questions on approximate date of symptom onset. The 653 participants with NIH-CPSI pain scores 8 or greater who first experienced symptoms after 1986 were considered incident chronic prostatitis/chronic pelvic pain syndrome cases and the 19,138 who completed chronic prostatitis/chronic pelvic pain syndrome questions but did not report chronic prostatitis/chronic pelvic pain syndrome related pain were considered noncases. No associations were observed for baseline body mass index, waist circumference, waist-to-hip ratio, cigarette smoking and hypertension with chronic prostatitis/chronic pelvic pain syndrome risk (each OR ≤1.34). In this large cohort study none of the lifestyle factors examined was associated with chronic prostatitis/chronic pelvic pain syndrome risk. As the etiology of chronic prostatitis/chronic pelvic pain syndrome remains unknown, additional prospective studies are needed to elucidate modifiable risk factors for this common condition. Copyright © 2015 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.

Development and external validation of a prostate health index-based nomogram for predicting prostate cancer

PubMed Central

Zhu, Yao; Han, Cheng-Tao; Zhang, Gui-Ming; Liu, Fang; Ding, Qiang; Xu, Jian-Feng; Vidal, Adriana C.; Freedland, Stephen J.; Ng, Chi-Fai; Ye, Ding-Wei

2015-01-01

To develop and externally validate a prostate health index (PHI)-based nomogram for predicting the presence of prostate cancer (PCa) at biopsy in Chinese men with prostate-specific antigen 4–10 ng/mL and normal digital rectal examination (DRE). 347 men were recruited from two hospitals between 2012 and 2014 to develop a PHI-based nomogram to predict PCa. To validate these results, we used a separate cohort of 230 men recruited at another center between 2008 and 2013. Receiver operator curves (ROC) were used to assess the ability to predict PCa. A nomogram was derived from the multivariable logistic regression model and its accuracy was assessed by the area under the ROC (AUC). PHI achieved the highest AUC of 0.839 in the development cohort compared to the other predictors (p < 0.001). Including age and prostate volume, a PHI-based nomogram was constructed and rendered an AUC of 0.877 (95% CI 0.813–0.938). The AUC of the nomogram in the validation cohort was 0.786 (95% CI 0.678–0.894). In clinical effectiveness analyses, the PHI-based nomogram reduced unnecessary biopsies from 42.6% to 27% using a 5% threshold risk of PCa to avoid biopsy with no increase in the number of missed cases relative to conventional biopsy decision. PMID:26471350

Chronic bacterial seminal vesiculitis as a potential disease entity in men with chronic prostatitis.

PubMed

Park, Soo-Hwan; Ryu, Ji-Kan; Choo, Gwoan-Youb; Chung, Yeun-Goo; Seong, Do-Hwan; Kim, Chang-Ho; Choe, Won-Sik; Ryu, Dong-Soo; Hyun, In Young; Suh, Jun-Kyu

2015-05-01

To investigate bacterial infection in the seminal vesicles by bacteriological examination and radionuclide imaging in men with chronic prostatitis. The study included 50 patients with chronic prostatitis who showed hot uptake in seminal vesicles on Tc-99m ciprofloxacin imaging and eight patients who did not show hot uptake. The evaluation included the National Institutes of Health Chronic Prostatitis Symptom Index and four-glass test. In all participants, transperineal aspiration of seminal vesicle fluid under the guidance of transrectal ultrasonography and bacteriological examination was carried out. Of the 50 patients who showed hot uptake in the seminal vesicles on the isotope study, microorganisms were isolated from the seminal vesicle fluid in 17 patients (positive predictive value, 34%). The most common causative organisms were Escherichia coli in 13 patients (26%), followed by coagulase-negative Staphylococcus species in two patients (4%), Enterococcus faecalis in one patient (2%) and Chlamydia trachomatis in one patient (2%). No microorganisms were isolated in the eight patients who did not show hot uptake in the seminal vesicles (negative predictive value, 100%). However, there were no significant differences in National Institutes of Health Chronic Prostatitis Symptom Index total scores and subscores between the study groups. Chronic bacterial seminal vesiculitis might simultaneously affect a considerable portion of patients with chronic prostatitis, although the clinical implication of the disease remains to be further investigated. © 2015 The Japanese Urological Association.

Procyanidin B2 ameliorates carrageenan-induced chronic nonbacterial prostatitis in rats via anti-inflammatory and activation of the Nrf2 pathway.

PubMed

Wang, Wei; Chen, Renzong; Wang, Jiye

2017-11-04

Prostatitis is one of the most prevalent problems in andriatry and urinary surgery. In the present study, we evaluated the effect of procyanidin B2 (PB) on carrageenan-induced chronic nonbacterial prostatitis in rats. Results showed that PB significantly decreased the prostatic index and enhanced the body weight inhibited by carrageenan. Biochemical results revealed that PB significantly lowered the prostatic specific antigen (PSA) and alleviated oxidative stress in serum. The levels of TNF-α, IL-6, and IL-10 in prostatic homogenate were also significantly decreased after PB treatment. We also found evidence that PB treatment reversed the suppression of Nrf2 nuclear translocation, and increased the expressions of NQO1 and HO-1 in the prostate glands. In conclusion, treatment with PB attenuates carrageenan-induced chronic nonbacterial prostatitis via anti-inflammatory and activation of the Nrf2 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

The influence of the image registration method on the adaptive radiotherapy. A proof of the principle in a selected case of prostate IMRT.

PubMed

Berenguer, Roberto; de la Vara, Victoria; Lopez-Honrubia, Veronica; Nuñez, Ana Teresa; Rivera, Miguel; Villas, Maria Victoria; Sabater, Sebastia

2018-01-01

To analyse the influence of the image registration method on the adaptive radiotherapy of an IMRT prostate treatment, and to compare the dose accumulation according to 3 different image registration methods with the planned dose. The IMRT prostate patient was CT imaged 3 times throughout his treatment. The prostate, PTV, rectum and bladder were segmented on each CT. A Rigid, a deformable (DIR) B-spline and a DIR with landmarks registration algorithms were employed. The difference between the accumulated doses and planned doses were evaluated by the gamma index. The Dice coefficient and Hausdorff distance was used to evaluate the overlap between volumes, to quantify the quality of the registration. When comparing adaptive vs no adaptive RT, the gamma index calculation showed large differences depending on the image registration method (as much as 87.6% in the case of DIR B-spline). The quality of the registration was evaluated using an index such as the Dice coefficient. This showed that the best result was obtained with DIR with landmarks compared with the rest and it was always above 0.77, reported as a recommended minimum value for prostate studies in a multi-centre review. Apart from showing the importance of the application of an adaptive RT protocol in a particular treatment, this work shows that the election of the registration method is decisive in the result of the adaptive radiotherapy and dose accumulation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Detection of prostate cancer with multiparametric MRI (mpMRI): effect of dedicated reader education on accuracy and confidence of index and anterior cancer diagnosis

PubMed Central

Garcia-Reyes, Kirema; Passoni, Niccolò M.; Palmeri, Mark L.; Kauffman, Christopher R.; Choudhury, Kingshuk Roy; Polascik, Thomas J.; Gupta, Rajan T.

2015-01-01

Purpose To evaluate the impact of dedicated reader education on accuracy/confidence of peripheral zone index cancer and anterior prostate cancer (PCa) diagnosis with mpMRI; secondary aim was to assess the ability of readers to differentiate low-grade cancer (Gleason 6 or below) from high-grade cancer (Gleason 7+). Materials and methods Five blinded radiology fellows evaluated 31 total prostate mpMRIs in this IRB-approved, HIPAA-compliant, retrospective study for index lesion detection, confidence in lesion diagnosis (1–5 scale), and Gleason grade (Gleason 6 or lower vs. Gleason 7+). Following a dedicated education program, readers reinterpreted cases after a memory extinction period, blinded to initial reads. Reference standard was established combining whole mount histopathology with mpMRI findings by a board-certified radiologist with 5 years of prostate mpMRI experience. Results Index cancer detection: pre-education accuracy 74.2%; post-education accuracy 87.7% (p = 0.003). Confidence in index lesion diagnosis: pre-education 4.22 ± 1.04; post-education 3.75 ± 1.41 (p = 0.0004). Anterior PCa detection: pre-education accuracy 54.3%; post-education accuracy 94.3% (p = 0.001). Confidence in anterior PCa diagnosis: pre-education 3.22 ± 1.54; post-education 4.29 ± 0.83 (p = 0.0003). Gleason score accuracy: pre-education 54.8%; post-education 73.5% (p = 0.0005). Conclusions A dedicated reader education program on PCa detection with mpMRI was associated with a statistically significant increase in diagnostic accuracy of index cancer and anterior cancer detection as well as Gleason grade identification as compared to pre-education values. This was also associated with a significant increase in reader diagnostic confidence. This suggests that substantial interobserver variability in mpMRI interpretation can potentially be reduced with a focus on education and that this can occur over a fellowship training year. PMID:25034558

Relationship between premature ejaculation and chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Lee, Jun Ho; Lee, Sung Won

2015-03-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common etiology of premature ejaculation (PE). However, the current data are insufficient to explain this relationship and to support routine screening of men with PE. This study aims to evaluate the relationship between PE and CP/CPPS. A cross-sectional study was conducted that included 8,261 men who had participated in a health examination. The Premature Ejaculation Diagnostic Tool (PEDT), the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), and the International Index of Erectile Function-5 (IIEF) were used for assessment of symptoms. A full metabolic work-up and serum testosterone level checks were also performed. We then investigated the relationship using the Spearman correlation test, multiple linear regression, and logistic regression analyses. Associations of PEDT with NIH-CPSI. The mean age was 50.4 ± 5.5 years. In total, 2,205 (24.9%) men had prostatitis-like symptoms (NIH-CPSI pain score of ≥4 and perineal or ejaculatory pain), and 618 (7.0%) men had moderate to severe symptoms (NIH-CPSI pain score of ≥8). Additionally, 2,144 men (24.2%) were classified as demonstrating PE (PEDT > 10). The PEDT score was found to have a significant positive correlation with the NIH-CPSI pain domain score (correlation coefficient = 0.206; P < 0.001). After adjusting for age, metabolic syndrome status, testosterone level, and IIEF score, there was no change in the positive correlation between the NIH-CPSI pain domain score and PEDT score (Beta = 0.175; P < 0.001). After adjusting for age, testosterone level, metabolic syndrome, and IIEF score, the odds ratio (OR) for PE significantly increased with the severity of pelvic pain (mild prostatitis-like symptoms, OR for PE: 1.269, 95% confidence interval: 1.113-1.447; moderate to severe symptoms, OR for PE: 2.134: 95% confidence interval: 1.782-2.557). Our data showed a significant correlation between the PEDT score and the NIH-CPSI score. We suggest routine screening for CP/CPPS in men with PE and PE in men with CP/CPPS. © 2014 International Society for Sexual Medicine.

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

PubMed Central

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

2007-01-01

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

Robot-Assisted Radical Prostatectomy After Previous Prostate Surgery

PubMed Central

Tugcu, Volkan; Sahin, Selcuk; Kargi, Taner; Gokhan Seker, Kamil; IlkerComez, Yusuf; IhsanTasci, Ali

2015-01-01

Background and Objectives: Our objective is to clarify the effect of previous transurethral resection of the prostate (TURP) or open prostatectomy (OP) on surgical, oncological, and functional outcomes after robot-assisted radical prostatectomy (RARP). Methods: Between August 1, 2009, and March 31, 2013, 380 patients underwent RARP. Of these, 25 patients had undergone surgery for primary bladder outlet obstruction (TURP, 20 patients; OP, 5 patents) (group 1). A match-paired analysis was performed to identify 36 patients without a history of prostate surgery with equivalent clinicopathologic characteristics to serve as a control group (group 2). Patients followed up for 12 months were assessed. Results: Both groups were similar with respect to preoperative characteristics, as mean age, body mass index, median prostate-specific antigen, prostate volume, clinical stage, the biopsy Gleason score, D'Amico risk, the American Society of Anesthesiologists (ASA) classification score, the International Prostate Symptom Score, continence, and potency status. RARP resulted in longer console and anastomotic time, as well as higher blood loss compared with surgery-naive patients. We noted a greater rate of urinary leakage (pelvic drainage, >4 d) in group 1 (12% vs 2,8%). The anastomotic stricture rate was significantly higher in group 1 (16% vs 2.8%). No difference was found in the pathologic stage, positive surgical margin, and nerve-sparing procedure between the groups. Biochemical recurrence was observed in 12% (group 1) and 11.1% (group 2) of patients, respectively. No significant difference was found in the continence and potency rates. Conclusions: RARP after TURP or OP is a challenging but oncologically promising procedure with a longer console and anastomosis time, as well as higher blood loss and higher anastomotic stricture rate. PMID:26648678

Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials.

PubMed

Saad, F; Ivanescu, C; Phung, D; Loriot, Y; Abhyankar, S; Beer, T M; Tombal, B; Holmstrom, S

2017-03-01

We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo. Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments. First SREs caused HRQoL deterioration in both trials. Spinal cord compression had the largest impact, with clinically meaningful reductions in seven of nine FACT-P domains in PREVAIL and all three in AFFIRM (mean (95% confidence interval (CI)) change in FACT-P total score -16.95 (-26.47, -7.44) and -9.69 (-16.10, -3.27), respectively). In PREVAIL, first SREs caused clinically meaningful declines in EQ-5D utility index, irrespective of category; spinal cord compression had the largest impact (mean (95% CI) change -0.24 (-0.39, -0.08)). In AFFIRM, FACT-P and FACT-General total scores showed clinically meaningful declines after radiation/surgery to bone. SREs were associated with clinically meaningful functional declines in the daily lives of patients with mCRPC. Spinal cord compression had the largest impact on HRQoL.

Quality of Life After Whole Pelvic Versus Prostate-Only External Beam Radiotherapy for Prostate Cancer: A Matched-Pair Comparison

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

Pinkawa, Michael, E-mail: mpinkawa@ukaachen.de; Piroth, Marc D.; Holy, Richard

Purpose: Comparison of health-related quality of life after whole pelvic (WPRT) and prostate-only (PORT) external beam radiotherapy for prostate cancer. Methods and Materials: A group of 120 patients (60 in each group) was surveyed prospectively before radiation therapy (RT) (time A), at the last day of RT (time B), at a median time of 2 months (time C) and >1 year after RT (time D) using a validated questionnaire (Expanded Prostate Cancer Index Composite). All patients were treated with 1.8- to 2.0-Gy fractions up to 70.2 to 72.0 Gy with or without WPRT up to 45 to 46 Gy. Pairsmore » were matched according to the following criteria: age {+-} 5years, planning target volume {+-} 10 cc (considering planning target volume without pelvic nodes for WPRT patients), urinary/bowel/sexual function score before RT {+-} 10, and use of antiandrogens. Results: With the exception of prognostic risk factors, both groups were well balanced with respect to baseline characteristics. No significant differences were found with regard to urinary and sexual score changes. Mean bladder function scores reached baseline levels in both patient subgroups after RT. However, bowel function scores decreased significantly more for patients after WPRT than in those receiving PORT at all times (p < 0.01, respectively). Significant differences were found for most items in the bowel domain in the acute phase. At time D, patients after WPRT reported rectal urgency (>once a day in 15% vs. 3%; p = 0.03), bloody stools ({>=}half the time in 7% vs. 0%; p = 0.04) and frequent bowel movements (>two on a typical day in 32% vs. 7%; p < 0.01) more often than did patients after PORT. Conclusion: In comparison to PORT, WPRT (larger bladder and rectum volumes in medium dose levels, but similar volumes in high dose levels) was associated with decreased bowel quality of life in the acute and chronic phases after treatment but remained without adverse long-term urinary effects.« less

Predictive value of different prostate-specific antigen-based markers in men with baseline total prostate-specific antigen <2.0 ng/mL.

PubMed

Fujizuka, Yuji; Ito, Kazuto; Oki, Ryo; Suzuki, Rie; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

2017-08-01

To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen <2.0 ng/mL. The case cohort comprised 150 men with a baseline prostate-specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance. © 2017 The Japanese Urological Association.

Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment.

PubMed

Jordan, Brian C; Mock, Charlotta D; Thilagavathi, Ramasamy; Selvam, Chelliah

2016-05-01

Primary prostate cancer, also known as prostate adenocarcinoma (PCa), is a devastating cancer in men worldwide. Europe and developing countries of Asia have fewer reported cases of prostate cancer compared to increasing cases in the United States with higher incidence in Black men. Risk factors associated with prostate cancer are aging, genetics, lifestyle, high body mass index as well as carcinogenic exposure to carbon-containing fuels, tobacco, and charbroiled meats. Hormone therapy and radical prostatectomy are commonly implemented treatments. The >20.000 prostate cancer deaths of 2013 suggest that there exists a need for enhanced chemopreventive and therapeutic agents for prostate cancer treatment. Fruits, vegetables, and red wines contain high levels of polyphenolic levels. Consumption of these products may provide chemoprevetion of PCa. Curcumin, the major compound from the turmeric rhizome Curcuma longa has long been used for medicinal purposes as an antiseptic and wound healing. This review focuses on curcumin's therapeutic effectiveness in vitro and in vivo in prostate cancer models. The review will highlight the mechanisms of actions of curcumin in the signaling pathways of prostate cancer. Published by Elsevier Inc.

Apoptosis-Dependent and Apoptosis-Independent Functions Bim in Prostate Cancer Cells

DTIC Science & Technology

2004-03-01

AD_ Award Number: DAMD17-03-1-0146 TITLE: Apoptosis-Dependent and Apoptosis-Independent Functions of Bim in Prostate Cancer Cells PRINCIPAL...FUNDING NUMBERS Apoptosis-Dependent and Apoptosis-Independent Functions of DAMD17-03-1-0146 Bim in Prostate Cancer Cells 6. A UTHORs) Junwei Liu, M.D...extended cell survival have been implicated in prostate cancer (PCa) development and progression. We recently found that Bim , a BH3-only pro

Assessing quality of life in patients with prostate cancer: a systematic and standardized comparison of available instruments.

PubMed

Schmidt, Stefanie; Garin, Olatz; Pardo, Yolanda; Valderas, José M; Alonso, Jordi; Rebollo, Pablo; Rajmil, Luis; Garcia-Forero, Carlos; Ferrer, Montse

2014-10-01

The objective was to obtain a standardized evaluation of available prostate cancer-specific quality of life instruments used in patients with early-stage disease. We carried out systematic literature reviews in the PubMed database to identify manuscripts which contained information regarding either the development process or metric properties of prostate cancer-specific quality of life instruments. Each instrument was evaluated by two experts, independently, using the Evaluating Measures of Patient-Reported Outcomes (EMPRO) tool. An overall and seven attribute-specific EMPRO scores were calculated (range 0-100, worst to best): measurement model, reliability, validity, responsiveness, interpretability, burden and alternative forms. Eight instruments and 57 manuscripts (2-15 per instrument) were identified. The Expanded Prostate Cancer Index Composite (EPIC) was the best rated (overall EMPRO score 83.1 points). Good results were also obtained by University of California Los Angeles-Prostate Cancer Index (UCLA-PCI), Patient-Oriented Prostate Utility Scale (PORPUS) and Prostate Cancer Quality of Life Instrument (PC-QoL) with 77.3, 70.5 and 64.8 points, respectively. These four instruments passed with distinction the validity and responsiveness evaluation. Insufficient reliability results were observed for UCLA-PCI and PORPUS. Current evidence supports the choice of EPIC, PORPUS or PC-QoL. Attribute-specific EMPRO results facilitate selecting the adequate instrument for every purpose. For longitudinal studies or clinical trials, where responsiveness is the priority, EPIC or PC-QoL should be considered. We recommend the PORPUS for economic evaluations because it allows cost-utility analysis, and EPIC short versions to minimize administration burden.

The interactions of dietary tomato powder and soy germ on prostate carcinogenesis in the TRAMP model

PubMed Central

Zuniga, Krystle E.; Clinton, Steven K; Erdman, John W.

2013-01-01

The interactions between bioactive rich food components within a complex human diet for the inhibition of prostate carcinogenesis (PCa) are largely unknown and difficult to quantify in humans. Tomato and soy products have each shown anti-PCa activity in laboratory studies. The objective of this study was to determine the efficacy of dietary tomato and soy germ, alone and in combination, for the inhibition of prostate carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. At 4 weeks of age, male C57BL/6 × FVB TRAMP mice (n=119) were randomized to consume: AIN-93G control, 10% whole tomato powder (TP), 2% soy germ powder (SG) or 10% tomato powder with 2% soy germ powder (TP+SG) for 14 weeks. 100% of mice fed the control diet had PCa, while PCa incidence was significantly lower in mice consuming TP (61%, p<0.001), SG (66%, p<0.001) and TP+SG (45%, p<0.001). Although the protection offered by the combination of TP and SG was not synergistic, it was the most effective intervention. TP, SG and TP+SG increased apoptotic index (AI) and modestly reduced the proliferative index (PI) in the prostate epithelium of TRAMP mice exhibiting primarily prostatic intraepithelial neoplasia. The dramatic reduction in the PI/AI ratio by the dietary interventions suggests that the control mice experience a stronger stimulus for malignant progression in the prostate microenvironment. Maximally effective and safe strategies for PCa prevention may result from optimizing combinations of nutrients and bioactives through an orchestration of dietary patterns. PMID:23592738

PSA and Prostate Health Index based prostate cancer screening in a hereditary migration complicated population: implications in precision diagnosis.

PubMed

Akizhanova, Mariyam; Iskakova, Elzira E; Kim, Valdemir; Wang, Xiao; Kogay, Roman; Turebayeva, Aiym; Sun, Qinglei; Zheng, Ting; Wu, Shenghui; Miao, Lixia; Xie, Yingqiu

2017-01-01

Precision diagnosis requires specific markers for differential ethnic populations. Prostate-Specific Antigen (PSA) level (threshold of 4ng/ml) has been widely used to screen prostate cancer and as reference of pro-biopsy but false diagnosis frequently occurs. Prostate health Index (PHI) is a new diagnosis marker which combines PSA, free PSA and p2PSA4. Overall the PCa screening database is lacking in Kazakhstani patients. We analyzed the PSA levels and Gleason scores of 222 biopsies collected in 2015 in Almaty area, Kazakhstan approved by institutional ethics board. We found using PSA of 4ng/ml as threshold, only 25.68% of patients have cancer with Gleason score ranged 6-8 and 65.77% of patients have no character of cancer. Moreover, there is no significant correlation between PSA and cancerous (P=0.266) or Gleason grade (P=0.3046) based on pathological biopsy. In addition, PHI is not correlated to prostate cancer (P=0.4301). Our data suggest that false-positive rate is much higher than the correct-positive diagnosis when using PSA as the first screening. Thus in this cohort study, most patients can not get benefit from the PSA screening for precision PCa diagnosis. As Kazakhstani family trees are unique and complicated because of history and migration, the high rate of over diagnosis might be due to the hyperexpression of PSA via heterosis in Eurasian men. Therefore we should be cautious when using pro-biopsy in precision diagnosis for Eurasian prostate cancer patients.

Functional Imaging for Prostate Cancer: Therapeutic Implications

PubMed Central

Aparici, Carina Mari; Seo, Youngho

2012-01-01

Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities CT or MRI (SPECT/CT, PET/CT, and PET/MRI) are promising tools for the management of prostate cancer particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection, to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regards to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, while the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects. PMID:22840598

Causes of Mortality After Dose-Escalated Radiation Therapy and Androgen Deprivation for High-Risk Prostate Cancer

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

Tendulkar, Rahul D., E-mail: tendulr@ccf.org; Hunter, Grant K.; Reddy, Chandana A.

Purpose: Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population. Methods and Materials: A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (≥74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival. Results: The median radiation dose was 78 Gy, median duration of AD was 6more » months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ≥1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ≥1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60). Conclusions: Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not.« less

Single center experience with third-generation cryosurgery for management of organ-confined prostate cancer: critical evaluation of short-term outcomes, complications, and patient quality of life.

PubMed

Hubosky, Scott G; Fabrizio, Michael D; Schellhammer, Paul F; Barone, Bethany B; Tepera, Christopher M; Given, Robert W

2007-12-01

Technical refinements such as improved ultrasonographic localization and the routine use of urethral warmers and small-gauge needle delivery systems have renewed interest in cryosurgical treatment as a minimally invasive option for selected patients with localized prostate cancer. Only three reports of quality of life (QoL) in prostate cryoablation exist, and none report on patients treated with third-generation cryoablative technology. We critically examine our initial series of consecutive patients at a single institution undergoing primary third-generation cryosurgical treatment of localized prostate cancer with respect to treatment outcome, morbidity profile, and QoL parameters. To our knowledge, this is the first QoL report on third-generation cryoablation of the prostate. We retrospectively review the records of 89 consecutive patients with median followup of 11 months (1-32) who have undergone third-generation cryosurgical ablation of the prostate as primary treatment for localized prostate cancer with intention to cure. Patients were risk stratified according to preprocedural parameters of prostate-specific antigen (PSA), clinical stage, and Gleason score. PSA trends were recorded and treatment effectiveness was observed using different definitions of biochemical failure. Charts were reviewed for postprocedure complications. Quality of life was measured prospectively using the University of California, Los Angeles, Prostate Cancer Index as well as American Urological Association symptom scores. We compare a percent of baseline score (%BS) for various domains between our series of patients treated with primary cryoablation with a series of patients undergoing brachytherapy for localized prostate cancer. Treatment success was defined by achievement of a PSA nadir of < or =0.1 ng/mL and by biochemical disease-free survival (BDFS) assessed with both a PSA threshold of < or =0.4 ng/dL over time and the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of three consecutive rises in PSA. According to risk stratification, 86%, 81.5%, and 78% of low-, intermediate-, and high-risk patients, respectively, achieved a PSA nadir of < or =0.1 ng/mL. Overall, at 12 months follow-up, 94% of patients achieved BDFS using ASTRO criteria while 70% achieved BDFS using a PSA threshold of < or =0.4 ng/mL. With risk stratification, 74%, 70%, and 60% of low-, intermediate-, and high-risk patients, respectively, achieved BDFS defined by PSA threshold of < or =0.4 ng/mL. Complications were rare. The response rate for Health Related Quality of Life (HRQoL) questionnaires was 71% for cryoablation patients and 51% for brachytherapy patients. At 12 months follow-up, patients undergoing cryoablation on average achieved urinary and bowel domain scores comparable to baseline, but sexual domains remained well below baseline. When compared with a brachytherapy series with better baseline sexual function (P = 0.04) and urinary function (P = 0.03), cryotherapy patients experienced more negative impact on sexual function steadily for up to 12 months (P = 0.02). Urinary function was similar between the groups until 18 months, at which time cryoablation patients fared better (P = 0.01); this was sustained up to 24 months (P = 0.04). Treatment success with cryosurgery varies with definition; however, our results are comparable to other series with regard to short-term cancer control. Complication rates in this series of third-generation cryosurgical patients are low. QoL characteristics of third-generation cryoablation are similar to those described in second-generation cryoablation series. Compared with brachytherapy, cryotherapy results in less irritative and obstructive voiding symptoms in the early post-treatment period and may improve urinary function up to 24 months after treatment. In a small group of older patients with baseline erectile dysfunction undergoing cryoablation, sexual function returns to 20% of its baseline value with up to 12 months follow-up.

18F-DCFBC Prostate-Specific Membrane Antigen-Targeted PET/CT Imaging in Localized Prostate Cancer: Correlation With Multiparametric MRI and Histopathology.

PubMed

Turkbey, Baris; Mena, Esther; Lindenberg, Liza; Adler, Stephen; Bednarova, Sandra; Berman, Rose; Ton, Anita T; McKinney, Yolanda; Eclarinal, Philip; Hill, Craig; Afari, George; Bhattacharyya, Sibaprasad; Mease, Ronnie C; Merino, Maria J; Jacobs, Paula M; Wood, Bradford J; Pinto, Peter A; Pomper, Martin G; Choyke, Peter L

2017-10-01

To assess the ability of (N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-F-fluorobenzyl-L-cysteine) (F-DCFBC), a prostate-specific membrane antigen-targeted PET agent, to detect localized prostate cancer lesions in correlation with multiparametric MRI (mpMRI) and histopathology. This Health Insurance Portability and Accountability Act of 1996-compliant, prospective, institutional review board-approved study included 13 evaluable patients with localized prostate cancer (median age, 62.8 years [range, 51-74 years]; median prostate-specific antigen, 37.5 ng/dL [range, 3.26-216 ng/dL]). Patients underwent mpMRI and F-DCFBC PET/CT within a 3 months' window. Lesions seen on mpMRI were biopsied under transrectal ultrasound/MRI fusion-guided biopsy, or a radical prostatectomy was performed. F-DCFBC PET/CT and mpMRI were evaluated blinded and separately for tumor detection on a lesion basis. For PET image analysis, MRI and F-DCFBC PET images were fused by using software registration; imaging findings were correlated with histology, and uptake of F-DCFBC in tumors was compared with uptake in benign prostatic hyperplasia nodules and normal peripheral zone tissue using the 80% threshold SUVmax. A total of 25 tumor foci (mean size, 1.8 cm; median size, 1.5 cm; range, 0.6-4.7 cm) were histopathologically identified in 13 patients. Sensitivity rates of F-DCFBC PET/CT and mpMRI were 36% and 96%, respectively, for all tumors. For index lesions, the largest tumor with highest Gleason score, sensitivity rates of F-DCFBC PET/CT and mpMRI were 61.5% and 92%, respectively. The average SUVmax for primary prostate cancer was higher (5.8 ± 4.4) than that of benign prostatic hyperplasia nodules (2.1 ± 0.3) or that of normal prostate tissue (2.1 ± 0.4) at 1 hour postinjection (P = 0.0033). The majority of index prostate cancers are detected with F-DCFBC PET/CT, and this may be a prognostic indicator based on uptake and staging. However, for detecting prostate cancer with high sensitivity, it is important to combine prostate-specific membrane antigen PET/CT with mpMRI.

New Bacterial Infection in the Prostate after Transrectal Prostate Biopsy.

PubMed

Seo, Yumi; Lee, Gilho

2018-04-23

The prostate is prone to infections. Hypothetically, bacteria can be inoculated into the prostate during a transrectal prostate biopsy (TRPB) and progress into chronic bacterial prostatitis. Therefore, we examined new bacterial infections in biopsied prostates after TRPB and whether they affect clinical characteristics in the biopsied patients. Of men whose prostate cultures have been taken prior to TRPB, 105 men with bacteria-free benign prostate pathology underwent an additional repeated prostate culture within a year after TRPB. Twenty out of 105 men (19.05%) acquired new bacteria in their naïve prostates after TRPB. Except for one single case of Escherichia coli infection, 19 men had acquired gram-positive bacteria species. Between the culture-positive and negative groups, there were no significant differences in age, serum prostate-specific antigen (PSA) level, white blood cell (WBC) counts in expressed prostatic secretion (EPS), prostate volume, symptom severities in Korean version of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) questionnaire, and patient-specific risk factors for biopsy associated infectious complications. Additionally, the TRPB procedure increased the WBC counts in post-biopsy EPS ( P = 0.031, McNemar test), but did not increase the serum PSA level and symptoms of NIH-CPSI in 20 men who acquired new bacteria after TRPB. The TRPB procedure was significantly associated with acquiring new bacterial infections in the biopsied prostate, but these localized bacteria did not affect patients' serum PSA level and symptoms after biopsy.

Smooth muscle cell-specific knockout of androgen receptor: a new model for prostatic disease.

PubMed

Welsh, Michelle; Moffat, Lindsey; McNeilly, Alan; Brownstein, David; Saunders, Philippa T K; Sharpe, Richard M; Smith, Lee B

2011-09-01

Androgen-driven stromal-epithelial interactions play a key role in normal prostate development and function as well as in the progression of common prostatic diseases such as benign prostatic hyperplasia and prostate cancer. However, exactly how, and via which cell type, androgens mediate their effects in the adult prostate remains unclear. This study investigated the role for smooth muscle (SM) androgen signaling in normal adult prostate homeostasis and function using mice in which androgen receptor was selectively ablated from prostatic SM cells. In adulthood the knockout (KO) mice displayed a 44% reduction in prostate weight and exhibited histological abnormalities such as hyperplasia, inflammation, fibrosis, and reduced expression of epithelial, SM, and stem cell identify markers (e.g. p63 reduced by 27% and Pten by 31%). These changes emerged beyond puberty and were not explained by changes in serum hormones. Furthermore, in response to exogenous estradiol, adult KO mice displayed an 8.5-fold greater increase in prostate weight than controls and developed urinary retention. KO mice also demonstrated a reduced response to castration compared with controls. Together these results demonstrate that prostate SM cells are vital in mediating androgen-driven stromal-epithelial interactions in adult mouse prostates, determining cell identity and function and limiting hormone-dependent epithelial cell proliferation. This novel mouse model provides new insight into the possible role for SM androgen action in prostate disease.

MRI Fusion-Targeted Transrectal Prostate Biopsy and the Role of Prostate-Specific Antigen Density and Prostate Health Index for the Detection of Clinically Significant Prostate Cancer in Southeast Asian Men.

PubMed

Tan, Teck Wei; Png, Keng Siang; Lee, Chau Hung; Yuwono, Arianto; Yeow, Yuyi; Chong, Kian Tai; Lee, Yee Mun; Tan, Cher Heng; Tan, Yung Khan

2017-11-01

To test the hypothesis that targeted biopsy has a higher detection rate for clinically significant prostate cancer (csPCa) than systematic biopsy. We defined csPCa as any Gleason sum ≥7 cancer. In patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, to determine if factors, such as prostate-specific antigen density (PSAD) and prostate health index (PHI), can predict csPCa and help select patients for biopsy. We report the first series of targeted biopsies in Southeast Asian men, with comparison against systematic biopsy. Consecutive patients were registered into a prospective institutional review board-approved database in our institution. We reviewed patients who underwent biopsy from May 2016 to June 2017. Inclusion criteria for our study were patients with at least one PI-RADS ≥3, and who underwent both targeted and systematic biopsies in the same sitting. There were 115 patients in the study, of whom 74 (64.3%) had a previous negative systematic biopsy. Targeted biopsies detected significantly less Gleason 6 cancers than systematic biopsies (p < 0.01), and demonstrated significantly higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for the detection of csPCa. For patients with PI-RADS 3 lesions, PHI and PSAD were found to be the best predictors for csPCa. PSAD <0.10 ng/mL/mL had an NPV of 93% and sensitivity of 92%, while allowing 20% of patients to avoid biopsy. PHI cutoff of <27 would allow 34% of patients to avoid biopsy, with both sensitivity and NPV of 100%. Targeted prostate biopsies were found to be significantly superior to systematic biopsies for the detection of csPCa, while detecting less Gleason 6 cancer. Usage of PSAD and PHI cutoff levels in patients with PI-RADS 3 lesions may enable a number of patients to avoid unnecessary biopsy.

Robotic radical prostatectomy in patients with high-risk disease: a review of short-term outcomes from a high-volume center.

PubMed

Jayram, Gautam; Decastro, Guarionex J; Large, Michael C; Razmaria, Aria; Zagaja, Gregory P; Shalhav, Arieh L; Brendler, Charles B

2011-03-01

Patients with high-risk prostate cancer have historically been treated with multimodal therapy and considered poor candidates for minimally invasive surgery. We reviewed our experiences with robot-assisted radical prostatectomy (RARP) in patients with high-risk clinical features. Clinical database review identified high-risk patients undergoing RARP by two high-volume robotic surgeons. D'Amico's criteria for high-risk prostate cancer were utilized: prostate-specific antigen ≥ 20 ng/mL, clinical stage ≥ T2c, or preoperative Gleason grade ≥ 8. About 148 patients were identified in the study group. Mean age at surgery was 60.9 years, and mean body mass index was 27.9. Mean estimated blood loss was 150 cc and the transfusion rate was 2.7%. Median hospital stay was 1 day and the rate of major complications (Clavien grade ≥ 3) was 3.4%. Bilateral nerve preservation was feasible in 28.4%, and the rate of positive surgical margins was 20.9%. Final pathology demonstrated extra-capsular disease in 54.1% of patients and 12.3% had lymph node involvement. At 2 years of follow-up, 21.3% of patients had experienced biochemical recurrence or had persistent disease after treatment. Continence was 91.2% (1 pad or less) and total impotence (inability to masturbate) was 48.3%. RARP does not compromise oncologic or functional outcomes in patients with high-risk prostate cancer. Although long-term study is necessary to validate oncologic and functional outcomes, our data suggest that the presence of high-risk disease is not a contraindication to a minimally invasive approach for radical prostatectomy at experienced centers.

Laparoscopic Radical Prostatectomy after Previous Transurethral Resection of the Prostate in Clinical T1a and T1b Prostate Cancer: A Matched-Pair Analysis.

PubMed

Yang, Yi; Luo, Yun; Hou, Guo-Liang; Huang, Qun-Xiong; Lu, Min-Hua; Si-tu, Jie; Gao, Xin

2015-07-01

To analyze and compare surgical, oncological and functional outcomes of laparoscopic radi­cal prostatectomy (LRP) in patients with and without previous transurethral resection of the prostate (TURP). In total, 785 men underwent LRP at our institution from January 2002 to December 2012. TURP had been performed previously in 35 of these patients (TURP group). A matched-pair analysis iden­tified 35 additional men without previous TURP who exhibited equivalent clinicopathological characteristics to serve as a control group. Perioperative complications and surgical, functional, and oncological outcomes were compared between the two groups. The groups were similar in age, body mass index, serum prostate-specific antigen level, and pre- and post-operative Gleason scores. Patients in the TURP group had greater blood loss (231 vs. 139 mL), longer opera­tive times (262 vs. 213 min), a greater probability of transfusion (8.6% vs. 0%), and a higher rate of complications (37.1% vs. 11.4%) compared with the control group. The positive surgical margin rate was higher in the TURP group, but this difference was not statistically significant (P = .179). The continence rates at one year after surgery were similar, but a lower continence rate was identified in the TURP group (42.9% vs. 68.6%) at 3 months. Bio­chemical recurrence developed in 17.1% and 11.4% of the patients in the TURP and control groups, respectively, after a mean follow-up of 57.6 months. LRP is feasible but challenging after TURP. LRP entails longer operating times, greater blood loss, higher complication rates and worse short-term continence outcomes. However, the radical nature of this cancer surgery is not compromised.

Effect of Interventions for Premature Ejaculation in the Treatment of Chronic Prostatitis with Secondary Premature Ejaculation.

PubMed

Chen, Chang-Qing; Yi, Qing-Tong; Chen, Chu-Hong; Gong, Min

2016-08-01

Objective To evaluate the effect of interventions for premature ejaculation (PE) in the management of patients with chronic prostatitis and secondary premature ejaculation. Methods Totally 90 patients diagnosed as chronic prostatitis with PE were randomly divided into control group (n=45) and interventional group (n=45). Control group received a conventional therapy consisted of oral administration of antibiotics,α-receptor blocker,and proprietary Chinese medicine for clearing away heat and promoting diuresis. Interventional group received a conventional therapy combined with treatment for ameliorating the PE symptom (oral dapoxetine on-demand and ejaculation control exercise).National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI),Chinese Index of Sexual Function for Premature Ejaculation (CIPE)-5 questionnaires,intravaginal ejaculatory latency time,and the number of coituses per week were applied for evaluating the treatment outcomes. Results Follow-up was accomplished in 35 and 38 patients in the control and interventional group.The CIPE-5 score,intravaginal ejaculatory latency time,and the number of coituses per week were significantly improved in both two groups but more significantly in interventional group (all P<0.05). The NIH-CPSI pain,urination,and quality of life subscores and total score were improved significantly in both two groups after treatment,but the NIH-CPSI pain and quality of life subscores had been improved more significantly in the interventional group (all P<0.05). The variation of NIH-CPSI was negatively correlated with that of CIPE-5 in both two groups (r=-0.362,P=0.016;r=-0.330,P=0.021). Conclusions For CP with secondary PE patients,the interventions for PE can not only improve the quality of sexual life but also help improve the NIH-CPSI pain and quality of life subscores. PE should be routinely screened and treated during the management of CP.p.

Prevalence of Prostatitis-Like Symptoms and Outcomes of NIH-CPSI in Outpatients with Lifelong and Acquired PE: Based on a Large Cross-Sectional Study in China.

PubMed

Zhu, Daofang; Dou, Xianming; Tang, Liang; Tang, Dongdong; Liao, Guiyi; Fang, Weihua; Zhang, Xiansheng

2017-01-01

Premature ejaculation (PE) is one of the most common sexual dysfunctions, which were associated with prostatitis-like symptoms (PLS). We intended to explore the prevalence of prostatitis-like symptoms and outcomes of National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores in outpatients with lifelong (LPE) and acquired premature ejaculation (APE). From December 2013 to December 2015, a total of 498 consecutive heterosexual men with PE and 322 male healthy subjects without PE were enrolled. Each of them completed a detailed questionnaire on demographics information, sexual and medical histories, and the NIH-CPSI. Assessment of NIH-CPSI and definition of PLS and PE were used to measure the PLS and NIH-CPSI scores and ejaculatory function for all subjects. Finally, a total of 820 subjects (including 498 men in PE group and 322 men in control group) were enrolled in our study. The mean ages were significantly different between PE and no PE groups. Men with PE reported worse PLS and higher NIH-CPSI scores ( P < 0.001 for all). Similar findings were also observed between men with LPE and APE. Men with APE also reported higher rates of PLS and scores of NIH-CPSI ( P < 0.001 for all). Multivariate analysis showed that PLS and NIH-CPSI scores were significantly associated with PE.

Nutritional status and nutritional habits of men with benign prostatic hyperplasia or prostate cancer - preliminary investigation.

PubMed

Goluch-Koniuszy, Zuzanna; Rygielska, Magda; Nowacka, Ilona

2013-01-01

The ageing in men, the most frequent pathologic lesions affecting the prostatic gland in this period are benign prostatic hyperplasia (BPH) and prostate cancer (PC), the course of which may be influenced by the improper nutritional status of patients and their nutritional habits. The aim of this study was, therefore, to evaluate the nutritional status and eating habits of men diagnosed and treated for one of the above diseases. MATERIAL AND METODS: The nutritional status of 30 male patients with clinically confirmed and treated disease of the prostatic gland, including 15 men (aged 51-75 years) with BPH and 15 men (aged 51-73 years) with PC, was evaluated based on their BMI, WC, WHR, and WHtR parameters. In turn, the energy and nutritive value of 90 daily food rations (DFRs) was evaluated. Finally, calculations were made for the Key's index of diet atherogenicity, resultant Glycemic Index (GI) and Glycemic Load (GL). Higher values of the BMI, WC, WHR and WHtR parameters were noted in the men with PC, they were also characterized by a higher incidence of peripheral subcutaneous obesity and visceral obesity. The DFRs of the men were characterized by a low energy value and by a low intake of available carbohydrates, dietary fi ber, K, Ca, Mg, vitamins D and C, and fl uids at a simultaneously high intake of total and animal protein, cholesterol, Na, P, Fe, Cu as well as vitamins B2 and PP. The contribution of energy derived from the basic nutrients diverged from the recommended values. In addition, the DFRs were characterized by high values of Key's index and 24-h GL. Differences in meeting the RDA for selected nutrients between the analysed groups of men were statistically significant. The improper nutritional status of the men may result from their incorrect nutritional habits which fail to improve their health status, and even predispose them to the development of some diet-dependent diseases. In view of that, both correction of diets of the surveyed men, as well as their health-promoting nutritional education in the aspect of prostate diseases seem necessary.

Serial Magnetic Resonance Imaging in Active Surveillance of Prostate Cancer: Incremental Value.

PubMed

Felker, Ely R; Wu, Jason; Natarajan, Shyam; Margolis, Daniel J; Raman, Steven S; Huang, Jiaoti; Dorey, Fred; Marks, Leonard S

2016-05-01

We assessed whether changes in serial multiparametric magnetic resonance imaging can help predict the pathological progression of prostate cancer in men on active surveillance. A retrospective cohort study was conducted of 49 consecutive men with Gleason 6 prostate cancer who underwent multiparametric magnetic resonance imaging at baseline and again more than 6 months later, each followed by a targeted prostate biopsy, between January 2011 and May 2015. We evaluated whether progression on multiparametric magnetic resonance imaging (an increase in index lesion suspicion score, increase in index lesion volume or decrease in index lesion apparent diffusion coefficient) could predict pathological progression (Gleason 3 + 4 or greater on subsequent biopsy, in systematic or targeted cores). Diagnostic performance of multiparametric magnetic resonance imaging was determined with and without clinical data using a binary logistic regression model. The mean interval between baseline and followup multiparametric magnetic resonance imaging was 28.3 months (range 11 to 43). Pathological progression occurred in 19 patients (39%). The sensitivity, specificity, positive predictive value and negative predictive value of multiparametric magnetic resonance imaging was 37%, 90%, 69% and 70%, respectively. Area under the receiver operating characteristic curve was 0.63. A logistic regression model using clinical information (maximum cancer core length greater than 3 mm on baseline biopsy or a prostate specific antigen density greater than 0.15 ng/ml(2) at followup biopsy) had an AUC of 0.87 for predicting pathological progression. The addition of serial multiparametric magnetic resonance imaging data significantly improved the AUC to 0.91 (p=0.044). Serial multiparametric magnetic resonance imaging adds incremental value to prostate specific antigen density and baseline cancer core length for predicting Gleason 6 upgrading in men on active surveillance. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Changes in physical functioning and muscle strength in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison.

PubMed

Gonzalez, Brian D; Jim, Heather S L; Small, Brent J; Sutton, Steven K; Fishman, Mayer N; Zachariah, Babu; Heysek, Randy V; Jacobsen, Paul B

2016-05-01

The purpose of the study is to examine changes in muscle strength and self-reported physical functioning in men receiving androgen deprivation therapy (ADT) for prostate cancer compared to matched controls. Prostate cancer patients scheduled to begin ADT (n = 62) were assessed within 20 days of starting ADT and 6 and 12 months later. Age and geographically matched prostate cancer controls treated with prostatectomy only (n = 86) were assessed at similar time intervals. Grip strength measured upper body strength, the Chair Rise Test measured lower body strength, and the SF-12 Physical Functioning scale measured self-reported physical functioning. As expected, self-reported physical functioning and upper body muscle strength declined in ADT recipients but remained stable in prostate cancer controls. Contrary to expectations, lower body muscle strength remained stable in ADT recipients but improved in prostate cancer controls. Higher Gleason scores, more medical comorbidities, and less exercise at baseline predicted greater declines in physical functioning in ADT recipients. ADT is associated with declines in self-reported physical functioning and upper body muscle strength as well as worse lower body muscle strength relative to prostate cancer controls. These findings should be included in patient education regarding the risks and benefits of ADT. Findings also underscore the importance of conducting research on ways to prevent or reverse declines in physical functioning in this patient population.

Efficacy and safety of prostate artery embolization on lower urinary tract symptoms related to benign prostatic hyperplasia: a systematic review and meta-analysis.

PubMed

Wang, Xiao-Yan; Zong, Huan-Tao; Zhang, Yong

2016-01-01

Prostate artery embolization (PAE) is emerging and is a promising minimally invasive therapy that improves lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). The purpose of this article was to evaluate the efficacy and safety of PAE on LUTS related to BPH. A literature review was performed to identify all published articles of PAE for BPH. The sources included MEDLINE, EMBASE and Cochrane Library from 1980 to 2016. A systematic review and meta-analysis was conducted. The outcome measurements were combined by calculating the mean difference with 95% confidence interval. Statistical analysis was carried out using Review Manager 5.3.0. Twelve studies involving 840 participants were included. Compared with baseline, the International Index of Erectile Function (IIEF-5; International Prostate Symptom Score) scores, the quality of life scores, peak urinary flow rate ( Q max ) and postvoid residual volume all had significant improvements during the 24-month follow-up (all P <0.00001). Both prostate volume (PV) and prostate-specific antigen had significant decrease during the 12-month follow-up ( P <0.00001 and P =0.005, respectively), except postoperative 24 months ( P =0.47 and P =0.32, respectively). The IIEF-5 short form scores had significant increase at postoperative 6 months ( P =0.002) and 12 months ( P <0.0001), except postoperative 1 month ( P =0.23) and 24 months ( P =0.21). For large volume (PV ≥80 mL) BPH, the results were similar. There were no life-threatening complications. PAE is an effective, safe and well-tolerable treatment for LUTS related to BPH, including large volume (PV ≥80 mL) BPH, with a good short-term follow-up. Studies with large number of cases and longer follow-up time are needed to validate our results.

Comparative Study Using 100–300 Versus 300–500 μm Microspheres for Symptomatic Patients Due to Enlarged-BPH Prostates

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

Gonçalves, Octavio Meneghelli, E-mail: octaviogalvao@hotmail.com; Carnevale, Francisco Cesar, E-mail: francisco.carnevale@criep.com.br; Moreira, Airton Mota, E-mail: motamoreira@gmail.com

PurposeThe purpose of the study was to compare safety and efficacy outcomes following prostate artery embolization (PAE) for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) with 100–300 versus 300–500 μm tris-acryl gelatin microspheres.Materials and MethodsPatients were prospectively treated between August 2011 and June 2013 to receive PAE with 100–300 μm (group A) or 300–500 μm (group B) tris-acryl gelatin microspheres. Patients were followed for a minimum of 12 months and were assessed for changes in International Prostate Symptom Score (IPSS), quality of life (QoL) index, prostate volume determined by magnetic resonance imaging, serum prostate specific antigen (PSA),more » and maximum urine flow rate (Q{sub max}), as well as any treatment-related adverse events.ResultsFifteen patients were included in each group, and PAE was technically successful in all cases. Both groups experienced significant improvement in mean IPSS, QoL, prostate volume, PSA, and Q{sub max} (p < 0.05 for all). The differences observed between the two groups included a marginally insignificant more adverse events (p = 0.066) and greater mean serum PSA reduction at 3 months of follow-up (p = 0.056) in group A.ConclusionsBoth 100–300 and 300–500 μm microspheres are safe and effective embolic agents for PAE to treat LUTS-related to BPH. Although functional and imaging outcomes did not differ significantly following use of the two embolic sizes, the greater incidence of adverse events with 100–300 μm microspheres suggests that 300–500 μm embolic materials may be more appropriate.« less

Economic evaluation of prostate cancer screening test as a national cancer screening program in South Korea.

PubMed

Shin, Sangjin; Kim, Youn Hee; Hwang, Jin Sub; Lee, Yoon Jae; Lee, Sang Moo; Ahn, Jeonghoon

2014-01-01

Prostate cancer is rapidly increasing in Korea and professional societies have requested adding prostate specific antigen (PSA) testing to the National Cancer Screening Program (NCSP), but this started a controversy in Korea and neutral evidence on this issue is required more than ever. The purpose of this study was to provide economic evidence to the decision makers of the NCSP. A cost-utility analysis was performed on the adoption of PSA screening program among men aged 50-74-years in Korea from the healthcare system perspective. Several data sources were used for the cost-utility analysis, including general health screening data, the Korea Central Cancer Registry, national insurance claims data, and cause of mortality from the National Statistical Office. To solicit the utility index of prostate cancer, a face-to-face interview for typical men aged 40 to 69 was conducted using a Time-Trade Off method. As a result, the increase of effectiveness was estimated to be very low, when adopting PSA screening, and the incremental cost effectiveness ratio (ICER) was analyzed as about 94 million KRW. Sensitivity analyses were performed on the incidence rate, screening rate, cancer stage distribution, utility index, and treatment costs but the results were consistent with the base analysis. Under Korean circumstances with a relatively low incidence rate of prostate cancer, PSA screening is not cost-effective. Therefore, we conclude that adopting national prostate cancer screening would not be beneficial until further evidence is provided in the future.

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.

Sexual steroids in serum and prostatic tissue of human non-cancerous prostate (STERPROSER trial).

PubMed

Neuzillet, Yann; Raynaud, Jean-Pierre; Radulescu, Camélia; Fiet, Jean; Giton, Franck; Dreyfus, Jean-François; Ghoneim, Tarek P; Lebret, Thierry; Botto, Henry

2017-11-01

The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume. Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI). Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates. STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase. © 2017 Wiley Periodicals, Inc.

Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: association with asymptomatic inflammatory prostatitis NIH category IV.

PubMed

Engelhardt, Paul Friedrich; Seklehner, Stephan; Brustmann, Hermann; Lusuardi, Lukas; Riedl, Claus R

2015-04-01

This study prospectively investigated the immunohistochemical expression of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) in patients with prostate cancer and benign prostatic hyperplasia (BPH), and a possible association of these conditions with asymptomatic inflammatory prostatitis National Institutes of Health (NIH) category IV. The study included 139 consecutive patients who underwent transurethral resection of the prostate and transvesical enucleation of the prostate (n = 82) or radical prostatectomy (n = 57). To characterize inflammatory changes the criteria proposed by Irani et al. [J Urol 1997;157:1301-3] were used. IL-2R and IL-6 expression was studied by a standard immunohistochemical method. Results were correlated with tumour, node, metastasis stage, Gleason scores, total prostate-specific antigen, International Prostate Symptom Score and body mass index. IL-2R and IL-6 expression was significantly higher in neoplastic prostate cancer tissue than in normal tissue of prostate cancer patients (p < 0.001 and p < 0.04, respectively). Prostate cancer patients with prostatitis showed significantly higher IL-2R expression than those without inflammation (p < 0.03). In patients with BPH, expression of IL-2R as well as IL-6 was higher in patients with prostatitis than in those without (p < 0.01 and p < 0.02, respectively). IL-2R and IL-6 expression was significantly higher in prostate cancer tissue than in normal tissue. Patients with asymptomatic inflammatory prostatitis NIH category IV showed significantly greater activity.

A polysaccharide from Dictyophora indusiata inhibits the immunosuppressive function of cancer-associated fibroblasts.

PubMed

Han, Shuyu; Ma, Chaoxiong; Hu, Minghua; Wang, Yuanyuan; Ma, Fangli; Tao, Ning; Qin, Zhihai

2017-10-01

Reversing the function of cancer-associated fibroblasts (CAFs) may improve the efficacy of cancer therapy. Here, we isolated a novel polysaccharide from Dictyophora indusiata (ZSP4) and examined its effects on the function of prostate CAFs. The supernatant of prostate CAFs can stimulate the proliferation of immune cells and inhibit the growth of CD4+/CD8+ T cells. However, after ZSP4 stimulation, the functions of prostate CAFs were inhibited. The mechanism experiment shows that ZSP4 can stimulate prostate CAFs by down-regulating the expression of α-smooth muscle actin. Polysaccharides extracted from Dictyophora indusiata stimulate the proliferation of immune cells and reverse the immune-suppressive functions of prostate CAFs, shedding new light on the development of novel anticancer strategies. The endocrine therapy used to treat prostate cancer aims to eliminate androgenic activity from prostatic tissue; these therapies are painful and of poor therapeutic effect. In this study, we found that polysaccharides extracted from Dictyophora indusiata may affect the micro-environment of tumours and inhibit the growth of the tumours. Our results suggest that polysaccharides may modulate negative immune regulation and enhance antitumour immunity, which is important for clinical therapy. Copyright © 2017 John Wiley & Sons, Ltd.

Network diffusion-based analysis of high-throughput data for the detection of differentially enriched modules

PubMed Central

Bersanelli, Matteo; Mosca, Ettore; Remondini, Daniel; Castellani, Gastone; Milanesi, Luciano

2016-01-01

A relation exists between network proximity of molecular entities in interaction networks, functional similarity and association with diseases. The identification of network regions associated with biological functions and pathologies is a major goal in systems biology. We describe a network diffusion-based pipeline for the interpretation of different types of omics in the context of molecular interaction networks. We introduce the network smoothing index, a network-based quantity that allows to jointly quantify the amount of omics information in genes and in their network neighbourhood, using network diffusion to define network proximity. The approach is applicable to both descriptive and inferential statistics calculated on omics data. We also show that network resampling, applied to gene lists ranked by quantities derived from the network smoothing index, indicates the presence of significantly connected genes. As a proof of principle, we identified gene modules enriched in somatic mutations and transcriptional variations observed in samples of prostate adenocarcinoma (PRAD). In line with the local hypothesis, network smoothing index and network resampling underlined the existence of a connected component of genes harbouring molecular alterations in PRAD. PMID:27731320

PROSTATE REGULATION: MODELING ENDOGENOUS ...

EPA Pesticide Factsheets

Prostate function is an important indicator of androgen status in toxicological studies making predictive modeling of the relevant pharmacokinetics and pharmacodynamics desirable. Prostate function is an important indicator of androgen status in toxicological studies making predictive modeling of the relevant pharmacokinetics and pharmacodynamics desirable.

Understanding PSA and its derivatives in prediction of tumor volume: Addressing health disparities in prostate cancer risk stratification.

PubMed

Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

2017-03-28

To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives' ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer.

68Ga-PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: correlation with final histopathology.

PubMed

Berger, I; Annabattula, C; Lewis, J; Shetty, D V; Kam, J; Maclean, F; Arianayagam, M; Canagasingham, B; Ferguson, R; Khadra, M; Ko, R; Winter, M; Loh, H; Varol, C

2018-06-01

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can be used to locate lesions based on PSMA avidity, however guidelines on its use are limited by its infancy. We aimed to compare multiparametric magnetic resonance imaging (mpMRI) and PSMA PET/CT to prostatectomy histopathology. We conducted a chart review from February 2015 to January 2017 of 50 male patients staged for prostate cancer using PSMA PET/CT and mpMRI who then underwent radical prostatectomy. Pre-operative PSMA PET/CT and mpMRI were paired with corresponding histopathology. Correlations, sensitivity, and specificity were used for comparisons. A total of 81 lesions were confirmed by histopathology. Fifty index lesions were detected by histopathology, all of which were detected by PSMA PET/CT (100% detection), and 47 by mpMRI (94% detection). Thirty-one histologically confirmed secondary lesions were detected, 29 of which were detected by PSMA PET/CT (93.5% detection), and 16 by mpMRI (51.6% detection). PSMA had better sensitivity for index lesion localization than mpMRI (81.1 vs. 64.8%). Specificity was similar for PSMA PET/CT and mpMRI (84.6 vs. 82.7%). SUV max of index lesions ranged from 2.9 to 39.6 (M = 9.27 ± 6.41). Index lesion SUV max was positively correlated with PSA (rho = 0.48, p < 0.001) and ISUP grade (rho = 0.51, p < 0.001). PSMA-PET/CT provided superior detection of prostate cancer lesions with better sensitivity than mpMRI. PSMA-PET/CT can be used to enhance locoregional mpMRI to provide improved detection and characterization of lesions.

Long-Term Outcomes of Laser Prostatectomy for Storage Symptoms: Comparison of Serial 5-Year Followup Data between High Performance System Photoselective Vaporization and Holmium Laser Enucleation of the Prostate.

PubMed

Cho, Min Chul; Song, Won Hoon; Park, Juhyun; Cho, Sung Yong; Jeong, Hyeon; Oh, Seung-June; Paick, Jae-Seung; Son, Hwancheol

2018-06-01

We compared long-term storage symptom outcomes between photoselective laser vaporization of the prostate with a 120 W high performance system and holmium laser enucleation of the prostate. We also determined factors influencing postoperative improvement of storage symptoms in the long term. Included in our study were 266 men, including 165 treated with prostate photoselective laser vaporization using a 120 W high performance system and 101 treated with holmium laser enucleation of the prostate, on whom 60-month followup data were available. Outcomes were assessed serially 6, 12, 24, 36, 48 and 60 months postoperatively using the International Prostate Symptom Score, uroflowmetry and the serum prostate specific antigen level. Postoperative improvement in storage symptoms was defined as a 50% or greater reduction in the subtotal storage symptom score at each followup visit after surgery compared to baseline. Improvements in frequency, urgency, nocturia, subtotal storage symptom scores and the quality of life index were maintained up to 60 months after photoselective laser vaporization or holmium laser enucleation of the prostate. There was no difference in the degree of improvement in storage symptoms or the percent of patients with postoperative improvement in storage symptoms between the 2 groups throughout the long-term followup. However, the holmium laser group showed greater improvement in voiding symptoms and quality of life than the laser vaporization group. On logistic regression analysis a higher baseline subtotal storage symptom score and a higher BOOI (Bladder Outlet Obstruction Index) were the factors influencing the improvement in storage symptoms 5 years after prostate photoselective laser vaporization or holmium laser enucleation. Our serial followup data suggest that storage symptom improvement was maintained throughout the long-term postoperative period for prostate photoselective laser vaporization with a 120 W high performance system and holmium laser enucleation without any difference between the 2 surgeries. Also, more severe storage symptoms at baseline and a more severe BOOI predicted improved storage symptoms in the long term after each surgery. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Predictors of Urinary Morbidity in Cs-131 Prostate Brachytherapy Implants

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

Smith, Ryan P., E-mail: smithrp@upmc.edu; Jones, Heather A.; Beriwal, Sushil

2011-11-01

Purpose: Cesium-131 is a newer radioisotope being used in prostate brachytherapy (PB). This study was conducted to determine the predictors of urinary morbidity with Cs-131 PB. Methods and Materials: A cohort of 159 patients underwent PB with Cs-131 at our institution and were followed by using Expanded Prostate Cancer Index Composite (EPIC) surveys to determine urinary morbidity over time. EPIC scores were obtained preoperatively and postoperatively at 2 and 4 weeks, and 3 and 6 months. Different factors were evaluated to determine their individual effect on urinary morbidity, including patient characteristics, disease characteristics, treatment, and dosimetry. Multivariate analysis of covariancemore » was carried out to identify baseline determinants affecting urinary morbidity. Factors contributing to the need for postoperative catheterization were also studied and reported. Results: At 2 weeks, patient age, dose to 90% of the organ (D90), bladder neck maximum dose (D{sub max}), and external beam radiation therapy (EBRT) predicted for worse function. At 4 weeks, age and EBRT continued to predict for worse function. At the 3-month mark, better preoperative urinary function, preoperative alpha blockers, bladder neck D{sub max}, and EBRT predicted for worse urinary morbidity. At 6 months, better preoperative urinary function, preoperative alpha blockers, bladder neck D{sub max}, and EBRT were predictive of increased urinary problems. High bladder neck D{sub max} and poor preoperative urinary function predicted for the need for catheterization. Conclusions: The use of EBRT plus Cs-131 PB predicts for worse urinary toxicity at all time points studied. Patients should be cautioned about this. Age was a consistent predictor of worsened morbidity immediately following Cs-131 PB, while bladder D{sub max} was the only consistent dosimetric predictor. Paradoxically, patients with better preoperative urinary function had worse urinary morbidity at 3 and 6 months, consistent with recently published literature.« less

Patient-reported ejaculatory function and satisfaction in men with lower urinary tract symptoms/benign prostatic hyperplasia.

PubMed

Cho, Min Chul; Kim, Jung Kwon; Song, Sang Hoon; Cho, Sung Yong; Lee, Sang Wook; Kim, Soo Woong; Paick, Jae-Seung

2018-01-01

This study aimed to investigate perceived ejaculatory function/satisfaction before treatment for lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) and to identify associations between specific categories of ejaculatory dysfunctions (EjDs) and LUTS. A total of 1574 treatment-naïve men with LUTS/BPH were included in this study. All patients underwent routine evaluation for LUTS/BPH including the International Index of Erectile Function and a 5-item questionnaire developed to assess ejaculatory volume/force/pain/satisfaction/latency time. Patients who had sexual intercourse over the past 4 weeks were classified as sexually active group. A total of 783 patients were categorized as sexually active group. Decreased ejaculatory volume and force were reported by 53.4% and 55.7% of 783 sexually active men, respectively. There was a strong correlation between ejaculatory volume and force. Ejaculatory pain/discomfort, premature ejaculation (PE), and delayed ejaculation (DE) were reported in 41.0%, 16.3%, and 41.4% of the patients, respectively. Over 40.0% of men without decreased ejaculation volume/force were satisfied with ejaculatory function, whereas approximately 6.0% of men with decreased volume/force were satisfied with ejaculatory function. About 30.0% of men with decreased volume/force had orgasmic dysfunction, while approximately 10.0% of men without decreased volume/force did. Decreased ejaculatory volume or force was associated with LUTS severity after adjusting for other influential factors including testosterone level, erectile function, and prostate size on ultrasonography, but PE or DE or ejaculatory pain/discomfort was not. In conclusion, a considerable portion of men with LUTS/BPH appear to have a variety of EjDs. Ejaculatory volume/force and satisfaction/orgasm do not always appear to be concordant. Ejaculatory volume or force is independently associated with LUTS severity, whereas PE or DE or ejaculatory pain/discomfort is not.

Mitochondrial β-Carotene 9',10' Oxygenase Modulates Prostate Cancer Growth via NF-κB Inhibition: A Lycopene-Independent Function.

PubMed

Gong, Xiaoming; Marisiddaiah, Raju; Zaripheh, Susan; Wiener, Doris; Rubin, Lewis P

2016-10-01

Despite numerous inquiries into protective roles of lycopene in prostate cancer prevention or therapy, little is known about mechanisms by which lycopene or its metabolites inhibit prostate cancer. The enzyme β-carotene 9',10'-oxygenase (BCO2), which catalyzes asymmetric cleavage of several carotenoids, is the principal regulator of lycopene metabolism, but the range of BCO2 biological functions is incompletely understood. This study investigated expression and functional roles of BCO2 in human prostate cancer. Expression of the bco2 gene is dramatically decreased in prostate cancer tissue and in a range of prostate cancer cell lines as compared with nonneoplastic prostate tissue and normal prostatic epithelial cells, respectively. Inhibition of DNA methyltransferase activity restored bco2 expression in prostate cancer cell lines tested. Treatment with lycopene or its metabolite, apo-10-lycopenal, also increased bco2 expression and reduced cell proliferation in androgen-sensitive cell lines, but lycopene neither altered bco2 expression nor cell growth in androgen-resistant cells. Notably, restoring bco2 expression in prostate cancer cells inhibited cell proliferation and colony formation, irrespective of lycopene exposure. Exogenous expression of either wild-type BCO2 or a mutant (enzymatically inactive) BCO2 in prostate cancer cells reduced NF-κB activity and decreased NF-κB nuclear translocation and DNA binding. Together, these results indicate epigenetic loss of BCO2 expression is associated with prostate cancer progression. Moreover, these findings describe previously unanticipated functions of BCO2 that are independent of its enzymatic role in lycopene metabolism. This study identifies BCO2 as a tumor suppressor in prostate cancer. BCO2-mediated inhibition of NF-κB signaling implies BCO2 status is important in prostate cancer progression. Mol Cancer Res; 14(10); 966-75. ©2016 AACR. ©2016 American Association for Cancer Research.

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.

Human Prostate Cancer Hallmarks Map

PubMed Central

Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

2016-01-01

Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

Significance and outcome of nuclear anaplasia and mitotic index in prostatic adenocarcinomas.

PubMed

Kır, Gozde; Sarbay, Billur Cosan; Gumus, Eyup

2016-10-01

The Gleason grading system measures architectural differentiation and disregards nuclear atypia and the cell proliferation index. Several studies have reported that nuclear grade and mitotic index (MI) are prognostically useful. This study included 232 radical prostatectomy specimens. Nuclear anaplasia (NA) was determined on the basis of nucleomegali (at least 20µm); vesicular chromatin; eosinophilic macronucleoli, nuclear lobulation, and irregular thickened nuclear membranei. The proportion of area of NA was recorded in each tumor in 10% increments. The MI was defined as the number of mitotic figures in 10 consecutive high-power fields (HPF). In univariate analysis, significant differences included associations between biochemical prostate-specific antigen recurrence (BCR) and Gleason score, extraprostatic extension, positive surgical margin, the presence of high-pathologic stage, NA≥10% of tumor area, MI≥3/10 HPF, and preoperative prostate-specific antigen. In a stepwise Cox regression model, a positive surgical margin, the presence of a NA≥10% of tumor area, and a MI of≥3/10 HPF were independent predictors of BCR after radical prostatectomy. NA≥10% of tumor area appeared to have a stronger association with outcome than MI≥3/10 HPF, as still associated with BCR when Gleason score was in the model. The results of our study showed that, in addition to the conventional Gleason grading system, NA, and MI are useful prognostic parameters while evaluating long-term prognosis in prostatic adenocarcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

PubMed

Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

2014-11-01

Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score. During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%. In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.

PubMed

Sehrawat, Archana; Gao, Lina; Wang, Yuliang; Bankhead, Armand; McWeeney, Shannon K; King, Carly J; Schwartzman, Jacob; Urrutia, Joshua; Bisson, William H; Coleman, Daniel J; Joshi, Sunil K; Kim, Dae-Hwan; Sampson, David A; Weinmann, Sheila; Kallakury, Bhaskar V S; Berry, Deborah L; Haque, Reina; Van Den Eeden, Stephen K; Sharma, Sunil; Bearss, Jared; Beer, Tomasz M; Thomas, George V; Heiser, Laura M; Alumkal, Joshi J

2018-05-01

Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.

Obesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts

PubMed Central

Ascui, Natasha; Frydenberg, Mark; Risbridger, Gail P.; Taylor, Renea A.; Watt, Matthew J.

2016-01-01

There are established epidemiological links between obesity and the severity of prostate cancer. We directly tested this relationship by assessing tumorigenicity of patient-derived xenografts (PDXs) of moderate-grade localized prostate cancer in lean and obese severe combined immunodeficiency (SCID) mice. Mice were rendered obese and insulin resistant by high-fat feeding for 6 weeks prior to transplantation, and PDXs were assessed 10 weeks thereafter. Histological analysis of PDX grafts showed no differences in tumor pathology, prostate-specific antigen, androgen receptor and homeobox protein Nkx-3.1 expression, or proliferation index in lean versus obese mice. Whilst systemic obesity per se did not promote prostate tumorigenicity, we next asked whether the peri-prostatic adipose tissue (PPAT), which covers the prostate anteriorly, plays a role in prostate tumorigenesis. In vitro studies in a cellularized co-culture model of stromal and epithelial cells demonstrated that factors secreted from human PPAT are pro-tumorigenic. Accordingly, we recapitulated the prostate-PPAT spatial relationship by co-grafting human PPAT with prostate cancer in PDX grafts. PDX tissues were harvested 10 weeks after grafting, and histological analysis revealed no evidence of enhanced tumorigenesis with PPAT compared to prostate cancer grafts alone. Altogether, these data demonstrate that prostate cancer tumorigenicity is not accelerated in the setting of diet-induced obesity or in the presence of human PPAT, prompting the need for further work to define the at-risk populations of obesity-driven tumorigenesis and the biological factors linking obesity, adipose tissue and prostate cancer pathogenesis. PMID:27351281

Regucalcin is an androgen-target gene in the rat prostate modulating cell-cycle and apoptotic pathways.

PubMed

Vaz, Cátia V; Maia, Cláudio J; Marques, Ricardo; Gomes, Inês M; Correia, Sara; Alves, Marco G; Cavaco, José E; Oliveira, Pedro F; Socorro, Sílvia

2014-09-01

Regucalcin (RGN) is a calcium (Ca(2+) )-binding protein underexpressed in prostate adenocarcinoma comparatively to non-neoplastic prostate or benign prostate hyperplasia cases. Moreover, RGN expression is negatively associated with the cellular differentiation of prostate adenocarcinoma, suggesting that loss of RGN may be associated with tumor onset and progression. However, the RGN actions over the control of prostate cell growth have not been investigated. Androgens are implicated in the promotion of prostate cell proliferation, thus we studied the in vivo effect of androgens on RGN expression in rat prostate. The role of RGN modulating cell proliferation and apoptotic pathways in rat prostate was investigated using transgenic animals (Tg-RGN) overexpressing the protein. In vivo stimulation with 5α-dihydrotestosterone (DHT) down-regulated RGN expression in rat prostate. Cell proliferation index and prostate weight were reduced in Tg-RGN, which was concomitant with altered expression of cell-cycle regulators. Tg-RGN presented diminished expression of the oncogene H-ras and increased expression of cell-cycle inhibitor p21. Levels of anti-apoptotic Bcl-2, as well as the Bcl-2/Bax protein ratio were increased in prostates overexpressing RGN. Both caspase-3 expression and enzyme activity were decreased in the prostates of Tg-RGN. Overexpression of RGN resulted in inhibition of cell proliferation and apoptotic pathways, which demonstrated its role maintaining prostate growth balance. Thus, deregulation of RGN expression may be an important event favoring the development of prostate cancer. Moreover, the DHT effect down-regulating RGN expression in rat prostate highlighted for the importance of this protein in prostatic physiology. © 2014 Wiley Periodicals, Inc.

Impact of Body Mass Index on Outcomes After Conformal Radiotherapy in Patients With Prostate Cancer

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

Geinitz, Hans, E-mail: hans.geinitz@lrz.tu-muenchen.de; Thamm, Reinhard; Mueller, Tobias

2011-09-01

Purpose: Several retrospective analyses have suggested that obese men with prostate cancer treated with external beam radiotherapy (EBRT) have outcomes inferior to those of normal-weight men. However, a recently presented analysis for the first time challenged this association between body mass index (BMI) and treatment failure. It is therefore important to provide further data on this issue. Methods and Materials: This was a retrospective analysis of 564 men treated with risk-adapted conformal EBRT at a single institution. Low-risk patients received EBRT alone, and the other patients received EBRT plus endocrine treatment. In addition, high-risk patients were treated to higher EBRTmore » doses (74 Gy). A rectal balloon catheter for internal immobilization, which can be identified on portal images, was used in 261 patients (46%). Thus, localization did not rely on bony landmarks alone in these cases. Results: The median BMI was 26, and 15% of patients had BMI {>=}30. Neither univariate nor multivariate analyses detected any significant impact of BMI on biochemical relapse, prostate cancer-specific survival, or overall survival. The 5-year biochemical relapse rate was 21% and prostate cancerspecific survival 96%. Conclusions: The present analysis of a large cohort of consecutively treated patients suggests that efforts to reduce prostate movement and geographic miss might result in comparable outcomes in obese and normal-weight patients.« less

Apoptosis-Dependent and Apoptosis-Independent Functions of Bim in Prostate Cancer Cells

DTIC Science & Technology

2005-03-01

Independent Functions of Bim in Prostate Cancer Cells PRINCIPAL INVESTIGATOR: Dr. Dean Tang...SUBTITLE 5a. CONTRACT NUMBER Apoptosis-Dependent and Apoptosis-Independent Functions of Bim in Prostate Cancer Cells 5b. GRANT NUMBER DAMD17-03-1...Unlimited 13. SUPPLEMENTARY NOTES Original contains colored plates: ALL DTIC reproductions will be in black and white. 14. ABSTRACT

Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials

PubMed Central

Saad, F; Ivanescu, C; Phung, D; Loriot, Y; Abhyankar, S; Beer, T M; Tombal, B; Holmstrom, S

2017-01-01

Background: We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo. Methods: Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments. Results: First SREs caused HRQoL deterioration in both trials. Spinal cord compression had the largest impact, with clinically meaningful reductions in seven of nine FACT-P domains in PREVAIL and all three in AFFIRM (mean (95% confidence interval (CI)) change in FACT-P total score –16.95 (–26.47, –7.44) and –9.69 (–16.10, –3.27), respectively). In PREVAIL, first SREs caused clinically meaningful declines in EQ-5D utility index, irrespective of category; spinal cord compression had the largest impact (mean (95% CI) change –0.24 (–0.39, –0.08)). In AFFIRM, FACT-P and FACT-General total scores showed clinically meaningful declines after radiation/surgery to bone. Conclusions: SREs were associated with clinically meaningful functional declines in the daily lives of patients with mCRPC. Spinal cord compression had the largest impact on HRQoL. PMID:28045115

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.

Genome Wide Association Study to Identify SNPs and CNPs Associated with Development of Radiation Injury in Prostate Cancer Patients Treated With Radiotherapy

DTIC Science & Technology

2010-10-01

reproducibility of genotype c alls among the four batches by comparing the HapMap samples across batches. We also calculated identity-by- descent (IBD...used to aid clinicians in per sonalizing dosage to improve the therapeutic index of radiotherapy treatment for prostate cancer. References None Appendices None

Human Development Inequality Index and Cancer Pattern: a Global Distributive Study.

PubMed

Rezaeian, Shahab; Khazaei, Salman; Khazaei, Somayeh; Mansori, Kamyar; Sanjari Moghaddam, Ali; Ayubi, Erfan

2016-01-01

This study aimed to quantify associations of the human development inequality (HDI) index with incidence, mortality, and mortality to incidence ratios for eight common cancers among different countries. In this ecological study, data about incidence and mortality rates of cancers was obtained from the Global Cancer Project for 169 countries. HDI indices for the same countries was obtained from the United Nations Development Program (UNDP) database. The concentration index was defined as the covariance between cumulative percentage of cancer indicators (incidence, mortality and mortality to incidence ratio) and the cumulative percentage of economic indicators (country economic rank). Results indicated that incidences of cancers of liver, cervix and esophagus were mainly concentrated in countries with a low HDI index while cancers of lung, breast, colorectum, prostate and stomach were concentrated mainly in countries with a high HDI index. The same pattern was observed for mortality from cancer except for prostate cancer that was more concentrated in countries with a low HDI index. Higher MIRs for all cancers were more concentrated in countries with a low HDI index. It was concluded that patterns of cancer occurrence correlate with care disparities at the country level.

Body mass index and mortality in men with prostate cancer.

PubMed

Cantarutti, Anna; Bonn, Stephanie E; Adami, Hans-Olov; Grönberg, Henrik; Bellocco, Rino; Bälter, Katarina

2015-08-01

Body Mass index (BMI) has been shown to affect risk and mortality of several cancers. Prostate cancer and obesity are major public health concerns for middle-aged and older men. Previous studies of pre-diagnostic BMI have found an increased risk of prostate cancer mortality in obese patients. To study the associations between BMI at time of prostate cancer diagnosis and prostate cancer specific and overall mortality. BMI was analyzed both as a continuous variable and categorized into four groups based on the observed distribution in the cohort (BMI < 22.5, 22.5 < 25, 25 < 27.5 and ≥27.5 kg/m2). The association between BMI and mortality was assessed using stratified Cox proportional hazards models and by fitting regression splines for dose response analysis in 3,161 men diagnosed with prostate cancer. After 11 years of follow up via linkage to the population-based cause of death registry, we identified 1,161 (37%) deaths off which 690 (59%) were due to prostate cancer. High BMI (BMI ≥ 27.5 kg/m2) was associated with a statistically significant increased risk of prostate cancer specific mortality (HR:1.44, 95% CI: 1.09-1.90) and overall mortality (HR:1.33, 95% CI: 1.09-1.63) compared to the reference group (BMI 22.5 < 25 kg/m2). Additionally, men with a low BMI (<22.5 kg/m2 ), had a statistically significant increased risk of prostate cancer specific mortality (HR:1.33, 95% CI: 1.02-1.74) and overall mortality (HR:1.36, 95% CI: 1.11-1.67) compared to the reference. However, this effect disappeared when men who died within the first two years of follow-up were excluded from the analyses while the increased risk of prostate cancer specific mortality and overall mortality remained statistically significant for men with a BMI ≥ 27.5 kg/m2 (HR:1.44, 95% CI: 1.09-1.90 and HR: 1.33, 95% CI: 1.09-1.63, respectively). This study showed that a high BMI at time of prostate cancer diagnosis was associated with increased overall mortality. © 2015 Wiley Periodicals, Inc.

Expression of Pleiotrophin in the Prostate is Androgen Regulated and it Functions as an Autocrine Regulator of Mesenchyme and Cancer Associated Fibroblasts and as a Paracrine Regulator of Epithelia

PubMed Central

Orr, Brigid; Vanpoucke, Griet; Grace, O Cathal; Smith, Lee; Anderson, Richard A; Riddick, Antony CP; Franco, Omar E; Hayward, Simon W; Thomson, Axel A

2011-01-01

BACKGROUND Androgens and paracrine signaling from mesenchyme/stroma regulate development and disease of the prostate, and gene profiling studies of inductive prostate mesenchyme have identified candidate molecules such as pleiotrophin (Ptn). METHODS Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR. Ptn function was examined by addition of hPTN protein to rat ventral prostate organ cultures, primary human fetal prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. RESULTS During development, Ptn transcripts and protein were expressed in ventral mesenchymal pad (VMP) and prostatic mesenchyme. Ptn was localized to mesenchyme surrounding ductal epithelial tips undergoing branching morphogenesis, and was located on the surface of epithelia. hPTN protein stimulated branching morphogenesis and stromal and epithelial proliferation, when added to rat VP cultures, and also stimulated growth of fetal human prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. PTN mRNA was enriched in patient-matched normal prostate fibroblasts versus prostate cancer associated fibroblasts. PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice. Transcripts for PTN were upregulated by testosterone in fetal human prostate fibroblasts and organ cultures of female rat VMP. Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female. CONCLUSIONS Our data suggest that in the prostate Ptn functions as a regulator of both mesenchymal and epithelial proliferation, and that androgens regulate Ptn levels. Prostate 71:305–317, 2011. © 2010 Wiley-Liss, Inc. PMID:20812209

High serum concentration of estradiol may be a risk factor of prostate enlargement in aging male in China.

PubMed

Xu, Ding; Wu, Yu; Shen, Haibo; Qian, Subo; Qi, Jun

2018-06-18

Assess the association between serum sex hormone level and prostate volume in men with benign prostatic hyperplasia (BPH). The study involved 239 BPH patients from January 2013 to June 2015 in our hospital. Each patient collected age, medical history, height, weight, body mass index, as well as a full examination of sex hormones, and transrectal ultrasound results. Estradiol (E2) was significantly associated with prostate volume (r = 0.151, p = .02) and transitional zone volume (r = 0.136, p = .035). The association was more significant after adjusting age and BMI (r = 0.253 and 0.250, p <.001). Patients were divided into two groups according to prostate volume and E2, respectively. E2 in patients with prostate volume ≤50 ml was significantly lower than those with prostate volume >50 ml. Prostate volume, transitional zone volume and age were all significantly higher in the patients with E2 ≥ 160 umol/l than those in the patients with E2 < 160 umol/l. Through logistics regression, E2 (p = .012, OR = 1.004) are the only independent risk factor for prostate volume. E2 is significantly associated with prostate volume. High concentrations of E2 may be a risk factor for the large volume of prostate.

Penile vascular evaluation and sexual function before and after radical retropubic prostatectomy: 5-year follow-up.

PubMed

Dubbelman, Yvette D; Wildhagen, Mark F; Dohle, Gert R

2008-09-01

Sexual dysfunction is common after surgery for prostate cancer. The aetiology of changes in sexual potency after radical prostatectomy is probably multifactorial, including neurogenic, vascular and psychosexual factors. A prospective study was designed to investigate haemodynamic and psychosexual changes before and after radical retropubic prostatectomy (RRP) for organ-confined prostate cancer. Penile haemodynamic evaluation and an assessment of sexual excitement were performed preoperatively and 3 months after RRP by colour Doppler ultrasonography (CDU) with visual erotic stimulation combined with a single intracavernous injection of a mixture of papaverine/phentolamine. Questionnaires on sexual function [International Index of Erectile Function (IIEF)], general health and quality of life were sent to the patients preoperative, 3 months and 5 years after operation. Forty-eight men participated in the study. Mean age was 62.6 years (range 55-69). CDU did not show any significant reduction in mean peak systolic flow velocity and mean resistance index. From the men who preoperatively had normal arterial inflow 18% developed arteriogenic insufficiency. Some form of veno-occlusive insufficiency and low resistance indices were already present in the majority of normal potent men preoperatively. Surgical technique did not influence penile arterial blood flow after the operation. Three months and 5 years postoperatively, there was a highly significant reduction in erectile function, intercourse satisfaction, overall satisfaction, orgasmic function and sexual desire. However, with respect to the outcome at 3 months there was a significant improvement of orgasmic function 5 years after operation, especially after a bilateral nerve sparing procedure. Erections sufficient for vaginal penetration (questions 3 and 4 of the IIEF, score >or=8) improved from 2% to 11% 3 months and 5 years after RRP respectively. Total IIEF score was significantly better after a bilateral nerve-sparing procedure compared with non-nerve sparing. No structural vascular changes were observed 3 months after operation. Vascular factors appear to be less important in the aetiology of ED after RRP. There seems to be a trend of a better improvement of sexual function over time, especially orgasmic function, in patients with bilateral nerve-sparing surgery.

Tadalafil - a therapeutic option in the management of BPH-LUTS.

PubMed

Carson, C C; Rosenberg, M; Kissel, J; Wong, D G

2014-01-01

Men with signs of benign prostatic hyperplasia (BPH) may experience lower urinary tract symptoms (LUTS) such as urinary frequency, urgency, intermittence, nocturia, straining, incomplete emptying or a weak urinary stream. The effective management of LUTS suggestive of BPH (BPH-LUTS) requires careful consideration of several factors, including the severity of a patient's symptoms, concurrent or other coexisting medical conditions, the ability to improve symptoms and impact quality of life (QOL), as well as the potential side effects of available treatment options. Several clinical studies have assessed phosphodiesterase type 5 (PDE5) inhibitors in reducing LUTS; however, tadalafil is the only PDE5 inhibitor approved for the treatment of signs and symptoms of BPH, as well as in men with both erectile dysfunction (ED) and the signs and symptoms of BPH. This review examined articles that assessed tadalafil in patients with signs and symptoms of BPH, with or without erectile dysfunction (ED), which led to regulatory approval in the United States and Europe. In dose-ranging and confirmatory studies, results demonstrate that tadalafil significantly improved total International Prostate Symptom Score (IPSS) following 12 weeks of treatment with once daily tadalafil 5 mg. Statistically significant improvements in Benign Prostatic Hyperplasia Impact Index (BII), IPSS subscores, IPSS QOL and International Index of Erectile Function (IIEF) were also observed. Improvement in urinary symptoms occurred regardless of age, previous treatment with an α1 -adrenergic blocker, BPH-LUTS severity at baseline or ED status. While tadalafil is most frequently recognised as a standard treatment option for men with ED, it also represents a well-tolerated and effective treatment option in men with moderate to severe BPH-LUTS. © 2013 John Wiley & Sons Ltd.

Intraprostatic injection of botulinum toxin type- A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs

PubMed Central

Chuang, Yao-Chi; Tu, Chieh-Hsien; Huang, Chao-Cheng; Lin, Hsin-Ju; Chiang, Po-Hui; Yoshimura, Naoki; Chancellor, Michael B

2006-01-01

Background With the increasing interest with botulinum toxin – A (BTX-A) application in the lower urinary tract, we investigated the BTX-A effects on the canine prostate and also in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH). Methods Transperineal injection into the prostate using transrectal ultrasound (TRUS) was performed throughout the study. Saline with or without 100 U of BTX-A was injected into mongrel dogs prostate. One or 3 months later, the prostate was harvested for morphologic and apoptotic study. In addition, eight BPH patients refractory to α-blockers were treated with ultrasound guided intraprostatic injection of 200 U of BTX-A. Results In the BTX-A treated dogs, atrophy and diffuse apoptosis was observed with H&E stain and TUNEL stain at 1 and 3 months. Clinically, the mean prostate volume, symptom score, and quality of life index were significantly reduced by 18.8%, 73.1%, and 61.5% respectively. Maximal flow rate significantly increased by 72.0%. Conclusion Intraprostatic BTX-A injection induces prostate apotosis in dogs and relieves BOO in humans. It is therefore a promising alternative treatment for refractory BOO due to BPH. PMID:16620393

Robotic Assisted Simple Prostatectomy versus Holmium Laser Enucleation of the Prostate for Lower Urinary Tract Symptoms in Patients with Large Volume Prostate: A Comparative Analysis from a High Volume Center.

PubMed

Umari, Paolo; Fossati, Nicola; Gandaglia, Giorgio; Pokorny, Morgan; De Groote, Ruben; Geurts, Nicolas; Goossens, Marijn; Schatterman, Peter; De Naeyer, Geert; Mottrie, Alexandre

2017-04-01

We report a comparative analysis of robotic assisted simple prostatectomy vs holmium laser enucleation of the prostate in patients who had benign prostatic hyperplasia with a large volume prostate (greater than 100 ml). A total of 81 patients underwent robotic assisted simple prostatectomy and 45 underwent holmium laser enucleation of the prostate in a 7-year period. Patients were preoperatively assessed with transrectal ultrasound and uroflowmetry. Functional parameters were assessed postoperatively during followup. Perioperative outcomes included operative time, postoperative hemoglobin, catheterization time and hospitalization. Complications were reported according to the Clavien-Dindo classification. Compared to the holmium laser enucleation group, patients treated with prostatectomy were significantly younger (median age 69 vs 74 years, p = 0.032) and less healthy (Charlson comorbidity index 2 or greater in 62% vs 29%, p = 0.0003), and had a lower rate of suprapubic catheterization (23% vs 42%, p = 0.028) and a higher preoperative I-PSS (International Prostate Symptom Score) (25 vs 21, p = 0.049). Both groups showed an improvement in the maximum flow rate (15 vs 11 ml per second, p = 0.7), and a significant reduction in post-void residual urine (-73 vs -100 ml, p = 0.4) and I-PSS (-20 vs -18, p = 0.8). Median operative time (105 vs 105 minutes, p = 0.9) and postoperative hemoglobin (13.2 vs 13.8 gm/dl, p = 0.08) were similar for robotic assisted prostatectomy and holmium laser enucleation, respectively. Median catheterization time (3 vs 2 days, p = 0.005) and median hospitalization (4 vs 2 days, p = 0.0001) were slightly shorter in the holmium laser group. Complication rates were similar with no Clavien grade greater than 3 in either group. Our results from a single center suggest comparable outcomes for robotic assisted simple prostatectomy and holmium laser enucleation of the prostate in patients with a large volume prostate. These findings require external validation at other high volume centers. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Fermented whey-based product improves the quality of life of males with moderate lower urinary tract symptoms: A randomized double-blind study.

PubMed

Ausmees, Kristo; Ehrlich-Peets, Kersti; Vallas, Mirjam; Veskioja, Andre; Rammul, Kadi; Rehema, Aune; Zilmer, Mihkel; Songisepp, Epp; Kullisaar, Tiiu

2018-01-01

The purpose of this research was to evaluate the effect of a specific fermented whey product on lower urinary tract symptoms, main prostate related indices and oxidative stress/inflammatory markers in urine and seminal plasma in men with moderate dysuric symptoms. An additional purpose was to clarify associations between different parameters with special emphasis on pain. This was a prospective randomized double-blind 4-weeks study on men with moderate lower urinary tract symptoms who underwent the evaluation for quality of life at the baseline and at the end of the study. The symptoms were characterized by International Prostate Symptom Score (I-PSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-PSI), the maximum urinary flow and the main prostate-related indices. In order to obtain more comprehensive information about the effects of fermented whey product on systemic oxidative stress marker 8-EPI and seminal plasma inflammatory markers (interleukin-6 and interleukin-8) were also measured. After 4 weeks consumption of fermented whey product there was a statistically significant decrease of prostate-specific antigen level in serum and systemic stress marker 8-EPI in urine compared to control group. Maximum urinary flow and NIH-PSI all studied scores and sub-scores had also significant improvement. In addition, seminal plasma interleukin-8 level substantially decreased. The consumption of special fermented whey product improved urinary function, reduced lower urinary tract symptoms, systemic oxidative stress marker and seminal plasma inflammatory status. Thus it contributed to an improvement of the quality of life in men with moderate lower urinary tract symptoms.

Health-Related Quality of Life After Stereotactic Body Radiation Therapy for Localized Prostate Cancer: Results From a Multi-institutional Consortium of Prospective Trials

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

King, Christopher R., E-mail: crking@mednet.ucla.edu; Collins, Sean; Fuller, Donald

Purpose: To evaluate the early and late health-related quality of life (QOL) outcomes among prostate cancer patients following stereotactic body radiation therapy (SBRT). Methods and Materials: Patient self-reported QOL was prospectively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer. Data from the Expanded Prostate Cancer Index Composite (EPIC) instrument were obtained at baseline and at regular intervals up to 6 years. SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions. A short course of androgen deprivation therapy was given to 14% of patients. Results: Median follow-up was 3 yearsmore » and 194 patients remained evaluable at 5 years. A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years. The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities. Sexual QOL decline was predominantly observed within the first 9 months, a pattern not altered by the use of androgen deprivation therapy or patient age. Conclusion: Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL. A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels. With a large number of patients evaluable up to 5 years following SBRT, it is unlikely that unexpected late adverse effects will manifest themselves.« less

Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

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

Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R., E-mail: ms@ctu.mrc.ac.u

2010-07-01

Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Managementmore » (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.« less

Poster - 47: A parametrized prediction model of rectal toxicity in focal SBRT of low risk prostate cancer

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

Stevens, Todd; Bauman, Glenn

There has been a recent trend towards watchful waiting in place of intervention for early stage prostate cancer (CaP). However, this approach can allow for disease progression, and subsequent whole-gland therapies such as prostatectomy and whole gland irradiation can result in functional deficits or rectal toxicities or both. A controversial alternative approach for this patient cohort is the use of focal therapy, where the treatment is focussed on an identified dominant index lesion (DIL). This work aims to investigate the treatment parameters for focal SBRT of the prostate under which clinically acceptable rectal NTCP levels can be achieved. For eachmore » of 25 low risk CaP patients, a hypothetical 2 cc DIL was modeled in the right-posterior quadrant of the prostate, and was used to build a PTV as the target for SBRT simulation. An SBRT prescriptions of 41 Gy and 37 Gy in 5 fractions were chosen, corresponding to the boost levels used in previous CaP dose escalation studies. DVH data were exported and used to calculate rectal NTCP values based on the Lyman-Kutcher-Burman (LKB) model using the QUANTEC reccommended model parameters. Rectal NTCP dependence on DIL-to-rectum separation, dose level, and DIL volume were investigated. The final goal of this ongoing work is to create a map of the maximum allowable prescription dose for a given patient geometry that achieves a clinically acceptable rectal NTCP level.« less

Resveratrol regulates PTEN/Akt pathway through inhibition of MTA1/HDAC unit of the NuRD complex in prostate cancer.

PubMed

Dhar, Swati; Kumar, Avinash; Li, Kun; Tzivion, Guri; Levenson, Anait S

2015-02-01

Metastasis associated protein 1 (MTA1) is a component of the nucleosome remodeling and deacetylating (NuRD) complex which mediates gene silencing and is overexpressed in several cancers. We reported earlier that resveratrol, a dietary stilbene found in grapes, can down-regulate MTA1. In the present study, we show that PTEN is inactivated by MTA1 in prostate cancer cells. Further, we show that resveratrol promotes acetylation and reactivation of PTEN via inhibition of the MTA1/HDAC complex, resulting in inhibition of the Akt pathway. In addition, we show that MTA1 knockdown is sufficient to augment acetylation of PTEN indicating a crucial role of MTA1 itself in the regulation of PTEN acetylation contributing to its lipid phosphatase activity. Acetylated PTEN preferentially accumulates in the nucleus where it binds to MTA1. We also show that MTA1 interacts exclusively with PTEN acetylated on Lys¹²⁵ and Lys¹²⁸, resulting in diminished p-Akt levels. Finally, using orthotopic prostate cancer xenografts, we demonstrate that both resveratrol treatment and MTA1 knockdown enhance PTEN levels leading to a decreased p-Akt expression and proliferation index. Taken together, our results indicate that MTA1/HDAC unit is a negative regulator of PTEN which facilitates survival pathways and progression of prostate cancer and that resveratrol can reverse this process through its MTA1 inhibitory function. Copyright © 2014 Elsevier B.V. All rights reserved.

A pilot study analyzing PSA, serum testosterone, lipid profile, body mass index and race in a small sample of patients with and without carcinoma of the prostate.

PubMed

Mydlo, J H; Tieng, N L; Volpe, M A; Chaiken, R; Kral, J G

2001-01-01

Androgens, diet, race and obesity are thought to play some roles in the pathogenesis of prostate cancer. We wanted to evaluate if there were any inter-relationships between prostate specific antigen (PSA), serum testosterone, serum cholesterol, HDL, triglycerides, body mass index (BMI) and race, in older patients with and without prostate cancer (CaP). We evaluated 308 patients referred to urologists in private practice offices and clinics with and without prostate cancer with regard to race, serum PSA, age, serum testosterone, full lipid profile, height and weight, and stage of cancer. We used multivariate analysis, Fisher's exact test and t-tests as well as logistic regression analysis. Data was analyzed using SPSS computer software, and P-values<0.05 were considered statistically significant. Significantly higher levels of serum testosterone were found in black men with CaP than black men without CaP (526+/-28 vs 404+/-19, respectively.) We also found significantly higher levels of serum testosterone in white men with CaP than white men without CaP (409+/-20 vs 302+/-14, respectively, P<0.05). HDL was higher in black men than white men, and triglycerides were higher in white men than black men. Cholesterol was similar across all groups, but BMI was highest in white men with CaP. We also found a significant association between BMI and pathological stage of prostate cancer patients among both black and white men (P<0.05). Our study demonstrated that black men who developed CaP had higher serum testosterone levels, on average, than white men who developed CaP. Furthermore, BMI was highest in white men developing CaP compared to black men, but we found a significant association between pathological stage and BMI in both black and white patients. Although it is controversial whether obesity is considered to be a risk factor for prostate cancer, this small pilot study suggests that BMI may play a role in the progression of the disease once it is established.Prostate Cancer and Prostatic Diseases (2001) 4, 101-105

Detection of the index tumour and tumour volume in prostate cancer using T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) alone.

PubMed

Rud, Erik; Klotz, Dagmar; Rennesund, Kristin; Baco, Eduard; Berge, Viktor; Lien, Diep; Svindland, Aud; Lundeby, Eskild; Berg, Rolf E; Eri, Lars M; Eggesbø, Heidi B

2014-12-01

To examine the performance of T2-weighted (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for detecting the index tumour in patients with prostate cancer and to examine the agreement between MRI and histology when assessing tumour volume (TV) and overall tumour burden. The study included 199 consecutive patients with biopsy confirmed prostate cancer randomised to MRI before radical prostatectomy from December 2009 to July 2012. MRI-detected tumours (MRTs) were ranked from 1 to 3 according to decreasing volume and were compared with histologically detected tumours (HTs) ranked from 1 to 3, with HT 1 = index tumour. Whole-mount section histology was used as a reference standard. The TVs of true-positive MRTs (MRTVs 1-3) were compared with the TVs found by histology (HTVs 1-3). All tumours were registered on a 30-sector map and by classifying each sector as positive/negative, the rate of true-positive and -negative sectors was calculated. The detection rate for the HT 1 (index tumour) was 92%; HT 2, 45%; and HT 3, 37%. The MRTV 1-3 vs the HTV 1-3 were 2.8 mL vs 4.0 mL (index tumour, P < 0.001), 1.0 mL vs 0.9 mL (tumour 2, P = 0.413), and 0.6 mL vs 0.5 mL (tumour 3, P = 0.492). The rate of true-positive and -negative sectors was 50% and 88%, κ = 0.39. A combination of T2W and DW MRI detects the index tumour in 92% of cases, although MRI underestimates both TV and tumour burden compared with histology. © 2014 The Authors. BJU International © 2014 BJU International.

Urinary Bother as a Predictor of Postsurgical Changes in Urinary Function After Robotic Radical Prostatectomy.

PubMed

Murphy, Gregory; Haddock, Peter; Doak, Hoyt; Jackson, Max; Dorin, Ryan; Meraney, Anoop; Kesler, Stuart; Staff, Ilene; Wagner, Joseph R

2015-10-01

To characterize changes in indices of urinary function in prostatectomy patients with presurgical voiding symptoms. A retrospective analysis of our prostate cancer database identified robot-assisted radical prostatectomy patients between April 2007 and December 2011 who completed pre- and postsurgical (24 months) Expanded Prostate Cancer Index Composite-26 surveys. Gleason score, margins, D'Amico risk, prostate-specific antigen, radiotherapy, and nerve-sparing status were tabulated. Survey questions addressed urinary irritation/obstruction, incontinence, and overall bother. Responses were averaged to calculate a urinary sum (US) score. Patients were stratified according to the severity of their baseline urinary bother (UB), and changes in urinary indices determined at 24 months. A total of 737 patients were included. Postsurgical improvement in urinary obstruction, bother, and sum score was related to baseline UB (P <.001). Men with severe baseline bother had the greatest improvement in US (+9.3), whereas those with asymptomatic baseline UB experienced a decline in US (-2.8). All patients experienced a decline in urinary incontinence of 6.3-8.3 that was independent of baseline bother (P = .507). Patients with severe UB experienced positive outcomes, whereas those at asymptomatic baseline experienced negative US outcomes. Negative urinary incontinence outcomes were unrelated to baseline UB. Age, radiotherapy, and nerve-sparing status were not associated with improved UB (P = .029). However, baseline UB was significantly associated with improvement in postsurgical UB (P = .001). Baseline UB is a predictor of postsurgical improvement in urinary function. These data are helpful when counseling a subset of robot-assisted laparoscopic radical prostatectomy patients with severe preoperative urinary symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Suicidal ideation in prostate cancer survivors: understanding the role of physical and psychological health outcomes.

PubMed

Recklitis, Christopher J; Zhou, Eric S; Zwemer, Eric K; Hu, Jim C; Kantoff, Philip W

2014-11-01

Epidemiological studies have shown prostate cancer (PC) survivors are at an increased risk of suicide compared with the general population, but to the authors' knowledge very little is known regarding what factors are associated with this increased risk. The current study examined the prevalence of suicidal ideation (SI) and its association with cancer treatment and posttreatment physical and emotional health in a cohort of long-term PC survivors. A total of 693 PC survivors (3-8 years after diagnosis) completed a mailed survey on physical and psychological functioning, including cancer treatments, the Short Form-12 (SF-12), the Expanded Prostate Cancer Index Composite Instrument (EPIC-26), a depression rating scale, and 8 items regarding recent suicidal thoughts and behaviors. A total of 86 PC survivors (12.4%) endorsed SI, with 10 individuals (1.4%) reporting serious SI. Serious SI was more common in this sample compared with age-adjusted and sex-adjusted normative data. SI was not associated with most demographic variables, or with PC stage or treatments. However, SI was found to be significantly associated with employment status, poor physical and emotional functioning, greater symptom burden on the EPIC-26, higher frequency of significant pain, and clinically significant depression (P < .01). In an adjusted logistic model, poor physical and emotional function, including disability status and pain, were found to be associated with SI (P < .05), even after adjusting for depression. A significant percentage of PC survivors report recent SI, which is associated with both physical and psychological dysfunction, but not PC treatments. The results of the current study help to explain the increased risk of suicide previously reported in PC survivors and have important implications for identifying and treating those survivors at greatest risk of suicidality. © 2014 American Cancer Society.

Neuropilin-1-targeted gold nanoparticles enhance therapeutic efficacy of platinum(IV) drug for prostate cancer treatment.

PubMed

Kumar, Anil; Huo, Shuaidong; Zhang, Xu; Liu, Juan; Tan, Aaron; Li, Shengliang; Jin, Shubin; Xue, Xiangdong; Zhao, YuanYuan; Ji, Tianjiao; Han, Lu; Liu, Hong; Zhang, XiaoNing; Zhang, Jinchao; Zou, Guozhang; Wang, Tianyou; Tang, Suoqin; Liang, Xing-Jie

2014-05-27

Platinum-based anticancer drugs such as cisplatin, oxaliplatin, and carboplatin are some of the most potent chemotherapeutic agents but have limited applications due to severe dose-limiting side effects and a tendency for cancer cells to rapidly develop resistance. The therapeutic index can be improved through use of nanocarrier systems to target cancer cells efficiently. We developed a unique strategy to deliver a platinum(IV) drug to prostate cancer cells by constructing glutathione-stabilized (Au@GSH) gold nanoparticles. Glutathione (GSH) has well-known antioxidant properties, which lead to cancer regression. Here, we exploit the advantages of both the antioxidant properties and high surface-area-to-volume ratio of Au@GSH NPs to demonstrate their potential for delivery of a platinum(IV) drug by targeting the neuropilin-1 receptor (Nrp-1). A lethal dose of a platinum(IV) drug functionalized with the Nrp-1-targeting peptide (CRGDK) was delivered specifically to prostate cancer cells in vitro. Targeted peptide ensures specific binding to the Nrp-1 receptor, leading to enhanced cellular uptake level and cell toxicity. The nanocarriers were themselves nontoxic, but exhibited high cytotoxicity and increased efficacy when functionalized with the targeting peptide and drug. The uptake of drug-loaded nanocarriers is dependent on the interaction with Nrp-1 in cell lines expressing high (PC-3) and low (DU-145) levels of Nrp-1, as confirmed through inductively coupled plasma mass spectrometry and confocal microscopy. The nanocarriers have effective anticancer activity, through upregulation of nuclear factor kappa-B (NF-κB) protein (p50 and p65) expression and activation of NF-κB-DNA-binding activity. Our preliminary investigations with platinum(IV)-functionalized gold nanoparticles along with a targeting peptide hold significant promise for future cancer treatment.

Association between penile dynamic contrast-enhanced MRI-derived quantitative parameters and self-reported sexual function in patients with newly diagnosed prostate cancer.

PubMed

Vargas, Hebert Alberto; Donati, Olivio F; Wibmer, Andreas; Goldman, Debra A; Mulhall, John P; Sala, Evis; Hricak, Hedvig

2014-10-01

The high incidence of prostate cancer, coupled with excellent prostate cancer control rates, has resulted in growing interest in nononcological survivorship issues such as sexual function. Multiparametric magnetic resonance imaging (MRI) is increasingly being performed for local staging of prostate cancer, and due to the close anatomical relationship to the prostate, penile enhancement is often depicted in prostate MRI. To evaluate the associations between quantitative perfusion-related parameters derived from dynamic contrast-enhanced (DCE)-MRI of the penis and self-reported sexual function in patients with newly diagnosed prostate cancer. This retrospective study included 50 patients who underwent DCE-MRI for prostate cancer staging before prostatectomy. The following perfusion-related parameters were calculated: volume transfer constant (K(trans)), rate constant (k(ep)), extracellular-extravascular volume fraction (v(e)), contrast enhancement ratio (CER), area under the gadolinium curve after 180 seconds (AUC180), and slope of the time/signal intensity curve of the corpora cavernosa. Associations between perfusion-related parameters and self-reported sexual function were evaluated using the Wilcoxon Rank-Sum test. Patient responses to the sexual function domain of the Prostate Quality of Life survey. Five of the six DCE-MRI parameters (K(trans), v(e), CER, AUC180, and slope) were significantly associated with the overall score from the sexual domain of the survey (P = 0.0020-0.0252). CER, AUC180, and slope were significantly associated with the answers to all six questions (P = 0.0020-0.0483), ve was significantly associated with the answers to five of six questions (P = 0.0036-0.1029), and K(trans) was significantly associated with the answers to three of six questions (P = 0.0252-0.1023). k(ep) was not significantly associated with the overall survey score (P = 0.7665) or the answers to any individual questions (P = 0.4885-0.8073). Penile DCE-MRI parameters were significantly associated with self-reported sexual function in patients with prostate cancer. These parameters are readily available when performing prostate MRI for staging and may be relevant to the management of patients considering prostate cancer therapies. © 2014 International Society for Sexual Medicine.

Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

PubMed Central

O'Hurley, Gillian; Busch, Christer; Fagerberg, Linn; Hallström, Björn M.; Stadler, Charlotte; Tolf, Anna; Lundberg, Emma; Schwenk, Jochen M.; Jirström, Karin; Bjartell, Anders; Gallagher, William M.; Uhlén, Mathias; Pontén, Fredrik

2015-01-01

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL. PMID:26237329

PHI in the Early Detection of Prostate Cancer.

PubMed

Fuchsova, Radka; Topolcan, Ondrej; Windrichova, Jindra; Hora, Milan; Dolejsova, Olga; Pecen, Ladislav; Kasik, Petr; Novak, Jaroslav; Casova, Miroslava; Smejkal, Jiri

2015-09-01

To evaluate changes in the serum levels of prostate specific antigen (PSA), %free PSA and -2proPSA biomarkers, and prostate health index (PHI) in the diagnostic algorithm of early prostate cancer. The Immunoanalytical Laboratory of the University Hospital in Pilsen examined sera from 263 patients being treated at the Hospital's Urology Department with suspected prostate cancer who had undergone biopsies and were divided into a benign and malignant group. The monitored biomarkers were measured using chemiluminescence. All statistical analyses were calculated using the SAS software. We found statistically significantly increased levels of -2proPSA, PHI and PSA and decreased levels of %freePSA in patients diagnosed with prostate cancer by prostate biopsy vs. patients with benign prostatic hypertrophy (median values: -2proPSA: 16 vs. 21 ng/l, PHI: 35 vs. 62, total PSA: 7.2 vs. 7.7 μg/l and %free PSA: 16.7 vs. 11.7%). Receiver operating characteristic curves showed the best performance for PHI compared to other markers. The assessment of -2proPSA and the calculation of PHI appear to be of great benefit for a more accurate differential diagnosis of benign hyperplasia and prostate cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Open vs Laparoscopic Simple Prostatectomy: A Comparison of Initial Outcomes and Cost.

PubMed

Demir, Aslan; Günseren, Kadir Ömür; Kordan, Yakup; Yavaşçaoğlu, İsmet; Vuruşkan, Berna Aytaç; Vuruşkan, Hakan

2016-08-01

We compared the cost-effectiveness of laparoscopic simple prostatectomy (LSP) vs open prostatectomy (OP). A total of 73 men treated for benign prostatic hyperplasia were enrolled for OP and LSP in groups 1 and 2, respectively. The findings were recorded perioperative, including operation time (OT), blood lost, transfusion rate, conversion to the open surgery, and the complications according to the Clavien Classification. The postoperative findings, including catheterization and drainage time, the amount of analgesic used, hospitalization time, postoperative complications, international prostate symptom score (IPSS) and International Index of Erectile Function (IIEF) scores, the extracted prostate weight, the uroflowmeter, as well as postvoiding residual (PVR) and quality of life (QoL) score at the postoperative third month, were analyzed. The cost of both techniques was also compared statistically. No statistical differences were found in the preoperative parameters, including age, IPSS and QoL score, maximum flow rate (Qmax), PVR, IIEF score, and prostate volumes, as measured by transabdominal ultrasonography. No statistical differences were established in terms of the OT and the weight of the extracted prostate. No differences were established with regard to complications according to Clavien's classification in groups. However, the bleeding rate was significantly lower in group 2. The drainage, catheterization, and hospitalization times and the amount of analgesics were significantly lower in the second group. The postoperative third month findings were not different statistically. Only the Qmax values were significantly greater in group 2. While there was only a $52 difference between groups with regard to operation cost, this difference was significantly different. The use of LSP for the prostates over 80 g is more effective than the OP in terms of OT, bleeding amount, transfusion rates, catheterization time, drain removal time, hospitalization time, consumed analgesic amount, and Qmax values. On the other hand, the mean cost of the LSP is higher than OP. Better effectiveness comes with higher cost.

Association between preoperative erectile dysfunction and prostate cancer features--an analysis from the Duke Prostate Center Database.

PubMed

Kimura, Masaki; Bañez, Lionel L; Gerber, Leah; Qi, Jim; Tsivian, Matvey; Freedland, Stephen J; Satoh, Takefumi; Polascik, Thomas J; Baba, Shiro; Moul, Judd W

2012-04-01

Erectile dysfunction (ED) is related to several co-morbidities including obesity, metabolic syndrome, cigarette smoking, and low testosterone, all of which have been reported to be associated with adverse prostate cancer features. To examine whether preoperative ED has a relationship with adverse prostate cancer features in patients who underwent radical prostatectomy (RP). We analyzed data from our institution on 676 patients who underwent RP between 2001 and 2010. Crude and adjusted logistic regression models were used to investigate the association between preoperative ED and several pathological parameters. The log-rank test and multivariate proportional hazards model were conducted to determine the association of preoperative ED with biochemical recurrence (BCR). The expanded prostate cancer index composite (EPIC) instrument was used to evaluate preoperative erectile function (EF). Preoperative normal EF was defined as EPIC-SF ≥ 60 points while ED was defined as preoperative EPIC-SF lower than 60 points. Preoperatively, a total of 343 (50.7%) men had normal EF and 333 (49.3%) men had ED. After adjusting for covariates, preoperative ED was identified a risk factor for positive extracapsular extension (OR 1.57; P = 0.029) and high percentage of tumor involvement (OR 1.56; P = 0.047). In a Kaplan-Meier curve, a trend was identified that patients with ED had higher incidence of BCR than men with normal EF (P = 0.091). Moreover, using a multivariate Cox model, higher preoperative EF was negatively associated with BCR (HR 0.99; P = 0.014). These results suggest that the likelihood for adverse pathological outcomes as well as BCR following prostatectomy is higher among men with preoperative ED, though these results require validation in larger datasets. The present study indicates that preoperative ED might be a surrogate for adverse prostate cancer outcomes following RP. © 2011 International Society for Sexual Medicine.

Patient-reported outcomes following stereotactic body radiation therapy for clinically localized prostate cancer

PubMed Central

2014-01-01

Background Stereotactic body radiation therapy (SBRT) delivers high doses of radiation to the prostate while minimizing radiation to adjacent normal tissues. Large fraction sizes may increase the risk of functional decrements. Treatment-related bother may be more important to a patient than treatment-related dysfunction. This study reports on patient-reported outcomes following SBRT for clinically localized prostate cancer. Methods Between August 2007 and July 2011, 228 consecutive hormone-naïve patients with clinically localized prostate cancer were treated with 35–36.25 Gy SBRT delivered using the CyberKnife Radiosurgical System (Accuray) in 5 fractions. Quality of life was assessed using the American Urological Association Symptom Score (AUA) and the Expanded Prostate Cancer Index Composite (EPIC)-26. Urinary symptom flare was defined as an AUA score 15 or more with an increase of 5 or more points above baseline 6 months after treatment. Results 228 patients (88 low-, 126 intermediate- and 14 high-risk) at a median age of 69 (44–90) years received SBRT with a minimum follow-up of 24 months. EPIC urinary and bowel summary scores declined transiently at 1 month and experienced a second, more protracted decline between 9 months and 18 months before returning to near baseline 2 years post-SBRT. 14.5% of patients experienced late urinary symptom flare following treatment. Patients who experienced urinary symptom flare had poorer bowel quality of life following SBRT. EPIC scores for urinary bother declined transiently, first at 1 month and again at 12 months, before approaching pre-treatment scores by 2 years. Bowel bother showed a similar pattern, but the second decline was smaller and lasted 9 months to 18 months. EPIC sexual summary and bother scores progressively declined over the 2 years following SBRT without recovery. Conclusions In the first 2 years, the impact of SBRT on urination and defecation was minimal. Transient late increases in urinary and bowel dysfunction and bother were observed. However, urinary and bowel function and bother recovered to near baseline by 2 years post-SBRT. Sexual dysfunction and bother steadily increased following treatment without recovery. SBRT for clinically localized prostate cancer was well tolerated with treatment-related dysfunction and bother comparable to conventionally fractionated radiation therapy or brachytherapy. PMID:24512837

Androgen receptor: structure, role in prostate cancer and drug discovery

PubMed Central

Tan, MH Eileen; Li, Jun; Xu, H Eric; Melcher, Karsten; Yong, Eu-leong

2015-01-01

Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. PMID:24909511

Detecting microRNAs of high influence on protein functional interaction networks: a prostate cancer case study

PubMed Central

2012-01-01

Background The use of biological molecular network information for diagnostic and prognostic purposes and elucidation of molecular disease mechanism is a key objective in systems biomedicine. The network of regulatory miRNA-target and functional protein interactions is a rich source of information to elucidate the function and the prognostic value of miRNAs in cancer. The objective of this study is to identify miRNAs that have high influence on target protein complexes in prostate cancer as a case study. This could provide biomarkers or therapeutic targets relevant for prostate cancer treatment. Results Our findings demonstrate that a miRNA’s functional role can be explained by its target protein connectivity within a physical and functional interaction network. To detect miRNAs with high influence on target protein modules, we integrated miRNA and mRNA expression profiles with a sequence based miRNA-target network and human functional and physical protein interactions (FPI). miRNAs with high influence on target protein complexes play a role in prostate cancer progression and are promising diagnostic or prognostic biomarkers. We uncovered several miRNA-regulated protein modules which were enriched in focal adhesion and prostate cancer genes. Several miRNAs such as miR-96, miR-182, and miR-143 demonstrated high influence on their target protein complexes and could explain most of the gene expression changes in our analyzed prostate cancer data set. Conclusions We describe a novel method to identify active miRNA-target modules relevant to prostate cancer progression and outcome. miRNAs with high influence on protein networks are valuable biomarkers that can be used in clinical investigations for prostate cancer treatment. PMID:22929553

Hemi salvage high-intensity focused ultrasound (HIFU) in unilateral radiorecurrent prostate cancer: a prospective two-centre study.

PubMed

Baco, Eduard; Gelet, Albert; Crouzet, Sébastien; Rud, Erik; Rouvière, Olivier; Tonoli-Catez, Hélène; Berge, Viktor; Chapelon, Jean-Yves; Eggesbø, Heidi B

2014-10-01

To report the oncological and functional outcomes of hemi salvage high-intensity focused ultrasound (HSH) in patients with unilateral radiorecurrent prostate cancer. Between 2009 and 2012, 48 patients were prospectively enrolled in two European centres. Inclusion criteria were biochemical recurrence (BCR) after primary radiotherapy (RT), positive magnetic resonance imaging and ≥1 positive biopsy in only one lobe. BCR was defined using Phoenix criteria (a rise by ≥2 ng/mL above the nadir prostate specific antigen [PSA] level). The following schemes and criteria for functional outcomes were used: Ingelman-Sundberg score using International Continence Society (ICS) questionnaire (A and B), International prostate symptom score (IPSS), International Index of Erectile Function-5 (IIEF-5) points, the European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaires (QLQ C-30). HSH was performed under spinal or general anaesthesia using the Ablatherm® Integrated Imaging device. Patients with obstructive voiding symptoms at the time of treatment underwent an endoscopic bladder neck resection or incision during the same anaesthesia to prevent the risk of postoperative obstruction. After HSH the mean (sd) PSA nadir was 0.69 (0.83) ng/mL at a median (interquartile range) follow-up of 16.3 (10.5-24.5) months. Disease progression occurred in 16/48 (33%). Of these, four had local recurrence in the untreated lobe and four bilaterally, six developed metastases, and two had rising PSA levels without local recurrence or radiological confirmed metastasis. Progression-free survival rates at 12, 18, and 24 months were 83%, 64%, and 52%. Severe incontinence occurred in four of the 48 patients (8%), eight (17%) required one pad a day, and 36/48 (75%) were pad-free. The ICS questionnaire showed a mean (sd) deterioration from 0.7 (2.0) to 2.3 (4.5) for scores A and 0.6 (1.4) to 1.6 (3.0) for B. The mean (sd) IPSS and erectile function (IIEF-5) scores decreased from a mean (sd) of 7.01 (5.6) to 8.6 (5.1) and from 11.2 (8.6) to 7.0 (5.8), respectively. The mean (sd) EORTC QLC-30 scores before and after HSH were 35.7 (8.6) vs 36.8 (8.6). HSH is a feasible therapeutic option in patients with unilateral radiorecurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves health-related quality of life. © 2013 The Authors. BJU International © 2013 BJU International.

Diet and Exercise Intervention Adherence and Health-Related Outcomes among Older Long-Term Breast, Prostate, and Colorectal Cancer Survivors

PubMed Central

Winger, Joseph G.; Mosher, Catherine E.; Rand, Kevin L.; Morey, Miriam C.; Snyder, Denise C.; Demark-Wahnefried, Wendy

2014-01-01

Background Diet and exercise interventions for cancer survivors result in health benefits; however, few studies have examined health outcomes in relation to adherence. Purpose We examined associations between adherence to components of a diet–exercise intervention and survivors’ physical and mental health. Methods A randomized controlled trial tested a telephone and mailed print intervention among 641 older, overweight, long-term survivors of breast, prostate, and colorectal cancer. Dietary and exercise behaviors were assessed at 14 time points throughout the year-long intervention; health outcomes were examined postintervention. Results Telephone session attendance had significant indirect relationships with health outcomes through intervention-period exercise and dietary behavior. Attendance showed positive indirect relationships with physical function (β= 0.11, p<0.05), basic and advanced lower extremity function (β=0.10, p<0.05/β=0.09, p<0.05), and mental health (β= 0.05, p<0.05), and a negative indirect relationship with body mass index (β=−0.06, p<0.05). Conclusions Session attendance is vital in facilitating improvement in health behaviors and attendant outcomes (Clinicaltrials.gov number NCT00303875). PMID:24648018

Diet and exercise intervention adherence and health-related outcomes among older long-term breast, prostate, and colorectal cancer survivors.

PubMed

Winger, Joseph G; Mosher, Catherine E; Rand, Kevin L; Morey, Miriam C; Snyder, Denise C; Demark-Wahnefried, Wendy

2014-10-01

Diet and exercise interventions for cancer survivors result in health benefits; however, few studies have examined health outcomes in relation to adherence. We examined associations between adherence to components of a diet-exercise intervention and survivors' physical and mental health. A randomized controlled trial tested a telephone and mailed print intervention among 641 older, overweight, long-term survivors of breast, prostate, and colorectal cancer. Dietary and exercise behaviors were assessed at 14 time points throughout the year-long intervention; health outcomes were examined postintervention. Telephone session attendance had significant indirect relationships with health outcomes through intervention-period exercise and dietary behavior. Attendance showed positive indirect relationships with physical function (β = 0.11, p < 0.05), basic and advanced lower extremity function (β = 0.10, p < 0.05/β = 0.09, p < 0.05), and mental health (β = 0.05, p < 0.05), and a negative indirect relationship with body mass index (β = -0.06, p < 0.05). Session attendance is vital in facilitating improvement in health behaviors and attendant outcomes (Clinicaltrials.gov number NCT00303875).

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.

Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without (18)F-choline PET-CT detected simultaneous integrated boost.

PubMed

Pinkawa, Michael; Piroth, Marc D; Holy, Richard; Klotz, Jens; Djukic, Victoria; Corral, Nuria Escobar; Caffaro, Mariana; Winz, Oliver H; Krohn, Thomas; Mottaghy, Felix M; Eble, Michael J

2012-01-30

In comparison to the conventional whole-prostate dose escalation, an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity. Quality of life after radiotherapy (RT) with vs. without (18)F-choline PET-CT detected simultaneous integrated boost (SIB) was prospectively evaluated in this study. Whole body image acquisition in supine patient position followed 1 h after injection of 178-355MBq (18)F-choline. SIB was defined by a tumor-to-background uptake value ratio > 2 (GTV(PET)). A dose of 76Gy was prescribed to the prostate (PTV(prostate)) in 2Gy fractions, with or without SIB up to 80Gy. Patients treated with (n = 46) vs. without (n = 21) SIB were surveyed prospectively before (A), at the last day of RT (B) and a median time of two (C) and 19 month (D) after RT to compare QoL changes applying a validated questionnaire (EPIC - expanded prostate cancer index composite). With a median cut-off standard uptake value (SUV) of 3, a median GTV(PET) of 4.0 cm(3) and PTV(boost) (GTV(PET) with margins) of 17.3 cm(3) was defined. No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B, C and D (mean differences ≤3 points for all comparisons). Significantly decreasing acute urinary and bowel score changes (mean changes > 5 points in comparison to baseline level at time A) were found for patients with and without SIB. However, long-term urinary and bowel QoL (time D) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups (median changes = 0 points). Only sexual function scores decreased significantly (> 5 points) at time D. Treatment planning with (18)F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity.

Men's Health Index: a pragmatic approach to stratifying and optimizing men's health.

PubMed

Tan, Hui Meng; Tan, Wei Phin; Wong, Jun Hoe; Ho, Christopher Chee Kong; Teo, Chin Hai; Ng, Chirk Jenn

2014-11-01

The proposed Men's Health Index (MHI) aims to provide a practical and systematic framework for comprehensively assessing and stratifying older men with the intention of optimising their health and functional status. A literature search was conducted using PubMed from 1980 to 2012. We specifically looked for instruments which: assess men's health, frailty and fitness; predict life expectancy, mortality and morbidities. The instruments were assessed by the researchers who then agreed on the tools to be included in the MHI. When there was disagreements, the researchers discussed and reached a consensus guided by the principle that the MHI could be used in the primary care setting targetting men aged 55-65 years. The instruments chosen include the Charlson's Combined Comorbidity-Age Index; the International Index of Erectile Function-5; the International Prostate Symptom Score; the Androgen Deficiency in Aging Male; the Survey of Health, Ageing and Retirement in Europe Frailty Instrument; the Sitting-Rising Test; the Senior Fitness Test; the Fitness Assessment Score; and the Depression Anxiety Stress Scale-21. A pilot test on eight men was carried out and showed that the men's health index is viable. The concept of assessing, stratifying, and optimizing men's health should be incorporated into routine health care, and this can be implemented by using the MHI. This index is particularly useful to primary care physicians who are in a strategic position to engage men at the peri-retirement age in a conversation about their life goals based on their current and predicted health status.

Dual-Modality PET/Ultrasound imaging of the Prostate

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

Huber, Jennifer S.; Moses, William W.; Pouliot, Jean

2005-11-11

Functional imaging with positron emission tomography (PET)will detect malignant tumors in the prostate and/or prostate bed, as well as possibly help determine tumor ''aggressiveness''. However, the relative uptake in a prostate tumor can be so great that few other anatomical landmarks are visible in a PET image. Ultrasound imaging with a transrectal probe provides anatomical detail in the prostate region that can be co-registered with the sensitive functional information from the PET imaging. Imaging the prostate with both PET and transrectal ultrasound (TRUS) will help determine the location of any cancer within the prostate region. This dual-modality imaging should helpmore » provide better detection and treatment of prostate cancer. LBNL has built a high performance positron emission tomograph optimized to image the prostate.Compared to a standard whole-body PET camera, our prostate-optimized PET camera has the same sensitivity and resolution, less backgrounds and lower cost. We plan to develop the hardware and software tools needed for a validated dual PET/TRUS prostate imaging system. We also plan to develop dual prostate imaging with PET and external transabdominal ultrasound, in case the TRUS system is too uncomfortable for some patients. We present the design and intended clinical uses for these dual imaging systems.« less

Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers.

PubMed

Stumm, Laura; Burkhardt, Lia; Steurer, Stefan; Simon, Ronald; Adam, Meike; Becker, Andreas; Sauter, Guido; Minner, Sarah; Schlomm, Thorsten; Sirma, Hüseyin; Michl, Uwe

2013-07-01

Transcription factors of the forkhead box P (FOXP1-4) family have been implicated in various human cancer types before. The relevance and role of neuronal transcription factor FOXP2 in prostate cancer is unknown. A tissue microarray containing samples from more than 11 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data was analysed for FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre-existing ERG fusion (by fluorescence in situ hybridisation and immunohistochemistry) and cell proliferation (Ki67 labelling index) data. There was a moderate to strong FOXP2 protein expression in basal and secretory cells of normal prostatic glands. As compared with normal cells, FOXP2 expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was linked to advanced tumour stage, high Gleason score, presence of lymph node metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative, but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status. These data demonstrate that similar high FOXP2 protein levels as in normal prostate epithelium exert a 'paradoxical' oncogenic role in 'non fusion-type' prostate cancer. It may be speculated that interaction of FOXP2 with members of pathways that are specifically activated in 'non fusion-type' cancers may be responsible for this phenomenon.

Complex relationship between sex hormones, insulin resistance and leptin in men with and without prostatic disease.

PubMed

Grosman, Halina; Fabre, Bibiana; Lopez, Miguel; Scorticati, Carlos; Lopez Silva, Maximiliano; Mesch, Viviana; Mazza, Osvaldo; Berg, Gabriela

2016-01-01

To assess sex hormones, leptin and insulin-resistance in men with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and to study associations between androgens and histologic score of prostate tissue in PCa. Two hundred ten men older than 45 years selected from 2906 participants of a population screening for PCa were studied: 70 with PCa, 70 with BPH and 70 controls (CG), matched by body mass index and age. Insulin, IGF-1, PSA, leptin, total, free (fT) and bioavailable testosterone (bT) and estradiol were measured. Each group was subdivided into two subgroups considering the presence of metabolic syndrome (MS); androgens and leptin levels were analyzed in the subgroups. Prostate cancer and BPH patients presented higher total, fT and bT levels than CG. IGF-1, insulin and HOMA index were higher in BPH than in the other two groups. PCa presented higher leptin [median (range) 6.5 (1.3-28.0) versus 4.8 (1.1-12.3) ng/ml; p < 0.01] and estradiol [median (range) 37.0 (20-90) versus 29.0 (20-118) pg/ml; p = 0.025] levels than CG. After dividing men considering the presence of MS, leptin was higher and total testosterone was lower in MS patients in all the groups. It was observed a coexistence of an altered hormone profile with increased sex hormones and leptin in PCa patients, in accordance with the new perspective of PCa pathogenesis.

Are urge incontinence and aging risk factors of erectile dysfunction in patients with male lower urinary tract symptoms?

PubMed

Amano, Toshiyasu; Earle, Carolyn; Imao, Tetsuya; Takemae, Katsuro

2016-01-01

Several studies have indicated that erectile dysfunction (ED) patients also suffer from lower urinary tract symptoms (LUTS). We investigated a group of men with LUTS and assessed their sexual function with the aim of being able to predict ED risk factors and introduce ED treatments earlier for this patient group. International Prostate Symptom Score (IPSS), Overactive Bladder Symptoms Score (OABSS) and Sexual Health Inventory for Men (SHIM) score were obtained from 236 men with LUTS at their first out-patients visit. Clinical parameters such as body mass index, prostate volume, residual urine volume and prostate specific antigen were also evaluated. The relationship between the SHIM score and other clinical data was analyzed. According to the SHIM score, ED in men with LUTS was severe 15%, moderate 19%, moderate to mild 28%, mild 17%, normal 7% and data was incomplete in 14%. Based on the results of a multivariate analysis, aging (p < 0.001) and OAB severity (p = 0.024) were significantly correlated to severe and moderate ED. Furthermore, among OAB symptoms score items, urge urinary incontinence was a risk factor for severe and moderate ED (p = 0.005). Aging and OAB (notably urinary urge incontinence) are risk factors for severe and moderate ED in men with LUTS.

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.

Color Doppler quantitative measures to predict outcome of biopsies in prostate cancer

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

Strigari, Lidia; Marsella, Annelisa; Canitano, Stefano

2008-11-15

Purpose: The aim was to correlate the color Doppler flow activity pre- and postradiotherapy, using transrectal color Doppler ultrasonography (CDUS) and the 2 year positive biopsy rate after radiotherapy in patients with prostate cancer. Methods and materials: Analysis was carried out in 69 out of 160 patients who had undergone treatment with 3D-conformal radiotherapy (3D-CRT) to prostate and seminal vesicles. Patients were randomized to receive 80 Gy in 40 fractions in 8 weeks (arm A) and 62 Gy in 20 fractions in 5 weeks, 4 fractions per week (arm B). Color Doppler flow activity (CDFA) was evaluated calculating the vascularizationmore » index (VI), defined as the ratio between the colored and total pixels in the whole and peripheral prostate, delineated by a radiation oncologist on CDUS images, using EcoVasc a home-made software. The difference between the 2 year post- and pre-3D-CRT maximum VI (VI{sub max}), named {Delta}VI{sub max}, was calculated in the whole and peripheral prostate for each patient. Then, {Delta}VI{sub max} and the detected 2 year biopsy outcome were analyzed using the receiver operating characteristics (ROC) technique. Results: The VI{sub max} increased or decreased in patients with positive or negative biopsies, respectively, compared to the value before RT in both arms. The area under the ROC curve for {Delta}VI{sub max} in the whole and peripheral prostate is equal to 0.790 and 0.884, respectively. Conclusion: The {Delta}VI{sub max} index, comparing CDFA at 2 years compared to that before RT, allows the 2 year postradiotherapy positive biopsy rate to be predicted.« less

Expression and Function of the Progesterone Receptor in Human Prostate Stroma Provide Novel Insights to Cell Proliferation Control

PubMed Central

Yu, Yue; Liu, Liangliang; Xie, Ning; Xue, Hui; Fazli, Ladan; Buttyan, Ralph; Wang, Yuzhuo; Gleave, Martin

2013-01-01

Context: Like other tissues, the prostate is an admixture of many different cell types that can be segregated into components of the epithelium or stroma. Reciprocal interactions between these 2 types of cells are critical for maintaining prostate homeostasis, whereas aberrant stromal cell proliferation can disrupt this balance and result in diseases such as benign prostatic hyperplasia. Although the androgen and estrogen receptors are relatively well studied for their functions in controlling stromal cell proliferation and differentiation, the role of the progesterone receptor (PR) remains unclear. Objective: The aim of the study was to investigate the expression and function of the PR in the prostate. Design and Setting: Human prostate biopsies, renal capsule xenografts, and prostate stromal cells were used. Immunohistochemistry, Western blotting, real-time quantitative PCR, cell proliferation, flow cytometry, and gene microarray analyses were performed. Results: Two PR isoforms, PRA and PRB, are expressed in prostate stromal fibroblasts and smooth muscle cells, but not in epithelial cells. Both PR isoforms suppress prostate stromal cell proliferation through inhibition of the expression of cyclinA, cyclinB, and cdc25c, thus delaying cell cycling through S and M phases. Gene microarray analyses further demonstrated that PRA and PRB regulated different transcriptomes. However, one of the major gene groups commonly regulated by both PR isoforms was the one associated with regulation of cell proliferation. Conclusion: PR plays an inhibitory role in prostate stromal cell proliferation. PMID:23666965

The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review

PubMed Central

Capurso, Cristiano; Vendemiale, Gianluigi

2017-01-01

Prostate cancer is the second most common cancer in the world among men, and is the fifth most common cause of cancer death among men. The aim of our review was to analyze observational and case–control studies to point out the effects of overweight and diets components on the cancer risk, particularly on risk of prostate cancer, and the effect of the Mediterranean diet (MD) on the reduction of risk and mortality of prostate cancer. It is known that incidence and progression of cancer is multifactorial. Cancer of the large bowel, breast, endometrium, and prostate are due also to a high body mass index and to high consumption of high carcinogenic dietary factors, as red and processed meat or saturated fats rich foods, and to a low consumption of vegetables and fruits. Previous meta-analysis suggested that high adherence to diet model based on the traditional MD pattern gives a significant protection from incidence and mortality of cancer of all types. The main component of the MD is olive oil, consumed in high amount by Mediterranean basin populations. In addition, phenolic compounds exert some strong chemo-preventive effects, which are due to several mechanisms, including both antioxidant effects and actions on cancer cell signaling and cell cycle progression and proliferation. The protective effect of the MD against the prostate cancer is also due to the high consumption of tomato sauce. Lycopene is the most relevant functional component in tomatoes; after activating by the cooking of tomato sauce, it exerts antioxidant properties by acting in the modulation of downregulation mechanisms of the inflammatory response. MD, therefore, represents a healthy dietary pattern in the context of a healthy lifestyle habits. In conclusion, our narrative review allows us to reaffirm how nutritional factors play an important role in cancer initiation and development, and how a healthy dietary pattern represented by MD and its components, especially olive oil, could exert a protective role by the development and progression of prostate cancer. PMID:28884114

[Longjintonglin Capsules for type IIIA prostatitis accompanied by abnormal semen liquefaction: A clinical observation].

PubMed

Cai, Hong-cai; Wan, Chang-chun; Geng, Qiang; Liu, Wei; Zhang, Guo-wei; Shang, Xue-jun; Huang, Yu-feng

2016-01-01

To evaluate the therapeutic effect of Longjintonglin Capsules on type IIIA prostatitis accompanied by abnormal semen liquefaction. We selected 140 patients with type IIIA prostatitis accompanied by abnormal semen liquefaction according to the diagnostic standards of the American Institutes of Health (NIH) and treated them with Longjintonglin Capsules orally 3 capsules once tid for 12 weeks. We obtained the NIH Chronic Prostatitis Symptom Indexes (NIH-CPSI), traditional Chinese medicine (TCM) syndrome scores, leukocyte count in the expressed prostatic secretion (EPS), semen liquefaction time, and the results of semen analysis and compared these indicators before and after the treatment. Of the 140 cases, 132 were included in this study, excluding 8 due to their incomplete case histories. Before and after 4, 8 and 12 weeks of medication, the total NIH-CPSI scores were 24.52 ± 5.43, 21.28 ± 4.85, 18.01 ± 4.28, and 14.49 ± 3.65 (P < 0.01), the TCM syndrome scores were 35.63 ± 6.07, 26.66 ± 5.03, 17.37 ± 4.18, and 11.11 ± 3.96 (P < 0.01), and the leukocyte counts (/HP) were 27.50 ± 7.01, 22.38 ± 5.22, 16:76 ± 4.10, and 11.40 ± 4.74 (P < 0.01), respectively. After 12 weeks of treatment, 31 of the patients with type IIIA prostatitis were cured and another 72 well responded, with an overall response rate of 78.0%. Of those with abnormal semen liquefaction, 61 were cured, 39 well responded, and 32 failed to respond, with an overall effectiveness rate of 75.8%. Semen analysis showed significantly increased percentage of progressively motile sperm after 4, 8 and 12 weeks of medication as compared with the baseline (P < 0.01). No abnormal liver or renal function or other adverse reactions were observed during the treatment. Longjintonglin Capsules, with its advantages of safety, effectiveness and no obvious adverse effects, deserve to be recommended for the treatment of type IIIA prostatitis accompanied by abnormal semen liquefaction.

Validity of Prostate Health Index and Percentage of [-2] Pro-Prostate-Specific Antigen as Novel Biomarkers in the Diagnosis of Prostate Cancer: Omani Tertiary Hospitals Experience

PubMed Central

Al Saidi, Safana S.; Al Riyami, Nafila B.; Al Marhoon, Mohammed S.; Al Saraf, Mohammed S.; Al Busaidi, Salim S.; Bayoumi, Riad; Mula-Abed, Waad-Allah S.

2017-01-01

Objectives Prostate cancer is the leading cancer in older men. The Ministry of Health Oman Cancer Incidence Registry 2013 lists cancer of the prostate as the first most common cancer in males. Therefore, early detection is important and prostate-specific antigen (PSA) is widely used as an established laboratory test. However, despite its wide use, its value in screening, particularly in asymptomatic males, is controversial when considering the risks and benefits of early detection. Methods This prospective, observational study included 136 males (67.0±8.9 years; range 45–90) who were scheduled for a prostate biopsy in two different tertiary care teaching hospitals in Oman: the Royal Hospital and Sultan Qaboos University Hospital. Blood specimens from these patients were collected at the same setting before obtaining a prostatic biopsy. Three PSA markers (total PSA (tPSA), free PSA (fPSA), and [-2]proPSA (p2PSA)) were measured and the Prostate Health Index (phi) calculated. The histopathological report of the prostatic biopsy for each patient was obtained from the histopathology laboratory of the concerned hospital along with clinical and laboratory data through the hospital information system. Results Phi has the highest validity markers compared with other prostate markers, with a sensitivity of 82.1%, specificity of 80.6%, and area under the curve (AUC) value of 0.81 at a cutoff of 41.9. The other prostatic markers showed sensitivities and specificities of 78.6% and 25.9% for tPSA; 35.7% and 92.6% for %fPSA; and 64.3% and 82.4% for %p2PSA, respectively. The AUCs at the best cutoff values were 0.67 at 10.1 µg/L for tPSA; 0.70 at 11.6% for %fPSA; and 0.55 at 1.4% for %p2PSA. An association between phi values and aggressiveness of prostate malignancy was noted. Of the 28 patients with prostate cancer, 22 patients had tPSA > 4 µg/L. However, no patient had phi in the low-risk category, and five, six, and 17 patients had phi in the moderate-, high-, and very high-risk categories, respectively. Conclusions Phi outperforms tPSA and fPSA when used alone or in combination, and appears to be more accurate than both markers in excluding prostate cancer before biopsy. Use of this biomarker helps clinicians to avoid unnecessary biopsies, particularly in patients with gray-zone tPSA level. Phi is the strongest marker that correlates proportionally with Gleason Score; therefore, it is also useful in predicting the aggressiveness of the disease. This is the first reported experience for the use of p2PSA and phi in Oman, the Middle East, and North Africa. PMID:28804579

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

PubMed

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

2008-12-01

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

Prostate cancer, benign prostatic hyperplasia and physical activity in Shanghai, China.

PubMed

Lacey, J V; Deng, J; Dosemeci, M; Gao, Y T; Mostofi, F K; Sesterhenn, I A; Xie, T; Hsing, A W

2001-04-01

Studies suggest that increased levels of physical activity might decrease the risk of prostate cancer. We ascertained lifetime measures of activity in a population-based case-control study of prostate cancer in Shanghai, China to investigate physical activity in a population where the incidence of prostate cancer is low but rising. In all, 238 men with prostate cancer, diagnosed 1993-1995, were identified through a rapid reporting system. A second group of 206 men with benign prostatic hyperplasia (BPH) was matched to prostate cancer cases, and 471 age-matched and population-based controls were identified from urban Shanghai. Through personal interviews, we ascertained all daily, occupational, and recreational activities at ages 20-29, ages 40-49, and in 1988 to generate hours spent sleeping, sitting, in moderate activity, and in vigorous activity. Time spent per week in different activities was converted to metabolic equivalents (MET-h) and energy expended. Time spent in, MET-h of, and energy expended in physical activities were not consistently related to either prostate cancer or BPH when compared to controls. Few men reported regular vigorous activity. Occupational activity, based on an energy expenditure index using job titles, was suggestively associated with a decreased risk of BPH, but not associated with prostate cancer. Associations did not vary according to age or stage of prostate cancer at diagnosis. Our results, based on regular physical activity, occupational activity, hours in activities, MET-h, and energy expended, did not support a protective role of physical activity in prostate cancer or BPH for men in a low-risk population.

Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation

PubMed Central

Chua, Chee Wai; Epsi, Nusrat J; Leung, Eva Y; Xuan, Shouhong; Lei, Ming; Li, Bo I; Bergren, Sarah K; Hibshoosh, Hanina; Mitrofanova, Antonina

2018-01-01

Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor cell that functions in prostate regeneration. Using genetically--engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo. Furthermore, AR loss suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs; however, combined Pten deletion and activation of oncogenic Kras in AR-deleted CARNs result in tumors with focal neuroendocrine differentiation. Our findings show that AR modulates specific progenitor properties of CARNs, including their ability to serve as a cell of origin for prostate cancer. PMID:29334357

Investigation of c-KIT and Ki67 expression in normal, preneoplastic and neoplastic canine prostate.

PubMed

Fonseca-Alves, Carlos Eduardo; Kobayashi, Priscilla Emiko; Palmieri, Chiara; Laufer-Amorim, Renée

2017-12-06

c-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines. Eleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive. The present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer.

A supervoxel-based segmentation method for prostate MR images

NASA Astrophysics Data System (ADS)

Tian, Zhiqiang; Liu, LiZhi; Fei, Baowei

2015-03-01

Accurate segmentation of the prostate has many applications in prostate cancer diagnosis and therapy. In this paper, we propose a "Supervoxel" based method for prostate segmentation. The prostate segmentation problem is considered as assigning a label to each supervoxel. An energy function with data and smoothness terms is used to model the labeling process. The data term estimates the likelihood of a supervoxel belongs to the prostate according to a shape feature. The geometric relationship between two neighboring supervoxels is used to construct a smoothness term. A threedimensional (3D) graph cut method is used to minimize the energy function in order to segment the prostate. A 3D level set is then used to get a smooth surface based on the output of the graph cut. The performance of the proposed segmentation algorithm was evaluated with respect to the manual segmentation ground truth. The experimental results on 12 prostate volumes showed that the proposed algorithm yields a mean Dice similarity coefficient of 86.9%+/-3.2%. The segmentation method can be used not only for the prostate but also for other organs.

Understanding PSA and its derivatives in prediction of tumor volume: addressing health disparities in prostate cancer risk stratification

PubMed Central

Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

2017-01-01

Objectives To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Results Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). Materials and Methods We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Conclusions Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives’ ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer. PMID:28160549

5α-Reductase inhibitor is less effective in men with small prostate volume and low serum prostatic specific antigen level.

PubMed

Lin, Victor C; Liao, Chun-Hou; Wang, Chung-Cheng; Kuo, Hann-Chorng

2015-09-01

Large total prostate volumes (TPVs) or high serum prostate-specific antigen (PSA) levels indicate high-risk clinical progression of benign prostatic hyperplasia. This prospective study investigated the treatment outcome of combined 5α-reductase inhibitor and α-blocker in patients with and without large TPVs or high PSA levels. Men aged ≥ 45 years with International Prostate Symptom scores (IPSS) ≥ 8, TPV ≥ 20 mL, and maximum flow rate ≤ 15 mL/s received a combination therapy (dutasteride plus doxaben) for 2 years. Patients with baseline PSA ≥ 4 ng/mL underwent prostatic biopsy for excluding malignancy. The changes in the parameters from baseline to 24 months after combination therapy were compared in those with and without TPV ≥ 40 mL or PSA levels ≥ 1.5 ng/mL. A total of 285 patients (mean age 72 ± 9 years) completed the study. Combination therapy resulted in significant continuous improvement in IPSS, quality of life index, maximum flow rate, and postvoid residual (all p < 0.0001) regardless of baseline TPV or PSA levels. However, only patients with baseline TPV ≥ 40 mL had significant improvements in IPSS-storage subscore, voided volume, reduction in TPV, transitional zone index, and PSA levels. In addition, patients with baseline TPV < 40 mL and PSA < 1.5 ng/mL had neither a reduction in TPV nor a decrease in serum PSA level. A high TPV indicates more outlet resistance, whereas elevated serum PSA level reflects glandular proliferation. Thus, patients with TPV<40 mL and low PSA levels has less benefit from 5α-reductase inhibitor therapy. The therapeutic effect of combined treatment may arise mainly from the α-blocker in these patients. Copyright © 2013. Published by Elsevier B.V.

Development of Castration Resistant Prostate Cancer can be Predicted by a DNA Hypermethylation Profile.

PubMed

Angulo, Javier C; Andrés, Guillermo; Ashour, Nadia; Sánchez-Chapado, Manuel; López, Jose I; Ropero, Santiago

2016-03-01

Detection of DNA hypermethylation has emerged as a novel molecular biomarker for prostate cancer diagnosis and evaluation of prognosis. We sought to define whether a hypermethylation profile of patients with prostate cancer on androgen deprivation would predict castrate resistant prostate cancer. Genome-wide methylation analysis was performed using a methylation cancer panel in 10 normal prostates and 45 tumor samples from patients placed on androgen deprivation who were followed until castrate resistant disease developed. Castrate resistant disease was defined according to EAU (European Association of Urology) guideline criteria. Two pathologists reviewed the Gleason score, Ki-67 index and neuroendocrine differentiation. Hierarchical clustering analysis was performed and relationships with outcome were investigated by Cox regression and log rank analysis. We found 61 genes that were significantly hypermethylated in greater than 20% of tumors analyzed. Three clusters of patients were characterized by a DNA methylation profile, including 1 at risk for earlier castrate resistant disease (log rank p = 0.019) and specific mortality (log rank p = 0.002). Hypermethylation of ETV1 (HR 3.75) and ZNF215 (HR 2.89) predicted disease progression despite androgen deprivation. Hypermethylation of IRAK3 (HR 13.72), ZNF215 (HR 4.81) and SEPT9 (HR 7.64) were independent markers of prognosis. Prostate specific antigen greater than 25 ng/ml, Gleason pattern 5, Ki-67 index greater than 12% and metastasis at diagnosis also predicted a negative response to androgen deprivation. Study limitations included the retrospective design and limited number of cases. Epigenetic silencing of the mentioned genes could be novel molecular markers for the prognosis of advanced prostate cancer. It might predict castrate resistance during hormone deprivation and, thus, disease specific mortality. Gene hypermethylation is associated with disease progression in patients who receive hormone therapy. It could serve as a marker of the treatment response. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy.

PubMed

Braadland, Peder R; Giskeødegård, Guro; Sandsmark, Elise; Bertilsson, Helena; Euceda, Leslie R; Hansen, Ailin F; Guldvik, Ingrid J; Selnæs, Kirsten M; Grytli, Helene H; Katz, Betina; Svindland, Aud; Bathen, Tone F; Eri, Lars M; Nygård, Ståle; Berge, Viktor; Taskén, Kristin A; Tessem, May-Britt

2017-11-21

Robust biomarkers that identify prostate cancer patients with high risk of recurrence will improve personalised cancer care. In this study, we investigated whether tissue metabolites detectable by high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) were associated with recurrence following radical prostatectomy. We performed a retrospective ex vivo study using HR-MAS MRS on tissue samples from 110 radical prostatectomy specimens obtained from three different Norwegian cohorts collected between 2002 and 2010. At the time of analysis, 50 patients had experienced prostate cancer recurrence. Associations between metabolites, clinicopathological variables, and recurrence-free survival were evaluated using Cox proportional hazards regression modelling, Kaplan-Meier survival analyses and concordance index (C-index). High intratumoural spermine and citrate concentrations were associated with longer recurrence-free survival, whereas high (total-choline+creatine)/spermine (tChoCre/Spm) and higher (total-choline+creatine)/citrate (tChoCre/Cit) ratios were associated with shorter time to recurrence. Spermine concentration and tChoCre/Spm were independently associated with recurrence in multivariate Cox proportional hazards modelling after adjusting for clinically relevant risk factors (C-index: 0.769; HR: 0.72; P=0.016 and C-index: 0.765; HR: 1.43; P=0.014, respectively). Spermine concentration and tChoCre/Spm ratio in prostatectomy specimens were independent prognostic markers of recurrence. These metabolites can be noninvasively measured in vivo and may thus offer predictive value to establish preoperative risk assessment nomograms.

Lower urinary tract symptoms/benign prostatic hypertrophy and vascular function: Role of the nitric oxide-phosphodiesterase type 5-cyclic guanosine 3',5'-monophosphate pathway.

PubMed

Higashi, Yukihito

2017-06-01

It is well known that there is an association of lower urinary tract symptoms/benign prostatic hypertrophy with cardiovascular disease, suggesting that lower urinary tract symptoms/benign prostatic hypertrophy is a risk factor for cardiovascular events. Vascular function, including endothelial function and vascular smooth muscle function, is involved in the pathogenesis, maintenance and development of atherosclerosis, leading to cardiovascular events. Vascular dysfunction per se should also contribute to lower urinary tract symptoms/benign prostatic hypertrophy. Both lower urinary tract symptoms/benign prostatic hypertrophy and vascular dysfunction have cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes mellitus, aging, obesity and smoking. Inactivation of the phosphodiesterase type 5-cyclic guanosine 3',5'-monophosphate-nitric oxide pathway causes lower urinary tract symptoms/benign prostatic hypertrophy through an enhancement of sympathetic nervous activity, endothelial dysfunction, increase in Rho-associated kinase activity and vasoconstriction, and decrease in blood flow of pelvic viscera. Both endogenous nitric oxide and exogenous nitric oxide act as vasodilators on vascular smooth muscle cells through an increase in the content of cyclic guanosine 3',5'-monophosphate, which is inactivated by phosphodiesterase type 5. In a clinical setting, phosphodiesterase type 5 inhibitors are widely used in patients with lower urinary tract symptoms/benign prostatic hypertrophy. Phosphodiesterase type 5 inhibitors might have beneficial effects on vascular function through not only inhibition of cyclic guanosine 3',5'-monophosphate degradation, but also increases in testosterone levels and nitric oxide bioavailability, increase in the number and improvement of the function of endothelial progenitor cells, and decrease in insulin resistance. In the present review, the relationships between lower urinary tract symptoms/benign prostatic hypertrophy, the phosphodiesterase type 5-nitric oxide-cyclic guanosine 3',5'-monophosphate pathway, vascular function and cardiovascular outcomes are examined. © 2017 The Japanese Urological Association.

Contemporary Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

PubMed

Magistro, Giuseppe; Wagenlehner, Florian M E; Grabe, Magnus; Weidner, Wolfgang; Stief, Christian G; Nickel, J Curtis

2016-02-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition that causes severe symptoms, bother, and quality-of-life impact in the 8.2% of men who are believed to be affected. Research suggests a complex pathophysiology underlying this syndrome that is mirrored by its heterogeneous clinical presentation. Management of patients diagnosed with CP/CPPS has always been a formidable task in clinical practice. Due to its enigmatic etiology, a plethora of clinical trials failed to identify an efficient monotherapy. A comprehensive review of published randomized controlled trials (RCTs) on the treatment of CP/CPPS and practical best evidence recommendations for management. Medline and the Cochrane database were screened for RCTs on the treatment of CP/CPPS from 1998 to December 2014, using the National Institutes of Health Chronic Prostatitis Symptom Index as an objective outcome measure. Published data in concert with expert opinion were used to formulate a practical best evidence statement for the management of CP/CPPS. Twenty-eight RCTs identified were eligible for this review and presented. Trials evaluating antibiotics, α-blockers, anti-inflammatory and immune-modulating substances, hormonal agents, phytotherapeutics, neuromodulatory drugs, agents that modify bladder function, and physical treatment options failed to reveal a clear therapeutic benefit. With its multifactorial pathophysiology and its various clinical presentations, the management of CP/CPPS demands a phenotypic-directed approach addressing the individual clinical profile of each patient. Different categorization algorithms have been proposed. First studies applying the UPOINTs classification system provided promising results. Introducing three index patients with CP/CPPS, we present practical best evidence recommendations for management. Our current understanding of the pathophysiology underlying CP/CPPS resulting in this highly variable syndrome does not speak in favor of a monotherapy for management. No efficient monotherapeutic option is available. The best evidence-based management of CP/CPPS strongly suggests a multimodal therapeutic approach addressing the individual clinical phenotypic profile. Chronic prostatitis/chronic pelvic pain syndrome presents a variable syndrome. Successful management of this condition is challenging. It appears that a tailored treatment strategy addressing individual patient characteristics is more effective than one single therapy. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Progesterone receptor in the prostate: A potential suppressor for benign prostatic hyperplasia and prostate cancer.

PubMed

Chen, RuiQi; Yu, Yue; Dong, Xuesen

2017-02-01

Advanced prostate cancer undergoing androgen receptor pathway inhibition (ARPI) eventually progresses to castrate-resistant prostate cancer (CRPC), suggesting that (i) androgen receptor (AR) blockage is incomplete, and (ii) there are other critical molecular pathways contributing to prostate cancer (PCa) progression. Although most PCa occurs in the epithelium, prostate stroma is increasingly believed to play a crucial role in promoting tumorigenesis and facilitating tumor progression. In the stroma, sex steroid hormone receptors such as AR and estrogen receptor-α are implicated to have important functions, whereas the progesterone receptor (PR) remains largely under-investigated despite the high sequence and structural similarities between PR and AR. Stromal progesterone/PR signaling may play a critical role in PCa development and progression because not only progesterone is a critical precursor for de novo androgen steroidogenesis and an activator of mutant androgen receptors, but also PR functions in a ligand-independent manner in various important pathways. In fact, recent progress in our understanding of stromal PR function suggests that this receptor may exert an inhibitory effect on benign prostatic hyperplasia (BPH), reactive stroma development, and PCa progression. These early findings of stromal PR warrant further investigations as this receptor could be a potential biomarker and therapeutic target in PCa management. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prediction of individual genetic risk to prostate cancer using a polygenic score.

PubMed

Szulkin, Robert; Whitington, Thomas; Eklund, Martin; Aly, Markus; Eeles, Rosalind A; Easton, Douglas; Kote-Jarai, Z Sofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Southey, Melissa C; Fitzgerald, Liesel M; Henderson, Brian E; Schumacher, Fredrick; Haiman, Christopher A; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo L J; Nordestgaard, Børge G; Key, Tim J; Travis, Ruth C; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S; Cybulski, Cezary; Lubiński, Jan; Kluźniak, Wojciech; Cannon-Albright, Lisa; Brenner, Hermann; Butterbach, Katja; Stegmaier, Christa; Park, Jong Y; Sellers, Thomas; Lin, Hui-Yi; Lim, Hui-Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Clements, Judith A; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Gronberg, Henrik; Wiklund, Fredrik

2015-09-01

Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. © 2015 Wiley Periodicals, Inc.

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids.

PubMed

Karandish, Fataneh; Haldar, Manas K; You, Seungyong; Brooks, Amanda E; Brooks, Benjamin D; Guo, Bin; Choi, Yongki; Mallik, Sanku

2016-11-30

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly ( p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems.

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids

PubMed Central

2016-01-01

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly (p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems. PMID:27917408

Performance of the American Urological Association Symptom Index with and without an additional urge incontinence item.

PubMed

Barry, Michael J; Avins, Andrew L; Meleth, Sreelatha

2011-09-01

To examine the value of adding an urge incontinence question to the American Urological Association Symptom Index (AUASI) among men in the Complementary and Alternative Medicine for Urological Symptoms (CAMUS) trial. The CAMUS study was a randomized trial of Saw palmetto fruit extract versus placebo among men aged ≥45 years with an AUASI score of ≥8 and ≤24. The baseline measurements included the AUASI, a question about urge incontinence (UI), the International Prostate Symptom Score quality of life question, and the Benign Prostatic Hyperplasia Impact Index. We correlated the items and scales and examined whether adding the UI question resulted in better prediction of disease-specific health status. The mean age of the 369 men in the CAMUS trial was 61 years, and mean baseline AUASI score was 14.6. UI was reported infrequently; about 82% of the respondents answered the question "not at all" or "<1 time in 5." UI correlated significantly with all other AUASI items, except for weak stream; the strongest correlation was to urgency (R=0.51, P<.0001). The correlation between the AUASI score and the AUASI+UI score was 0.98 (P<.0001). In a logistic regression analysis predicting the International Prostate Symptom Score quality of life score, adding UI to the AUASI slightly increased the discriminating ability (c statistic increased from 0.77 to 0.78, P<.0001). Similarly, in a linear regression analysis predicting the Benign Prostatic Hyperplasia Impact Index score, adding UI to the AUASI slightly increased the predictive ability (R2 statistic increased from 0.22 to 0.26, P<.0001). According to our analysis in the CAMUS trial population, the value of adding a UI question to the AUASI in terms of predicting bother seemed small at best. Copyright © 2011 Elsevier Inc. All rights reserved.

Racial and Ethnic Variation in Time to Prostate Biopsy After an Elevated Screening Level of Serum Prostate-specific Antigen.

PubMed

Reading, Stephanie R; Porter, Kimberly R; Hsu, Jin-Wen Y; Wallner, Lauren P; Loo, Ronald K; Jacobsen, Steven J

2016-10-01

To examine the racial and ethnic variation in time to prostate biopsy after an elevated screening level of serum prostate-specific antigen (PSA). Male members of the Kaiser Permanente of Southern California health plan, 45 years of age or older, with no history of prostate cancer or a prostate biopsy, and at least 1 elevated screening level of serum PSA between January 1, 1998 and December 31, 2007 were retrospectively identified (n = 59,506). All participants were passively followed via electronic health records until their time of prostate biopsy, death, membership disenrollment, or study conclusion (December 31, 2014), whichever was the initial event. Proportional hazard regression analyses were used to estimate the association between time from an elevated screening level of serum PSA to prostate biopsy, adjusting for age, benign prostatic hyperplasia, prostatitis, type 2 diabetes mellitus, hypertension, and Charlson Comorbidity Index score. Median time until biopsy was 0.6 years (214 days), with approximately 41% of participants receiving a prostate biopsy within the study period. Results from the fully adjusted analysis indicated that the non-Hispanic Asian or Pacific Islanders (hazard ratio: 1.10, 95% confidence interval: [1.04, 1.15]) and the non-Hispanic blacks (hazard ratio: 1.04, 95% confidence interval: [1.00, 1.08]) had a slightly shorter time to prostate biopsy after an elevated screening level of serum PSA compared to the non-Hispanic whites. These data suggest that, within an integrated healthcare organization, minimal differences exist between racial and ethnic subgroups in their time to prostate biopsy after an elevated screening level of serum PSA. Copyright © 2016. Published by Elsevier Inc.

There Is No Correlation Between Erectile Dysfunction and Dose to Penile Bulb and Neurovascular Bundles Following Real-Time Low-Dose-Rate Prostate Brachytherapy

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

Solan, Amy N.; Cesaretti, Jamie A.; Stone, Nelson N.

2009-04-01

Purpose: We evaluated the relationship between the onset of erectile dysfunction and dose to the penile bulb and neurovascular bundles (NVBs) after real-time ultrasound-guided prostate brachytherapy. Methods and Materials: One hundred forty-seven patients who underwent prostate brachytherapy met the following eligibility criteria: (1) treatment with {sup 125}I brachytherapy to a prescribed dose of 160 Gy with or without hormones without supplemental external beam radiation therapy, (2) identification as potent before the time of implantation based on a score of 2 or higher on the physician-assigned Mount Sinai Erectile Function Score and a score of 16 or higher on the abbreviatedmore » International Index of Erectile Function patient assessment, and (3) minimum follow-up of 12 months. Median follow-up was 25.7 months (range, 12-47 months). Results: The 3-year actuarial rate of impotence was 23% (34 of 147 patients). An additional 43% of potent patients (49 of 113 patients) were using a potency aid at last follow-up. The penile bulb volume receiving 100% of the prescription dose (V{sub 100}) ranged from 0-0.05 cc (median, 0 cc), with a dose to the hottest 5% (D{sub 5}) range of 12.5-97.9 Gy (median, 40.8 Gy). There was no correlation between penile bulb D{sub 5} or V{sub 100} and postimplantation impotency on actuarial analysis. For the combined right and left NVB structures, V{sub 100} range was 0.3-5.1 cc (median, 1.8 cc), and V{sub 150} range was 0-1.5 cc (median, 0.31 cc). There was no association between NVB V{sub 100} or V{sub 150} and postimplantation impotency on actuarial analysis. Conclusion: Penile bulb doses are low after real-time ultrasound-guided prostate brachytherapy. We found no correlation between dose to either the penile bulb or NVBs and the development of postimplantation impotency.« less

A randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of tadalafil (Cialis[reg]) in the treatment of erectile dysfunction following three-dimensional conformal external-beam radiotherapy for prostatic carcinoma

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

Incrocci, Luca; Slagter, Cleo; Slob, A. Koos

2006-10-01

Purpose: Erectile dysfunction after three-dimensional conformal external-beam radiotherapy (3DCRT) for prostatic carcinoma is reported in as many as 64% of those patients. The purpose of this study was to determine the efficacy of the oral drug tadalafil (Cialis (registered) ) in patients with erectile dysfunction after radiotherapy for prostatic carcinoma. Methods and Materials: Patients (N = 358) who completed radiotherapy at least 12 months before the study were approached by mail. All patients had been treated by 3DCRT; 60 patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received 20 mg of tadalafil or placebomore » for 6 weeks. Drug or placebo was taken on demand at patient's discretion, with no restrictions regarding the consumption of alcohol or food, at least once a week and no more than once daily. At 6 weeks patients crossed over to the alternative treatment. Data were collected using the Sexual Encounter Profile (SEP) and the International Index of Erectile Function (IIEF) questionnaires. Side effects were also recorded. Results: Mean age at study entry was 69 years. All patients completed the study. For almost all questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with tadalafil, but not with placebo. Sixty-seven percent of the patients reported an improvement of erectile function with tadalafil (placebo: 20%), and 48% reported successful intercourse with tadalafil (placebo: 9%) (p < 0.0001). Side effects were mild or moderate. Conclusions: Tadalafil is an effective treatment for erectile dysfunction after 3DCRT for prostatic carcinoma with successful intercourse reported in almost 50% of the patients, and it is well tolerated.« less

Potency preservation following stereotactic body radiation therapy for prostate cancer

PubMed Central

2013-01-01

Background Erectile dysfunction after prostate radiation therapy remains an ongoing challenge and critical quality of life issue. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT impotency would be higher than conventional radiation therapy approaches. This study sought to evaluate potency preservation and sexual function following SBRT for prostate cancer. Methods Between February 2008 and March 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. Potency was defined as the ability to have an erection firm enough for intercourse with or without sexual aids while sexual activity was defined as the ability to have an erection firm enough for masturbation and foreplay. Patients who received androgen deprivation therapy (ADT) were excluded from this study. Ninety-seven hormone-naïve men were identified as being potent at the initiation of therapy and were included in this review. All patients were treated to 35–36.25 Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Prostate specific antigen (PSA) and total testosterone levels were obtained pre-treatment, every 3 months for the first year and every 6 months for the subsequent year. Sexual function was assessed with the Sexual Health Inventory for Men (SHIM), the Expanded Prostate Index Composite (EPIC)-26 and Utilization of Sexual Medication/Device questionnaires at baseline and all follow-up visits. Results Ninety-seven men (43 low-, 50 intermediate- and 4 high-risk) at a median age of 68 years (range, 48–82 years) received SBRT. The median pre-treatment PSA was 5.9 ng/ml and the minimum follow-up was 24 months. The median pre-treatment total serum testosterone level was 11.4 nmol/L (range, 4.4-27.9 nmol/L). The median baseline SHIM was 22 and 36% of patients utilized sexual aids prior to treatment. Although potency rates declined following treatment: 100% (baseline); 68% (6 months); 62% (12 months); 57% (18 months) and 54.4% (24 months), 78% of previously potent patients had erections sufficient for sexual activity at 24 months post-treatment. Overall sexual aid utilization increased from 36% at baseline to 49% at 24 months. Average EPIC sexual scores showed a slow decline over the first two years following treatment: 77.6 (baseline); 68.7 (6 months); 63.2 (12 months); 61.9 (18 months); 59.3 (24 months). All sexual functions including orgasm declined with time. Prior to treatment, 13.4% of men felt their sexual function was a moderate to big problem which increased to 26.7% two years post treatment. Post-treatment testosterone levels gradually decreased with a median value at two year follow-up of 10.7 nmol/L. However, the average EPIC hormonal scores did not illustrate a statistically significant difference two years post-treatment. Review of the radiation doses to the penile bulb in this study, a potential marker of post-treatment sexual function, revealed that the dose was relatively low and at these low doses the percentage of the penile bulb receiving 29.5 Gy did not correlate with the development of ED. Conclusions Men undergoing SBRT monotherapy for prostate cancer report sexual outcomes comparable to those reported for conventional radiation modalities within the first 24 months after treatment. Longer follow-up is required to confirm the durability of these findings. PMID:24180317

USE OF THE PROSTATE HEALTH INDEX FOR DETECTION OF PROSTATE CANCER: RESULTS FROM A LARGE ACADEMIC PRACTICE

PubMed Central

Tosoian, Jeffrey J.; Druskin, Sasha C.; Andreas, Darian; Mullane, Patrick; Chappidi, Meera; Joo, Sarah; Ghabili, Kamyar; Agostino, Joseph; Macura, Katarzyna J.; Carter, H. Ballentine; Schaeffer, Edward M.; Partin, Alan W.; Sokoll, Lori J.; Ross, Ashley E.

2016-01-01

BACKGROUND The Prostate Health Index (phi) outperforms PSA and other PSA derivatives for the diagnosis of prostate cancer (PCa). The impact of phi testing in the real-world clinical setting has not been previously assessed. METHODS In a single, large, academic center, phi was tested in 345 patients presenting for diagnostic evaluation for PCa. Findings on prostate biopsy (including Grade Group [GG], defined as GG1: Gleason score [GS] 6, GG2: GS 3+4=7, GG3: GS 4+3=7, GG4: GS 8, and GG5: GS 9-10), magnetic resonance imaging (MRI), and radical prostatectomy (RP) were prospectively recorded. Biopsy rates and outcomes were compared to a contemporary cohort that did not undergo phi testing (n=1318). RESULTS Overall, 39% of men with phi testing underwent prostate biopsy. No men with phi<19.6 were diagnosed with PCa, and only 3 men with phi<27 had cancer of GG≥2. Phi was superior to PSA for the prediction of any PCa (AUC 0.72 vs. 0.47) and GG≥2 PCa (AUC 0.77 vs. 0.53) on prostate biopsy. Among men undergoing MRI and phi, no men with phi<27 and PI-RADS≤3 had GG≥2 cancer. For those men proceeding to RP, increasing phi was associated with higher pathologic GG (p=0.002) and stage (p=0.001). Compared to patients who did not undergo phi testing, the use of phi was associated with a 9% reduction in the rate of prostate biopsy (39% vs. 48%; p<0.001). Importantly, the reduction in biopsy among the phi population was secondary to decreased incidence of negative (8%) and GG1 (1%) biopsies, while the proportion of biopsies detecting GG≥2 cancers remained unchanged. CONCLUSIONS In this large, real-time clinical experience, phi outperformed PSA alone, was associated with high-grade PCa, and provided complementary information to MRI. Incorporation of phi into clinical practice reduced the rate of unnecessary biopsies without changing the frequency of detection of higher grade cancers. PMID:28117387

Performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and the prostate health index (PHI) in a Chinese hospital-based biopsy population.

PubMed

Na, Rong; Ye, Dingwei; Liu, Fang; Chen, Haitao; Qi, Jun; Wu, Yishuo; Zhang, Guiming; Wang, Meilin; Wang, Wenying; Sun, Jielin; Yu, Guopeng; Zhu, Yao; Ren, Shancheng; Zheng, S Lilly; Jiang, Haowen; Sun, Yinghao; Ding, Qiang; Xu, Jianfeng

2014-11-01

The use of serum [-2]proPSA (p2PSA) and its derivative, the prostate health index (PHI), in detecting prostate cancer (PCa) have been consistently shown to have better performance than total prostate-specific antigen (tPSA) in discriminating biopsy outcomes in western countries. However, little is known about their performance in Chinese men. Our objective is to test the performance of p2PSA and PHI and their added value to tPSA in discriminating biopsy outcomes in Chinese men. Consecutive patients who underwent prostate biopsy in three tertiary hospitals in Shanghai, China during 2012-2013 were recruited. Serum tPSA, free PSA (fPSA), and p2PSA were measured centrally using Beckman Coulter's DxI 800 Immunoassay System. The primary outcome is PCa and the secondary outcome is high-grade PCa (Gleason Score of 4 + 3 or worse). Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC), detection rate and Decision Curve Analysis (DCA). Among 636 patients who underwent prostate biopsy, PHI was a significant predictor of biopsy outcomes, independent of other clinical variables. The AUC in discriminating PCa from non-PCa was consistently higher for PHI than tPSA in the entire cohort (0.88 vs. 0.81) as well as in patients with tPSA at 2-10 ng/ml (0.73 vs. 0.53), at 10.1-20 ng/ml (0.81 vs. 0.58), and at tPSA >20 ng/ml (0.90 vs. 0.80). The differences were statistically significant in all comparisons, P < 0.01. To detect 90% of all PCa in the cohort, 362 and 457 patients would need to be biopsied based on PHI and tPSA cutoff, respectively, a 21% reduction for PHI. Similar results were found for discriminating high-grade PCa. PHI provides added value over tPSA in discriminating PCa and high-grade PCa in patients who underwent prostate biopsy in China. © 2014 Wiley Periodicals, Inc.

Time trends in prostate cancer surgery: data from an Internet-based multicentre database.

PubMed

Schostak, Martin; Baumunk, Daniel; Jagota, Anita; Klopf, Christian; Winter, Alexander; Schäfers, Sebastian; Kössler, Robert; Brennecke, Volker; Fischer, Tom; Hagel, Susanne; Höchel, Steffen; Jäkel, Dierk; Lehsnau, Mike; Krege, Susanne; Rüffert, Bernd; Pretzer, Jana; Becht, Eduard; Zegenhagen, Thomas; Miller, Kurt; Weikert, Steffen

2012-02-01

To report our experience with an Internet-based multicentre database that enables tumour documentation, as well as the collection of quality-related parameters and follow-up data, in surgically treated patients with prostate cancer. The system was used to assess the quality of prostate cancer surgery and to analyze possible time-dependent trends in the quality of care. An Internet-based database system enabled a standardized collection of treatment data and clinical findings from the participating urological centres for the years 2005-2009. An analysis was performed aiming to evaluate relevant patient characteristics (age, pathological tumour stage, preoperative International Index of Erectile Function-5 score), intra-operative parameters (operating time, percentage of nerve-sparing operations, complication rate, transfusion rate, number of resected lymph nodes) and postoperative parameters (hospitalization time, re-operation rate, catheter indwelling time). Mean values were calculated and compared for each annual cohort from 2005 to 2008. The overall survival rate was also calculated for a subgroup of the Berlin patients. A total of 914, 1120, 1434 and 1750 patients submitted to radical prostatectomy in 2005, 2006, 2007 and 2008 were documented in the database. The mean age at the time of surgery remained constant (66 years) during the study period. More than half the patients already had erectile dysfunction before surgery (median International Index of Erectile Function-5 score of 19-20). During the observation period, there was a decrease in the percentage of pT2 tumours (1% in 2005; 64% in 2008) and a slight increase in the percentage of patients with lymph node metastases (8% in 2005; 10% in 2008). No time trend was found for the operating time (142-155 min) or the percentage of nerve-sparing operations (72-78% in patients without erectile dysfunction). A decreasing frequency was observed for the parameters: blood transfusions (1.9% in 2005; 0.5% in 2008), postoperative bleeding (2.6%; 1.2%) and re-operations (4.5%; 2.8%). The mean hospitalization time decreased accordingly (10 days in 2005; 8 days in 2008). The examined subcohort had an overall mortality of 1.5% (median follow-up of 3 years). An Internet-based database system for tumour documentation in patients with prostate cancer enables the collection and assessment of important parameters for the quality of care and outcomes. The participating centres show an improvement in the quality of surgical management, including a reduction of the complication rate. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

A prospective study of health-related quality-of-life outcomes for patients with low-risk prostate cancer managed by active surveillance or radiation therapy.

PubMed

Banerji, John S; Hurwitz, Lauren M; Cullen, Jennifer; Wolff, Erika M; Levie, Katherine E; Rosner, Inger L; Brand, Timothy C; LʼEsperance, James O; Sterbis, Joseph R; Porter, Christopher R

2017-05-01

Patients with low-risk prostate cancer (PCa) often have excellent oncologic outcomes. However, treatment with curative intent can lead to decrements in health-related quality of life (HRQoL). Patients treated with radical prostatectomy have been shown to suffer declines in urinary and sexual HRQoL as compared to those managed with active surveillance (AS). Similarly, patients treated with external-beam radiation therapy (EBRT) are hypothesized to experience greater declines in bowel HRQoL. As health-related quality-of-life (HRQoL) concerns are paramount when selecting among treatment options for low-risk PCa, this study examined HRQoL outcomes in men undergoing EBRT as compared to AS in a prospective, racially diverse cohort. A prospective study of HRQoL in patients with PCa enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database was initiated in 2007. The current study included patients diagnosed through April 2014. HRQoL was assessed with the Expanded Prostate Cancer Index Composite (EPIC) and the Medical Outcomes Study Short Form (SF-36). Temporal changes in HRQoL were compared for patients with low-risk PCa managed on AS vs. EBRT at baseline, 1-, 2-, and 3 years post-PCa diagnosis. Longitudinal patterns were modeled using linear regression models fitted with generalized estimating equations (GEE), adjusting for baseline HRQoL, demographic, and clinical patient characteristics. Of the 499 eligible patients with low-risk PCa, 103 (21%) selected AS and 60 (12%) were treated with EBRT. Demographic characteristics of the treatment groups were similar, though a greater proportion of patients in the EBRT group were African American (P = 0.0003). At baseline, both treatment groups reported comparable HRQoL. EBRT patients experienced significantly worse bowel function and bother at 1 year (adjusted mean score: 87 vs. 95, P = 0.001 and 89 vs. 95, P = 0.008, respectively) and 2 years (87 vs. 93, P = 0.007 and 87 vs. 96, P = 0.002, respectively) compared to patients managed on AS. In contrast to those on AS, more than half the number of patients who received EBRT experienced a decline in bowel function (52% vs. 17%, p=0.003) and bother (52% vs. 15%, P = 0.002) from baseline to 1 year. Patients who received EBRT were significantly more likely to experience a decrease in more than one functional domain (urinary, sexual, bowel, or hormonal) at 1 year when compared with those on AS (60% vs. 28%, P = 0.004). Patients receiving EBRT for low-risk prostate cancer suffer declines in bowel HRQoL. These declines are not experienced by patients on AS, suggesting that management of low-risk prostate cancer with AS may offer a means for preserving HRQoL following prostate cancer diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Computer-Assisted Quantitative Assessment of Prostatic Calcifications in Patients with Chronic Prostatitis.

PubMed

Boltri, Matteo; Magri, Vittorio; Montanari, Emanuele; Perletti, Gianpaolo; Trinchieri, Alberto

2018-04-26

The aim of this study was the development of quantitative assessment of prostatic calcifications at prostatic ultrasound examination by the use of an image analyzer. A group of 82 patients was evaluated by medical history, physical, and transrectal ultrasound examination. Patients had a urethral swab, a 4-specimen study and culture of the seminal fluid. Patients were classified according to National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health. Subjective symptoms were scored by Chronic Prostatitis Symptom Index (CPSI) questionnaire. Ultrasound images were analyzed by the digital processing software Image J to quantitatively assess the presence of calcifications. Computer-assessed calcified areas were significantly higher in chronic bacterial prostatitis (n = 18; group II; 6.76 ± 8.09%) than in the chronic pelvic pain syndrome group IIIa (n = 26; 2.07 ± 1.01%) and IIIb (n = 38; 2.31 ± 2.18%). The area of calcification of the prostate was significantly related to the CPSI score for domains of micturition (r = 0.278, p = 0.023), Prostatic Specific Antigen values (r = 0341, p = 0.005), postvoiding residual urine (r = 0.262, p = 0.032), total prostate volume (r = 0.592, p = 0.000), and adenoma volume (r = 0.593; p = 0.000). The presence of calcifications is more frequently observed in patients with chronic bacterial prostatitis and is related to urinary symptoms. © 2018 S. Karger AG, Basel.

The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years.

PubMed

Boegemann, Martin; Stephan, Carsten; Cammann, Henning; Vincendeau, Sébastien; Houlgatte, Alain; Jung, Klaus; Blanchet, Jean-Sebastien; Semjonow, Axel

2016-01-01

To prospectively test the diagnostic accuracy of the percentage of prostate specific antigen (PSA) isoform [-2]proPSA (%p2PSA) and the Prostate Health Index (PHI), and to determine their role for discrimination between significant and insignificant prostate cancer at initial and repeat prostate biopsy in men aged ≤65 years. The diagnostic performance of %p2PSA and PHI were evaluated in a multicentre study. In all, 769 men aged ≤65 years scheduled for initial or repeat prostate biopsy were recruited in four sites based on a total PSA (t-PSA) level of 1.6-8.0 ng/mL World Health Organization (WHO) calibrated (2-10 ng/mL Hybritech-calibrated). Serum samples were measured for the concentration of t-PSA, free PSA (f-PSA) and p2PSA with Beckman Coulter immunoassays on Access-2 or DxI800 instruments. PHI was calculated as (p2PSA/f-PSA × √t-PSA). Uni- and multivariable logistic regression models and an artificial neural network (ANN) were complemented by decision curve analysis (DCA). In univariate analysis %p2PSA and PHI were the best predictors of prostate cancer detection in all patients (area under the curve [AUC] 0.72 and 0.73, respectively), at initial (AUC 0.67 and 0.69) and repeat biopsy (AUC 0.74 and 0.74). t-PSA and %f-PSA performed less accurately for all patients (AUC 0.54 and 0.62). For detection of significant prostate cancer (based on Prostate Cancer Research International Active Surveillance [PRIAS] criteria) the %p2PSA and PHI equally demonstrated best performance (AUC 0.70 and 0.73) compared with t-PSA and %f-PSA (AUC 0.54 and 0.59). In multivariate analysis PHI we added to a base model of age, prostate volume, digital rectal examination, t-PSA and %f-PSA. PHI was strongest in predicting prostate cancer in all patients, at initial and repeat biopsy and for significant prostate cancer (AUC 0.73, 0.68, 0.78 and 0.72, respectively). In DCA for all patients the ANN showed the broadest threshold probability and best net benefit. PHI as single parameter and the base model + PHI were equivalent with threshold probability and net benefit nearing those of the ANN. For significant cancers the ANN was the strongest parameter in DCA. The present multicentre study showed that %p2PSA and PHI have a superior diagnostic performance for detecting prostate cancer in the PSA range of 1.6-8.0 ng/mL compared with t-PSA and %f-PSA at initial and repeat biopsy and for predicting significant prostate cancer in men aged ≤65 years. They are equally superior for counselling patients before biopsy. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

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.

Novel Radiobiological Gamma Index for Evaluation of 3-Dimensional Predicted Dose Distribution

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

Sumida, Iori, E-mail: sumida@radonc.med.osaka-u.ac.jp; Yamaguchi, Hajime; Kizaki, Hisao

2015-07-15

Purpose: To propose a gamma index-based dose evaluation index that integrates the radiobiological parameters of tumor control (TCP) and normal tissue complication probabilities (NTCP). Methods and Materials: Fifteen prostate and head and neck (H&N) cancer patients received intensity modulated radiation therapy. Before treatment, patient-specific quality assurance was conducted via beam-by-beam analysis, and beam-specific dose error distributions were generated. The predicted 3-dimensional (3D) dose distribution was calculated by back-projection of relative dose error distribution per beam. A 3D gamma analysis of different organs (prostate: clinical [CTV] and planned target volumes [PTV], rectum, bladder, femoral heads; H&N: gross tumor volume [GTV], CTV,more » spinal cord, brain stem, both parotids) was performed using predicted and planned dose distributions under 2%/2 mm tolerance and physical gamma passing rate was calculated. TCP and NTCP values were calculated for voxels with physical gamma indices (PGI) >1. We propose a new radiobiological gamma index (RGI) to quantify the radiobiological effects of TCP and NTCP and calculate radiobiological gamma passing rates. Results: The mean RGI gamma passing rates for prostate cases were significantly different compared with those of PGI (P<.03–.001). The mean RGI gamma passing rates for H&N cases (except for GTV) were significantly different compared with those of PGI (P<.001). Differences in gamma passing rates between PGI and RGI were due to dose differences between the planned and predicted dose distributions. Radiobiological gamma distribution was visualized to identify areas where the dose was radiobiologically important. Conclusions: RGI was proposed to integrate radiobiological effects into PGI. This index would assist physicians and medical physicists not only in physical evaluations of treatment delivery accuracy, but also in clinical evaluations of predicted dose distribution.« less

Alzheimer's disease is associated with prostate cancer: a population-based study.

PubMed

Lin, Herng-Ching; Kao, Li-Ting; Chung, Shiu-Dong; Huang, Chung-Chien; Shia, Ben-Chang; Huang, Chao-Yuan

2018-01-26

Alzheimer's disease and cancer are increasingly prevalent with advancing age. However, the association between Alzheimer's disease and prostate cancer remains unclear. The aim of this study was to examine the relationship between prior Alzheimer's disease and subsequent prostate cancer using a population-based dataset in Taiwan. Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2005. This case-control study included 2101 prostate cancer patients as cases and 6303 matched controls. We used conditional logistic regression analyses to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for Alzheimer's disease between prostate cancer patients and controls. We found that of the 8404 sampled patients, 128 (1.5%) had been diagnosed with Alzheimer's disease prior to the index date. A Chi-squared test showed that there was a significant difference in the prevalences of prior Alzheimer's disease between prostate cancer patients and controls (2.1% vs. 1.3%, p < 0.001). The conditional logistic regression analysis showed that the OR of prior Alzheimer's disease for prostate cancer patients was 1.53 (95% CI: 1.06∼2.21) compared to controls. Furthermore, the OR of prior Alzheimer's disease for prostate cancer patients was 1.52 (95% CI: 1.04∼2.22) compared to controls after adjusting for hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, prostatitis, gonorrhea or chlamydia infection, testitis or epididymitis, and alcohol abuse/alcohol dependency syndrome. This study revealed an association between prior Alzheimer's disease and prostate cancer. We suggest that clinicians be alert to the increased risk of prostate cancer when caring for elderly individuals with Alzheimer's disease.

Utility Estimates of Disease-Specific Health States in Prostate Cancer from Three Different Perspectives.

PubMed

Gries, Katharine S; Regier, Dean A; Ramsey, Scott D; Patrick, Donald L

2017-06-01

To develop a statistical model generating utility estimates for prostate cancer specific health states, using preference weights derived from the perspectives of prostate cancer patients, men at risk for prostate cancer, and society. Utility estimate values were calculated using standard gamble (SG) methodology. Study participants valued 18 prostate-specific health states with the five attributes: sexual function, urinary function, bowel function, pain, and emotional well-being. Appropriateness of model (linear regression, mixed effects, or generalized estimating equation) to generate prostate cancer utility estimates was determined by paired t-tests to compare observed and predicted values. Mixed-corrected standard SG utility estimates to account for loss aversion were calculated based on prospect theory. 132 study participants assigned values to the health states (n = 40 men at risk for prostate cancer; n = 43 men with prostate cancer; n = 49 general population). In total, 792 valuations were elicited (six health states for each 132 participants). The most appropriate model for the classification system was a mixed effects model; correlations between the mean observed and predicted utility estimates were greater than 0.80 for each perspective. Developing a health-state classification system with preference weights for three different perspectives demonstrates the relative importance of main effects between populations. The predicted values for men with prostate cancer support the hypothesis that patients experiencing the disease state assign higher utility estimates to health states and there is a difference in valuations made by patients and the general population.

A critical analysis of the current knowledge of surgical anatomy related to optimization of cancer control and preservation of continence and erection in candidates for radical prostatectomy.

PubMed

Walz, Jochen; Burnett, Arthur L; Costello, Anthony J; Eastham, James A; Graefen, Markus; Guillonneau, Bertrand; Menon, Mani; Montorsi, Francesco; Myers, Robert P; Rocco, Bernardo; Villers, Arnauld

2010-02-01

Detailed knowledge of the anatomy of the prostate and adjacent tissues is mandatory during radical prostatectomy to ensure reliable oncologic and functional outcomes. To review critically and to summarize the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control, erectile function, and urinary continence. A search of the PubMed database was performed using the keywords radical prostatectomy, anatomy, neurovascular bundle, fascia, pelvis, and sphincter. Relevant articles and textbook chapters were reviewed, analyzed, and summarized. Anatomy of the prostate and the adjacent tissues varies substantially. The fascia surrounding the prostate is multilayered, sometimes either fused with the prostate capsule or clearly separated from the capsule as a reflection of interindividual variations. The neurovascular bundle (NVB) is situated between the fascial layers covering the prostate. The NVB is composed of numerous nerve fibers superimposed on a scaffold of veins, arteries, and variable amounts of adipose tissue surrounding almost the entire lateral and posterior surfaces of the prostate. The NVB is also in close, cage-like contact to the seminal vesicles. The external urethral sphincter is a complex structure in close anatomic and functional relationship to the pelvic floor, and its fragile innervation is in close association to the prostate apex. Finally, the shape and size of the prostate can significantly modify the anatomy of the NVB, the urethral sphincter, the dorsal vascular complex, and the pubovesical/puboprostatic ligaments. The surgical anatomy of the prostate and adjacent tissues involved in radical prostatectomy is complex. Precise knowledge of all relevant anatomic structures facilitates surgical orientation and dissection during radical prostatectomy and ideally translates into both superior rates of cancer control and improved functional outcomes postoperatively. Copyright 2009 European Association of Urology. All rights reserved.

Orphan nuclear receptor TLX functions as a potent suppressor of oncogene-induced senescence in prostate cancer via its transcriptional co-regulation of the CDKN1A (p21(WAF1) (/) (CIP1) ) and SIRT1 genes.

PubMed

Wu, Dinglan; Yu, Shan; Jia, Lin; Zou, Chang; Xu, Zhenyu; Xiao, Lijia; Wong, Kam-Bo; Ng, Chi-Fai; Chan, Franky L

2015-05-01

Oncogene-induced senescence is an important tumour-suppressing mechanism to prevent both premalignant transformation and cancer progression. Overcoming this process is a critical step in early cancer development. The druggable orphan nuclear receptor TLX (NR2E1) is characterized as an important regulator of neural stem cells and is also implicated in the development of some brain tumours. However, its exact functional roles in cancer growth regulation still remain unclear. Here we report that TLX can act as a promoter of tumourigenesis in prostate cancer by suppressing oncogene-induced senescence. We determined that TLX exhibited an increased expression in high-grade prostate cancer tissues and many prostate cancer cell lines. Functional studies revealed that TLX could perform an oncogenic function in prostate cancer cells, as its knockdown triggered cellular senescence and cell growth arrest in vitro and in vivo, whereas its over-expression promoted the malignant growth of prostate cancer cells. Furthermore, enhancement of TLX activity, by either ectopic expression or ligand stimulation, could potently prevent doxorubicin-induced senescence in prostate cancer cells and also allow prostatic epithelial cells to escape oncogene-induced senescence induced either by activated oncogene H-Ras(G12V) or knockdown of tumour suppressor PTEN, via a mechanism of direct but differential transcriptional regulation of two senescence-associated genes, repression of CDKN1A and transactivation of SIRT1. Together, our present study shows, for the first time, that TLX may play an important role in prostate carcinogenesis through its suppression of oncogene-induced senescence, and also suggests that targeting the senescence-regulatory TLX is of potential therapeutic significance in prostate cancer. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[Anatomo-functional changes in the prostate and seminal vesicles with aging].

PubMed

Mantovani, F; Mastromarino, G; Colombo, F; Canclini, L; Fenice, O

1993-10-01

The anatomo-functional modifications of the prostate and the seminal pathways during the genital apparatus aging, (prostatic hyperplasia and hypotrophy of the seminal pathways and testis), are caused by hormonal modifications (inconstant increase of the gonadotropins LH-FSH, decrease of the peripheric utilization of testosterone, alterations of the adrenal secretion), by anatomical involutions (degenerations of the glandular, stromal and vascular components).

[Will the climate change affect the mortality from prostate cancer?].

PubMed

Santos Arrontes, Daniel; García González, Jesús Isidro; Martín Muñoz, Manuel Pablo; Castro Pita, Miguel; Mañas Pelillo, Antonio; Paniagua Andrés, Pedro

2007-03-01

The global heating of the atmosphere, as well as the increase of the exposition to sunlight, will be associated with a decrease of the mortality from prostate cancer, due to an increase of the plasmatic levels of vitamin D. To evaluate if climatological factors (temperature, rainfall, and number of sunlight hours per year) may influence the mortality associated with prostate cancer over a five-year period. In this ecology type study we will evaluate the trends of prostate tumors associated mortality in the period between January 1st 1998 and December 31st 2002, in the geographic area of Spain (17 Autonomic communities-CA-and 2 Autonomic cities- Ceuta and Melilla-, 43 million inhabitants). Demographic and mortality data were obtained from the National Institute of Statistics (INE) and climatological data about temperature and rainfall were obtained from the National Institute of Meteorology (INM). The provinces were classified using the climatic index of Martonne (defined as the quotient between annual rainfall and mean annual temperature plus 10). Areas with a quotient below 5 ml/m2/o C are considered extremely arid zones; between 5 and 15 ml/m2/o C are considered arid zones, between 15 and 20 ml/m2/o C semiarid zones; between 20 and 30 ml/m2/o C subhumid zones; between 30 and 60 ml/m2/o C humid zones; and over 60 ml/m2/o C superhumid zones. We compared mortality rates between different climatic areas using the Jonckheere-Terpstra test for six independent samples following the index of Martonne. All calculations were performed using the SPSS v 13.0 for Windows software. A logistic regression model was performed to identify climate factors associated with prostate cancer mortality. A likeliness of the null hypotheses inferior to 0.05 was considered significant. Prostate cancer mortality presented statistically significant differences, being higher in provinces with higher Martonne index (p < 0.001) and lower in areas with a greater number of sunlight hours per year (p = 0.041). The adjusted mortality rate associated with extreme aridity regions and was 21.51 cases/100,000 males year, whereas in humid zones it was 35.87 cases/100,000 males years. Mortality associated with prostate cancer is significantly superior in regions with less exposition to the sunlight. The climate change may lead to a modification of the main epidemiologic patterns, and it may be associated with a modification of cancer mortality rates. Nevertheless, these results should be taken with caution and should be confirmed by prospective studies.

Long-term supplementation of decaffeinated green tea extract does not modify body weight or abdominal obesity in a randomized trial of men at high risk for prostate cancer

PubMed Central

Kumar, Nagi B.; Patel, Roshni; Pow-Sang, Julio; Spiess, Philippe E.; Salup, Raoul; Williams, Christopher R.; Schell, Michael J.

2017-01-01

Background Evidence continues to demonstrate the role of obesity in prostate carcinogenesis and prognosis, underscoring the need to identify and continue to evaluate the effective interventions to reduce obesity in populations at high risk. The aim of the study was to determine the effect of daily consumption of decaffeinated green tea catechins (GTC) formulation (Polyphenon E® (PolyE)) for 1 year on biomarkers of obesity in men who are at high risk for prostate cancer. Materials and Methods A randomized, double-blinded trial was conducted targeting 97 men diagnosed with HGPIN or ASAP. Subjects were randomized to receive GTC (PolyE) (n = 49) or placebo (n = 48) for 1 year. Anthropometric data were collected at baseline, 6 and 12 months and data analyzed to observe change in weight, body mass index (indicator of obesity) and waist: hip ratio (indicator of abdominal obesity). Results Decaffeinated GTC containing 400 mgs of the bioactive catechin, EGCG administered for 1 year to men diagnosed with ASAP and HGPIN appears to be bioavailable, well tolerated but not effective in reducing biomarkers of obesity including body weight, body mass index and waist: hip ratio. Conclusions The results of our trial demonstrates that men who are obese and at high risk for prostate cancer should resort to effective weight management strategies to reduce obesity and not resort to ineffective measures such as taking supplements of green tea to reduce biomarkers of obesity. Changes in body mass index and abdominal obesity seen in other studies were potentially due to caffeine and not GTC. PMID:29228755

Diagnostic test accuracy study of 18F-sodium fluoride PET/CT, 99mTc-labelled diphosphonate SPECT/CT, and planar bone scintigraphy for diagnosis of bone metastases in newly diagnosed, high-risk prostate cancer

PubMed Central

Fonager, Randi F; Zacho, Helle D; Langkilde, Niels C; Fledelius, Joan; Ejlersen, June A; Haarmark, Christian; Hendel, Helle W; Lange, Mine Benedicte; Jochumsen, Mads R; Mortensen, Jesper C; Petersen, Lars J

2017-01-01

The aim of this study was to prospectively compare planar, bone scan (BS) versus SPECT/CT and NaF PET/CT in detecting bone metastases in prostate cancer. Thirty-seven consecutive, newly diagnosed, prostate cancer patients with prostate specific antigen (PSA) levels ≥ 50 ng/mL and who were considered eligible for androgen-deprivation therapy (ADT) were included in this study. BS, SPECT/CT, and NaF PET/CT, were performed prior to treatment and were repeated after six months of ADT. Baseline images from each index test were independently read by two experienced readers. The reference standard was based on a consensus decision made by a multidisciplinary team on the basis of baseline and follow-up images of the index tests, the findings of the baseline index tests by the experienced readers, and any available imaging, biochemical, and clinical data, including the response to ADT. Twenty-seven (73%) of the 37 patients had bone metastases according to the reference standard. The sensitivities for BS, SPECT/CT and NaF PET/CT were 78%, 89%, and 89%, respectively, and the specificities were 90%, 100%, and 90%, respectively. The positive predictive values of BS, SPECT/CT and NaF PET/CT were 96%, 100%, and 96%, respectively, and the negative predictive values were 60%, 77% and 75%, respectively. No statistically significant difference among the three imaging modalities was observed. All three imaging modalities showed high sensitivity and specificity. NaF PET/CT and SPECT/CT showed numerically improved, but not statistically superior, sensitivity compared with BS in this limited and selected patient cohort. PMID:29181269

Effects of Nonlinear Aerobic Training on Erectile Dysfunction and Cardiovascular Function Following Radical Prostatectomy for Clinically Localized Prostate Cancer

PubMed Central

Jones, Lee W.; Hornsby, Whitney E.; Freedland, Stephen J.; Lane, Amy; West, Miranda J.; Moul, Judd W.; Ferrandino, Michael N.; Allen, Jason D.; Kenjale, Aarti A.; Thomas, Samantha M.; Herndon, James E.; Koontz, Bridget F.; Chan, June M.; Khouri, Michel G.; Douglas, Pamela S.; Eves, Neil D.

2014-01-01

Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n = 25 per group) after RP. AT consisted of five walking sessions per week at 55– 100% of peak oxygen uptake (VO2peak) for 30–60 min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow–mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤21) decreased by 20% in the AT group and by 24% in the UC group (difference: p = 0.406). There were no significant between-group differences in any erectile function subscale (p > 0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs. In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP. PMID:24315706

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.

Assessment of accuracy and efficiency of atlas-based autosegmentation for prostate radiotherapy in a variety of clinical conditions.

PubMed

Simmat, I; Georg, P; Georg, D; Birkfellner, W; Goldner, G; Stock, M

2012-09-01

The goal of the current study was to evaluate the commercially available atlas-based autosegmentation software for clinical use in prostate radiotherapy. The accuracy was benchmarked against interobserver variability. A total of 20 planning computed tomographs (CTs) and 10 cone-beam CTs (CBCTs) were selected for prostate, rectum, and bladder delineation. The images varied regarding to individual (age, body mass index) and setup parameters (contrast agent, rectal balloon, implanted markers). Automatically created contours with ABAS(®) and iPlan(®) were compared to an expert's delineation by calculating the Dice similarity coefficient (DSC) and conformity index. Demo-atlases of both systems showed different results for bladder (DSC(ABAS) 0.86 ± 0.17, DSC(iPlan) 0.51 ± 0.30) and prostate (DSC(ABAS) 0.71 ± 0.14, DSC(iPlan) 0.57 ± 0.19). Rectum delineation (DSC(ABAS) 0.78 ± 0.11, DSC(iPlan) 0.84 ± 0.08) demonstrated differences between the systems but better correlation of the automatically drawn volumes. ABAS(®) was closest to the interobserver benchmark. Autosegmentation with iPlan(®), ABAS(®) and manual segmentation took 0.5, 4 and 15-20 min, respectively. Automatic contouring on CBCT showed high dependence on image quality (DSC bladder 0.54, rectum 0.42, prostate 0.34). For clinical routine, efforts are still necessary to either redesign algorithms implemented in autosegmentation or to optimize image quality for CBCT to guarantee required accuracy and time savings for adaptive radiotherapy.

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.

Psychosocial issues related to sexual functioning among African-American prostate cancer survivors and their spouses†

PubMed Central

Rivers, Brian M.; August, Euna M.; Gwede, Clement K.; Hart, Alton; Donovan, Kristine A.; Pow-Sang, Julio M.; Quinn, Gwendolyn P.

2015-01-01

Objective Focus on cancer survivorship and quality of life (QOL) is a growing priority. The aim of this study was to identify and describe the most salient psychosocial concerns related to sexual functioning among African-American (AA) prostate cancer survivors and their spouses. Methods Twelve AA prostate cancer survivors and their spouses participated in semi-structured individual interviews. The interviews assessed couples’ experiences with psychosocial adjustment and sexual functioning posttreatment for localized prostate cancer. The data were analyzed using the constant comparison method and content analysis. Results In this qualitative study of couples surviving prostate cancer, there were divergent views between the male prostate cancer survivors and their female partners, particularly regarding sexual functioning. For the males, QOL issues emerged as the primary area of concern, whereas survival of their husbands was considered most important among the female spouses. The male respondents expressed unease with the sexual side effects of their cancer treatment, such as erectile dysfunction and decreased sexual desire and satisfaction. Female spouses recognized decreased sexual desire in their partners following treatment, but this was not considered a primary concern. Conclusions Patients and their spouses may have differing perceptions regarding QOL and the impact of sexual functioning on survivorship. This study points to the need for further research and intervention development to address these domains with a goal to improve QOL. PMID:20187071

PHF21B overexpression promotes cancer stem cell-like traits in prostate cancer cells by activating the Wnt/β-catenin signaling pathway.

PubMed

Li, Qiji; Ye, Liping; Guo, Wei; Wang, Min; Huang, Shuai; Peng, Xinsheng

2017-06-23

PHF21B is newly identified to be involved in the tumor progression; however, its biological role and molecular mechanism in prostate cancer have not been defined. This study is aimed to study the role of PHF21B in the progression of prostate cancer. Real-time PCR, immunohistochemistry and western blotting analysis were used to determine PHF21B expression in prostate cancer cell lines and clinical specimens. The role of PHF21B in maintaining prostate cancer stem cell-like phenotype was examined by tumor-sphere formation assay and expression levels of stem cell markers. Luciferase reporter assay, western blot analysis, enzyme-linked immunosorbent assay and ChIP assay were used to determine whether PHF21B activates the Wnt/β-catenin signaling by transcriptionally downregulating SFRP1 and SFRP2. Our results revealed that PHF21B was markedly upregulated in prostate cancer cell lines and tissues. High PHF21B levels predicted poorer recurrence-free survival in prostate cancer patients. Gain-of-function and loss-of-function studies showed that overexpression of PHF21B enhanced, while downregulation suppressed, the cancer stem cell-like phenotype in prostate cancer cells. Xenograft tumor model showed that silencing PHF21B decreased the ability of tumorigenicity in vivo. Notably, Wnt/β-catenin signaling was hyperactivated in prostate cancer cells overexpressing PHF21B, and mediated PHF21B-induced cancer stem cell-like phenotype. Furthermore, PHF21B suppressed repressors of the Wnt/β-catenin signaling cascade, including SFRP1 and SFRP2. These results demonstrated that PHF21B constitutively activated wnt/β-catenin signaling by transcriptionally downregulating SFRP1 and SFRP2, which promotes prostate cancer stem cell-like phenotype. Our results revealed that PHF21B functions as an oncogene in prostate cancer, and may represent a promising prognostic biomarker and an attractive candidate for target therapy of prostate cancer.

Efficacy of Low-Intensity Extracorporeal Shock Wave Therapy on Men With Chronic Pelvic Pain Syndrome Refractory to 3-As Therapy.

PubMed

Guu, Shiao-Jin; Geng, Jiun-Hung; Chao, I-Ting; Lin, Hui-Tzu; Lee, Yung-Chin; Juan, Yung-Shun; Liu, Chia-Chu; Wang, Chii-Jye; Tsai, Chia-Chun

2018-03-01

Managing patients with chronic pelvic pain syndrome (CPPS) refractory to the traditional 3-As therapy (antibiotics, alpha-blockers, and anti-inflammatories) is a challenging task. Low-intensity extracorporeal shock wave therapy (LI-ESWT) was recently reported to be able to improve pain, urinary symptoms, and even sexual function by inducing neovascularization and anti-inflammation, reducing muscle tone, and influencing nerve impulses. This study evaluates whether combined treatment with LI-ESWT can restore clinical ability and quality of life (QoL) in patients refractory to 3-As therapy. This was an open-label, single-arm prospective study. Patients with CPPS without more than a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score under the maximal dosage of 3-As therapy were enrolled. LI-ESWT treatment consisted of 3,000 shock waves administered once weekly for 4 weeks. The NIH-CPSI, visual analog scale (VAS) score, International Prostate Symptom Score (IPSS), and the five-item version of the International Index of Erectile Function (IIEF-5) were used to evaluate efficacy at 1, 4, and 12 weeks after LI-ESWT. Thirty-three patients were enrolled in this study. After LI-ESWT treatment, 27 of the 33 patients (81.82%) had a successful response to LI-ESWT, with a decrease of 3.29 and 5.97 in the VAS score and total IPSS at the 3-month follow-up. Waist circumference was the only significant predictor of a successful response to LI-ESWT. LI-ESWT can serve as a salvage therapy for patients with CPPS refractory to traditional 3-As therapy. Further studies are needed to determine an adequate therapeutic protocol and important predictors in patients with different CPPS etiologies.

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial.

PubMed

Chin, Joseph L; Billia, Michele; Relle, James; Roethke, Matthias C; Popeneciu, Ionel V; Kuru, Timur H; Hatiboglu, Gencay; Mueller-Wolf, Maya B; Motsch, Johann; Romagnoli, Cesare; Kassam, Zahra; Harle, Christopher C; Hafron, Jason; Nandalur, Kiran R; Chronik, Blaine A; Burtnyk, Mathieu; Schlemmer, Heinz-Peter; Pahernik, Sascha

2016-09-01

Magnetic resonance imaging-guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). A single-arm prospective phase 1 study was performed at three tertiary referral centers in Canada, Germany, and the United States. Thirty patients (median age: 69 yr; interquartile range [IQR]: 67-71 yr) with biopsy-proven low-risk (80%) and intermediate-risk (20%) PCa were treated and followed for 12 mo. MRI-TULSA treatment was delivered with the therapeutic intent of conservative whole-gland ablation including 3-mm safety margins and 10% residual viable prostate expected around the capsule. Primary end points were safety (adverse events) and feasibility (technical accuracy and precision of conformal thermal ablation). Exploratory outcomes included quality of life, prostate-specific antigen (PSA), and biopsy at 12 mo. Median treatment time was 36min (IQR: 26-44) and prostate volume was 44ml (IQR: 38-48). Spatial control of thermal ablation was ±1.3mm on MRI thermometry. Common Terminology Criteria for Adverse Events included hematuria (43% grade [G] 1; 6.7% G2), urinary tract infections (33% G2), acute urinary retention (10% G1; 17% G2), and epididymitis (3.3% G3). There were no rectal injuries. Median pretreatment International Prostate Symptom Score 8 (IQR: 5-13) returned to 6 (IQR: 4-10) at 3 mo (mean change: -2; 95% confidence interval [CI], -4 to 1). Median pretreatment International Index of Erectile Function 13 (IQR: 6-28) recovered to 13 (IQR: 5-25) at 12 mo (mean change: -1; 95% CI, -5 to 3). Median PSA decreased 87% at 1 mo and was stable at 0.8 ng/ml (IQR: 0.6-1.1) to 12 mo. Positive biopsies showed 61% reduction in total cancer length, clinically significant disease in 9 of 29 patients (31%; 95% CI, 15-51), and any disease in 16 of 29 patients (55%; 95% CI, 36-74). MRI-TULSA was feasible, safe, and technically precise for whole-gland prostate ablation in patients with localized PCa. Phase 1 data are sufficiently compelling to study MRI-TULSA further in a larger prospective trial with reduced safety margins. We used magnetic resonance imaging-guided transurethral ultrasound to heat and ablate the prostate in men with prostate cancer. We showed that the treatment can be targeted within a narrow range (1mm) and has a well-tolerated side effect profile. A larger study is under way. NCT01686958, DRKS00005311. Copyright © 2016. Published by Elsevier B.V.

Androgen-responsive circular RNA circSMARCA5 is up-regulated and promotes cell proliferation in prostate cancer.

PubMed

Kong, Zhe; Wan, Xuechao; Zhang, Yalong; Zhang, Pu; Zhang, Yingyi; Zhang, Xiaona; Qi, Xiaoxiang; Wu, Hai; Huang, Jianfeng; Li, Yao

2017-11-25

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in males worldwide. Circular RNA (circRNA) is a unique class of RNA transcribed by RNA polymerase II characterized by jointing 3' and 5' ends together via exon or intron circularization. However, the molecular functions of circRNAs in prostate cancer have rarely been explored. In present study, we found circ-SMARCA5 was up-regulated in prostate cancer samples compared to match normal tissues. We also observed circ-SMARCA5 expression was significantly induced after DHT treatment. Functional experiments showed circ-SMARCA5 acted as an oncogene in prostate cancer by promoting cell cycle and inhibiting cell apoptosis. We thought this study provided useful information for exploring circRNAs as potential therapeutic and prognostic targets for prostate cancer. Copyright © 2017. Published by Elsevier Inc.

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

PubMed

Rieken, M; Bachmann, A; Gratzke, C

2013-03-01

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

Overexpression and knock-down studies highlight that a disintegrin and metalloproteinase 28 controls proliferation and migration in human prostate cancer.

PubMed

Rudnicka, Caroline; Mochizuki, Satsuki; Okada, Yasunori; McLaughlin, Claire; Leedman, Peter J; Stuart, Lisa; Epis, Michael; Hoyne, Gerard; Boulos, Sherif; Johnson, Liam; Schlaich, Markus; Matthews, Vance

2016-10-01

Prostate cancer is one of the most prevalent cancers in men. It is critical to identify and characterize oncogenes that drive the pathogenesis of human prostate cancer. The current study builds upon previous research showing that a disintegrin and metallproteinase (ADAM)28 is involved in the pathogenesis of numerous cancers. Our novel study used overexpression, pharmacological, and molecular approaches to investigate the biological function of ADAM28 in human prostate cancer cells, with a focus on cell proliferation and migration. The results of this study provide important insights into the role of metalloproteinases in human prostate cancer.The expression of ADAM28 protein levels was assessed within human prostate tumors and normal adjacent tissue by immunohistochemistry. Immunocytochemistry and western blotting were used to assess ADAM28 protein expression in human prostate cancer cell lines. Functional assays were conducted to assess proliferation and migration in human prostate cancer cells in which ADAM28 protein expression or activity had been altered by overexpression, pharmacological inhibition, or by siRNA gene knockdown.The membrane bound ADAM28 was increased in human tumor biopsies and prostate cancer cell lines. Pharmacological inhibition of ADAM28 activity and/or knockdown of ADAM28 significantly reduced proliferation and migration of human prostate cancer cells, while overexpression of ADAM28 significantly increased proliferation and migration.ADAM28 is overexpressed in primary human prostate tumor biopsies, and it promotes human prostate cancer cell proliferation and migration. This study supports the notion that inhibition of ADAM28 may be a potential novel therapeutic strategy for human prostate cancer.

An Interaction with Ewing's Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer.

PubMed

Kedage, Vivekananda; Selvaraj, Nagarathinam; Nicholas, Taylor R; Budka, Justin A; Plotnik, Joshua P; Jerde, Travis J; Hollenhorst, Peter C

2016-10-25

More than 50% of prostate tumors have a chromosomal rearrangement resulting in aberrant expression of an oncogenic ETS family transcription factor. However, mechanisms that differentiate the function of oncogenic ETS factors expressed in prostate tumors from non-oncogenic ETS factors expressed in normal prostate are unknown. Here, we find that four oncogenic ETS (ERG, ETV1, ETV4, and ETV5), and no other ETS, interact with the Ewing's sarcoma breakpoint protein, EWS. This EWS interaction was necessary and sufficient for oncogenic ETS functions including gene activation, cell migration, clonogenic survival, and transformation. Significantly, the EWS interacting region of ERG has no homology with that of ETV1, ETV4, and ETV5. Therefore, this finding may explain how divergent ETS factors have a common oncogenic function. Strikingly, EWS is fused to various ETS factors by the chromosome translocations that cause Ewing's sarcoma. Therefore, these findings link oncogenic ETS function in both prostate cancer and Ewing's sarcoma. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Baseline characteristics predict risk of progression and response to combined medical therapy for benign prostatic hyperplasia (BPH).

PubMed

Kozminski, Michael A; Wei, John T; Nelson, Jason; Kent, David M

2015-02-01

To better risk stratify patients, using baseline characteristics, to help optimise decision-making for men with moderate-to-severe lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) through a secondary analysis of the Medical Therapy of Prostatic Symptoms (MTOPS) trial. After review of the literature, we identified potential baseline risk factors for BPH progression. Using bivariate tests in a secondary analysis of MTOPS data, we determined which variables retained prognostic significance. We then used these factors in Cox proportional hazard modelling to: i) more comprehensively risk stratify the study population based on pre-treatment parameters and ii) to determine which risk strata stood to benefit most from medical intervention. In all, 3047 men were followed in MTOPS for a mean of 4.5 years. We found varying risks of progression across quartiles. Baseline BPH Impact Index score, post-void residual urine volume, serum prostate-specific antigen (PSA) level, age, American Urological Association Symptom Index score, and maximum urinary flow rate were found to significantly correlate with overall BPH progression in multivariable analysis. Using baseline factors permits estimation of individual patient risk for clinical progression and the benefits of medical therapy. A novel clinical decision tool based on these analyses will allow clinicians to weigh patient-specific benefits against possible risks of adverse effects for a given patient. © 2014 The Authors. BJU International © 2014 BJU International.

Functional anatomy of the prostate: implications for treatment planning.

PubMed

McLaughlin, Patrick W; Troyer, Sara; Berri, Sally; Narayana, Vrinda; Meirowitz, Amichay; Roberson, Peter L; Montie, James

2005-10-01

To summarize the functional anatomy relevant to prostate cancer treatment planning. Coronal, axial, and sagittal T2 magnetic resonance imaging (MRI) and MRI angiography were fused by mutual information and registered with computed tomography (CT) scan data sets to improve definition of zonal anatomy of the prostate and critical adjacent structures. The three major prostate zones (inner, outer, and anterior fibromuscular) are visible by T2 MRI imaging. The bladder, bladder neck, and internal (preprostatic) sphincter are a continuous muscular structure and clear definition of the preprostatic sphincter is difficult by MRI. Transition zone hypertrophy may efface the bladder neck and internal sphincter. The external "lower" sphincter is clearly visible by T2 MRI with wide variations in length. The critical erectile structures are the internal pudendal artery (defined by MRI angiogram or T2 MRI), corpus cavernosum, and neurovascular bundle. The neurovascular bundle is visible along the posterior lateral surface of the prostate on CT and MRI, but its terminal branches (cavernosal nerves) are not visible and must be defined by their relationship to the urethra within the genitourinary diaphragm. Visualization of the ejaculatory ducts within the prostate is possible on sagittal MRI. The anatomy of the prostate-rectum interface is clarified by MRI, as is the potentially important distinction of rectal muscle and rectal mucosa. Improved understanding of functional anatomy and imaging of the prostate and critical adjacent structures will improve prostate radiation therapy by improvement of dose and toxicity correlation, limitation of dose to critical structures, and potential improvement in post therapy quality of life.

Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth.

PubMed

Xue, Y; Sonke, G; Schoots, C; Schalken, J; Verhofstad, A; de la Rosette, J; Smedts, F

2001-10-01

To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity. Consecutive sections from 43 prostates taken during autopsy representing fetuses (12-38 weeks of gestation), infants, prepubertal males and adults were double stained for chromogranin A and MIB-1. MIB-1 labeling index (LI) was calculated in the budding tips, forming acini, major collecting ducts, adjacent and non-adjacent stromal compartments. Furthermore, the topographic relationship between proliferating cells and NE cells was evaluated. In the first half of gestation, cell proliferation as revealed by MIB-1 LI was significantly higher in epithelial structures and stroma than in older fetuses and other age groups. MIB-1 LI was higher in budding tips than in other epithelial regions. MIB-1 LI in stroma adjacent to budding tips was not higher than that adjacent to other epithelial branching segments. Co-expression of chromogranin A and MIB-1 staining was not observed. MIB-1 LI was lower in cells in the direct vicinity of chromogranin A positive NE cells than at a distance from NE cells. Prostate development in the first half of gestation is explosive. Thereafter, the prostate basically is a slow-growing organ. Budding tips are the major growth foci during early prostate development, while stromal growth is evenly distributed throughout the prostate, probably indicating that stromal-epithelial interactions do not manifest in enhanced proliferation at their interface. NE cells may have an inhibitory effect on proliferation of exocrine epithelial cells and are probably only associated with differentiation of prostate exocrine cells in the prostate. Copyright 2001 Wiley-Liss, Inc.

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.

Impact of Oxidative Stress Biomarkers and Carboxymethyllysine (An Advanced Glycation End Product) on Prostate Cancer: A Prospective Study

PubMed Central

Yang, Shuman; Pinney, Susan M.; Mallick, Palash; Ho, Shuk-Mei; Bracken, Bruce; Wu, Tianying

2015-01-01

Introduction Biomarkers of oxidative stress and advanced glycation end products (AGE) have been linked to the development of prostate cancer, but evidence from human studies is either scarce or controversial. Materials and Methods We conducted a prospective nested case-control study among 48 men (24 prostate cancer cases and 24 controls) aged 48–76 years at baseline. The participants of our study were a part of the Fernald Community Cohort (FCC). Prostate cancer cases and controls were matched individually on age (± 3 years) with 1:1 ratio. Biomarkers included urine F2-isoprostanes (markers of lipid oxidation), plasma fluorescent oxidation products (FlOPs; markers of global oxidation) and carboxymethyllysine (CML; a major end-stage AGE). Results At baseline, cases had similar age, body mass index, proportion of family history of prostate cancer, history of benign prostatic hyperplasia, history of hypertension, history of diabetes, smokers and plasma glucose levels as compared to controls. Levels of plasma CML were significantly higher in cases than in controls (182 vs. 152 μg/ml, P < 0.05). In the conditional logistic regression model, an increase in CML equivalent to one standard deviation was associated with increased risk of incident prostate cancer (Relative risk = 1.79, 95% confidence interval = 1.00–3.21), and accounted for ~8% variance of prostate cancer liability. Urine F2-isoprostanes and plasma FlOPs were not associated with prostate cancer incidence. Conclusion Higher levels of plasma CML were associated with increased risk of prostate cancer. This suggests a potential new pathway for prostate cancer prediction and treatment. PMID:25972296

Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

PubMed

Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

2017-11-01

Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.

PubMed

Petimar, Joshua; Wilson, Kathryn M; Wu, Kana; Wang, Molin; Albanes, Demetrius; van den Brandt, Piet A; Cook, Michael B; Giles, Graham G; Giovannucci, Edward L; Goodman, Gary E; Goodman, Phyllis J; Håkansson, Niclas; Helzlsouer, Kathy; Key, Timothy J; Kolonel, Laurence N; Liao, Linda M; Männistö, Satu; McCullough, Marjorie L; Milne, Roger L; Neuhouser, Marian L; Park, Yikyung; Platz, Elizabeth A; Riboli, Elio; Sawada, Norie; Schenk, Jeannette M; Tsugane, Shoichiro; Verhage, Bas; Wang, Ying; Wilkens, Lynne R; Wolk, Alicja; Ziegler, Regina G; Smith-Warner, Stephanie A

2017-08-01

Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear. Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model. Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index. Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer. Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR . ©2017 American Association for Cancer Research.

Timp3 loss accelerates tumour invasion and increases prostate inflammation in a mouse model of prostate cancer.

PubMed

Adissu, Hibret A; McKerlie, Colin; Di Grappa, Marco; Waterhouse, Paul; Xu, Qiang; Fang, Hui; Khokha, Rama; Wood, Geoffrey A

2015-12-01

Altered expression and activity of proteases is implicated in inflammation and cancer progression. An important negative regulator of protease activity is TIMP3 (tissue inhibitor of metalloproteinase 3). TIMP3 expression is lacking in many cancers including advanced prostate cancer, and this may facilitate invasion and metastasis by allowing unrestrained protease activity. To investigate the role of TIMP3 in prostate cancer progression, we crossed TIMP3-deficient mice (Timp3(-/-)) to mice with prostate-specific deletion of the tumor suppressor Pten (Pten(-/-)), a well-established mouse model of prostate cancer. Tumor growth and progression were compared between Pten(-/-), Timp3(-/-) and control (Pten(-/-), Timp3(+/+)) mice at 16 weeks of age by histopathology and markers of proliferation, vascularity, and tumor invasion. Metalloproteinase activity within the tumors was assessed by gelatin zymography. Inflammatory infiltrates were assessed by immunohistochemistry for macrophages and lymphocytes whereas expression of cytokines and other inflammatory mediators was assessed by quantitative real time PCR and multiplex ELISA. Increased tumor growth, proliferation index, increased microvascular density, and invasion was observed in Pten(-/-), Timp3(-/-) prostate tumors compared to Pten(-/-), Timp3(+/+) tumors. Tumor cell invasion in Pten(-/-), Timp3(-/-) mice was associated with increased expression of matrix metalloprotease (MMP)-9 and activation of MMP-2. There was markedly increased inflammatory cell infiltration into the TIMP3-deficient prostate tumors along with increased expression of monocyte chemoattractant protein-1, cyclooxygenase-2, TNF-α, and interleukin-1β; all of which are implicated in inflammation and cancer. This study provides important insights into the role of altered protease activity in promoting prostate cancer invasion and implicates prostate inflammation as an important promoting factor in prostate cancer progression. © 2015 Wiley Periodicals, Inc.

Outcome of Robotic Radical Prostatectomy in Men Over 74

PubMed Central

Ubrig, Burkhard; Boy, Anselm; Heiland, Markus

2018-01-01

Abstract Introduction: We set out to evaluate outcomes in patients over 74 after robotic radical prostatectomy. Materials and Methods: Six hundred forty-seven patients over 74 (≥75) were analyzed for preoperative factors (body mass index [BMI], American Society of Anestesiologists classification [ASA], prostate-specific antigen [PSA], International prostate symptome score [IPSS], International index of erectile function [IIEF]), operative and perioperative characteristics (technique, erythrocyte conc., complications), and histopathological results. After 12 months, following items were assessed: PSA, frequency of urine loss, number of pads used (including safety), incontinence at night, and potency as quantified by IIEF-5. Results: Mean age in the group <75 was 64.8 years (range 46–74 years) and in the group ≥75 76.9 years (75–88). No statistically significant differences could be detected in terms of BMI, ASA score, or preoperative PSA, respectively. IPSS and IIEF were significantly worse in the group ≥75. Major complications (>Clavien-Dindo III) were found in 1.6% vs. 1.3% (≥75) of cases. Minor complications were encountered in 22.8% vs. 26.3% (≥75). There was a remarkably high percentage of locally advanced disease (73.3% vs. 71.0%) in both groups. Patients ≥75 showed a tendency toward more aggressive cancer and more frequent nodal involvement; we found a higher percentage of R1-resections (19.5% vs. 30.4%, p < 0.05) and PSA relapse after 1 year (12.3% vs. 22.8%, p < 0.05). Twelve months pad-free continence rate (69.9% vs. 63.2%) showed no statistically significant difference between both groups as did the preservation rate of erectile function. Conclusion: We could show that robotic prostatectomy can be carried out safely with good functional and histopathological results in patients ≥75. It is therefore questionable if elderly patients can be precluded from curative radical treatment solely because of their age. PMID:29232985

Outcome of Robotic Radical Prostatectomy in Men Over 74.

PubMed

Ubrig, Burkhard; Boy, Anselm; Heiland, Markus; Roosen, Alexander

2018-02-01

We set out to evaluate outcomes in patients over 74 after robotic radical prostatectomy. Six hundred forty-seven patients over 74 (≥75) were analyzed for preoperative factors (body mass index [BMI], American Society of Anestesiologists classification [ASA], prostate-specific antigen [PSA], International prostate symptome score [IPSS], International index of erectile function [IIEF]), operative and perioperative characteristics (technique, erythrocyte conc., complications), and histopathological results. After 12 months, following items were assessed: PSA, frequency of urine loss, number of pads used (including safety), incontinence at night, and potency as quantified by IIEF-5. Mean age in the group <75 was 64.8 years (range 46-74 years) and in the group ≥75 76.9 years (75-88). No statistically significant differences could be detected in terms of BMI, ASA score, or preoperative PSA, respectively. IPSS and IIEF were significantly worse in the group ≥75. Major complications (>Clavien-Dindo III) were found in 1.6% vs. 1.3% (≥75) of cases. Minor complications were encountered in 22.8% vs. 26.3% (≥75). There was a remarkably high percentage of locally advanced disease (73.3% vs. 71.0%) in both groups. Patients ≥75 showed a tendency toward more aggressive cancer and more frequent nodal involvement; we found a higher percentage of R1-resections (19.5% vs. 30.4%, p < 0.05) and PSA relapse after 1 year (12.3% vs. 22.8%, p < 0.05). Twelve months pad-free continence rate (69.9% vs. 63.2%) showed no statistically significant difference between both groups as did the preservation rate of erectile function. We could show that robotic prostatectomy can be carried out safely with good functional and histopathological results in patients ≥75. It is therefore questionable if elderly patients can be precluded from curative radical treatment solely because of their age.

Roles for the Stem Cell–Associated Intermediate Filament Nestin in Prostate Cancer Migration and Metastasis

PubMed Central

Kleeberger, Wolfram; Bova, G. Steven; Nielsen, Matthew E.; Herawi, Mehsati; Chuang, Ai-Ying; Epstein, Jonathan I.; Berman, David M.

2011-01-01

The intermediate filament protein Nestin identifies stem/progenitor cells in adult tissues, but the function of Nestin is poorly understood. We investigated Nestin expression and function in common lethal cancers. Nestin mRNA was detected in cell lines from small cell lung, and breast cancers, and particularly elevated in cell lines derived from prostate cancer metastases. Whereas the androgen-independent lines PC3, 22RV1, and DU145 all expressed Nestin transcripts under standard culture conditions, the androgen-dependent line LnCaP expressed Nestin only on androgen withdrawal. We confirmed associations of Nestin expression, androgen withdrawal, and metastatic potential by immunohistochemical analysis of samples from 254 prostate cancer patients. Cytoplasmic Nestin protein was readily identifiable in prostate cancer cells from 75% of patients with lethal androgen-independent disease, even in cancer sampled from the prostate itself. However, Nestin expression was undetectable in localized androgen-deprived tumors and in metastases without prior androgen deprivation. To address its function, we reduced Nestin levels with short hairpin RNAs, markedly inhibiting in vitro migration and invasion in prostate cancer cells but leaving cell growth intact. Nestin knockdown also diminished metastases 5-fold compared with controls despite uncompromised tumorigenicity at the site of inoculation. These results specify a function for Nestin in cell motility and identify a novel pathway for prostate cancer metastasis. Activity of this pathway may be selected by the extraprostatic environment or, as supported by our data, may originate within the prostate after androgen deprivation. Further dissection of this novel Nestin migration pathway may lead to strategies to prevent and neutralize metastatic spread. PMID:17909025

Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer.

PubMed

Shah, Neel; Wang, Ping; Wongvipat, John; Karthaus, Wouter R; Abida, Wassim; Armenia, Joshua; Rockowitz, Shira; Drier, Yotam; Bernstein, Bradley E; Long, Henry W; Freedman, Matthew L; Arora, Vivek K; Zheng, Deyou; Sawyers, Charles L

2017-09-11

In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals. Remarkably, BET bromodomain inhibition resensitizes drug-resistant tumors to Enz by selectively impairing the GR signaling axis via this enhancer. In addition to revealing an underlying molecular mechanism of GR-driven drug resistance, these data suggest that inhibitors of broadly active chromatin-readers could have utility in nuanced clinical contexts of acquired drug resistance with a more favorable therapeutic index.

[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.

Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression

PubMed Central

Blessing, Alicia M.; Rajapakshe, Kimal; Reddy Bollu, Lakshmi; Shi, Yan; White, Mark A.; Pham, Alexander H.; Lin, Chenchu; Jonsson, Philip; Cortes, Constanza J.; Cheung, Edwin; La Spada, Albert R.; Bast, Robert C.; Merchant, Fatima A.; Coarfa, Cristian; Frigo, Daniel E.

2017-01-01

ABSTRACT AR (androgen receptor) signaling is crucial for the development and maintenance of the prostate as well as the initiation and progression of prostate cancer. Despite the AR's central role in prostate cancer progression, it is still unclear which AR-mediated processes drive the disease. Here, we identified 4 core autophagy genes: ATG4B, ATG4D, ULK1, and ULK2, in addition to the transcription factor TFEB, a master regulator of lysosomal biogenesis and function, as transcriptional targets of AR in prostate cancer. These findings were significant in light of our recent observation that androgens promoted prostate cancer cell growth in part through the induction of autophagy. Expression of these 5 genes was essential for maximal androgen-mediated autophagy and cell proliferation. In addition, expression of each of these 5 genes alone or in combination was sufficient to increase prostate cancer cell growth independent of AR activity. Further, bioinformatic analysis demonstrated that the expression of these genes correlated with disease progression in 3 separate clinical cohorts. Collectively, these findings demonstrate a functional role for increased autophagy in prostate cancer progression, provide a mechanism for how autophagy is augmented, and highlight the potential of targeting this process for the treatment of advanced prostate cancer. PMID:27977328

Transcriptional regulation of core autophagy and lysosomal genes by the androgen receptor promotes prostate cancer progression.

PubMed

Blessing, Alicia M; Rajapakshe, Kimal; Reddy Bollu, Lakshmi; Shi, Yan; White, Mark A; Pham, Alexander H; Lin, Chenchu; Jonsson, Philip; Cortes, Constanza J; Cheung, Edwin; La Spada, Albert R; Bast, Robert C; Merchant, Fatima A; Coarfa, Cristian; Frigo, Daniel E

2017-03-04

AR (androgen receptor) signaling is crucial for the development and maintenance of the prostate as well as the initiation and progression of prostate cancer. Despite the AR's central role in prostate cancer progression, it is still unclear which AR-mediated processes drive the disease. Here, we identified 4 core autophagy genes: ATG4B, ATG4D, ULK1, and ULK2, in addition to the transcription factor TFEB, a master regulator of lysosomal biogenesis and function, as transcriptional targets of AR in prostate cancer. These findings were significant in light of our recent observation that androgens promoted prostate cancer cell growth in part through the induction of autophagy. Expression of these 5 genes was essential for maximal androgen-mediated autophagy and cell proliferation. In addition, expression of each of these 5 genes alone or in combination was sufficient to increase prostate cancer cell growth independent of AR activity. Further, bioinformatic analysis demonstrated that the expression of these genes correlated with disease progression in 3 separate clinical cohorts. Collectively, these findings demonstrate a functional role for increased autophagy in prostate cancer progression, provide a mechanism for how autophagy is augmented, and highlight the potential of targeting this process for the treatment of advanced prostate cancer.

Distinct function of estrogen receptor α in smooth muscle and fibroblast cells in prostate development.

PubMed

Vitkus, Spencer; Yeh, Chiuan-Ren; Lin, Hsiu-Hsia; Hsu, Iawen; Yu, Jiangzhou; Chen, Ming; Yeh, Shuyuan

2013-01-01

Estrogen signaling, through estrogen receptor (ER)α, has been shown to cause hypertrophy in the prostate. Our recent report has shown that epithelial ERα knockout (KO) will not affect the normal prostate development or homeostasis. However, it remains unclear whether ERα in different types of stromal cells has distinct roles in prostate development. This study proposed to elucidate how KO of ERα in the stromal smooth muscle or fibroblast cells may interrupt cross talk between prostate stromal and epithelial cells. Smooth muscle ERαKO (smERαKO) mice showed decreased glandular infolding with the proximal area exhibiting a significant decrease. Fibroblast ERαKO mouse prostates did not exhibit this phenotype but showed a decrease in the number of ductal tips. Additionally, the amount of collagen observed in the basement membrane was reduced in smERαKO prostates. Interestingly, these phenotypes were found to be mutually exclusive among smERαKO or fibroblast ERαKO mice. Compound KO of ERα in both fibroblast and smooth muscle showed combined phenotypes from each of the single KO. Further mechanistic studies showed that IGF-I and epidermal growth factor were down-regulated in prostate smooth muscle PS-1 cells lacking ERα. Together, our results indicate the distinct functions of fibroblast vs. smERα in prostate development.

ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor.

PubMed

Mounir, Zineb; Korn, Joshua M; Westerling, Thomas; Lin, Fallon; Kirby, Christina A; Schirle, Markus; McAllister, Gregg; Hoffman, Greg; Ramadan, Nadire; Hartung, Anke; Feng, Yan; Kipp, David Randal; Quinn, Christopher; Fodor, Michelle; Baird, Jason; Schoumacher, Marie; Meyer, Ronald; Deeds, James; Buchwalter, Gilles; Stams, Travis; Keen, Nicholas; Sellers, William R; Brown, Myles; Pagliarini, Raymond A

2016-05-16

The TMPRSS2:ERG gene fusion is common in androgen receptor (AR) positive prostate cancers, yet its function remains poorly understood. From a screen for functionally relevant ERG interactors, we identify the arginine methyltransferase PRMT5. ERG recruits PRMT5 to AR-target genes, where PRMT5 methylates AR on arginine 761. This attenuates AR recruitment and transcription of genes expressed in differentiated prostate epithelium. The AR-inhibitory function of PRMT5 is restricted to TMPRSS2:ERG-positive prostate cancer cells. Mutation of this methylation site on AR results in a transcriptionally hyperactive AR, suggesting that the proliferative effects of ERG and PRMT5 are mediated through attenuating AR's ability to induce genes normally involved in lineage differentiation. This provides a rationale for targeting PRMT5 in TMPRSS2:ERG positive prostate cancers. Moreover, methylation of AR at arginine 761 highlights a mechanism for how the ERG oncogene may coax AR towards inducing proliferation versus differentiation.

Low Testosterone Alters the Activity of Mouse Prostate Stem Cells.

PubMed

Zhou, Ye; Copeland, Ben; Otto-Duessel, Maya; He, Miaoling; Markel, Susan; Synold, Tim W; Jones, Jeremy O

2017-04-01

Low serum testosterone (low T) has been repeatedly linked to worse outcomes in men with newly diagnosed prostate cancer (PC). How low T contributes to these outcomes is unknown. Here we demonstrate that exposure to low T causes significant changes in the mouse prostate and prostate stem cells. Mice were castrated and implanted with capsules to achieve castrate, normal, or sub-physiological levels of T. After 6 weeks of treatment, LC-MS/MS was used to quantify the levels of T and dihydrotestosterone (DHT) in serum and prostate tissue. FACS was used to quantify the percentages of purported prostate stem and transit amplifying (TA) cells in mouse prostates. Prostate tissues were also stained for the presence of CD68+ cells and RNA was extracted from prostate tissue or specific cell populations to measure changes in transcript levels with low T treatment. Despite having significantly different levels of T and DHT in the serum, T and DHT concentrations in prostate tissue from different T treatment groups were similar. Low T treatment resulted in significant alterations in the expression of androgen biosynthesis genes, which may be related to maintaining prostate androgen levels. Furthermore, the expression of androgen-regulated genes in the prostate was similar among all T treatment groups, demonstrating that the mouse prostate can maintain functional levels of androgens despite low serum T levels. Low T increased the frequency of prostate stem and TA cells in adult prostate tissue and caused major transcriptional changes in those cells. Gene ontology analysis suggested that low T caused inflammatory responses and immunofluorescent staining indicated that low T treatment led to the increased presence of CD68+ macrophages in prostate tissue. Low T alters the AR signaling axis which likely leads to maintenance of functional levels of prostate androgens. Low T also induces quantitative and qualitative changes in prostate stem cells which appear to lead to inflammatory macrophage infiltration. These changes are proposed to lead to an aggressive phenotype once cancers develop and may contribute to the poor outcomes in men with low T. Prostate 77:530-541, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Association between exercise and primary incidence of prostate cancer: does race matter?

PubMed

Singh, Abhay A; Jones, Lee W; Antonelli, Jodi A; Gerber, Leah; Calloway, Elizabeth E; Shuler, Kathleen H; Freedland, Stephen J; Grant, Delores J; Hoyo, Cathrine; Bañez, Lionel L

2013-04-01

Exercise is a modifiable lifestyle risk factor associated with prostate cancer risk reduction. However, whether this association is different as a function of race is unclear. In the current study, the authors attempted to characterize the link between exercise and prostate cancer (CaP) in white and black American men. Using a prospective design, 307 men (164 of whom were white and 143 of whom were black) who were undergoing prostate biopsy completed a self-reported survey that assessed exercise behavior (metabolic equivalent [MET] hours per week). Crude and adjusted logistic regression analyses were used to estimate the risk of prostate cancer controlling for age, body mass index, digital rectal examination findings, previous biopsy, Charlson comorbidity score, and family history of CaP stratified by self-reported race. There was no significant difference noted with regard to the amount of exercise between racial groups (P = .12). Higher amounts of MET hours per week were associated with a decreased risk of CaP for white men in both crude (P = .02) and adjusted (P = .04) regression models. Among whites, men who exercised ≥ 9 MET hours per week were less likely to have a positive biopsy result compared with men exercising < 9 MET hours per week (odds ratio, 0.47; 95% confidence interval, 0.22-0.99 [P = .047]). There was no association noted between MET hours per week and risk of CaP among black men in both crude (P = .79) and adjusted (P = .76) regression models. In a prospective cohort of men undergoing biopsy, increased exercise, measured as MET hours per week, was found to be associated with CaP risk reduction among white but not black men. Investigating race-specific mechanisms by which exercise modifies CaP risk and why these mechanisms disfavor black men in particular are warranted. Copyright © 2013 American Cancer Society.

Morbidity of focal therapy in the treatment of localized prostate cancer.

PubMed

Barret, Eric; Ahallal, Youness; Sanchez-Salas, Rafael; Galiano, Marc; Cosset, Jean-Marc; Validire, Pierre; Macek, Petr; Durand, Matthieu; Prapotnich, Dominique; Rozet, François; Cathelineau, Xavier

2013-04-01

Focal therapy (FT) for prostate cancer (PCa) seems to be part of a natural evolution in the quest to improve the management of early organ-confined disease. To assess the morbidity of the initial experience of FT in a tertiary referral center for PCa management. From 2009 to 2011, a total of 1213 patients with clinically localized PCa were treated at our institution. Of these patients, 547 were considered to have indolent disease according to the D'Amico criteria for low-risk disease plus unilateral disease with a maximum of three positive biopsies. A total of 106 patients underwent FT using high-intensity focused ultrasonography (HIFU), brachytherapy, cryotherapy, or vascular-targeted photodynamic therapy (VTP). Complications were prospectively recorded and graded according to the Clavien-Dindo scale. Data were prospectively collected and retrospectively analyzed. This study included 106 patients, median age 66.5 yr (interquartile range [IQR]): 61-73), who had a prostate hemiablation; 50 patients (47%) had cryotherapy, 23 patients (22%) had VTP, 21 patients (20%) received HIFU, and 12 patients (11%) had brachytherapy. The median prostate-specific antigen (PSA) level was 6.1 ng/ml (IQR: 5-8.1), all the patients had a biopsy Gleason score of 6, and the median prostate weight was 43 g (IQR: 33-55). The median International Prostate Symptom Score was 6 (IQR: 3-10), and the median International Index of Erectile Function score was 20 (IQR: 15-23). After treatment, the median PSA at 3, 6, and 12 mo was 3.1 2.9, and 2.7 ng/ml (IQR: 2-5.1, 1.1-4.7, and 1-4.4), respectively. Thirteen percent of the patients experienced treatment-related complications. There were 11 minor medical complications (10 grade 1 complications and 1 grade 2 complication), 2 grade 3 complications, and no grade 4 or higher complications. FT for a highly selected population with PCa is feasible and had an acceptable morbidity with <2% major complications. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Analysis of continence rates following robot-assisted radical prostatectomy: strict leak-free and pad-free continence.

PubMed

Reynolds, W Stuart; Shikanov, Sergey A; Katz, Mark H; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2010-02-01

To propose a strict and specific definition of continence (leak-free and pad-free [LFPF]) and apply it to robot-assisted radical prostatectomy (RARP) outcomes on the basis of University of California-Los Angeles-Prostate Cancer Index (UCLA-PCI), as postprostatectomy incontinence is not well defined. A single-institution RARP database was reviewed concerning continence variables prospectively recorded by the UCLA-PCI. Specific responses to urinary function and continence items were reviewed at baseline and 1, 3, 6, 12, and 24 months after surgery. From February 2003 to September 2007, a total of 1005 of 1500 RARP patients had data available for review. At baseline, only 73% of these patients were LFPF. This decreased to 4%, 9%, 17%, 24%, and 28% at 1, 3, 6, 12, and 24 months after surgery, respectively. Applying less strict definitions, at 24 months, 68% of patients reported no pad use and 90% of patients reported no pad use or the use of a security pad. When stratified by baseline LFPF status, patients not LFPF at baseline had higher baseline international prostate symptom score scores, lower urinary function scores, lower urinary bother scores, and larger prostate weights. Patients LFPF at baseline disproportionately regained LFPF continence starting 6 months after surgery compared with those not LFPF at baseline: 20% vs 9% (P = .005), 27% vs 15% (P = .0009), and 33% vs 15% (P = .0146) at 6, 12, and 24 months, respectively. A strict definition of urinary continence results in more conservative postoperative outcomes. Preoperative LFPF status can be predictive of postoperative LFPF continence. However, only one-third of patients LFPF at baseline returned to LFPF at 24 months. 2010 Elsevier Inc. All rights reserved.

Effect of Eischens Yoga During Radiation Therapy on Prostate Cancer Patient Symptoms and Quality of Life: A Randomized Phase II Trial.

PubMed

Ben-Josef, Avital Mazar; Chen, Jerry; Wileyto, Paul; Doucette, Abigail; Bekelman, Justin; Christodouleas, John; Deville, Curtiland; Vapiwala, Neha

2017-08-01

A randomized phase II study was performed to measure the potential therapeutic effects of yoga on fatigue, erectile dysfunction, urinary incontinence, and overall quality of life (QOL) in prostate cancer (PCa) patients undergoing external beam radiation therapy (RT). The participants were randomized to yoga and no-yoga cohorts (1:1). Twice-weekly yoga interventions were offered throughout the 6- to 9-week courses of RT. Comparisons of standardized assessments were performed between the 2 cohorts for the primary endpoint of fatigue and the secondary endpoints of erectile dysfunction, urinary incontinence, and QOL before, during, and after RT. From October 2014 to January 2016, 68 eligible PCa patients underwent informed consent and agreed to participate in the study. Of the 68 patients, 18 withdrew early, mostly because of treatment schedule-related time constraints, resulting in 22 and 28 patients in the yoga and no-yoga groups, respectively. Throughout treatment, those in the yoga arm reported less fatigue than those in the control arm, with global fatigue, effect of fatigue, and severity of fatigue subscales showing statistically significant interactions (P<.0001). The sexual health scores (International Index of Erectile Function Questionnaire) also displayed a statistically significant interaction (P=.0333). The International Prostate Symptom Score revealed a statistically significant effect of time (P<.0001) but no significant effect of treatment (P=.1022). The QOL measures had mixed results, with yoga having a significant time by treatment effect on the emotional, physical, and social scores but not on functional scores. A structured yoga intervention of twice-weekly classes during a course of RT was associated with a significant reduction in pre-existing and RT-related fatigue and urinary and sexual dysfunction in PCa patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential for Higher Treatment Failure in Obese Patients: Correlation of Elevated Body Mass Index and Increased Daily Prostate Deviations From the Radiation Beam Isocenters in an Analysis of 1,465 Computed Tomographic Images

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

Wong, James R.; Gao Zhanrong; Merrick, Scott

2009-09-01

Purpose: Recent clinical outcome studies on prostate cancer have reported the influence of patient's obesity on the biochemical failure rates after various treatment modalities. In this study, we investigated the effect of patient's physical characteristics on prostate shift in external beam radiotherapy (EBRT) and hypothesized that there maybe a correlation between patient physique and tumor shift. Methods and Materials: A retrospective analysis was performed using data for 117 patients who received image-guided radiation therapy (IGRT) for prostate cancer between January 2005 and April 2007. A total of 1,465 CT scans were analyzed. The standard deviations (SDs) of prostate shifts formore » all patients, along with patient weight, body mass index (BMI), and subcutaneous adipose-tissue thickness (SAT), were determined. Spearman rank correlation analysis was performed. Results: Of the 117 patients, 26.5% were considered normal weight, 48.7% were overweight, 17.9% were mildly obese, and 6.9% were moderately to severely obese. Notably 1.3%, 1.5%, 2.0%, and 21.2% of the respective shifts were greater than 10 mm in the left-right (LR) direction for the four patient groups, whereas in the anterior-posterior direction the shifts are 18.2%, 12.6%, 6.7%, and 21.0%, respectively. Strong correlations were observed between SAT, BMI, patient weight, and SDs of daily shifts in the LR direction (p < 0.01). Conclusions: The strong correlation between obesity and shift indicates that without image-guided radiation therapy, the target volume (prostate with or without seminal vesicles) may not receive the intended dose for patients who are moderate to severely obese. This may explain the higher recurrence rate with conventional external beam radiation therapy.« less

Risk Assessment Among Prostate Cancer Patients Receiving Primary Androgen Deprivation Therapy

PubMed Central

Cooperberg, Matthew R.; Hinotsu, Shiro; Namiki, Mikio; Ito, Kazuto; Broering, Jeanette; Carroll, Peter R.; Akaza, Hideyuki

2009-01-01

Purpose Prostate cancer epidemiology has been marked overall by a downward risk migration over time. However, in some populations, both in the United States and abroad, many men are still diagnosed with high-risk and/or advanced disease. Primary androgen deprivation therapy (PADT) is frequently offered to these patients, and disease risk prediction is not well-established in this context. We compared risk features between large disease registries from the United States and Japan, and aimed to build and validate a risk prediction model applicable to PADT patients. Methods Data were analyzed from 13,740 men in the United States community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry and 19,265 men in the Japan Study Group of Prostate Cancer (J-CaP) database, a national Japanese registry of men receiving androgen deprivation therapy. Risk distribution was compared between the two datasets using three well-described multivariable instruments. A novel instrument (Japan Cancer of the Prostate Risk Assessment [J-CAPRA]) was designed and validated to be specifically applicable to PADT patients, and more relevant to high-risk patients than existing instruments. Results J-CaP patients are more likely than CaPSURE patients to be diagnosed with high-risk features; 43% of J-CaP versus 5% of CaPSURE patients had locally advanced or metastatic disease that could not be stratified with the standard risk assessment tools. J-CAPRA—scored 0 to 12 based on Gleason score, prostate-specific antigen level, and clinical stage—predicts progression-free survival among PADT patients in J-CaP with a c-index of 0.71, and cancer-specific survival among PADT patients in CaPSURE with a c-index of 0.84. Conclusion The novel J-CAPRA is the first risk instrument developed and validated for patients undergoing PADT. It is applicable to those with both localized and advanced disease, and performs well in diverse populations. PMID:19667269

Body Mass Index and Prostate-Specific Antigen Failure Following Brachytherapy for Localized Prostate Cancer

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

Efstathiou, Jason A.; Skowronski, Rafi Y.; Coen, John J.

2008-08-01

Purpose: Increasing body mass index (BMI) is associated with prostate-specific antigen (PSA) failure after radical prostatectomy and external beam radiation therapy (EBRT). We investigated whether BMI is associated with PSA failure in men treated with brachytherapy for clinically localized prostate cancer. Patients and Methods: Retrospective analyses were conducted on 374 patients undergoing brachytherapy for stage T1c-T2cNXM0 prostate cancer from 1996-2001. Forty-nine patients (13%) received supplemental EBRT and 131 (35%) received androgen deprivation therapy (ADT). Height and weight data were available for 353 (94%). Cox regression analyses were performed to evaluate the relationship between BMI and PSA failure (nadir + 2more » ng/ml definition). Covariates included age, race, preimplantation PSA, Gleason score, T category, percent of prescription dose to 90% of the prostate, use of supplemental EBRT, and ADT. Results: Median age, PSA, and BMI were 66 years (range, 42-80 years), 5.7 ng/ml (range, 0.4-22.6 ng/ml), and 27.1 kg/m{sup 2} (range, 18.2-53.6 kg/m{sup 2}), respectively. After a median follow-up of 6.0 years (range, 3.0-10.2 years), there were 76 PSA recurrences. The BMI was not associated with PSA failure. Six-year PSA failure rates were 30.2% for men with BMI less than 25 kg/m{sup 2}, 19.5% for BMI of 25 or greater to less than 30 kg/m{sup 2}, and 14.4% for BMI of 30 kg/m{sup 2} or greater (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, using alternative definitions of PSA failure, and excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure (adjusted hazard ratio, 1.12; 95% confidence interval, 1.05-1.20; p 0.0006). Conclusions: Unlike after surgery or EBRT, BMI is not associated with PSA failure in men treated with brachytherapy for prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy in obese patients.« less

A Multireader Exploratory Evaluation of Individual Pulse Sequence Cancer Detection on Prostate Multiparametric Magnetic Resonance Imaging (MRI).

PubMed

Gaur, Sonia; Harmon, Stephanie; Gupta, Rajan T; Margolis, Daniel J; Lay, Nathan; Mehralivand, Sherif; Merino, Maria J; Wood, Bradford J; Pinto, Peter A; Shih, Joanna H; Choyke, Peter L; Turkbey, Baris

2018-04-25

To determine independent contribution of each prostate multiparametric magnetic resonance imaging (mpMRI) sequence to cancer detection when read in isolation. Prostate mpMRI at 3-Tesla with endorectal coil from 45 patients (n = 30 prostatectomy cases, n = 15 controls with negative magnetic resonance imaging [MRI] or biopsy) were retrospectively interpreted. Sequences (T2-weighted [T2W] MRI, diffusion-weighted imaging [DWI], and dynamic contrast-enhanced [DCE] MRI; N = 135) were separately distributed to three radiologists at different institutions. Readers evaluated each sequence blinded to other mpMRI sequences. Findings were correlated to whole-mount pathology. Cancer detection sensitivity, positive predictive value for whole prostate (WP), transition zone, and peripheral zone were evaluated per sequence by reader, with reader concordance measured by index of specific agreement. Cancer detection rates (CDRs) were calculated for combinations of independently read sequences. 44 patients were evaluable (cases median prostate-specific antigen 6.83 [ range 1.95-51.13] ng/mL, age 62 [45-71] years; controls prostate-specific antigen 6.85 [2.4-10.87] ng/mL, age 65.5 [47-71] years). Readers had highest sensitivity on DWI (59%) vs T2W MRI (48%) and DCE (23%) in WP. DWI-only positivity (DWI+/T2W-/DCE-) achieved highest CDR in WP (38%), compared to T2W-only (CDR 24%) and DCE-only (CDR 8%). DWI+/T2W+/DCE- achieved CDR 80%, an added benefit of 56.4% from T2W-only and of 42% from DWI-only (P < .0001). All three sequences interpreted independently positive gave highest CDR of 90%. Reader agreement was moderate (index of specific agreement: T2W = 54%, DWI = 58%, DCE = 33%). When prostate mpMRI sequences are interpreted independently by multiple observers, DWI achieves highest sensitivity and CDR in transition zone and peripheral zone. T2W and DCE MRI both add value to detection; mpMRI achieves highest detection sensitivity when all three mpMRI sequences are positive. Published by Elsevier Inc.

Prostate health index significantly reduced unnecessary prostate biopsies in patients with PSA 2-10 ng/mL and PSA >10 ng/mL: Results from a Multicenter Study in China.

PubMed

Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Helfand, Brian T; Brendler, Charles B; Conran, Carly A; Packiam, Vignesh; Gong, Jian; Wu, Yishuo; Zheng, Siqun L; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng

2017-08-01

The performance of prostate health index (phi) in predicting prostate biopsy outcomes has been well established for patients with prostate-specific antigen (PSA) values between 2 and 10 ng/mL. However, the performance of phi remains unknown in patients with PSA >10 ng/mL, the vast majority in Chinese biopsy patients. We aimed to assess the ability of phi to predict prostate cancer (PCa) and high-grade disease (Gleason Score ≥7) on biopsy in a Chinese population. This is a prospective, observational, multi-center study of consecutive patients who underwent a transrectal ultrasound guided prostate biopsy at four hospitals in Shanghai, China from August 2013 to December 2014. In the cohort of 1538 patients, the detection rate of PCa was 40.2%. phi had a significantly better predictive performance for PCa than total PSA (tPSA). The areas under the receiver operating characteristic curve (AUC) were 0.90 and 0.79 for phi and tPSA, respectively, P < 0.0001. A considerable proportion of patients in the cohort had PSAs >10 ng/mL (N = 838, 54.5%). The detection rates of PCa were 35.9% and 57.7% in patients with tPSA 10.1-20 and 20.1-50 ng/mL, respectively. The AUCs of phi (0.79 and 0.89, for these two groups, respectively) were also significantly higher than tPSA (0.57 and 0.63, respectively), both P < 0.0001. If a phi ≤35 was used as the cutoff, 599/1538 (39%) biopsies could have been avoided at a cost of missing small numbers of PCa patients: 49 (7.93%) PCa patients, including 18 (3.69%) high-grade tumors. Results from this study suggest that phi can be used to predict PCa and high-grade disease in Chinese men with high PSA levels (>10 ng/mL). © 2017 Wiley Periodicals, Inc.

Micrornas in prostate cancer: an overview.

PubMed

Vanacore, Daniela; Boccellino, Mariarosaria; Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Di Franco, Rossella; Romano, Francesco Jacopo; Montanari, Micaela; La Mantia, Elvira; Piscitelli, Raffaele; Nocerino, Flavia; Cappuccio, Francesca; Grimaldi, Giovanni; Izzo, Alessandro; Castaldo, Luigi; Pepe, Maria Filomena; Malzone, Maria Gabriella; Iovane, Gelsomina; Ametrano, Gianluca; Stiuso, Paola; Quagliuolo, Lucio; Barberio, Daniela; Perdonà, Sisto; Muto, Paolo; Montella, Maurizio; Maiolino, Piera; Veneziani, Bianca Maria; Botti, Gerardo; Caraglia, Michele; Facchini, Gaetano

2017-07-25

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.

[Neuroendocrine differentiation in prostate adenocarcinoma].

PubMed

Ramírez-Balderrama, Lázaro; López-Briones, Sergio; Daza-Benítez, Leonel; Macías, Maciste H; López-Gaytán, Teresa; Pérez-Vázquez, Victoriano

2013-01-01

The human prostate is a gland composed of many types of cells and extracellular components with specific functions. The stromal compartment includes nerve tissue, fibroblasts, lymphocytes, macrophages, endothelial cells, and smooth muscular cells. The epithelial compartment is composed of luminal epithelial cells, basal cells, and a lesser number of neuroendocrine cells, which are transcendental in growth regulation, differentiation, and secretory function. In prostate cancer, neuroendocrine cells replicate especially in high grade and advanced stage, and hormonally treated tumoral cells adopt characteristics that make them resistant to hormonal deprivation. Androgen receptors have a crucial role in tumorigenesis of prostate adenocarcinoma. Deprivation hormone therapy blocks the expression of androgen receptors in the prostatic epithelial cells. Neuroendocrine cells lack androgen receptors; their growth is hormonally independent and that is why deprivation hormonal therapy does not eliminate the neoplasic neuroendocrine cells. In contrast, these types of cells proliferate after therapy and make a paracrine network, stimulating the proliferation of androgen-independent neoplastic cells, which finally lead to tumoral recurrence. In this work we describe the neuroendocrine function in normal tissue and in prostatic adenocarcinoma, including neoplasic proliferation stimulation, invasion, apoptosis resistance, and angiogenesis, and describe some molecular pathways involved in this neuroendocrine differentiation.

Prostate Cancer Patient Characteristics Associated With a Strong Preference to Preserve Sexual Function and Receipt of Active Surveillance.

PubMed

Broughman, James R; Basak, Ramsankar; Nielsen, Matthew E; Reeve, Bryce B; Usinger, Deborah S; Spearman, Kiayni C; Godley, Paul A; Chen, Ronald C

2018-04-01

Men with early-stage prostate cancer have multiple options that have similar oncologic efficacy but vary in terms of their impact on quality of life. In low-risk cancer, active surveillance is the option that best preserves patients' sexual function, but it is unknown if patient preference affects treatment selection. Our objectives were to identify patient characteristics associated with a strong preference to preserve sexual function and to determine whether patient preference and baseline sexual function level are associated with receipt of active surveillance in low-risk cancer. In this population-based cohort of men with localized prostate cancer, baseline patient-reported sexual function was assessed using a validated instrument. Patients were also asked whether preservation of sexual function was very, somewhat, or not important. Prostate cancer disease characteristics and treatments received were abstracted from medical records. A modified Poisson regression model with robust standard errors was used to compute adjusted risk ratio (aRR) estimates. All statistical tests were two-sided. Among 1194 men, 52.6% indicated a strong preference for preserving sexual function. Older men were less likely to have a strong preference (aRR = 0.98 per year, 95% confidence interval [CI] = 0.97 to 0.99), while men with normal sexual function were more likely (vs poor function, aRR = 1.59, 95% CI = 1.39 to 1.82). Among 568 men with low-risk cancer, there was no clear association between baseline sexual function or strong preference to preserve function with receipt of active surveillance. However, strong preference may differnetially impact those with intermediate baseline function vs poor function (Pinteraction = .02). Treatment choice may not always align with patients' preferences. These findings demonstrate opportunities to improve delivery of patient-centered care in early prostate cancer.

A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R-3327G and anabolic activity on skeletal muscle mass & function in castrated mice.

PubMed

Chisamore, Michael J; Gentile, Michael A; Dillon, Gregory Michael; Baran, Matthew; Gambone, Carlo; Riley, Sean; Schmidt, Azriel; Flores, Osvaldo; Wilkinson, Hilary; Alves, Stephen E

2016-10-01

The androgen receptor (AR) is a member of the nuclear hormone receptor super family of transcription factors. Androgens play an essential role in the development, growth, and maintenance of male sex organs, as well as the musculoskeletal and central nervous systems. Yet with advancing age, androgens can drive the onset of prostate cancer, the second leading cause of cancer death in males within the United States. Androgen deprivation therapy (ADT) by pharmacologic and/or surgical castration induces apoptosis of prostate cells and subsequent shrinkage of the prostate and prostate tumors. However, ADT is associated with significant musculoskeletal and behavioral adverse effects. The unique pharmacological activity of selective androgen receptor modulator (SARM) MK-4541 recently has been reported as an AR antagonist with 5α-reductase inhibitor function. The molecule inhibits proliferation and induces apoptosis in AR positive, androgen dependent prostate cancer cells. Importantly, MK-4541 inhibited androgen-dependent prostate growth in male rats yet maintained lean body mass and bone formation following ovariectomy in female rats. In the present study, we evaluated the effects of SARM MK-4541 in the androgen-dependent Dunning R3327-G prostate carcinoma xenograft mouse model as well as on skeletal muscle mass and function, and AR-regulated behavior in mice. MK-4541 significantly inhibited the growth of R3327-G prostate tumors, exhibited anti-androgen effects on the seminal vesicles, reduced plasma testosterone concentrations in intact males, and inhibited Ki67 expression. MK-4541 treated xenografts appeared similar to xenografts in castrated mice. Importantly, we demonstrate that MK-4541 exhibited anabolic activity in androgen deficient conditions, increasing lean body mass and muscle function in adult castrated mice. Moreover, MK-4541 treatment restored general activity levels in castrated mice. Thus, MK-4541 exhibits an optimum profile as an adjuvant therapy to ADT which may provide potent anti-androgenic activity at the prostate yet protective activity on skeletal muscle and behavior in patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

The German version of the Expanded Prostate Cancer Index Composite (EPIC): translation, validation and minimal important difference estimation.

PubMed

Umbehr, Martin H; Bachmann, Lucas M; Poyet, Cedric; Hammerer, Peter; Steurer, Johann; Puhan, Milo A; Frei, Anja

2018-02-20

No official German translation exists for the 50-item Expanded Prostate Cancer Index Composite (EPIC), and no minimal important difference (MID) has been established yet. The aim of the study was to translate and validate a German version of the EPIC with cultural adaptation to the different German speaking countries and to establish the MID. We translated and culturally adapted the EPIC into German. For validation, we included a consecutive subsample of 92 patients with localized prostate cancer undergoing radical prostatectomy who participated the Prostate Cancer Outcomes Cohort. Baseline and follow-up assessments took place before and six weeks after prostatectomy in 2010 and 2011. We assessed the EPIC, EORTC QLQ-PR25, Feeling Thermometer, SF-36 and a global rating of health state change variable. We calculated the internal consistency, test-retest reliability, construct validity, responsiveness and MID. For most EPIC domains and subscales, our a priori defined criteria for reliability were fulfilled (construct reliability: Cronbach's alpha 0.7-0.9; test-retest reliability: intraclass-correlation coefficient ≥ 0.7). Cross-sectional and longitudinal correlations between EPIC and EORTC QLQ-PR25 domains ranged from 0.14-0.79, and 0.06-0.5 and 0.08-0.72 for Feeling Thermometer and SF-36, respectively. We established MID values of 10, 4, 12, and 6 for the urinary, bowel, sexual and hormonal domain. The German version of the EPIC is reliable, responsive and valid to measure HRQL in prostate cancer patients and is now available in German language. With the suggested MID we provide interpretation to what extent changes in HRQL are clinically relevant for patients. Hence, study results are of interest beyond German speaking countries.

Haralick textural features on T2 -weighted MRI are associated with biochemical recurrence following radiotherapy for peripheral zone prostate cancer.

PubMed

Gnep, Khémara; Fargeas, Auréline; Gutiérrez-Carvajal, Ricardo E; Commandeur, Frédéric; Mathieu, Romain; Ospina, Juan D; Rolland, Yan; Rohou, Tanguy; Vincendeau, Sébastien; Hatt, Mathieu; Acosta, Oscar; de Crevoisier, Renaud

2017-01-01

To explore the association between magnetic resonance imaging (MRI), including Haralick textural features, and biochemical recurrence following prostate cancer radiotherapy. In all, 74 patients with peripheral zone localized prostate adenocarcinoma underwent pretreatment 3.0T MRI before external beam radiotherapy. Median follow-up of 47 months revealed 11 patients with biochemical recurrence. Prostate tumors were segmented on T 2 -weighted sequences (T 2 -w) and contours were propagated onto the coregistered apparent diffusion coefficient (ADC) images. We extracted 140 image features from normalized T 2 -w and ADC images corresponding to first-order (n = 6), gradient-based (n = 4), and second-order Haralick textural features (n = 130). Four geometrical features (tumor diameter, perimeter, area, and volume) were also computed. Correlations between Gleason score and MRI features were assessed. Cox regression analysis and random survival forests (RSF) were performed to assess the association between MRI features and biochemical recurrence. Three T 2 -w and one ADC Haralick textural features were significantly correlated with Gleason score (P < 0.05). Twenty-eight T 2 -w Haralick features and all four geometrical features were significantly associated with biochemical recurrence (P < 0.05). The most relevant features were Haralick features T 2 -w contrast, T 2 -w difference variance, ADC median, along with tumor volume and tumor area (C-index from 0.76 to 0.82; P < 0.05). By combining these most powerful features in an RSF model, the obtained C-index was 0.90. T 2 -w Haralick features appear to be strongly associated with biochemical recurrence following prostate cancer radiotherapy. 3 J. Magn. Reson. Imaging 2017;45:103-117. © 2016 International Society for Magnetic Resonance in Medicine.

Assessment of Volumetric-Modulated Arc Therapy for Constant and Variable Dose Rates

PubMed Central

De Ornelas-Couto, Mariluz; Mihaylov, Ivaylo; Dogan, Nesrin

2017-01-01

Purpose: The aim of this study is to compare the effects of dose rate on volumetric-modulated arc therapy plans to determine optimal dose rates for prostate and head and neck (HN) cases. Materials and Methods: Ten prostate and ten HN cases were retrospectively studied. For each case, seven plans were generated: one variable dose rate (VDR) and six constant dose rate (CDR) (100–600 monitor units [MUs]/min) plans. Prescription doses were: 80 Gy to planning target volume (PTV) for the prostate cases, and 70, 60, and 54 Gy to PTV1, PTV2, and PTV3, respectively, for HN cases. Plans were normalized to 95% of the PTV and PTV1, respectively, with the prescription dose. Plans were assessed using Dose-Volume-Histogram metrics, homogeneity index, conformity index, MUs, and delivery time. Results: For the prostate cases, significant differences were found for rectum D35 between VDR and all CDR plans, except CDR500. Furthermore, VDR was significantly different than CDR100 and 200 for bladder D50. Delivery time for all CDR plans and MUs for CDR400–600 were significantly higher when compared to VDR. HN cases showed significant differences between VDR and CDR100, 500 and 600 for D2 to the cord and brainstem. Significant differences were found for delivery time and MUs for all CDR plans, except CDR100 for number of MUs. Conclusion: The most significant differences were observed in delivery time and number of MUs. All-in-all, the best CDR for prostate cases was found to be 300 MUs/min and 200 or 300 MUs/min for HN cases. However, VDR plans are still the choice in terms of MU efficiency and plan quality. PMID:29296033

Anatomy and Histology of the Human and Murine Prostate.

PubMed

Ittmann, Michael

2018-05-01

The human and murine prostate glands have similar functional roles in the generation of seminal fluid to assist in reproduction. There are significant differences in the anatomy and histology of murine and human prostate and knowledge of the normal anatomy and histology of the murine prostate is essential to interpreting changes in genetically engineered mouse models. In this review, the normal anatomy and histology of both human and mouse prostate will be described. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Bladder neck contracture after robot-assisted laparoscopic radical prostatectomy: evaluation of incidence and risk factors and impact on urinary function.

PubMed

Msezane, Lambda P; Reynolds, W Stuart; Gofrit, Ofer N; Shalhav, Arieh L; Zagaja, Gregory P; Zorn, Kevin C

2008-01-01

Bladder neck contracture (BNC) after radical prostatectomy has been reported to occur in 5% to 32% of men after open retropubic prostatectomy (RRP) and in 0% to 3% after laparoscopic RRP. Optimal anastomotic closure involves creating a watertight, tension-free anastomosis with well-vascularized, mucosal apposition and correct realignment of the urethra. The cause of BNC is poorly understood; however, it is likely related to multiple factors, including excessive luminal narrowing at the site of reconstruction, local tissue ischemia, failed mucosal apposition, and urinary leakage. In this large series of patients who underwent robot-assisted laparoscopic radical prostatectomy (RLRP), we report the incidence of BNC, evaluate the influence of age, body mass index (BMI), estimated blood loss (EBL), surgical time, and prostate weight on its development and assess follow-up urinary function. Between February 2003 and July 2006, 650 consecutive men underwent RLRP at our institution. Patients with aborted or open conversion procedures were excluded from analysis. The mean overall follow-up for the remaining 634 patients was 19.5 months. Patients presenting with symptoms of outlet obstruction were evaluated with cystoscopy to confirm a BNC. Comparisons of age, BMI, EBL, operative time, and prostate weight were performed using the Student t-test and chi-square analysis. BNC was the diagnosis in seven patients (1.1%) with a mean time of presentation of 4.8 (3-12) months postoperatively. The BNC patients had comparable mean age, BMI, prostate weight, and EBL to the non-BNC cohort. Their operative time, however, was significantly longer (283 v 225 min., P = 0.04). The incidence of BNC after radical prostatectomy is 2.2% in a large series of men undergoing RLRP. The diagnosis was made within 1 year. No significant impact on urinary continence or quality-of-life urinary function was observed after BNC management. A running anastomosis, better visualization, improved instrument maneuverability, and decreased blood loss may account for such a low rate.

Bladder neck contracture after robot-assisted laparoscopic radical prostatectomy: evaluation of incidence and risk factors and impact on urinary function.

PubMed

Msezane, Lambda P; Reynolds, W Stuart; Gofrit, Ofer N; Shalhav, Arieh L; Zagaja, Gregory P; Zorn, Kevin C

2008-02-01

Bladder neck contracture (BNC) after radical prostatectomy has been reported to occur in 5% to 32% of men after open radical retropubic prostatectomy (RRP) and 0% to 3% after laparoscopic RRP. Optimal anastomotic closure involves creating a watertight, tension-free anastomosis with well-vascularized, mucosal apposition and correct realignment of the urethra. The cause of BNC is poorly understood; however, it is likely related to multiple factors, including excessive luminal narrowing at the site of reconstruction, local tissue ischemia, failed mucosal apposition, and urinary leakage. In this large series of patients who underwent robot-assisted laparoscopic radical prostatectomy (RLRP), we report the incidence of BNC, evaluate the influence of age, body mass index (BMI), estimated blood loss (EBL), surgical time, and prostate weight on its development and assess follow-up urinary function. Between February 2003 and July 2006, 650 consecutive men underwent RLRP at our institution. Patients with aborted or open conversion procedures were excluded from analysis. The mean overall follow-up for the remaining 634 patients was 19.5 months. Patients presenting with symptoms of outlet obstruction were evaluated with cystoscopy to confirm a BNC. Comparisons of age, BMI, EBL, operative time, and prostate weight were performed using the Student t-test and chi-square analysis. BNC was the diagnosis in seven patients (1.1%), with a mean time of presentation of 4.8 (3-12) months postoperatively. The BNC patients had comparable mean age, BMI, prostate weight, and EBL to the non-BNC cohort. Their operative time, however, was significantly longer (283 v 225 min, P = 0.04). The incidence of BNC after radical prostatectomy is 1.1% in a large series of men undergoing RLRP. The diagnosis was made within 1 year. No significant impact on urinary continence or quality-of-life urinary function was observed after BNC management. A running anastomosis, better visualization, improved instrument maneuverability, and decreased blood loss may account for such a low rate.

Investigating the Functional Role of Prostate-Specific Membrane Antigen and its Enzymatic Activity in Prostate Cancer Metastasis

DTIC Science & Technology

2007-02-01

saponin (Calbiochem, San Diego, CA) in PBS. Results, Significance, Obstacles and Alternative Approaches: We have generated several different fluorescent...1 integrin antibody P4C10 (Life technologies ). We will conjugate the fluorescent probes to these functional blocking antibodies for live cell...characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. Int. J. Cancer. 62:552-558. 1995. 9. Wright GL Jr

Communicating Value in Health Care Using Radar Charts: A Case Study of Prostate Cancer.

PubMed

Thaker, Nikhil G; Ali, Tariq N; Porter, Michael E; Feeley, Thomas W; Kaplan, Robert S; Frank, Steven J

2016-09-01

The transformation from volume to value will require communication of outcomes and costs of therapies; however, outcomes are usually nonstandardized, and cost of therapy differs among stakeholders. We developed a standardized value framework by using radar charts to visualize and communicate a wide range of patient outcomes and cost for three forms of prostate cancer treatment. We retrospectively reviewed data from men with low-risk prostate cancer who were treated with low-dose rate brachytherapy (LDR-BT), proton beam therapy, or robotic-assisted prostatectomy. Patient-reported outcomes comprised the Expanded Prostate Cancer Index Composite-50 domains for sexual function, urinary incontinence and/or bother, bowel bother, and vitality 12 months after treatment. Costs were measured by time-driven activity-based costing for the first 12 months of the care cycle. Outcome and cost data were plotted on a single radar chart for each treatment modality. Outcome and cost data from patients who were treated with robotic-assisted prostatectomy (n = 381), proton beam therapy (n = 165), and LDR-BT (n = 238) were incorporated into the radar chart. LDR-BT seemed to deliver the highest overall value of the three treatment modalities; however, incorporation of patient preferences regarding outcomes may allow other modalities to be considered high-value treatment options. Standardization and visualization of outcome and cost metrics may allow more comprehensive and collaborative discussions about the value of health care services. Communicating the value framework by using radar charts may be an effective method to present total value and the value of all outcomes and costs in a manner that is accessible to all stakeholders. Variations in plotting of costs and outcomes will require future focus group initiatives. Copyright © 2016 by American Society of Clinical Oncology.

Communicating Value in Health Care Using Radar Charts: A Case Study of Prostate Cancer

PubMed Central

Thaker, Nikhil G.; Ali, Tariq N.; Porter, Michael E.; Feeley, Thomas W.; Kaplan, Robert S.

2016-01-01

Purpose: The transformation from volume to value will require communication of outcomes and costs of therapies; however, outcomes are usually nonstandardized, and cost of therapy differs among stakeholders. We developed a standardized value framework by using radar charts to visualize and communicate a wide range of patient outcomes and cost for three forms of prostate cancer treatment. Materials and Methods: We retrospectively reviewed data from men with low-risk prostate cancer who were treated with low-dose rate brachytherapy (LDR-BT), proton beam therapy, or robotic-assisted prostatectomy. Patient-reported outcomes comprised the Expanded Prostate Cancer Index Composite-50 domains for sexual function, urinary incontinence and/or bother, bowel bother, and vitality 12 months after treatment. Costs were measured by time-driven activity-based costing for the first 12 months of the care cycle. Outcome and cost data were plotted on a single radar chart for each treatment modality. Results: Outcome and cost data from patients who were treated with robotic-assisted prostatectomy (n = 381), proton beam therapy (n = 165), and LDR-BT (n = 238) were incorporated into the radar chart. LDR-BT seemed to deliver the highest overall value of the three treatment modalities; however, incorporation of patient preferences regarding outcomes may allow other modalities to be considered high-value treatment options. Conclusion: Standardization and visualization of outcome and cost metrics may allow more comprehensive and collaborative discussions about the value of health care services. Communicating the value framework by using radar charts may be an effective method to present total value and the value of all outcomes and costs in a manner that is accessible to all stakeholders. Variations in plotting of costs and outcomes will require future focus group initiatives. PMID:27577622

Pleiotropy between genetic markers of obesity and risk of prostate cancer

PubMed Central

Edwards, Todd L.; Giri, Ayush; Motley, Saundra; Duong, Wynne; Fowke, Jay H.

2013-01-01

Background To address inconsistent findings of obesity and prostate cancer risk, we analyzed the association between prostate cancer (PC) and genetic markers of obesity and metabolism. Methods Analyses included 176,520 single nucleotide polymorphisms (SNPs) associated with 23 metabolic traits. We examined the association between SNPs and PC in 871 cases and 906 controls, including 427 high-grade cases with Gleason ≥7. Genetic risk scores (GRSs) for body mass index (BMI) and waist-to-hip ratio (WHR) were also created by summing alleles associated with increasing BMI or WHR. Results PC was associated with 5 loci, including cyclin M2, with p-values less than 1×10−4. In addition, the WHR GRS was associated with high-grade PC versus controls (OR: 1.05; 95% CI: 1.00 – 1.11, p-value = 0.048), and high-grade PC versus low-grade PC (OR: 1.07, 95% CI 1.01 – 1.13, p-value = 0.03). None of these findings exceed the threshold for significance after correction for multiple testing. Conclusions Variants in genes known to be associated with metabolism and obesity may be associated with PC. We show evidence for pleiotropy between WHR GRS and PC grade. This finding is consistent with the function of several WHR genes, and previously described relationships with cancer traits. Impact Limitations in standard obesity measures suggest alternative characterizations of obesity may be needed to understand the role of metabolic dysregulation in PC. The underlying genetics of WHR or other Metabochip SNPs, while not statistically significant beyond multiple testing thresholds within our sample size, support the metabolic hypothesis of prostate carcinogenesis and warrant further investigation in independent samples. PMID:23810916

Health perceptions in patients who undergo screening and workup for prostate cancer.

PubMed

Katz, David A; Jarrard, David F; McHorney, Colleen A; Hillis, Stephen L; Wiebe, Donald A; Fryback, Dennis G

2007-02-01

False-positive screening tests may induce persistent psychological distress. This study was designed to determine whether a positive screening test with negative biopsy findings for prostate cancer is associated with worsened mental health during short-term follow-up. We conducted a cross-sectional telephone survey of two groups of men approximately 2 months after testing: group 1, 109 men with an abnormal prostate-specific antigen level or digital rectal examination findings but with negative biopsy findings for prostate cancer; and group 2, 101 age-matched primary care patients with PSA screening levels in the reference range (less than 4 ng/mL). Primary outcomes included state anxiety and prostate cancer-related worry. Secondary outcomes included Medical Outcomes Study Short Form 36-item Health Survey subscales and sexual function items. Multivariate regression techniques were used to adjust for differences in baseline covariates. Group 1 patients were more worried than group 2 patients about getting prostate cancer (mean worry 3.9 versus 4.5, P = 0.0001, using a 5-point scale, with 1 indicating extreme worry and 5 no worry). Group 1 patients also perceived their risk of prostate cancer to be significantly greater than that of controls (P = 0.001). No significant differences were found across state anxiety or Medical Outcomes Study Short Form 36-item Health Survey subscales. Sexual bother was greater for group 1 patients, with 19% reporting that sexual function was a moderate to big problem compared with 10% of group 2 patients (P = 0.0001). Men with abnormal prostate cancer screening tests report increased cancer-related worry and more problems with sexual function, despite having a negative biopsy result. Effective counseling interventions are needed before prostate cancer screening and during follow-up.

Ubiquitin ligase CHIP functions as an oncogene and activates the AKT signaling pathway in prostate cancer.

PubMed

Cheng, Li; Zang, Jin; Dai, Han-Jue; Li, Feng; Guo, Feng

2018-07-01

Carboxyl terminus of Hsc-70-interacting protein (CHIP) is an E3 ubiquitin ligase that induces the ubiquitination and degradation of numerous tumor-associated proteins and serves as a suppressor or promoter in tumor progression. To date, the molecular mechanism of CHIP in prostate cancer remains unknown. Therefore, the present study investigated the biological function of CHIP in prostate cancer cells and obtained evidence that CHIP expression is upregulated in prostate cancer tissues. The CHIP vector was introduced into DU145 cancer cells and the cell biological behaviour was examined through a series of experiments, including cell growth, cell apoptosis and migration and invasion assays. The results indicated that the overexpression of CHIP in DU145 prostatic cancer cells promoted cell proliferation through activation of the protein kinase B (AKT) signaling pathway, which subsequently increased cyclin D1 protein levels and decreased p21 and p27 protein levels. The overexpression of CHIP significantly increased the migration and invasion of the DU145 cells, which is possible due to activation of the AKT signaling pathway and upregulation of vimentin. The expression level of CHIP was observed to be increased in human prostate cancer tissues compared with the adjacent normal tissue. Furthermore, the CHIP expression level exhibited a positively association with the Gleason score of the patents. These findings indicate that CHIP functions as an oncogene in prostate cancer.

Insidious enemy: downside to prolonged survival in prostate cancer.

PubMed

Lodhia, Vaishali; Puspanathan, Thevamalar

2017-08-02

An 83-year-old man, a prostate cancer survivor of 10 years with multiple vertebral metastases presented with sudden onset of double vision. On examination he was found to have an isolated partial left abducens palsy with no other neurological deficits. Despite having microvascular risk factors, given his history of prostate cancer, aMRI brain scan was requested to look for a neurological cause. The scan revealed a metastatic lesion in the clivus encasing the cavernous sinus and carotid artery. He was referred to his oncologist for further management, however he opted out of further treatment and succumbed to his illness a month later. This case report includes a literature review of cases with clivus metastases secondary to prostate cancer. It highlights the importance of carefully examining eye movements and having a high index of suspicion for the subtlest sign that may suggest brain metastases in elderly patients with prostate cancer with prolonged survival. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical and Biochemical Influence of Prostatic Stones.

PubMed

Soric, Tomislav; Selimovic, Mirnes; Bakovic, Lada; Šimurina, Tatjana; Selthofer, Robert; Dumic, Jerka

2017-01-01

The study aimed to explore clinical influence of prostatic stones on lower urinary tract symptoms (LUTS), seminal plasma cytokines, and serum biomarkers. A total of 70 men aged ≤50 years with LUTS divided into 2 groups: group with stones (GSt) and group without prostatic stones (GNoSt). All subjects completed the International Prostate Symptom Score (IPSS) questionnaire and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scoring questionnaire. Pre- and post-prostate massage test and uroflowmetry were performed. The serum concentration of total prostate specific antigen (PSA), free PSA, and free/total PSA (f/t PSA) ratio, seminal concentration of cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor-alpha were measured. GSt subjects had significantly more severe symptoms based on IPSS answers (p = 0.0289). All domains in NIH-CPSI scores were significantly higher in the GSt group: pain (p = 0.001), urinary symptoms (p = 0.023), quality of life (p = 0.008), and with overall (p = 0.003). GSt subjects also had significantly lower maximum urinary flow (Qmax; p = 0.011), lower f/t PSA ratio (p = 0.048), and higher concentration of IL-1β (p = 0.011) and IL-8 (p = 0.001). Prostatic stones may influence the severity of LUTS and the symptoms of chronic prostatitis. They might reduce Qmax rate and lead to reduction of the f/t PSA ratio and produce more severe inflammation causing increased seminal concentration of IL-1β and IL-8. © 2017 S. Karger AG, Basel.

Associations of adiponectin and leptin with stage and grade of PSA-detected prostate cancer: the ProtecT study.

PubMed

Burton, Anya; Martin, Richard M; Holly, Jeff; Lane, J Athene; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Tilling, Kate

2013-02-01

Obesity has been associated with an increased risk of advanced and fatal prostate cancer; adipokines may mediate this association. We examined associations of the adipokines leptin and adiponectin with the stage and grade of PSA-detected prostate cancer. We conducted a nested case-control study comparing 311 men with mainly locally advanced (≥T3, N1, or M1 cases) vs. 413 men with localized (T ≤2 & NX-0 & M0 controls) PSA-detected prostate cancer, recruited 2001-2009 from 9 UK regions to the ProtecT study. Associations of body mass index and adipokine levels with prostate cancer stage were determined by conditional logistic regression and with grade (Gleason score ≥7 vs. ≤6) by unconditional logistic regression. Adiponectin was inversely associated with prostate cancer stage in overweight and obese men (OR 0.62; 95 % CI 0.42-0.90; p = 0.01), but not in normal weight men (OR 1.48; 0.77-2.82; p = 0.24) (p for interaction 0.007), or all men (OR 0.86; 0.66-1.11; p = 0.24). There was no compelling evidence of associations between leptin or leptin to adiponectin ratio and prostate cancer stage. No strong associations of adiponectin, leptin, or leptin:adiponectin ratio with grade were seen. This study provides some evidence that adiponectin levels may be associated with prostate cancer stage, dependent on the degree of adiposity of the man. Our results are consistent with adiponectin countering the adverse effects of obesity on prostate cancer progression.

Early diagnostic role of PSA combined miR-155 detection in prostate cancer.

PubMed

Guo, T; Wang, X-X; Fu, H; Tang, Y-C; Meng, B-Q; Chen, C-H

2018-03-01

As a kind of malignant tumor in the male genitourinary system, prostate cancer exhibits significantly increased occurrence. Prostate-specific antigen (PSA) expression can be seen in the prostate cancer, prostatitis, and other diseases, therefore, lack of diagnostic specificity. The miR-155 expression is abnormally increased in the tumors. Therefore, this study aims to explore the clinical significance of PSA combined miR-155 detection in the early diagnosis of prostate cancer. A total of 86 patients diagnosed with prostate cancer were enrolled in this study. PSA and miR-155 gene expression in tumor tissue were detected by using Real-time PCR. The serum levels of PSA were measured by using enzyme-linked immunosorbent assay (ELISA). The correlation of PSA and miR-155 expression with age, body mass index (BMI), tumor volume, tumor-node-metastasis (TNM) stage, lymph node metastasis (LNM), and other clinicopathological features were analyzed, respectively. Serum PSA expression and PSA gene in tumor tissue were significantly higher compared to that in adjacent tissues (p<0.05). PSA gene and protein increased significantly with the clinical stage of TNM and decreased following the increase of grade (p<0.05). The miR-155 level was significantly elevated in the tumor tissue compared with para-carcinoma tissue (p<0.05). PSA and miR-155 expressions were positively correlated with TNM stage, tumor volume, and LNM, and negatively correlated with grade (p<0.05). PSA and miR-155 were closely related to the clinicopathological features of prostate cancer. Combined detection is helpful for the early diagnosis of prostate cancer.

Sedentary behavior and prostate cancer risk in the NIH-AARP Diet and Health Study.

PubMed

Lynch, Brigid M; Friedenreich, Christine M; Kopciuk, Karen A; Hollenbeck, Albert R; Moore, Steven C; Matthews, Charles E

2014-05-01

Sedentary behavior (sitting time) has been proposed as an independent risk factor for some cancers; however, its role in the development of prostate cancer has not been determined. We examined the prospective associations of self-reported daily sitting time and daily television/video viewing time with the risk of developing or dying from prostate cancer among 170,481 men in the NIH-AARP Diet and Health Study. We estimated HRs and 95% confidence intervals (CI) using Cox proportional hazards regression. Between 1996 and 2006, there were 13,751 incident (including 1,365 advanced) prostate cancer cases identified; prostate cancer mortality (through 2008) was 669. No strong or significant association with prostate cancer risk was seen in fully adjusted models for either daily sitting or television/video time. There were some suggestions of effect modification by body mass index (BMI; interaction for television/video time and BMI, P = 0.02). For total prostate cancer risk, television/video time was associated with a slightly elevated, but nonsignificant, increase amongst obese men (HR = 1.28; 95% CI, 0.98-1.69); a null association was observed amongst overweight men (HR = 1.04; 0.89-1.22); and, for men with a normal BMI, television/video time was associated with a nonsignificant risk decrease (HR = 0.82; 95% CI, 0.66-1.01). Similar patterns were observed for total daily sitting and television/video time in advanced prostate cancer and prostate cancer mortality. Sedentary behavior seems to play a limited role in the development of prostate cancer; however, we cannot rule out potential effect modification by BMI or the impact of measurement error on results. ©2014 AACR.

Bisphenol A and other environmental risk factors for prostate cancer in Hong Kong.

PubMed

Tse, Lap Ah; Lee, Priscilla Ming Yi; Ho, Wing Ming; Lam, Augustine Tsan; Lee, Man Kei; Ng, Simon Siu Man; He, Yonghua; Leung, Ka-Sing; Hartle, Jennifer C; Hu, Howard; Kan, Haidong; Wang, Feng; Ng, Chi Fai

2017-10-01

Environmental exposures are contributing factors to prostate cancer etiology, but these remain unclear. We aimed to document the associations between environmental risk factors and prostate cancer in Chinese, with special reference to bisphenol A (BPA). We recruited 431 newly diagnosed prostate cancer cases and 402 age-matched controls from Prince of Wales Hospital in Hong Kong. We obtained each participant's clinical data and epidemiological information on chronic BPA exposure and other environmental risk factors (e.g., dietary habits, occupation and shift work) using a standard questionnaire. A new assessment tool of environmental BPA exposure was developed and replicated. Multiple logistic regression analysis was performed to examine odds ratio (OR) and 95% confidence interval (95% CI) for the association of prostate cancer with a novel cumulative BPA exposure index (CBPAI) and other environmental risk factors. Weekly consumption of deep fried food (OR=1.85, 95% CI: 1.15-2.95) and pickled vegetable (OR=1.87, 95% CI: 1.07-3.28) was significantly associated with excessive prostate cancer risk. Prostate cancer was positively associated with nightshift work (OR=1.76, 95% CI: 1.07-2.89) and it was negatively associated with green tea drinking (OR=0.56, 95% CI: 0.34-0.91). There was a positive exposure-response relationship between CBPAI and prostate cancer, with the greatest and significant risk in the high versus reference category (OR=1.57, 95% CI: 1.01-2.44). Frequent consumption of deep fried food and pickled vegetable, non-habitual green tea drinking and nightshift work are the contributing risk factors to prostate cancer in Hong Kong Chinese. More importantly, this study provides the first epidemiological evidence on carcinogenicity of BPA on the human prostate. Copyright © 2017. Published by Elsevier Ltd.

High Frequency of Chronic Bacterial and Non-Inflammatory Prostatitis in Infertile Patients with Prostatitis Syndrome Plus Irritable Bowel Syndrome

PubMed Central

Vicari, Enzo; La Vignera, Sandro; Arcoria, Domenico; Condorelli, Rosita; Vicari, Lucia O.; Castiglione, Roberto; Mangiameli, Andrea; Calogero, Aldo E.

2011-01-01

Background Although prostatitis syndrome (PS) and irritable bowel syndrome (IBS) are common disorders, information on the prevalence of IBS in infertile patients with PS is relatively scanty. Therefore, this study was undertaken to estimate the frequency of PS and IBS and to evaluate the prevalence of the various diagnostic categories of prostatitis. Methodology/Principal Findings This study enrolled 152 patients with PS, diagnosed by the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) in an andrological setting, and 204 patients with IBS, diagnosed according to the Rome III diagnostic criteria in a gastroenterological setting. The patients with PS were asked to fulfill the Rome III questionnaire for IBS, whereas patients with IBS were asked to complete the NIH-CPSI. The simultaneous presence of PS and IBS was observed in 30.2% and 31.8% of the patients screened by andrologists and gastroenterologists, respectively. Altogether, 111 patients had PS plus IBS (31.2%). They had a total NIH-CPSI and pain subscale scores significantly higher than patients with PS alone. Gastrointestinal symptoms in patients with PS plus IBS were similar to those reported by patients with IBS alone and significantly greater in patients with PS alone. Patients with PS plus IBS had a significantly higher frequency of chronic bacterial prostatitis (category II) and lower of non-inflammatory prostatitis (category IIIB), compared to patients with PS alone. The frequency of inflammatory prostatitis (category IIIA) resulted similar. Conclusions/Significance Prostatitis syndromes and IBS are frequently associated in patients with PS- or IBS-related symptoms. These patients have an increased prevalence of chronic bacterial and non-inflammatory prostatitis. PMID:21494624

Health Changes in Low Income Men Transitioning from a State Funded Prostate Cancer Program to Comprehensive Insurance.

PubMed

Nabhani, Jamal A; Kuang, Ruby; Liu, Hui; Kwan, Lorna; Litwin, Mark S

2018-07-01

We evaluated the effect of transitioning from a prostate cancer specific treatment program to comprehensive insurance under the ACA (Patient Protection and Affordable Care Act) on the physical, mental and prostate cancer related health of poor, previously uninsured men. We assessed general and prostate cancer specific health related quality of life using the RAND SF-12v2™ (12-Item Short Form Survey, version 2) and the UCLA PCI (Prostate Cancer Index) at 3 time points in 24 men who transitioned to comprehensive insurance as the insured group relative to 39 who remained in the prostate cancer program as the control group. We used mixed effects models controlling for treatment and patient factors to measure health differences between the groups during the transition period. Demographics, prostate cancer treatment patterns, and mental, physical and general health were similar before transition in the control and insured groups. After transition men who gained insurance coverage reported significantly worse physical health than men who remained in the prostate cancer program (p = 0.0038). After adjustment in the mixed effects model physical health remained worse in men who gained insurance (p = 0.0036). Mental health and prostate cancer related quality of life did not differ with time between the groups. Compared to controls who remained in the state funded prostate cancer treatment program for poor, uninsured men, newly insured men reported worse physical health after transitioning to ACA coverage. Providers and policy makers may draw important lessons from understanding the mechanisms of this paradoxical worsening in physical health after gaining insurance. These results inform the development of disease specific models of care in the broader health insurance context. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Validation of the prognostic grouping of the seventh edition of the tumor-nodes-metastasis classification using a large-scale prospective cohort study database of prostate cancer treated with primary androgen deprivation therapy.

PubMed

Kimura, Tomokazu; Onozawa, Mizuki; Miyazaki, Jun; Kawai, Koji; Nishiyama, Hiroyuki; Hinotsu, Shiro; Akaza, Hideyuki

2013-09-01

In the TNM seventh edition, a prognostic grouping for prostate cancer incorporating prostate-specific antigen and Gleason score was advocated. The present study was carried out to evaluate and validate prognostic grouping in prostate cancer patients. The 15 259 study patients treated with primary androgen deprivation therapy were enrolled in the Japan Study Group of Prostate Cancer. Overall survival was stratified by tumor-nodes-metastasis, Gleason score and prostate-specific antigen, and extensively analyzed. The accuracy of grouping systems was evaluated by the concordance index. The 5-year overall survival in prognostic grouping-I, IIA, IIB, III and IV was 90.0%, 88.3%, 84.8%, 80.6% and 57.1%, respectively. When considering subgroup stratification, the 5-year overall survival of subgroups prognostic grouping-IIA, IIB, III and IV was 80.9∼90.5%, 75.4∼91.8%, 75.7∼89.0% and 46.9∼86.2%, respectively. When prognostic grouping-IIB was subclassified into IIB1 (except IIB2) and IIB2 (T1-2b, prostate-specific antigen >20, Gleason score ≥8, and T2c, Gleason score ≥8), the 5-year overall survival of IIB2 was significantly lower than that of IIB1 (79.4% and 87.3%, P < 0.0001). Also, when prognostic grouping-IV was subclassified into IV1 (except IV2) and IV2 (M1, prostate-specific antigen >100 or Gleason score ≥8), the 5-year overall survival of prognostic grouping-IV1 was superior to that of IV2 (72.9% and 49.5%, P < 0.0001). Prognostic groupings were reclassified into modified prognostic groupings, divided into modified prognostic grouping-A (prognostic grouping-I, IIA, and IIB1), modified prognostic grouping-B (prognostic grouping-IIB2 and III), modified prognostic grouping-C (prognostic grouping-IV1) and modified prognostic grouping-D (prognostic grouping-IV2). The concordance index of prognostic grouping and modified prognostic grouping for overall survival was 0.670 and 0.685, respectively. Prognostic grouping could stratify the prognosis of prostate cancer patients. However, there is considerable variation among the prognostic grouping subgroups. Thus, the use of a modified prognostic grouping for patients treated with primary androgen deprivation therapy is advisable. © 2013 The Japanese Urological Association.

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

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer

PubMed Central

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-01

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen–glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively. PMID:28134773

Association between systemic inflammatory markers and serum prostate-specific antigen in men without prostatic disease - the 2001-2008 National Health and Nutrition Examination Survey.

PubMed

McDonald, Alicia C; Vira, Manish A; Vidal, Adriana C; Gan, Wenqi; Freedland, Stephen J; Taioli, Emanuela

2014-05-01

Serum prostate specific antigen (PSA) may be elevated in otherwise healthy men; systemic inflammation has been associated with cancer. The study of systemic inflammatory markers in men without clinical prostate disease, but with elevated PSA may characterize the subgroup of men at higher risk for subsequent prostate cancer. We investigated the associations between systemic inflammatory markers and serum PSA in 3,164 healthy men without prostatic disease, aged >40 years, from the 2001 to 2008 U.S. National Health and Nutrition Examination Survey (NHANES). Serum total PSA levels and concentrations of serum C-reactive protein (CRP) and plasma fibrinogen, neutrophil count, lymphocyte count, and platelet count were recorded. Neutrophil-lymphocyte ratio (NLR) ratio and platelet-lymphocyte (PLR) ratio were calculated. PSA elevation was defined as levels equal or greater than 4 ng/ml. Elevated serum PSA (194 men, 6.1% of the total), was significantly associated with plasma fibrinogen (ORmultiv  = 1.88; 95% CI, 1.09-3.25), and NLR (ORmultiv  = 1.14; 95% CI, 1.03-1.26), after adjustment for age, smoking, body mass index, education, race, co-morbidities, and use of medications. Markers of systemic inflammation were associated with elevated PSA in men without known prostatic disease. Future studies are needed to examine these markers' relationship with prostate cancer occurrence and progression. © 2014 Wiley Periodicals, Inc.

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer.

PubMed

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-26

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen-glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c -index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.

[Perioperative stroke following transurethral resection of prostate: high index of suspicion and stabilization of physiological parameters can save lives].

PubMed

Nag, Deb Sanjay; Chatterjee, Abhishek; Samaddar, Devi Prasad; Agarwal, Ajay

2017-01-09

We report a case of a 72 year old hypertensive male who developed severe hypertension followed by neurological deterioration in the immediate postoperative period after transurethral resection of prostate. While arterial blood gas and laboratory tests excluded transurethral resection of prostate syndrome or any other metabolic cause, reduction of blood pressure failed to ameliorate the symptoms. A cranial CT done 4hours after the onset of neurological symptoms revealed bilateral gangliocapsular and right thalamic infarcts. Oral aspirin was advised to prevent early recurrent stroke. Supportive treatment and mechanical ventilation ensured physiological stability and the patient recovered completely over the next few days without any residual neurological deficit. Copyright © 2016. Publicado por Elsevier Editora Ltda.

Comparison of National Institutes of Health-Chronic Prostatitis Symptom Index with International Index of Erectile Function 5 in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Large Cross-Sectional Study in China.

PubMed

Gao, Jingjing; Gao, Pan; Hao, Zongyao; Zhou, Zengrong; Liu, Jihong; Li, Hongjun; Xing, Junping; Zhou, Zhansong; Deng, Chunhua; Deng, Liwen; Wei, Qiang; Zhang, Xiansheng; Zhou, Jun; Fan, Song; Tai, Sheng; Yang, Chen; Shi, Kai; Huang, Yuanyuan; Ye, Zhangqun; Liang, Chaozhao

2015-01-01

The purpose of the study is to evaluate the relationship between NIH-CPSI and IIEF-5 in Chinese men with CP/CPPS. A large cross-sectional and multicenter survey was conducted from July 2012 to January 2014. Men were recruited from urology clinics which were located at the five cities in China. All men participated in the survey by completing a verbal questionnaire (consisted of sociodemographics, past medical history, sexual history, and self-estimated scales). The results showed that 1,280 men completed the survey. Based on the CP/CPPS definition, a total of 801 men were diagnosed as having CP/CPPS. Men with CP/CPPS reported higher scores of NIH-CPSI and lower scores of IIEF-5 than men without CP/CPPS. NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. The total scores of NIH-CPSI were significantly more strongly correlated with question 5 than other questions of IIEF-5. The total scores of IIEF-5 were significantly more strongly correlated with pain symptoms scores of NIH-CPSI. Strongest correlation was found between QoL impact and question 5 of IIEF-5. The findings suggested that NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. Strongest correlation was found between QoL impact and question 5 of IIEF-5.

A supervoxel-based segmentation method for prostate MR images.

PubMed

Tian, Zhiqiang; Liu, Lizhi; Zhang, Zhenfeng; Xue, Jianru; Fei, Baowei

2017-02-01

Segmentation of the prostate on MR images has many applications in prostate cancer management. In this work, we propose a supervoxel-based segmentation method for prostate MR images. A supervoxel is a set of pixels that have similar intensities, locations, and textures in a 3D image volume. The prostate segmentation problem is considered as assigning a binary label to each supervoxel, which is either the prostate or background. A supervoxel-based energy function with data and smoothness terms is used to model the label. The data term estimates the likelihood of a supervoxel belonging to the prostate by using a supervoxel-based shape feature. The geometric relationship between two neighboring supervoxels is used to build the smoothness term. The 3D graph cut is used to minimize the energy function to get the labels of the supervoxels, which yields the prostate segmentation. A 3D active contour model is then used to get a smooth surface by using the output of the graph cut as an initialization. The performance of the proposed algorithm was evaluated on 30 in-house MR image data and PROMISE12 dataset. The mean Dice similarity coefficients are 87.2 ± 2.3% and 88.2 ± 2.8% for our 30 in-house MR volumes and the PROMISE12 dataset, respectively. The proposed segmentation method yields a satisfactory result for prostate MR images. The proposed supervoxel-based method can accurately segment prostate MR images and can have a variety of application in prostate cancer diagnosis and therapy. © 2016 American Association of Physicists in Medicine.

Global Prostate Cancer Incidence and Mortality Rates According to the Human Development Index.

PubMed

Khazaei, Salman; Rezaeian, Shahab; Ayubi, Erfan; Gholamaliee, Behzad; Pishkuhi, Mahin Ahmadi; Khazaei, Somayeh; Mansori, Kamyar; Nematollahi, Shahrzad; Sani, Mohadeseh; Hanis, Shiva Mansouri

2016-01-01

Prostate cancer (PC) is one of the leading causes of death, especially in developed countries. The human development index (HDI) and its dimensions seem correlated with incidence and mortality rates of PC. This study aimed to assess the association of the specific components of HDI (life expectancy at birth, education, gross national income per 1000 capita, health, and living standards) with burden indicators of PC worldwide. Information of the incidence and mortality rates of PC was obtained from the GLOBOCAN cancer project in year 2012 and data about the HDI 2013 were obtained from the World Bank database. The correlation between incidence, mortality rates, and the HDI parameters were assessed using STATA software. A significant inequality of PC incidence rates was observed according to concentration indexes=0.25 with 95% CI (0.22, 0.34) and a negative mortality concentration index of -0.04 with 95% CI (-0.09, 0.01) was observed. A positive significant correlation was detected between the incidence rates of PC and the HDI and its dimensions including life expectancy at birth, education, income, urbanization level and obesity. However, there was a negative significant correlation between the standardized mortality rates and the life expectancy, income and HDI.

[The value of PHI/PCA3 in the early diagnosis of prostate cancer].

PubMed

Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P

2016-01-12

To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

PPARGC1A and ADIPOQ polymorphisms are associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity.

PubMed

Canto, Patricia; Granados, Jesús Benítez; Feria-Bernal, Guillermo; Coral-Vázquez, Ramón Mauricio; García-García, Eduardo; Tejeda, María Elena; Tapia, André; Rojano-Mejía, David; Méndez, Juan Pablo

2017-07-04

Obesity constitutes a risk factor for the development of aggressive forms of prostate cancer. It has been proposed, that prostate cancer has a genetic predisposition and that PPARGC1A and ADIPOQ polymorphisms play a role in the development of this condition. To analyse the association of two PPARGC1A and ADIPOQ polymorphisms as well as their haplotypes, with the development of aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity. Two hundred fifty seven men with prostate cancer of Mexican-Mestizo origin were included. Body mass index (BMI) was determined and the degree of prostate cancer aggressiveness by the D'Amico classification. DNA was obtained. Rs7665116 and rs2970870 of PPARGC1A, and rs266729 and rs1501299 of ADIPOQ were studied by real-time PCR allelic discrimination. Pairwise linkage disequilibrium, between single nucleotide polymorphisms was calculated and haplotype analysis was performed. A higher-risk (D'Amico classification) was observed in 21.8% of patients. An association of cancer aggressiveness with rs2970870 of PPARGC1A, and rs501299 of ADIPOQ, as well as with one haplotype of ADIPOQ was documented. This is the first study regarding the relationship of PPARGC1A and ADIPOQ polymorphisms, and the aggressiveness of prostate cancer in men with overweight or obesity.

Saw palmetto for benign prostatic hyperplasia.

PubMed

Bent, Stephen; Kane, Christopher; Shinohara, Katsuto; Neuhaus, John; Hudes, Esther S; Goldberg, Harley; Avins, Andrew L

2006-02-09

Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration. In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects. There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups. In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.). Copyright 2006 Massachusetts Medical Society.

Prostate-Specific G-Protein Coupled Receptor, an Emerging Biomarker Regulating Inflammation and Prostate Cancer Invasion.

PubMed

Rodriguez, M; Siwko, S; Liu, M

2016-01-01

Prostate cancer is highly prevalent among men in developed countries, but a significant proportion of detected cancers remain indolent, never progressing into aggressive carcinomas. This highlights the need to develop refined biomarkers that can distinguish between indolent and potentially dangerous cases. The prostate-specific G-protein coupled receptor (PSGR, or OR51E2) is an olfactory receptor family member with highly specific expression in human prostate epithelium that is highly overexpressed in PIN and prostate cancer. PSGR has been functionally implicated in prostate cancer cell invasiveness, suggesting a potential role in the transition to metastatic PCa. Recently, transgenic mice overexpressing PSGR in the prostate were reported to develop an acute inflammatory response followed by emergence of low grade PIN, whereas mice with compound PSGR overexpression and loss of PTEN exhibited accelerated formation of invasive prostate adenocarcinoma. This article will review recent PSGR findings with a focus on its role as a potential prostate cancer biomarker and regulator of prostate cancer invasion and inflammation.

Sca-1 Identifies a Distinct Androgen-Independent Murine Prostatic Luminal Cell Lineage with Bipotent Potential

PubMed Central

Kwon, Oh-Joon; Zhang, Li; Xin, Li

2016-01-01

Recent lineage tracing studies support the existence of prostate luminal progenitors that possess extensive regenerative capacity, but their identity remains unknown. We show that Sca-1 (Stem Cell Antigen-1) identifies a small population of murine prostate luminal cells that reside in the proximal prostatic ducts adjacent to the urethra. Sca-1+ luminal cells do not express Nkx3.1. They do not carry the secretory function, although they express the androgen receptor. These cells are enriched in the prostates of castrated mice. In the in vitro prostate organoid assay, a small fraction of the Sca-1+ luminal cells are capable of generating budding organoids that are morphologically distinct from those derived from other cell lineages. Histologically, this type of organoid is composed of multiple inner layers of luminal cells surrounded by multiple outer layers of basal cells. When passaged, these organoids retain their morphological and histological features. Finally, the Sca-1+ luminal cells are capable of forming small prostate glands containing both basal and luminal cells in an in vivo prostate regeneration assay. Collectively, our study establishes the androgen-independent and bipotent organoid-forming Sca-1+ luminal cells as a functionally distinct cellular entity. These cells may represent a putative luminal progenitor population and serve as a cellular origin for castration resistant prostate cancer. PMID:26418304

Clinical Outcomes of Transurethral Enucleation with Bipolar for Benign Prostatic Hypertrophy.

PubMed

Kawamura, Yoshiaki; Tokunaga, Masatoshi; Hoshino, Hideaki; Matsushita, Kazuo; Terachi, Toshiro

2015-12-20

This study compared outcomes of transurethral enucleation with bipolar (TUEB) with transurethral resection in saline (TURis). Thirty patients who underwent TURis were compared with 30 who underwent TUEB. Perioperative treatment outcomes, preoperative and 1-month postoperative International Prostrate Symptom Scores (IPSS), quality of life (QOL) index, maximum flow rate, average urinary flow, post- void residual urinary volume, and complications were compared. There were no significant differences in IPSS, measurements of urinary flow, or duration of catheterization. However, the improvement of QOL index after surgery was significantly greater in the TUEB group than the TURis group. The TUEB group had significantly longer surgical time, but tended to have greater enucleated tissue weight than the TURis group. There was no significant difference in enucleated tissue weight per unit time between the groups. The TUEB group also tended to have less hemoglobin decrease at postoperative day 1; this tendency was more prominent in patients with an estimated prostate volume of ≥ 50 ml. No significant differences in postoperative complications were observed. This study confirmed that the previously reported safety and efficacy of TUEB are comparable to those of TURis. TUEB appears especially safe for those with a large benign hypertrophic prostate.

SU-E-J-164: Estimation of DVH Variation for PTV Due to Interfraction Organ Motion in Prostate VMAT Using Gaussian Error Function

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

Lewis, C; Jiang, R; Chow, J

2015-06-15

Purpose: We developed a method to predict the change of DVH for PTV due to interfraction organ motion in prostate VMAT without repeating the CT scan and treatment planning. The method is based on a pre-calculated patient database with DVH curves of PTV modelled by the Gaussian error function (GEF). Methods: For a group of 30 patients with different prostate sizes, their VMAT plans were recalculated by shifting their PTVs 1 cm with 10 increments in the anterior-posterior, left-right and superior-inferior directions. The DVH curve of PTV in each replan was then fitted by the GEF to determine parameters describingmore » the shape of curve. Information of parameters, varying with the DVH change due to prostate motion for different prostate sizes, was analyzed and stored in a database of a program written by MATLAB. Results: To predict a new DVH for PTV due to prostate interfraction motion, prostate size and shift distance with direction were input to the program. Parameters modelling the DVH for PTV were determined based on the pre-calculated patient dataset. From the new parameters, DVH curves of PTVs with and without considering the prostate motion were plotted for comparison. The program was verified with different prostate cases involving interfraction prostate shifts and replans. Conclusion: Variation of DVH for PTV in prostate VMAT can be predicted using a pre-calculated patient database with DVH curve fitting. The computing time is fast because CT rescan and replan are not required. This quick DVH estimation can help radiation staff to determine if the changed PTV coverage due to prostate shift is tolerable in the treatment. However, it should be noted that the program can only consider prostate interfraction motions along three axes, and is restricted to prostate VMAT plan using the same plan script in the treatment planning system.« less

Micrornas in prostate cancer: an overview

PubMed Central

Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Di Franco, Rossella; Romano, Francesco Jacopo; Montanari, Micaela; La Mantia, Elvira; Piscitelli, Raffaele; Nocerino, Flavia; Cappuccio, Francesca; Grimaldi, Giovanni; Izzo, Alessandro; Castaldo, Luigi; Pepe, Maria Filomena; Malzone, Maria Gabriella; Iovane, Gelsomina; Ametrano, Gianluca; Stiuso, Paola; Quagliuolo, Lucio; Barberio, Daniela; Perdonà, Sisto; Muto, Paolo; Montella, Maurizio; Maiolino, Piera; Veneziani, Bianca Maria; Botti, Gerardo; Caraglia, Michele; Facchini, Gaetano

2017-01-01

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis. PMID:28445135

Surgical Management of Adult-acquired Buried Penis: Impact on Urinary and Sexual Quality of Life Outcomes.

PubMed

Theisen, Katherine M; Fuller, Thomas W; Rusilko, Paul

2018-06-01

To assess postoperative patient-reported quality of life outcomes after surgical management of adult-acquired buried penis (AABP). We hypothesize that surgical treatment of AABP results in improvements in urinary and sexual quality of life. Patients that underwent surgical treatment of AABP were retrospectively identified. The Expanded Prostate Cancer Index (EPIC) questionnaire was completed at ≥3 months postoperatively, and completed retrospectively to define preoperative symptoms. EPIC is validated for local treatment of prostate cancer. Urinary and sexual domains were utilized. Questions are scored on a 5-point Likert scale, with higher scores indicating better quality of life. Preoperative scores were compared with postoperative scores. Sixteen patients completed pre- and postoperative questionnaires. Mean time from surgery to questionnaire was 12.6 months. There was a significant improvement in 10 of 12 urinary domain questions and 10 of 13 sexual domain questions. Fourteen of 16 patients (87.5%) reported significant improvement in overall sexual function (median score changed from 1.5 to 5, P <.0001). Similarly, 14 of 16 patients (87.5%) reported significant improvement in overall urinary function (median score changed from 1 to 4, P <.0001). AABP is a challenging condition to treat and often requires surgical intervention to improve hygiene and function. There are limited data on patient-reported quality of life outcomes. We found that surgical management of AABP results in significant improvements in both urinary and sexual quality of life outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

PubMed

Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

2018-06-01

Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Single Nucleotide Polymorphisms of Stemness Genes Predicted to Regulate RNA Splicing, microRNA and Oncogenic Signaling are Associated with Prostate Cancer Survival.

PubMed

Freedman, Jennifer A; Wang, Yanru; Li, Xuechan; Liu, Hongliang; Moorman, Patricia G; George, Daniel J; Lee, Norman H; Hyslop, Terry; Wei, Qingyi; Patierno, Steven R

2018-05-03

Prostate cancer is a clinically and molecularly heterogeneous disease, with variation in outcomes only partially predicted by grade and stage. Additional tools to distinguish indolent from aggressive disease are needed. Phenotypic characteristics of stemness correlate with poor cancer prognosis. Given this correlation, we identified single nucleotide polymorphisms (SNPs) of stemness-related genes and examined their associations with prostate cancer survival. SNPs within stemness-related genes were analyzed for association with overall survival of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Significant SNPs predicted to be functional were selected for linkage disequilibrium analysis and combined and stratified analyses. Identified SNPs were evaluated for association with gene expression. SNPs of CD44 (rs9666607), ABCC1 (rs35605 and rs212091) and GDF15 (rs1058587) were associated with prostate cancer survival and predicted to be functional. A role for rs9666607 of CD44 and rs35605 of ABCC1 in RNA splicing regulation, rs212091 of ABCC1 in miRNA binding site activity and rs1058587 of GDF15 in causing an amino acid change was predicted. These SNPs represent potential novel prognostic markers for overall survival of prostate cancer and support a contribution of the stemness pathway to prostate cancer patient outcome.

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer☆

PubMed Central

Costello, Leslie C.; Franklin, Renty B.

2016-01-01

The human prostate gland contains extremely high zinc levels; which is due to the specialized zinc-accumulating acinar epithelial of the peripheral zone. These cells evolved for their unique capability to produce and secrete extremely levels of citrate, which is achieved by the high cellular zinc level effects on the cell metabolism. This review highlights the specific functional and metabolic alterations that result from the accumulation of the high zinc levels, especially its effects on mitochondrial citrate metabolism and terminal oxidation. The implications of zinc in the development and progression of prostate cancer are described, which is the most consistent hallmark characteristic of prostate cancer. The requirement for decreased zinc resulting from down regulation of ZIP1 to prevent zinc cytotoxicity in the malignant cells is described as an essential early event in prostate oncogenesis. This provides the basis for the concept that an agent (such as the zinc ionophore, clioquinol) that facilitates zinc uptake and accumulation in ZIP1-deficient prostate tumors cells will markedly inhibit tumor growth. In the current absence of an efficacious chemotherapy for advanced prostate cancer, and for prevention of early development of malignancy; a zinc treatment regimen is a plausible approach that should be pursued. PMID:27132038

Prostate Health Index (PHI) Predicts High-stage Pathology in African American Men.

PubMed

Schwen, Zeyad R; Tosoian, Jeffrey J; Sokoll, Lori J; Mangold, Leslie; Humphreys, Elizabeth; Schaeffer, Edward M; Partin, Alan W; Ross, Ashley E

2016-04-01

To evaluate the association between the Prostate Health Index (PHI) and adverse pathology in a cohort of African American (AA) men undergoing radical prostatectomy. Eighty AA men with prostate-specific antigen (PSA) of 2-10 ng/mL underwent measurement of PSA, free PSA (fPSA), and p2PSA prior to radical prostatectomy. PHI was calculated as [(p2PSA/fPSA) × (PSA)(½)]. Biomarker association with pT3 disease was assessed using logistic regression, and covariates were added to a baseline multivariable model including digital rectal examination. Biomarker ability to predict pT3 disease was measured using the area under the receiver operator characteristic curve. Sixteen men (20%) demonstrated pT3 disease on final pathology. Mean age, PSA, and %fPSA were similar in men with and without pT3 disease (all P  >  .05), whereas PHI was significantly greater in men with pT3 disease (mean 57.2 vs 46.6, P  =  .04). Addition of PHI to the baseline multivariable model improved discriminative ability by 12.9% (P  =. .04) and yielded greater diagnostic accuracy than models, including other individual biomarkers. In AA men with PSA of 2-10 ng/mL, PHI was predictive of pT3 prostate cancer and may help to identify men at increased risk of adverse pathology. Additional studies are needed to substantiate these findings and identify appropriate thresholds for clinical use. Copyright © 2016 Elsevier Inc. All rights reserved.

OCT image segmentation of the prostate nerves

NASA Astrophysics Data System (ADS)

Chitchian, Shahab; Weldon, Thomas P.; Fried, Nathaniel M.

2009-08-01

The cavernous nerves course along the surface of the prostate and are responsible for erectile function. Improvements in identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery may improve nerve preservation and postoperative sexual potency. In this study, 2-D OCT images of the rat prostate were segmented to differentiate the cavernous nerves from the prostate gland. Three image features were employed: Gabor filter, Daubechies wavelet, and Laws filter. The features were segmented using a nearestneighbor classifier. N-ary morphological post-processing was used to remove small voids. The cavernous nerves were differentiated from the prostate gland with a segmentation error rate of only 0.058 +/- 0.019.

Wavelet denoising during optical coherence tomography of the prostate nerves using the complex wavelet transform.

PubMed

Chitchian, Shahab; Fiddy, Michael; Fried, Nathaniel M

2008-01-01

Preservation of the cavernous nerves during prostate cancer surgery is critical in preserving sexual function after surgery. Optical coherence tomography (OCT) of the prostate nerves has recently been studied for potential use in nerve-sparing prostate surgery. In this study, the discrete wavelet transform and complex dual-tree wavelet transform are implemented for wavelet shrinkage denoising in OCT images of the rat prostate. Applying the complex dual-tree wavelet transform provides improved results for speckle noise reduction in the OCT prostate image. Image quality metrics of the cavernous nerves and signal-to-noise ratio (SNR) were improved significantly using this complex wavelet denoising technique.

SU-G-201-15: Nomogram as an Efficient Dosimetric Verification Tool in HDR Prostate Brachytherapy

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

Liang, J; Todor, D

Purpose: Nomogram as a simple QA tool for HDR prostate brachytherapy treatment planning has been developed and validated clinically. Reproducibility including patient-to-patient and physician-to-physician variability was assessed. Methods: The study was performed on HDR prostate implants from physician A (n=34) and B (n=15) using different implant techniques and planning methodologies. A nomogram was implemented as an independent QA of computer-based treatment planning before plan execution. Normalized implant strength (total air kerma strength Sk*t in cGy cm{sup 2} divided by prescribed dose in cGy) was plotted as a function of PTV volume and total V100. A quadratic equation was used tomore » fit the data with R{sup 2} denoting the model predictive power. Results: All plans showed good target coverage while OARs met the dose constraint guidelines. Vastly different implant and planning styles were reflected on conformity index (entire dose matrix V100/PTV volume, physician A implants: 1.27±0.14, physician B: 1.47±0.17) and PTV V150/PTV volume ratio (physician A: 0.34±0.09, physician B: 0.24±0.07). The quadratic model provided a better fit for the curved relationship between normalized implant strength and total V100 (or PTV volume) than a simple linear function. Unlike the normalized implant strength versus PTV volume nomogram which differed between physicians, a unique quadratic model based nomogram (Sk*t)/D=−0.0008V2+0.0542V+1.1185 (R{sup 2}=0.9977) described the dependence of normalized implant strength on total V100 over all the patients from both physicians despite two different implant and planning philosophies. Normalized implant strength - total V100 model also generated less deviant points distorting the smoothed ones with a significantly higher correlation. Conclusion: A simple and universal, excel-based nomogram was created as an independent calculation tool for HDR prostate brachytherapy. Unlike similar attempts, our nomogram is insensitive to implant style and does not rely on reproducing dose calculations using TG-43 formalism, thus making it a truly independent check.« less

Non-dietary environmental risk factors in prostate cancer

PubMed Central

Ferrís-i-Tortajada, J; Berbel-Tornero, O; Garcia-i-Castell, J; López-Andreu, J.A.; Sobrino-Najul, E; Ortega-García, J.A.

2016-01-01

Introduction The aim is to update and disclose the main environmental risk factors, excluding dietary factors, involved in the etiopathology of prostate cancer. Materials and methods Bibliographic review of the last 25 years of non-dietary environmental risk factors associated with prostate cancer between 1985 and 2010, obtained from MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Environmental Risk Factors/Tobacco/Infectious-Inflammatory Factors/Pesticides/Vasectomy/Occupational Exposures/ Chemoprevention Agents/Radiation and Prostate Cancer. Results While some non-dietary environmental risk factors increase the risk of acquiring the disease, others decrease it. Of the former, it is worth mentioning exposal to tobacco smoke, chronic infectious-inflammatory prostatic processes and occupational exposure to cadmium, herbicides and pesticides. The first factors that reduce the risk are the use of chemopreventive drugs (Finasterida, Dutasteride) and exposure to ultraviolet solar radiation. With the current data, a vasectomy does not influence the risk of developing the disease. Conclusions The slow process of prostate carcinogenesis is the final result of the interaction of constitutional risk and environmental factors. Non-dietary environmental factors play an important role in the etiopathology of this disease. To appropriately assess the risk factors, extensive case studies that include all the possible variables must be analyzed. PMID:21439685

Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

PubMed

Killian, C S; Vargas, F P; Slack, N H; Murphy, G P; Chu, T M

1982-01-01

Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD.

Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives.

PubMed

Hu, Jieping; Wang, Gongxian; Sun, Ting

2017-05-01

Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

Prostatic arterial embolization: post-procedural follow-up.

PubMed

Fernandes, Lucia; Rio Tinto, Hugo; Pereira, Jose; Duarte, Marisa; Bilhim, Tiago; Martins Pisco, João

2012-12-01

Prostatic arterial embolization (PAE) gained special attention in the past years as a potential minimally invasive technique for benign prostatic hyperplasia. Treatment decisions are based on morbidity and quality-of-life issues and the patient has a central role in decision-making. Medical therapy is a first-line treatment option and surgery is usually performed to improve symptoms and decrease the progression of disease in patients who develop complications or who have inadequately controlled symptoms on medical treatment. The use of validated questionnaires to assess disease severity and sexual function, uroflowmetry studies, prostate-specific antigen and prostate volume measurements are essential when evaluating patients before PAE and to evaluate response to treatment. PAE may be performed safely with minimal morbidity and without associated mortality. The minimally invasive nature of the technique inducing a significant improvement in symptom severity associated with prostate volume reduction and a slight improvement in the sexual function are major advantages. However, as with other surgical therapies for benign prostatic hyperplasia, up to 15% of patients fail to show improvement significantly after PAE, and there is a modest improvement of the peak urinary flow. Copyright © 2012 Elsevier Inc. All rights reserved.

The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis

PubMed Central

Havens, AM; Jung, Y; Sun, YX; Wang, J; Shah, RB; Bühring, HJ; Pienta, KJ; Taichman, RS

2006-01-01

Background The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. Results Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. Conclusion Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes. PMID:16859559

TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth in vivo

NASA Astrophysics Data System (ADS)

Horak, Peter; Tomasich, Erwin; Vaňhara, Petr; Kratochvílová, Kateřina; Anees, Mariam; Marhold, Maximilian; Lemberger, Christof E.; Gerschpacher, Marion; Horvat, Reinhard; Sibilia, Maria; Pils, Dietmar; Krainer, Michael

2014-01-01

Prostate cancer is the most prevalent cancer in males in developed countries. Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular.

Epigenetics in Prostate Cancer

PubMed Central

Albany, Costantine; Alva, Ajjai S.; Aparicio, Ana M.; Singal, Rakesh; Yellapragada, Sarvari; Sonpavde, Guru; Hahn, Noah M.

2011-01-01

Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a “normal” epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases. PMID:22191037

Epigenetics in prostate cancer.

PubMed

Albany, Costantine; Alva, Ajjai S; Aparicio, Ana M; Singal, Rakesh; Yellapragada, Sarvari; Sonpavde, Guru; Hahn, Noah M

2011-01-01

Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a "normal" epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

External Beam Radiation Therapy or Brachytherapy With or Without Short-course Neoadjuvant Androgen Deprivation Therapy: Results of a Multicenter, Prospective Study of Quality of Life

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

Gay, Hiram A., E-mail: hiramgay@wustl.edu; Sanda, Martin G.; Liu, Jingxia

Purpose: The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. Methods and Materials: We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6,more » 12, and 24 months after the initiation of NADT. We used the χ{sup 2} or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level. Results: For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively. Conclusions: Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of energy, or change in body weight. The improved survival in intermediate- and high-risk patients receiving NADT and EBRT necessitates pretreatment counseling of the HRQOL effect of NADT and EBRT.« less

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model.

PubMed

Hu, Y; Niu, X; Wang, G; Huang, J; Liu, M; Peng, B

2016-11-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF-α, IL-1β, and IL-6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS-induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were all important for erectile function. © 2016 American Society of Andrology and European Academy of Andrology.

External Beam Radiation Therapy or Brachytherapy With or Without Short-course Neoadjuvant Androgen Deprivation Therapy: Results of a Multicenter, Prospective Study of Quality of Life.

PubMed

Gay, Hiram A; Sanda, Martin G; Liu, Jingxia; Wu, Ningying; Hamstra, Daniel A; Wei, John T; Dunn, Rodney L; Klein, Eric A; Sandler, Howard M; Saigal, Christopher S; Litwin, Mark S; Kuban, Deborah A; Hembroff, Larry; Regan, Meredith M; Chang, Peter; Michalski, Jeff M

2017-06-01

The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ 2 or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level. For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively. Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of energy, or change in body weight. The improved survival in intermediate- and high-risk patients receiving NADT and EBRT necessitates pretreatment counseling of the HRQOL effect of NADT and EBRT. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Correlation of thermocouple data with voiding function after prostate cryoablation.

PubMed

Levy, David A

2010-02-01

To identify possible correlations of thermocouple recorded data with altered postoperative voiding function after prostate cryosurgery. A retrospective analysis of the records of 58 patients treated with prostate cryoablation from October 2005 through April 2009 was conducted. Multivariate analysis of patient age, presenting prostate-specific antigen level, Gleason score, clinical T stage, prostate volume, maximum low temperature thermocouple recordings, history of radiation and or hormonal therapy, were studied as possible correlative factors for altered postoperative voiding function. Of 58 patients, 22 (37.9%) manifested postcryoablation urgency and frequency (n = 13) requiring medical therapy or retention (n = 9). On multivariate analysis, age (P = .037) and an external sphincter temperature < or = 23 degrees C (P = .012) were associated with voiding frequency, urgency, or retention (odds ratio = 6.26, 95% CI: 1.62-24.16), whereas anterior rectal wall temperature (Denon) was weakly associated (P = .079). Thermocouple data provide an objective means of assessing cryosurgical outcomes. This is the first report of a correlation of such data to post-treatment voiding function. A total of 37.9% of patients experienced urgency and/or frequency or urinary retention after cryoablation of the prostate for localized disease. Older age and external sphincter temperature < or = 23 degrees C were statistically significant predictors of these events. The data suggest that limiting the degree of freezing at the external sphincter may decrease procedure related morbidity. Further study is warranted to better delineate temperature-related data on treatment outcomes. 2010 Elsevier Inc. All rights reserved.

Bowel, Urinary, and Sexual Problems Among Long-Term Prostate Cancer Survivors: A Population-Based Study

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

Mols, Floortje; Comprehensive Cancer Centre South; Korfage, Ida J.

Purpose: To obtain insight into the long-term (5- to 10-year) effects of prostate cancer and treatment on bowel, urinary, and sexual function, we performed a population-based study. Prostate-specific function was compared with an age-matched normative population without prostate cancer. Methods and Materials: Through the population-based Eindhoven Cancer Registry, we selected all men diagnosed with prostate cancer between 1994 and 1998 in the southern Netherlands. In total, 964 patients, alive in November 2004, received questionnaire; 780 (81%) responded. Results: Urinary problems were most common after a prostatectomy; bowel problems were most common after radiotherapy. Compared with an age-matched normative population bothmore » urinary and bowel functioning and bother were significantly worse among survivors. Urinary incontinence was reported by 23-48% of survivors compared with 4% of the normative population. Bowel leakage occurred in 5-14% of patients compared with 2% of norms. Erection problems occurred in 40-74% of patients compared with 18% of norms. Conclusions: These results form an important contribution to the limited information available on prostate-specific problems in the growing group of long-term prostate cancer survivors. Bowel, urinary, and sexual problems occur more often among long-term survivors compared with a reference group and cannot be explained merely by age. Because these problems persist for many years, urologists should provide patients with adequate information before treatment. After treatment, there should be an appropriate focus on these problems.« less

Systematic evaluation of three different commercial software solutions for automatic segmentation for adaptive therapy in head-and-neck, prostate and pleural cancer.

PubMed

La Macchia, Mariangela; Fellin, Francesco; Amichetti, Maurizio; Cianchetti, Marco; Gianolini, Stefano; Paola, Vitali; Lomax, Antony J; Widesott, Lamberto

2012-09-18

To validate, in the context of adaptive radiotherapy, three commercial software solutions for atlas-based segmentation. Fifteen patients, five for each group, with cancer of the Head&Neck, pleura, and prostate were enrolled in the study. In addition to the treatment planning CT (pCT) images, one replanning CT (rCT) image set was acquired for each patient during the RT course. Three experienced physicians outlined on the pCT and rCT all the volumes of interest (VOIs). We used three software solutions (VelocityAI 2.6.2 (V), MIM 5.1.1 (M) by MIMVista and ABAS 2.0 (A) by CMS-Elekta) to generate the automatic contouring on the repeated CT. All the VOIs obtained with automatic contouring (AC) were successively corrected manually. We recorded the time needed for: 1) ex novo ROIs definition on rCT; 2) generation of AC by the three software solutions; 3) manual correction of AC.To compare the quality of the volumes obtained automatically by the software and manually corrected with those drawn from scratch on rCT, we used the following indexes: overlap coefficient (DICE), sensitivity, inclusiveness index, difference in volume, and displacement differences on three axes (x, y, z) from the isocenter. The time saved by the three software solutions for all the sites, compared to the manual contouring from scratch, is statistically significant and similar for all the three software solutions. The time saved for each site are as follows: about an hour for Head&Neck, about 40 minutes for prostate, and about 20 minutes for mesothelioma. The best DICE similarity coefficient index was obtained with the manual correction for: A (contours for prostate), A and M (contours for H&N), and M (contours for mesothelioma). From a clinical point of view, the automated contouring workflow was shown to be significantly shorter than the manual contouring process, even though manual correction of the VOIs is always needed.

SU-E-J-53: Dosimetric Evaluation at Volumetric Modulated Arc Therapy for Treatment of Prostate Cancer Using Single Or Double Arcs

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

Silva, D; Salmon, H; Pavan, G

2014-06-01

Purpose: Evaluate and compare retrospective prostate treatment plan using Volumetric Modulated Arc Therapy (RapidArc™ - Varian) technique with single or double arcs at COI Group. Methods: Ten patients with present prostate and seminal vesicle neoplasia were replanned as a target treatment volume and a prescribed dose of 78 Gy. A baseline planning, using single arc, was developed for each case reaching for the best result on PTV, in order to minimize the dose on organs at risk (OAR). Maintaining the same optimization objectives used on baseline plan, two copies for optimizing single and double arcs, have been developed. The plansmore » were performed with 10 MV photon beam energy on Eclipse software, version 11.0, making use of Trilogy linear accelerator with Millenium HD120 multileaf collimator. Comparisons on PTV have been performed, such as: maximum, minimum and mean dose, gradient dose, as well as the quantity of monitor units, treatment time and homogeneity and conformity index. OARs constrains dose have been evaluated, comparing both optimizations. Results: Regarding PTV coverage, the difference of the minimum, maximum and mean dose were 1.28%, 0.7% and 0.2% respectively higher for single arc. When analyzed the index of homogeneity found a difference of 0.99% higher when compared with double arcs. However homogeneity index was 0.97% lower on average by using single arc. The doses on the OARs, in both cases, were in compliance to the recommended limits RTOG 0415. With the use of single arc, the quantity of monitor units was 10,1% lower, as well as the Beam-On time, 41,78%, when comparing double arcs, respectively. Conclusion: Concerning the optimization of patients with present prostate and seminal vesicle neoplasia, the use of single arc reaches similar objectives, when compared to double arcs, in order to decrease the treatment time and the quantity of monitor units.« less

Overcoming Drug Resistant Prostate Cancer with APE1/Ref 1 Blockade

DTIC Science & Technology

2016-10-01

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

Irreversible Electroporation for Prostate Cancer as Salvage Treatment Following Prior Radiation and Cryotherapy.

PubMed

Murray, Katie S; Akin, Oguz; Coleman, Jonathan A

2017-01-01

Salvage treatment options after localized primary treatment failure of prostate cancer are limited and associated with risk for serious complications. We report on the management details of a 57-year-old African American man treated with partial-gland ablation using irreversible electroporation following local recurrence after brachytherapy and prior salvage cryoablation. Therapeutic and functional outcomes were assessed by conventional means, including serum prostate-specific antigen values and prostate biopsy results.

SMILE upregulated by metformin inhibits the function of androgen receptor in prostate cancer cells.

PubMed

Lee, Seung-Yon; Song, Chin-Hee; Xie, Yuan-Bin; Jung, Chaeyong; Choi, Hueng-Sik; Lee, Keesook

2014-11-28

Metformin, a diabetes drug, has been reported to inhibit the growth of prostate cancer cells. In this study, we investigated the effect and action mechanism of metformin on the function of androgen receptor (AR), a key molecule in the proliferation of prostate cancer cells. Metformin was found to reduce androgen-dependent cell growth and the expression of AR target genes by inhibiting AR function in prostate cancer cells such as LNCaP and C4-2 cells. Interestingly, metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function. Further studies revealed that SMILE protein itself suppressed the transactivation of AR, and its ectopic expression resulted in the repressed expression of endogenous AR target genes, PSA and NKX3.1, in LNCaP cells. In addition, SMILE protein physically interacted with AR and competed with the AR coactivator SRC-1 to modulate AR transactivation. As expected, SMILE repressed androgen-dependent growth of LNCaP and C4-2 cells. Taken together, these results suggest that SMILE, which is induced by metformin, functions as a novel AR corepressor and may mediate the inhibitory effect of metformin on androgen-dependent growth of prostate cancer cells. Copyright © 2014. Published by Elsevier Ireland Ltd.

The molecular biology of prostate cancer: current understanding and clinical implications.

PubMed

Gandhi, Jason; Afridi, Adil; Vatsia, Sohrab; Joshi, Gargi; Joshi, Gunjan; Kaplan, Steven A; Smith, Noel L; Khan, Sardar Ali

2018-04-01

With continuous progress over the past few decades in understanding diagnosis, treatment, and genetics, much has been learned about the prostate cancer-diagnosed genome. A comprehensive MEDLINE® and Google scholar literature search was conducted using keyword variations relating to the genetics of prostate cancer such as chromosomal alterations, androgen receptor, castration-resistant, inheritance, polymorphisms, oncogenes, metastasis, biomarkers, and immunotherapy. Traditionally, androgen receptors (AR) have been the focus of research. Recently, identification of recurrent chromosomal alterations that lead to either multiplication of regions (gain-of-function) or deletion of regions (loss-of-function) has opened the door to greater genetic accessibility. These chromosomal aberrations lead to variation in copy number and gene expression. Some of these chromosomal alterations are inherited, while others undergo somatic mutations during disease progression. Inherited gene mutations that make one susceptible to prostate cancer have been identified with familial-linked studies. Somatic genes that progress tumorigenesis have also been identified. Research on the molecular biology of prostate cancer has characterized these genes into tumor suppressor genes or oncogenes. Additionally, genome-wide assay studies have identified many high-risk single-nucleotide polymorphisms recurrent throughout the prostate cancer-diagnosed genome. Castration-resistant prostate cancer is the most aggressive form of prostate cancer, and its research has elucidated many types of mutations associated with AR itself, including enhanced expression and amplification, point mutations, and alternative splicing. Understanding the molecular biology of prostate cancer has permitted more accurate identification using advanced biomarkers and therapy for aggressive forms using immunotherapy. An age-related disease, prostate cancer commands profound attention. With increasing life expectancy and the continuous pursuit of it, prostate cancer is a powerful obstacle best defeated using targeted therapies specifically designed for the unique molecular profile of the malignancy.

Impact of prostate weight on probability of positive surgical margins in patients with low-risk prostate cancer after robotic-assisted laparoscopic radical prostatectomy.

PubMed

Marchetti, Pablo E; Shikanov, Sergey; Razmaria, Aria A; Zagaja, Gregory P; Shalhav, Arieh L

2011-03-01

To evaluate the impact of prostate weight (PW) on probability of positive surgical margin (PSM) in patients undergoing robotic-assisted radical prostatectomy (RARP) for low-risk prostate cancer. The cohort consisted of 690 men with low-risk prostate cancer (clinical stage T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason score ≤6) who underwent RARP with bilateral nerve-sparing at our institution by 1 of 2 surgeons from 2003 to 2009. PW was obtained from the pathologic specimen. The association between probability of PSM and PW was assessed with univariate and multivariate logistic regression analysis. A PSM was identified in 105 patients (15.2%). Patients with PSM had significant higher prostate-specific antigen (P = .04), smaller prostates (P = .0001), higher Gleason score (P = .004), and higher pathologic stage (P < .0001). After logistic regression, we found a significant inverse relation between PSM and PW (OR 0.97%; 95% confidence interval [CI] 0.96, 0.99; P = .0003) in univariate analysis. This remained significant in the multivariate model (OR 0.98%; 95% CI 0.96, 0.99; P = .006) adjusting for age, body mass index, surgeon experience, pathologic Gleason score, and pathologic stage. In this multivariate model, the predicted probability of PSM for 25-, 50-, 100-, and 150-g prostates were 22% (95% CI 16%, 30%), 13% (95% CI 11%, 16%), 5% (95% CI 1%, 8%), and 1% (95% CI 0%, 3%), respectively. Lower PW is independently associated with higher probability of PSM in low-risk patients undergoing RARP with bilateral nerve-sparing. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-05-01

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

Effects of cholesterol, C-reactive protein, and interleukin-6 on prostate cancer risk in a population of African ancestry.

PubMed

Tulloch-Reid, Marshall K; McFarlane-Anderson, Norma; Bennett, Franklyn I; Aiken, William D; Jackson, Maria D

2017-11-01

To investigate the association between serum cholesterol and prostate cancer and whether any effect may be mediated through inflammatory markers. Data from a case-control study of 40-80 years old Jamaican male patients (229 cases; 252 controls) were used. Cases had incident histologically-confirmed prostate cancer and controls were men with normal digital rectal examination and prostate-specific antigen (PSA) < 4 μg/L or free: total PSA > 0.15 obtained from the same clinic. Total and HDL cholesterol, interleukin-6 (IL-6), and C-reactive protein (CRP) were measured from a non-fasting sample. Multivariable logistic regression models were used to evaluate the associations between these factors and prostate cancer, adjusting for age, body mass index, waist circumference, family history of prostate cancer, diabetes, hypertension, use of cholesterol-lowering drugs, and smoking. Total cholesterol [Mean (cases, 4.71 ± 1.07; controls, 4.64 ± 1.07 mmol/L)], CRP [median (cases, 2.11; controls, 2.09 µg/ml)], and IL-6: [median (cases, 3.34; controls, 3.24 pg/ml)] did not differ by PCA status. Higher total cholesterol was associated with an increased risk of low-grade disease after adjusting for potential confounders [multivariable-adjusted OR (95% CI): tertile 2: 3.32(1.66, 6.45), tertile 3: 2.14(1.07, 4.32)]. Total cholesterol was unrelated to overall prostate cancer or high-grade disease. There was no significant association between HDL cholesterol or any of the inflammatory markers with prostate cancer. Increasing total cholesterol but not inflammatory markers were associated with low-grade prostate cancer in Caribbean men.

Prostate-specific antigen screening and mortality from prostate cancer.

PubMed

Marcella, Stephen W; Rhoads, George G; Carson, Jeffrey L; Merlino, Frances; Wilcox, Homer

2008-03-01

There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55-79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2-29.2% of cases and 21.8-26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality.

Prostate-Specific Antigen Screening and Mortality from Prostate Cancer

PubMed Central

Rhoads, George G.; Carson, Jeffrey L.; Merlino, Frances; Wilcox, Homer

2008-01-01

Background There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. Objective The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. Design, setting, and participants This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55–79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Results Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2–29.2% of cases and 21.8–26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. Conclusions PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality. PMID:18172740

Perinatal and childhood factors and risk of prostate cancer in adulthood: MCC-Spain case-control study.

PubMed

Lope, Virginia; García-Esquinas, Esther; Ruiz-Dominguez, José Manuel; LLorca, Javier; Jiménez-Moleón, José Juan; Ruiz-Cerdá, José L; Alguacil, Juan; Tardón, Adonina; Dierssen-Sotos, Trinidad; Tabernero, Ángel; Mengual, Lourdes; Kogevinas, Manolis; Aragonés, Nuria; Castaño-Vinyals, Gemma; Pollán, Marina; Pérez-Gómez, Beatriz

2016-08-01

In utero and early-life exposures are suspected to modulate the risk of prostate cancer. This study examines the influence of certain perinatal and childhood-related factors on prostate cancer risk overall and by Gleason score at biopsy. MCC-Spain is a multicase-control study where 1088 histologically-confirmed incident prostate cancer cases (aged 42-85years) and 1345 population-based controls (aged 38-85years), frequency matched by age and province of recruitment, were recruited in 7 Spanish provinces. Self-reported perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with prostate cancer risk, globally and according to Gleason score at biopsy, was evaluated using logistic and multinomial regression mixed models, adjusting for age, family history of prostate cancer, educational level and body mass index one year before the interview, and including the province as a random effect term. Most perinatal factors were not related to prostate cancer risk, with the exception of middle-high socioeconomic level at birth (OR for high grade tumors=1.36; 95%CI=1.09-1.68). Regarding puberty, risk rose by 6% for each year of delayed onset (OR=1.06; 95%CI=1.01-1.10; p trend=0.016), with a clear excess of risk in men who reached puberty after age 15 (OR:1.35; 95%CI=1.08-1.68). A borderline significant positive association with prepubertal height was also observed (p trend=0.094). Some exposures experienced in utero and during adolescence, when the prostate is still maturing, might be relevant for prostate cancer risk in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Prevalence of and Risk Factors for Asymptomatic Inflammatory (NIH-IV) Prostatitis in Chinese Men

PubMed Central

Wu, Chunlei; Zhang, Zhifu; Lu, Zheng; Liao, Ming; Zhang, Youjie; Xie, Yuanliang; Guo, Xuefeng; Yu, Xiaoxiang; Yang, Xiaobo; Gao, Yong; Tan, Aihua; Mo, Zengnan

2013-01-01

Background While many investigators have studied symptomatic prostatitis, little research has been done with regard to asymptomatic (NIH-IV) prostatitis. Purpose To describe the prevalence of and risk factors for NIH-IV prostatitis among a large male population. Methods The study population was comprised of 1,868 men at the second phase recruitment of a population-based cohort in China. Asymptomatic and symptomatic men were defined by the National Institutes of Health Chronic Prostatitis (CP) Symptom Index. Meanwhile, EPS specimens and their leukocyte count were collected. Lifestyle and demographic characteristics were obtained through a questionnaire. Results Prevalence of NIH-IV prostatitis was 21.1% among 1,868 asymptomatic men aged 19–78 years and increased with age. After adjusteing for potential confounding variables (age, smoking habits, alcohol drinking habits, education, physical activity, hypertension, dyslipidemia, obesity and diabetes), age remained a significant factor for NIH-IV prostatitis (OR = 1.35; 95% CI = 1.06–1.71; P = 0.01) and the risk of NIH-IV prostatitis was significantly higher in smokers≧15 pack/years than non-smokers (OR = 1.33; 95% CI = 1.01–1.75; P = 0.03). In addition, compared with non-drinkers, the OR of NIH-IV prostatitis in drinkers ≧1 drinks/week was 1.35 (95% CI = 1.03, 1.77, p = 0.02) after adjusting for the other variables above. In addition, having less than a college education may be a risk factor for NIH-IV prostatitis, although a statistically significant difference did not exist in our data (OR = 1.22; 95% CI = 0.97–1.52; P = 0.08). Conclusions Our findings suggest that NIH-IV prostatitis is prevalent in China. Age, smoking, drinking and lower education levels were associated with an increased risk of NIH-IV prostatitis. The prevalence of NIH-IV prostatitis should be taken into account when estimating the total prevalence of CP in future studies. PMID:23967188

Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk

PubMed Central

Rundle, Andrew; Wang, Yun; Sadasivan, Sudha; Chitale, Dhananjay A.; Gupta, Nilesh S.; Tang, Deliang; Rybicki, Benjamin A.

2017-01-01

BACKGROUND Obesity is associated with risk of aggressive prostate cancer (PCa), but not with over-all PCa risk. However, obese men have larger prostates which may lower biopsy accuracy and cause a systematic bias towards the null in epidemiologic studies of over-all risk. METHODS Within a cohort of 6,692 men followed-up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 495 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP and procedure date. Data on body mass index and prostate volume at the time of the initial procedure were abstracted from medical records. RESULTS Prior to consideration of differences in prostate volume, overweight (OR = 1.41; 95% CI 1.01, 1.97) and obese status (OR = 1.59; 95% CI 1.09, 2.33) at the time of the original benign biopsy or TURP were associated with PCa incidence during follow-up. Prostate volume did not significantly moderate the association between body-size and PCa, however it did act as an inverse confounder; adjustment for prostate volume increased the effect size for overweight by 22% (adjusted OR = 1.52; 95% CI 1.08, 2.14) and for obese status by 23% (adjusted OR = 1.77; 95% CI 1.20, 2.62). Larger prostate volume at the time of the original benign biopsy or TURP was inversely associated with PCa incidence during follow-up (OR = 0.92 per 10 cc difference in volume; 95% CI 0.88, 0.97). In analyses that stratified case-control pairs by tumor aggressiveness of the case, prostate volume acted as an inverse confounder in analyses of non-aggressive PCa but not in analyses of aggressive PCa. CONCLUSIONS In studies of obesity and PCa, differences in prostate volume cause a bias towards the null, particularly in analyses of non-aggressive PCa. A pervasive underestimation of the association between obesity and overall PCa risk may exist in the literature. PMID:28349547

Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk.

PubMed

Rundle, Andrew; Wang, Yun; Sadasivan, Sudha; Chitale, Dhananjay A; Gupta, Nilesh S; Tang, Deliang; Rybicki, Benjamin A

2017-06-01

Obesity is associated with risk of aggressive prostate cancer (PCa), but not with over-all PCa risk. However, obese men have larger prostates which may lower biopsy accuracy and cause a systematic bias toward the null in epidemiologic studies of over-all risk. Within a cohort of 6692 men followed-up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 495 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP, and procedure date. Data on body mass index and prostate volume at the time of the initial procedure were abstracted from medical records. Prior to consideration of differences in prostate volume, overweight (OR = 1.41; 95%CI 1.01, 1.97), and obese status (OR = 1.59; 95%CI 1.09, 2.33) at the time of the original benign biopsy or TURP were associated with PCa incidence during follow-up. Prostate volume did not significantly moderate the association between body-size and PCa, however it did act as an inverse confounder; adjustment for prostate volume increased the effect size for overweight by 22% (adjusted OR = 1.52; 95%CI 1.08, 2.14) and for obese status by 23% (adjusted OR = 1.77; 95%CI 1.20, 2.62). Larger prostate volume at the time of the original benign biopsy or TURP was inversely associated with PCa incidence during follow-up (OR = 0.92 per 10 cc difference in volume; 95%CI 0.88, 0.97). In analyses that stratified case-control pairs by tumor aggressiveness of the case, prostate volume acted as an inverse confounder in analyses of non-aggressive PCa but not in analyses of aggressive PCa. In studies of obesity and PCa, differences in prostate volume cause a bias toward the null, particularly in analyses of non-aggressive PCa. A pervasive underestimation of the association between obesity and overall PCa risk may exist in the literature. © 2017 Wiley Periodicals, Inc.

Office evaluation of male patients with lower urinary tract symptoms.

PubMed

Tabatabaei, Shahin; Talab, Saman Shafaat; Zangi, Mahdi; Woo, Henry H

2012-12-01

Lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) are one of the most common urologic disorders in men. Accurate history-taking and focused physical examination allows us to diagnose the majority of cases. A better understanding of risk factors helps us tailor our treatment and predict outcomes more accurately. Population studies are crucial in our understanding of LUTS/BPH natural history. Temporary prostatic urethral stents that are used for the management of urinary retention may also be used for evaluation of patients with detrusor hypo-contractility. The use of ultrasound to measure intravesical prostatic protrusion (IPP) and the Doppler study for prostate capsular artery resistive index are promising. Near-infrared spectroscopy (NIRS) examines the tissue oxygenation that may be affected by bladder outlet obstruction. The mathematical algorithm needs some fine-tuning, and its reproducibility is debatable. Serum and urinary biomarkers may help us to diagnose the disorder, and more effectively monitor patients' response to therapy. Among all, IPP is clinically more applicable at this time.

The Evolutionary Landscape of Localized Prostate Cancers Drives Clinical Aggression.

PubMed

Espiritu, Shadrielle Melijah G; Liu, Lydia Y; Rubanova, Yulia; Bhandari, Vinayak; Holgersen, Erle M; Szyca, Lesia M; Fox, Natalie S; Chua, Melvin L K; Yamaguchi, Takafumi N; Heisler, Lawrence E; Livingstone, Julie; Wintersinger, Jeff; Yousif, Fouad; Lalonde, Emilie; Rouette, Alexandre; Salcedo, Adriana; Houlahan, Kathleen E; Li, Constance H; Huang, Vincent; Fraser, Michael; van der Kwast, Theodorus; Morris, Quaid D; Bristow, Robert G; Boutros, Paul C

2018-05-03

The majority of newly diagnosed prostate cancers are slow growing, with a long natural life history. Yet a subset can metastasize with lethal consequences. We reconstructed the phylogenies of 293 localized prostate tumors linked to clinical outcome data. Multiple subclones were detected in 59% of patients, and specific subclonal architectures associate with adverse clinicopathological features. Early tumor development is characterized by point mutations and deletions followed by later subclonal amplifications and changes in trinucleotide mutational signatures. Specific genes are selectively mutated prior to or following subclonal diversification, including MTOR, NKX3-1, and RB1. Patients with low-risk monoclonal tumors rarely relapse after primary therapy (7%), while those with high-risk polyclonal tumors frequently do (61%). The presence of multiple subclones in an index biopsy may be necessary, but not sufficient, for relapse of localized prostate cancer, suggesting that evolution-aware biomarkers should be studied in prospective studies of low-risk tumors suitable for active surveillance. Copyright © 2018 Elsevier Inc. All rights reserved.

Common questions about the diagnosis and management of benign prostatic hyperplasia.

PubMed

Pearson, Ryan; Williams, Pamela M

2014-12-01

Benign prostatic hyperplasia (BPH) is a common condition that increases in prevalence with age. A history should include onset, duration, and severity of lower urinary tract symptoms and medication use to rule out other causes of symptoms. Physical examination includes a digital rectal examination and assessment for bladder distention or neurologic impairment. Recommended tests include serum prostate-specific antigen measurement and urinalysis to help identify infection, genitourinary cancer, or calculi as an alternative cause of lower urinary tract symptoms. BPH severity is assessed using validated, self-administered symptom questionnaires such as the American Urological Association Symptom Index or International Prostate Symptom Score. Mild or nonbothersome symptoms do not require treatment. Bothersome symptoms are managed with lifestyle modifications, medications, and surgery. Alpha blockers are first-line medications for BPH. Surgical referral is indicated if BPH-related complications develop, medical therapy fails, or the patient chooses it. Dietary supplements, such as saw palmetto, pygeum, cernilton, and beta sitosterols, and acupuncture are not recommended for the management of BPH.

The Reliability and Validity of Prostate Cancer Fatalism Inventory in Turkish Language.

PubMed

Aydoğdu, Nihal Gördes; Çapık, Cantürk; Ersin, Fatma; Kissal, Aygul; Bahar, Zuhal

2017-10-01

This study aimed to conduct the reliability and validity study of the Prostate Cancer Fatalism Inventory in Turkish language. The study carried out in methodological type and consisted of 171 men. The ages of the participants ranged between 40 and 82. The content validity index was determined to be 0.80, Kaiser-Meyer-Olkin value 0.825, Bartlett's test X 2  = 750.779 and p = 0.000. Then the principal component analysis was applied to the 15-item inventory. The inventory consisted of one dimension, and the load factors were over 0.30 for all items. The explained variance of the inventory was found 33.3 %. The Kuder-Richardson-20 coefficient was determined to be 0.849 and the item-total correlations ranged between 0.335 and 0.627. The Prostate Cancer Fatalism Inventory was a reliable and valid measurement tool in Turkish language. Integrating psychological strategies for prostate cancer screening may be required to strengthen the positive effects of nursing education.

Assessment of the contents related to screening on Portuguese language websites providing information on breast and prostate cancer.

PubMed

Ferreira, Daniel; Carreira, Helena; Silva, Susana; Lunet, Nuno

2013-11-01

The objective of this study was to assess the quality of the contents related to screening in a sample of websites providing information on breast and prostate cancer in the Portuguese language. The first 200 results of each cancer-specific Google search were considered. The accuracy of the screening contents was defined in accordance with the state of the art, and its readability was assessed. Most websites mentioned mammography as a method for breast cancer screening (80%), although only 28% referred to it as the only recommended method. Almost all websites mentioned PSA evaluation as a possible screening test, but correct information regarding its effectiveness was given in less than 10%. For both breast and prostate cancer screening contents, the potential for overdiagnosis and false positive results was seldom addressed, and the median readability index was approximately 70. There is ample margin for improving the quality of websites providing information on breast and prostate cancer in Portuguese.

From coagulation to enucleation: the use of lasers in surgery for benign prostatic hyperplasia.

PubMed

Wilson, Liam C; Gilling, Peter J

2005-09-01

The application of lasers for the treatment of benign prostatic hyperplasia has evolved over the past 15 years. Early-generation neodymium:yttrium aluminum garnet lasers were used to coagulate and ablate prostatic tissue, but significant postoperative irritative symptoms and high reoperation rates meant that this approach did not seriously challenge the status quo for long. Ablative techniques have recently become popular again with the marketing of the newer-generation, higher-power potassium titanyl phosphate and holmium lasers. Although short-term data are encouraging, there are no comparative trials of significant duration, so it is not yet possible to draw conclusions with regard to efficacy and durability. The holmium laser can also be used as an incisional and dissecting tool that allows resection or enucleation of whole lobes of the prostate, mimicking the action of the index finger in open prostatectomy. The safety, efficacy, durability and cost-effectiveness of the holmium laser have been shown in well-designed randomized controlled trials.

Dosimetric comparison between VMAT and RC3D techniques: case of prostate treatment

NASA Astrophysics Data System (ADS)

Chemingui, Fatima Zohra; Benrachi, Fatima; Bali, Mohamed Saleh; Ladjal, Hamid

2017-09-01

Considered as the second men cancer in Algeria, prostate cancer is treated in 70% by radiation. That's why radiation therapy is therapeutic weapon for prostate cancer. Conformational Radiotherapy in 3D is the most common technique [1-5]. The use of conventionally optimized treatment plans was compared at case scenario of optimized treatment plans VMAT for prostate cancer. The evaluation of the two optimizations strategies focused on the resulting plans ability to retain dose objectives under the influence of patient set up. Dose Volume Histogram in the Planning Target Volume and dose in the Organs At Risks were used to calculate the conformity index, and evaluation ratio of irradiated volume which represent the main tool of comparison [6,7]. The situation was analysed systematically. The 14% dose increase in the target leads to a decrease in the dose in adjacent organs with 39% in the bladder. Therefore, the criterion for better efficacy and less toxicity reveal that VMAT is the best choice.

Assessment of energy density usage during 180W lithium triborate laser photoselective vaporization of the prostate for benign prostatic hyperplasia. Is there an optimum amount of kilo-Joules per gram of prostate?

PubMed

Valdivieso, Roger; Meyer, Christian P; Hueber, Pierre-Alain; Meskawi, Malek; Alenizi, Abdullah M; Azizi, Mounsif; Trinh, Quoc-Dien; Misrai, Vincent; Rutman, Matthew; Te, Alexis E; Chughtai, Bilal; Barber, Neil J; Emara, Amr M; Munver, Ravi; Zorn, Kevin C

2016-10-01

To assess the effect of energy density (kJ/mL) applied on adenoma during photoselective vaporization of the prostate (PVP) treatment for benign prostate hyperplasia (BPH) on functional outcomes, prostate-specific antigen (PSA) reduction and complications. After exclusions, a total of 440 patients who underwent GreenLight (tm) laser XPS-180W lithium triborate PVP for the treatment of BPH were retrospectively reviewed. Data were collected from seven different international centres (Canada, USA, UK and France). Patients were stratified into four energy density groups (kJ/mL) according to intra-operative energy delivered and prostate volume as determined by preoperative transrectal ultrasonography (TRUS): group 1: <3 kJ/mL; group 2: 3-5 kJ/mL; group 3: 5-7 kJ/mL; and group 4: ≥7 kJ/mL. Energy density groups were chosen arbitrarily. PSA reduction and functional outcomes (International Prostate Symptom Score, quality of life, post-void residual urine volume, maximum urinary flow rate) were compared at 6, 12 and 24 months. Peri-operative complications and retreatment rates were also compared among the groups. The PSA reduction rates at 24 months after the procedure were 51, 61, 79 and 83% for the energy density groups <3, 3-5, 5-7 and ≥7 kJ/mL, respectively (P ≤ 0.01). This held true after accounting for baseline confounders. Energy density was not associated with higher complication rates, including haematuria, stricture formation, incontinence, refractory urinary retention, urinary tract infection and conversion to transurethral resection of the prostate. Functional outcomes at 2 years of follow-up were equivalent among the groups (P > 0.05 for all) and similar retreatment rates were observed (P = 0.36). Higher energy usage per cc of prostate was associated with a more significant reduction in PSA level (>50%) at 6, 12 and 24 months, suggesting increased vaporization of adenoma tissue; however, this did not translate into differences in functional outcomes at 2-year follow-up. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

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

Investigation of parameters affecting treatment time in MRI-guided transurethral ultrasound therapy

NASA Astrophysics Data System (ADS)

N'Djin, W. A.; Burtnyk, M.; Chopra, R.; Bronskill, M. J.

2010-03-01

MRI-guided transurethral ultrasound therapy shows promise for minimally invasive treatment of localized prostate cancer. Real-time MR temperature feedback enables the 3D control of thermal therapy to define an accurate region within the prostate. Previous in-vivo canine studies showed the feasibility of this method using transurethral planar transducers. The aim of this simulation study was to reduce the procedure time, while maintaining treatment accuracy by investigating new combinations of treatment parameters. A numerical model was used to simulate a multi-element heating applicator rotating inside the urethra in 10 human prostates. Acoustic power and rotation rate were varied based on the feedback of the temperature in the prostate. Several parameters were investigated for improving the treatment time. Maximum acoustic power and rotation rate were optimized interdependently as a function of prostate radius and transducer operating frequency, while avoiding temperatures >90° C in the prostate. Other trials were performed on each parameter separately, with the other parameter fixed. The concept of using dual-frequency transducers was studied, using the fundamental frequency or the 3rd harmonic component depending on the prostate radius. The maximum acoustic power which could be used decreased as a function of the prostate radius and the frequency. Decreasing the frequency (9.7-3.0 MHz) or increasing the power (10-20 W.cm-2) led to treatment times shorter by up to 50% under appropriate conditions. Dual-frequency configurations, while helpful, tended to have less impact on treatment times. Treatment accuracy was maintained and critical adjacent tissues like the rectal wall remained protected. The interdependence between power and frequency may require integrating multi-parametric functions inside the controller for future optimizations. As a first approach, however, even slight modifications of key parameters can be sufficient to reduce treatment time.

Morphological study of the prostate gland in viscacha (Lagostomus maximus maximus) during periods of maximal and minimal reproductive activity.

PubMed

Chaves, Maximiliano; Aguilera-Merlo, Claudia; Cruceño, Albana; Fogal, Teresa; Mohamed, Fabian

2015-11-01

The viscacha (Lagostomus maximus maximus) is a rodent with photoperiod-dependent seasonal reproduction. The aim of this work was to study the morphological variations of the prostate during periods of maximal (summer, long photoperiod) and minimal (winter, short photoperiod) reproductive activity. Prostates of adult male viscachas were studied by light and electron microscopy, immunohistochemistry for androgen receptor, and morphometric analysis. The prostate consisted of two regions: peripheral and central. The peripheral zone exhibited large adenomeres with a small number of folds and lined with a pseudostratified epithelium. The central zone had small adenomeres with pseudostratified epithelium and the mucosa showed numerous folds. The morphology of both zones showed variations during periods of maximal and minimal reproductive activity. The prostate weight, prostate-somatic index, luminal diameter of adenomeres, epithelial height and major nuclear diameter decreased during the period of minimal reproductive activity. Principal cells showed variations in their shape, size and ultrastructural characteristics during the period of minimal reproductive activity in comparison with the active period. The androgen receptor expression in epithelial and fibromuscular stromal cells was different between the studied periods. Our results suggest a reduced secretory activity of viscacha prostate during the period of minimal reproductive activity. Thus, the morphological variations observed in both the central and peripheral zones of the viscacha prostate agree with the results previously obtained in the gonads of this rodent of photoperiod-dependent reproduction. Additionally, the variations observed in the androgen receptors suggest a direct effect of the circulating testosterone on the gland. © 2015 Wiley Periodicals, Inc.

A pretreatment nomogram for prediction of biochemical failure after primary cryoablation of the prostate.

PubMed

Elshafei, Ahmed; Kovac, Evan; Dhar, Nivedita; Levy, David; Polascik, Thomas; Mouraviev, Vladimir; Yu, Changhong; Jones, J Stephen

2015-09-01

To create a predictive nomogram for biochemical failure following primary whole-gland cryoablation of the prostate for localized prostate cancer (LPCa). We retrospectively analyzed 2,242 patients from the Cryo On-Line Database (COLD) who were treatment naive and had undergone primary whole gland cryoablation of the prostate for biopsy-confirmed LPCa. Kaplan-Meier (KM) curves estimating 5 year biochemical progression-free survival (bPFS) were generated. Multivariable Cox proportional hazards analysis (CoxPH) was performed in order to construct the nomogram. The nomogram was internally validated using the bootstrap technique. Overall, the KM estimated 5 year bPFS was 72.8%. Stratified by D'Amico risk, The KM estimated 5 year bPFS was 82.6%, 71.1%, and 57.8% for low-, intermediate-, and high-risk groups, respectively. Statistically significant predictors of biochemical outcomes from CoxPH analysis were pre-treatment prostate specific antigen (PTPSA) (P < 0.001), total prostate volume (P = 0.004), clinical stage (P = 0.034), and Gleason score (0.004). A nomogram for predicted 5 year biochemical progression free probability was constructed with a concordance index of 0.652. An online risk calculator was also generated. To the best of our knowledge, this is the first predictive nomogram for biochemical outcomes after primary whole gland cryoablation of the prostate using socio-demographic, pretreatment, clinical, and prostate biopsy data. Our nomogram and online risk calculator can guide both patients and urologists for shared decision making regarding definitive treatment options. © 2015 Wiley Periodicals, Inc.

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.

Use of the Prostate Core Mitomic Test in Repeated Biopsy Decision-Making: Real-World Assessment of Clinical Utility in a Multicenter Patient Population.

PubMed

Legisi, Lorena; DeSa, Elise; Qureshi, M Nasar

2016-12-01

Prostate cancer is the most common cancer diagnosed in men in developed countries. Using molecular testing may help to improve outcomes in this clinically challenging group. Since 2011, the Prostate Core Mitomic Test (PCMT), which quantifies a 3.4-kb mitochondrial DNA deletion strongly associated with prostate cancer, has been used by more than 50 urology practices accessing pathology services through our laboratory in New Jersey. However, the use of a molecular test can only be beneficial if it affects patient management and improves outcomes. To determine whether repeated biopsy decision-making was affected in a quantifiable manner through the adjunct use of molecular testing with the PCMT. In this observational study we conducted 2 independent, structured query language database queries of our patient records at our laboratory, QDx Pathology Services, in Cranford, NJ. Query 1 included all men who had a negative prostate biopsy and a negative PCMT between February 1, 2011, and June 30, 2013. Men with a previous diagnosis of cancer were excluded. Query 2 included all men who had a negative prostate biopsy and a repeated biopsy between February 1, 2011, and September 30, 2013. The data exported for each query included the unique specimen number for an index biopsy, the interval between biopsies where present, the unique specimen number for a follow-up biopsy where present, histopathology for all biopsies, the biopsy procedure dates, the patient's date of birth, and the PCMT result when utilized. The patient rebiopsy rates and intervals were compared between the patients who were using PCMT and those who were not to assess whether the adjunct use of the PCMT impacted the rebiopsy decision-making process. Query 1 identified 644 men who had a negative biopsy and a negative PCMT result within the study period. Query 2 identified 823 men with a repeat biopsy after the initial negative index biopsy within the study period. Of these men, 132 had PCMT to inform their care. This patient population of 1467 men originated from US-based clinical urology practices. Evaluation of the impact on physician behavior demonstrated a general trend toward the earlier detection of prostate cancer on repeat biopsy by an average of 2.5 months and a coincident increase in cancer detection rates for urologists using the deletion assay in their rebiopsy decision-making process. Importantly, this trend was only observed when men with atypical small acinar proliferation (ASAP) on index biopsy were not considered. In the 644 men with a negative PCMT result, only 35 (5.4%) were subjected to a follow-up biopsy, with 5 (14.3%) of the 35 men identified as having cancer. Finally, the cohort of 132 men who had PCMT and repeat biopsy was compared with the published data supporting PCMT's ability to predict rebiopsy outcome. The key metrics of sensitivity and negative predictive value were comparable and within the 95% confidence intervals of the reported work. Molecular tests, such as the PCMT, are useful in addressing the sampling error of prostate needle biopsy and providing additional evidence to inform the clinical uncertainty regarding initial negative prostate biopsy when ASAP is not present. Longitudinal monitoring of clinical impact indicators provides the necessary inputs to better allocation of healthcare resources in the short- and long-term.

Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.

PubMed

Fowke, Jay H; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E

2016-01-01

BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association. Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI). Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation. The WHR, an estimate of centralized obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes.

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

Liu, X

Purpose: To explore the real-time dose verification method in volumetric modulated arc radiotherapy (VMAT) with a 2D array ion chamber array. Methods: The 2D ion chamber array was fixed on the panel of electronic portal imaging device (EPID). Source-detector distance (SDD)was 140cm. 8mm RW3 solid water was added to the detector panel to achieve maximum readings.The patient plans for esophageal, prostate and liver cancers were selected to deliver on the cylindrical Cheese phantom 5 times in order to validate the reproducibility of doses. Real-time patient transit dose measurements were performed at each fraction. Dose distributions wereevaluated using gamma index criteriamore » of 3mm DTA and 3% dose difference referred to the firsttime Result. Results: The gamma index pass rate in the Cheese phantom were about 98%; The gamma index pass rate for esophageal, liver and prostate cancer patient were about 92%,94%, and 92%, respectively; Gamma pass rate for all single fraction were more than 90%. Conclusion: The 2D array is capable of monitoring the real time transit doses during VMAT delivery. It is helpful to improve the treatment accuracy.« less

Medical Therapy for Benign Prostatic Hyperplasia: New Terminology, New Concepts, Better Choices

PubMed Central

Kaplan, Steven A

2006-01-01

This article discusses 3 areas of medical therapy for benign prostatic hyperplasia (BPH) that are undergoing extensive research and evaluation: 1) the use of muscarinic receptor antagonists to treat lower urinary tract symptoms (LUTS) in men with BPH; 2) the definition of an “enlarged prostate”; and 3) sexual function and LUTS. Fears of worsening obstructive symptoms or causing acute urinary retention often keep practitioners from prescribing muscarinic receptor antagonists to men who might have concomitant bladder outlet obstruction; a multicenter, multinational, double-blind study showed that tolterodine is safe for men with low postvoid residual volumes. Most urologists accept that a prostate volume of more than 40 mL is consistent with an enlarged prostate; there is more debate regarding prostate volumes of 30 to 40 mL. Recently presented data suggest that combination medical therapy might be effective for men having prostates with volumes of more than 25 mL. The association between voiding and sexual function has been increasingly recognized and investigated, and there seem to be common pathophysiologic mechanisms governing both conditions. Targeted treatment algorithms addressing both conditions seem warranted. PMID:16985556

[Evaluation and results of ablative therapies in prostate cancer].

PubMed

Renard-Penna, R; Sanchez-Salas, R; Barret, E; Cosset, J M; de Vergie, S; Sapetti, J; Ingels, A; Gangi, A; Lang, H; Cathelineau, X

2017-11-01

To perform a state of the art about methods of evaluation and present results in ablative therapies for localized prostate cancer. A review of the scientific literature was performed in Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of keywords. Publications obtained were selected based on methodology, language and relevance. After selection, 102 articles were analysed. Analyse the results of ablative therapies is presently difficult considering the heterogeneity of indications, techniques and follow-up. However, results from the most recent and homogeneous studies are encouraging. Oncologically, postoperative biopsies (the most important criteria) are negative (without any tumor cells in the treated area) in 75 to 95%. Functionally, urinary and sexual pre-operative status is spared (or recovered early) in more than 90% of the patients treated. More and more studies underline also the correlation between the results and the technique used considering the volume of the gland and, moreover, the "index lesion" localization. The post-treatment pathological evaluation by biopsies (targeted with MRI or, perhaps in a near future, with innovative ultrasonography) is the corner stone of oncological evaluation of ablative therapies. Ongoing trials will allow to standardize the follow-up and determine the best indication and the best techniques in order to optimize oncological and functional results for each patient treated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

Influence of the neural microenvironment on prostate cancer.

PubMed

Coarfa, Christian; Florentin, Diego; Putluri, NagiReddy; Ding, Yi; Au, Jason; He, Dandan; Ragheb, Ahmed; Frolov, Anna; Michailidis, George; Lee, MinJae; Kadmon, Dov; Miles, Brian; Smith, Christopher; Ittmann, Michael; Rowley, David; Sreekumar, Arun; Creighton, Chad J; Ayala, Gustavo

2018-02-01

Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non-neoplastic epithelial cells. Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements.

PubMed

McJimpsey, Erica L

2016-02-25

The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves.

Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements

NASA Astrophysics Data System (ADS)

McJimpsey, Erica L.

2016-02-01

The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves.

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.

Apparent diffusion coefficient value as a biomarker reflecting morphological and biological features of prostate cancer.

PubMed

Bae, Hyeyeol; Yoshida, Soichiro; Matsuoka, Yoh; Nakajima, Hiroshi; Ito, Eisaku; Tanaka, Hiroshi; Oya, Miyako; Nakayama, Takayuki; Takeshita, Hideki; Kijima, Toshiki; Ishioka, Junichiro; Numao, Noboru; Koga, Fumitaka; Saito, Kazutaka; Akashi, Takumi; Fujii, Yasuhisa; Kihara, Kazunori

2014-03-01

To assess whether there is an association between the apparent diffusion coefficient (ADC) value and the pathological characteristics of prostate cancer. The study cohort consisted of 29 consecutive patients with prostate cancer treated with radical prostatectomy. All patients underwent diffusion-weighted MRI before the prostate biopsy. In 42 tumor foci, the associations of the ADC values with the clinicopathological characteristics and Ki-67 labeling index (LI) were analyzed. High-grade cancers (Gleason score [GS] ≥ 4 + 3), larger cancers (maximum diameter (MD) ≥ 16 mm), and highly proliferating cancers (Ki-67 LI ≥ 4.43 %) had significantly lower ADC values, respectively (P < .001, P = .008, and P = .044, respectively). There was no significant difference in ADC value according to age, prostate-specific antigen, presence of extra-prostatic extension, and intra-tumoral stroma proportion. Multivariate analysis showed that GS, Ki-67 LI, and MD had independent and significant correlations with ADC value (P < .001, P = .006, and P = .002, respectively). Low ADC tumors (<0.52 × 10(-3) mm(2)/s) are likely to be high-grade cancer foci compared with high ADC tumors (relative risk: 65.2). The sensitivity and specificity of the ADC value to predict high-grade cancer foci are 81.8 and 93.5 %, respectively. A low ADC value reflects the morphological and biological features of prostate cancer. Analyzing the ADC value may make it possible to more precisely predict the cancer aggressiveness of each focus before treatment.

Transrectal microwave thermotherapy causing a short-time influence on sperm quality in Chinese chronic nonbacterial prostatitis patients.

PubMed

Jin, Jia-Xin; Wang, Han-Zhang; Zhai, Zheng-Xing; Ma, Bao-Liang; Li, Qin-Fang; Xiao, Nan; Wang, Zhi-Ping; Rodriguez, Ronald

2017-01-01

Chronic prostatitis can affect the sperm's quality. Previous studies have shown that transrectal microwave thermotherapy (TRMT) results in symptomatic relief in patients with chronic prostatitis, but the effects on sperm have not been carefully investigated. This study evaluates the impact of TRMT on the relief or decrease of symptoms and quality of sperm when used to treat patients with chronic nonbacterial prostatitis. Sixty patients were enrolled in the study. TRMT treatment was administered over 5 days, 1 h per day. Semen examination was carried out pretreatment and immediately at the conclusion of the 5-day treatment. Also, it was repeated 1 month, 3 months, and 6 months later. The treatment's symptom relief efficacy was evaluated using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). After the treatment, the overall NIH-CPSI scores were lower compared to those of pretreatment. In addition, the white blood cells and lecithin in expressed prostatic secretion were normal after the treatment. The sperm count was decreased by 23.8% 3 months after the treatment, sperm motility was reduced by 10.3% immediately after treatment, and sperm deformity was increased by 17.2%. The sperm volume and PH were not affected. However, the sperm quality recovered after treatment and the malformation rate was also lower at 6 months after treatment. TRMT is a favorable and safe treatment option for patients with nonbacterial chronic prostatitis. It could relieve the patient's symptoms and impact on sperm quality in the short-term.

Positive surgical margins after robotic assisted radical prostatectomy: a multi-institutional study.

PubMed

Patel, Vipul R; Coelho, Rafael F; Rocco, Bernardo; Orvieto, Marcelo; Sivaraman, Ananthakrishnan; Palmer, Kenneth J; Kameh, Darien; Santoro, Luigi; Coughlin, Geoff D; Liss, Michael; Jeong, Wooju; Malcolm, John; Stern, Joshua M; Sharma, Saurabh; Zorn, Kevin C; Shikanov, Sergey; Shalhav, Arieh L; Zagaja, Gregory P; Ahlering, Thomas E; Rha, Koon H; Albala, David M; Fabrizio, Michael D; Lee, David I; Chauhan, Sanket

2011-08-01

Positive surgical margins are an independent predictive factor for biochemical recurrence after radical prostatectomy. We analyzed the incidence of and associative factors for positive surgical margins in a multi-institutional series of 8,418 robotic assisted radical prostatectomies. We analyzed the records of 8,418 patients who underwent robotic assisted radical prostatectomy at 7 institutions. Of the patients 323 had missing data on margin status. Positive surgical margins were categorized into 4 groups, including apex, bladder neck, posterolateral and multifocal. The records of 6,169 patients were available for multivariate analysis. The variables entered into the logistic regression models were age, body mass index, preoperative prostate specific antigen, biopsy Gleason score, prostate weight and pathological stage. A second model was built to identify predictive factors for positive surgical margins in the subset of patients with organ confined disease (pT2). The overall positive surgical margin rate was 15.7% (1,272 of 8,095 patients). The positive surgical margin rate for pT2 and pT3 disease was 9.45% and 37.2%, respectively. On multivariate analysis pathological stage (pT2 vs pT3 OR 4.588, p<0.001) and preoperative prostate specific antigen (4 or less vs greater than 10 ng/ml OR 2.918, p<0.001) were the most important independent predictive factors for positive surgical margins after robotic assisted radical prostatectomy. Increasing prostate weight was associated with a lower risk of positive surgical margins after robotic assisted radical prostatectomy (OR 0.984, p<0.001) and a higher body mass index was associated with a higher risk of positive surgical margins (OR 1.032, p<0.001). For organ confined disease preoperative prostate specific antigen was the most important factor that independently correlated with positive surgical margins (4 or less vs greater than 10 ng/ml OR 3.8, p<0.001). The prostatic apex followed by a posterolateral site was the most common location of positive surgical margins after robotic assisted radical prostatectomy. Factors that correlated with cancer aggressiveness, such as pathological stage and preoperative prostate specific antigen, were the most important factors independently associated with an increased risk of positive surgical margins after robotic assisted radical prostatectomy. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Diagnostic accuracy of prostate health index to identify aggressive prostate cancer. An Institutional validation study.

PubMed

Morote, J; Celma, A; Planas, J; Placer, J; Ferrer, R; de Torres, I; Pacciuci, R; Olivan, M

2016-01-01

New generations of tumor markers used to detect prostate cancer (PCa) should be able to discriminate men with aggressive PCa of those without PCa or nonaggressive tumors. The objective of this study has been to validate Prostate Health Index (PHI) as a marker of aggressive PCa in one academic institution. PHI was assessed in 357 men scheduled to prostatic biopsy between June of 2013 and July 2014 in one academic institution. Thereafter a subset of 183 men younger than 75 years and total PSA (tPSA) between 3.0 and 10.0 ng/mL, scheduled to it first prostatic biopsy, was retrospectively selected for this study. Twelve cores TRUS guided biopsy, under local anaesthesia, was performed in all cases. Total PSA, free PSA (fPSA), and [-2] proPSA (p2PSA) and prostate volume were determined before the procedure and %fPSA, PSA density (PSAd) and PHI were calculated. Aggressive tumors were considered if any Gleason 4 pattern was found. PHI was compared to %fPSA and PSAd through their ROC curves. Thresholds to detect 90%, 95% of all tumors and 95% and 100% of aggressive tumors were estimated and rates of unnecessary avoided biopsies were calculated and compared. The rate of PCa detection was 37.2% (68) and the rate of aggressive tumors was 24.6% (45). The PHI area under the curve was higher than those of %fPSA and PSAd to detect any PCa (0.749 vs 0.606 and 0.668 respectively) or to detect only aggressive tumors (0.786 vs 0.677 and 0.708 respectively), however, significant differences were not found. The avoided biopsy rates to detect 95% of aggressive tumors were 20.2% for PHI, 14.8% for %fPSA, and 23.5% for PSAd. Even more, to detect all aggressive tumors these rates dropped to 4.9% for PHI, 9.3% for %fPSA, and 7.9% for PSAd. PHI seems a good marker to PCa diagnosis. However, PHI was not superior to %fPSA and PSAd to identify at least 95% of aggressive tumors. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

SU-F-T-625: Optimal Treatment Planning Strategy Among Arc Arrangements for Prostate SBRT with VMAT Technique

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

Chung, J; Kim, J; Eom, K

Purpose: The purpose of this study is to determine the optimal treatment planning strategy among the different arc arrangements for prostate stereotactic body radiotherapy (SBRT) plans with volumetric modulated arc therapy (VMAT). Methods: Ten patients with prostate cancer were selected. The SBRT-VMAT plans for each patient were generated with single-full (181° to 179°; 1FA), single-partial (240° to 120°; 1PA), double-full (181° to 179° and 179° to 181°; 2FA), and double-partial (240° to 120° and 120° to 240°; 2PA) arc arrangements. The prescription dose was 42.7 Gy in 7 fractions. Dose distribution was calculated using a 10-MV flattening-filter-free beam and themore » Acuros XB algorithm. Dosimetric parameters of target volume and organs at risk (OARs) were evaluated from cumulative dose-volume histograms on prostate SBRT-VMAT plans between single-arc (1FA and 1PA) and double-arc (2FA and 2PA) arrangements. Results: All plans using four arc arrangements were highly conformal with conformity index (CI)<1.05 and conformation number (CN)=0.91, and the doses to target volume were homogeneous (homogeneity index (HI)= 0.09 0.12). Pertaining to the dose to the OARs, there were significant differences in the rectum, left and right femoral head doses while having no difference in the bladder dose. The partial-arc (1PA and 2PA) had relatively high reductions for the mean rectum dose compared to full-arc (1FA and 2FA). The near-to-maximum dose (D2%) and mean dose of the left and right femoral head were always lower on prostate SBRT-VMAT plan using the full-arc, when compared to the partial-arc arrangement. Conclusion: This study confirmed that prostate SBRT-VMAT using 1PA was feasible fast delivery time and produced equivalent target coverage and better rectum sparing, although the D2% and mean dose of the left and right femoral head increased slightly. Therefore, the results of this study suggest that the use of 1PA is an attractive choice for delivering prostate SBRT-VMAT.« less

Accuracy of the prostate health index versus the urinary prostate cancer antigen 3 score to predict overall and significant prostate cancer at initial biopsy.

PubMed

Seisen, Thomas; Rouprêt, Morgan; Brault, Didier; Léon, Priscilla; Cancel-Tassin, Géraldine; Compérat, Eva; Renard-Penna, Raphaële; Mozer, Pierre; Guechot, Jérome; Cussenot, Olivier

2015-01-01

It remains unclear whether the Prostate Health Index (PHI) or the urinary Prostate-Cancer Antigen 3 (PCA-3) score is more accurate at screening for prostate cancer (PCa). The aim of this study was to prospectively compare the accuracy of PHI and PCA-3 scores to predict overall and significant PCa in men undergoing an initial prostate biopsy. Double-blind assessments of PHI and PCA-3 were conducted by referent physicians in 138 patients who subsequently underwent trans-rectal ultrasound-guided prostate biopsy according to a 12-core scheme. Predictive accuracies of PHI and PCA-3 were assessed using AUC and compared according to the DeLong method. Diagnostic performances with usual cut-off values for positivity (i.e., PHI >40 and PCA-3 >35) were calculated, and odds ratios associated with predicting PCa overall and significant PCa as defined by pathological updated Epstein criteria (i.e., Gleason score ≥7, more than three positive cores, or >50% cancer involvement in any core) were estimated using logistic regression. Prevalences of overall and significant PCa were 44.9% and 28.3%, respectively. PCA-3 (AUC = 0.71) was the most accurate predictor of PCa overall, and significantly outperformed PHI (AUC = 0.65; P = 0.03). However, PHI (AUC = 0.80) remained the most accurate predictor when screening exclusively for significant PCa and significantly outperformed PCA-3 (AUC = 0.55; P = 0.03). Furthermore, PCA-3 >35 had the best accuracy, and positive or negative predictive values when screening for PCa overall whereas these diagnostic performances were greater for PHI >40 when exclusively screening for significant PCa. PHI > 40 combined with PCA-3 > 35 was more specific in both cases. In multivariate analyses, PCA-3 >35 (OR = 5.68; 95%CI = [2.21-14.59]; P < 0.001) was significantly correlated with the presence of PCa overall, but PHI >40 (OR = 9.60; 95%CI = [1.72-91.32]; P = 0.001) was the only independent predictor for detecting significant PCa. Although PCA-3 score is the best predictor for PCa overall at initial biopsy, our findings strongly indicate that PHI should be used for population-based screening to avoid over-diagnosis of indolent tumors that are unlikely to cause death. © 2014 Wiley Periodicals, Inc.

Characterization of the seminal plasma proteome in men with prostatitis by mass spectrometry

PubMed Central

2012-01-01

Background Prostatitis is an inflammation of the prostate gland which affects approximately 10% of men. Despite its frequency, diagnosing prostatitis and monitoring patient response to treatment remains frustrating. As the prostate contributes a substantial percentage of proteins to seminal plasma, we hypothesized that a protein biomarker of prostatitis might be found by comparing the seminal plasma proteome of patients with and without prostatitis. Results Using mass spectrometry, we identified 1708 proteins in the pooled seminal plasma of 5 prostatitis patients. Comparing this list to a previously published list of seminal plasma proteins in the pooled seminal plasma of 5 healthy, fertile controls yielded 1464 proteins in common, 413 found only in the control group, and 254 found only in the prostatitis group. Applying a set of criteria to this dataset, we generated a high-confidence list of 59 candidate prostatitis biomarkers, 33 of which were significantly increased in prostatitis as compared to control, and 26 of which were decreased. The candidates were analyzed using Gene Ontology and Ingenuity Pathway analysis to delineate their subcellular localizations and functions. Conclusions Thus, in this study, we identified 59 putative biomarkers in seminal plasma that need further validation for diagnosis and monitoring of prostatitis. PMID:22309592

Study of penile circulation before and after radiation in patients with prostate cancer and its effect on impotence

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

Mittal, B.

1985-06-01

Decrease in penile blood flow has been implicated as the cause of erectile impotence in patients receiving pelvic irradiation. To determine any changes in the penile circulation secondary to pelvic irradiation, the authors measured the penile blood flow before and 6-9 months following completion of irradiation in six patients with prostate cancer. None of these patients had hormonal manipulation. The non-invasive techniques of Penile Brachial Index (PBI) and Penile Flow Index (PFI) were used to study penile circulation. Two patients developed impotence 2 to 4 1/2 months following completion of irradiation. There was no significant change in penile blood flowmore » following irradiation in any of the six patients studied. The etiology of post-irradiation impotence is probably multifactorial and it may be an oversimplification to attribute it to a single organic cause.« less

Comparison of Vela and holmium laser enucleation of the prostate: a retrospective clinical trial with a 12-month follow-up.

PubMed

Gu, Meng; Liu, Chong; Chen, Yan-Bo; Xu, Huan; Fu, Shi; Chen, Qi; Wang, Zhong

2018-05-01

This study aimed to estimate the validity and applicability of Vela laser enucleation of the prostate (VoLEP) in the management of benign prostatic hyperplasia (BPH). A retrospective chart review of 112 patients with BPH who underwent VoLEP (n = 60) or holmium laser enucleation of the prostate (HoLEP) (n = 56) was conducted at our institution from January 2015 to June 2015. The general and perioperative characteristics of the patients were collected. The 12-month follow-up data, including the lower urinary tract symptom (LUTS) indexes (International Prostate Symptom Score [I-PSS], quality-of-life [QoL] score and maximum flow rate [Qmax]), as well as rates of perioperative and late complications, were analyzed. No significant differences were observed in pre- and perioperative parameters, including operation time (58.05 ± 10.14 vs. 60.14 ± 12.30 min, P = 0.44), serum sodium decrease (3.49 ± 0.83 vs. 3.48 ± 0.84 mmol/L, P = 0.97), hemoglobin decrease (1.28 ± 0.38 vs. 1.24 ± 0.77 g/dL, P = 0.71), catheterization time (3.63 ± 1.10 vs. 3.89 ± 1.11 days, P = 0.21) and hospital stay (4.57 ± 1.25 vs. 4.68 ± 1.18 days, P = 0.63) between the two groups of patients. Compared with the HoLEP group, the noise during operation was lower in VoLEP group (47.22 ± 10.31 vs. 59.45 ± 9.65 db, P < 0.05). During 1, 6 and 12 months of follow-up visits, the LUTS indexes (I-PSS, QoL score and Qmax) were remarkably improved in both groups when comparing with the baseline values. Furthermore, LUTS indexes were comparable in both groups (P > 0.05). Similarly as the holmium laser, the Vela laser is a potent, safe, efficient durable and surgical treatment option for minimally invasive surgery in patients with BPH-induced LUTS.

Prostate volume did not affect voiding function improvements in diode laser enucleation of the prostate.

PubMed

Yang, Stephen Shei-Dei; Hsieh, Cheng-Hsing; Chiang, I-Ni; Lin, Chia-Da; Chang, Shang-Jen

2013-03-01

We compared safety and surgical outcomes in patients with different prostate sizes treated with diode laser enucleation of the prostate. From 2008 to 2012 consecutive patients with benign prostatic obstruction undergoing diode laser prostate enucleation at our institution were enrolled for analysis. A single surgeon performed diode laser prostate enucleation with an end firing, continuous wave diode laser (980 nm). Based on preoperative prostate volume on transrectal ultrasound, patients were stratified into 2 groups, including group 1-65 with less than 60 ml and group 2-55 with 60 ml or greater. Baseline and perioperative characteristics, and postoperative surgical outcomes were compared between the 2 groups. A total of 120 men with a mean ± SD age of 70.2 ± 9.0 years were enrolled for analysis. Compared with group 1 patients, those in group 2 had larger mean total prostate volume (85.0 ± 24.6 vs 40.9 ± 10.8 ml), longer mean operative time (117.7 ± 48.2 vs 60.7 ± 25.0 minutes), higher mean retrieved prostate weight (37.3 ± 16.1 vs 12.5 ± 7.3 gm) and a higher mean tissue retrieval ratio (74.4% ± 22.2% vs 58.8% ± 23.2%, p <0.01). There was no significant difference in the postoperative hemoglobin decrease in the 2 groups (median 0.5 vs 0.9 mg/dl, p = 0.11). The rate of temporary postoperative urinary retention after Foley catheter removal was significantly lower in group 2 (15.4% vs 3.6%, p = 0.04). Postoperative improvements in the peak flow rate, post-void residual urine volume and International Prostate Symptom Score were comparable in the 2 groups. Although patients with a larger prostate required significantly longer operative time and laser energy, voiding function improvements and surgical complication rates of diode laser prostate enucleation were comparable in patients with a larger vs smaller prostate. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

TU-CD-BRB-12: Radiogenomics of MRI-Guided Prostate Cancer Biopsy Habitats

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

Stoyanova, R; Lynne, C; Abraham, S

2015-06-15

Purpose: Diagnostic prostate biopsies are subject to sampling bias. We hypothesize that quantitative imaging with multiparametric (MP)-MRI can more accurately direct targeted biopsies to index lesions associated with highest risk clinical and genomic features. Methods: Regionally distinct prostate habitats were delineated on MP-MRI (T2-weighted, perfusion and diffusion imaging). Directed biopsies were performed on 17 habitats from 6 patients using MRI-ultrasound fusion. Biopsy location was characterized with 52 radiographic features. Transcriptome-wide analysis of 1.4 million RNA probes was performed on RNA from each habitat. Genomics features with insignificant expression values (<0.25) and interquartile range <0.5 were filtered, leaving total of 212more » genes. Correlation between imaging features, genes and a 22 feature genomic classifier (GC), developed as a prognostic assay for metastasis after radical prostatectomy was investigated. Results: High quality genomic data was derived from 17 (100%) biopsies. Using the 212 ‘unbiased’ genes, the samples clustered by patient origin in unsupervised analysis. When only prostate cancer related genomic features were used, hierarchical clustering revealed samples clustered by needle-biopsy Gleason score (GS). Similarly, principal component analysis of the imaging features, found the primary source of variance segregated the samples into high (≥7) and low (6) GS. Pearson’s correlation analysis of genes with significant expression showed two main patterns of gene expression clustering prostate peripheral and transitional zone MRI features. Two-way hierarchical clustering of GC with radiomics features resulted in the expected groupings of high and low expressed genes in this metastasis signature. Conclusions: MP-MRI-targeted diagnostic biopsies can potentially improve risk stratification by directing pathological and genomic analysis to clinically significant index lesions. As determinant lesions are more reliably identified, targeting with radiotherapy should improve outcome. This is the first demonstration of a link between quantitative imaging features (radiomics) with genomic features in MRI-directed prostate biopsies. The research was supported by NIH- NCI R01 CA 189295 and R01 CA 189295; E Davicioni is partial owner of GenomeDx Biosciences, Inc. M Takhar, N Erho, L Lam, C Buerki and E Davicioni are current employees at GenomeDx Biosciences, Inc.« less

The effect of asymptomatic histological prostatitis on sexual function and lower urinary tract symptoms.

PubMed

Urkmez, Ahmet; Yuksel, Ozgur Haki; Uruc, Fatih; Akan, Serkan; Yildirim, Caglar; Sahin, Aytac; Verit, Ayhan

2016-05-01

Prostatitis affects 10-14% of men of all ages and ethnicities. More than 50% of the men experience episodes of prostatitis at one time of their lives. Patients with CP typically have longlasting genitourinary/pelvic pain and obstructive and/or irritative voiding symptoms. Sexual dysfunction and psychological symptoms are frequently added to these symptoms. We also investigated the relationship between sexual functions, and lower urinary system symptoms, and asymptomatic histological prostatitis detected on transrectal ultrasound-guided (TRUS) biopsy performed with the indication of high PSA levels. Sixty cases compliant with the study criteria among patients who underwent prostate biopsies between September 2014 and June 2015 with the indication of higher PSA levels were included in the study. All patients were requested to complete IIEF-5 and IPSS forms one day previously. Based on histological analysis of biopsy materials, the patients were allocated into groups of BPH (simple BPH without histological prostatitis) (n:30) and histological chronic prostatitis (combination of BPH and histological prostatitis) (n:30). Mean age of the cases was 65.73±5.01 (range, 56-75 yrs) years. PSA levels ranged between 4-15 ng/ml. A statistically significant intergroup difference was not found regarding mean age, BMIs, PSA levels, incidence rates of hypertension and coronary artery disease (p>0.05). Prostate volumes of the HCP group were higher than those of the BPH group , with statistically significant differences (p:0.001; p<0.01). Questionnaire forms of the patients included in the study were statistically evaluated, and mean IPSS score of the HCP group was found to be higher when compared with that of the BPH group, with statistically significant differences. (p:0.016; p<0.05). However mean IIEF score of the BPH group was higher than that of the HCP group, with statistically significant differences (p:0.039; p<0.05). These findings suggested the presence of a correlation between chronic inflammation and lower urinary tract symptoms (LUTS). In addition, statistically significant lower IIEF values in patients with histological chronic prostatitis relative to those without suggested negative effects of even asymptomatic inflammation on sexual functions and mechanism of erection.

A dual yet opposite growth-regulating function of miR-204 and its target XRN1 in prostate adenocarcinoma cells and neuroendocrine-like prostate cancer cells

PubMed Central

Ding, Miao; Lin, Biaoyang; Li, Tao; Liu, Yuanyuan; Li, Yuhua; Zhou, Xiaoyu; Miao, Maohua; Gu, Jinfa; Pan, Hongjie; Yang, Fen; Li, Tianqi; Liu, Xin Yuan; Li, Runsheng

2015-01-01

Androgen deprivation therapy in prostate cancer (PCa) causes neuroendocrine differentiation (NED) of prostatic adenocarcinomas (PAC) cells, leading to recurrence of PCa. Androgen-responsive genes involved in PCa progression including NED remain largely unknown. Here we demonstrated the importance of androgen receptor (AR)-microRNA-204 (miR-204)-XRN1 axis in PCa cell lines and the rat ventral prostate. Androgens downregulate miR-204, resulting in induction of XRN1 (5′-3′ exoribonuclease 1), which we identified as a miR-204 target. miR-204 acts as a tumor suppressor in two PAC cell lines (LNCaP and 22Rv1) and as an oncomiR in two neuroendocrine-like prostate cancer (NEPC) cell lines (PC-3 and CL1). Importantly, overexpression of miR-204 and knockdown of XRN1 inhibited AR expression in PCa cells. Repression of miR-34a, a known AR-targeting miRNA, contributes AR expression by XRN1. Thus we revealed the AR-miR-204-XRN1-miR-34a positive feedback loop and a dual function of miR-204/XRN1 axis in prostate cancer. PMID:25797256

Deep Learning Role in Early Diagnosis of Prostate Cancer

PubMed Central

Reda, Islam; Khalil, Ashraf; Elmogy, Mohammed; Abou El-Fetouh, Ahmed; Shalaby, Ahmed; Abou El-Ghar, Mohamed; Elmaghraby, Adel; Ghazal, Mohammed; El-Baz, Ayman

2018-01-01

The objective of this work is to develop a computer-aided diagnostic system for early diagnosis of prostate cancer. The presented system integrates both clinical biomarkers (prostate-specific antigen) and extracted features from diffusion-weighted magnetic resonance imaging collected at multiple b values. The presented system performs 3 major processing steps. First, prostate delineation using a hybrid approach that combines a level-set model with nonnegative matrix factorization. Second, estimation and normalization of diffusion parameters, which are the apparent diffusion coefficients of the delineated prostate volumes at different b values followed by refinement of those apparent diffusion coefficients using a generalized Gaussian Markov random field model. Then, construction of the cumulative distribution functions of the processed apparent diffusion coefficients at multiple b values. In parallel, a K-nearest neighbor classifier is employed to transform the prostate-specific antigen results into diagnostic probabilities. Finally, those prostate-specific antigen–based probabilities are integrated with the initial diagnostic probabilities obtained using stacked nonnegativity constraint sparse autoencoders that employ apparent diffusion coefficient–cumulative distribution functions for better diagnostic accuracy. Experiments conducted on 18 diffusion-weighted magnetic resonance imaging data sets achieved 94.4% diagnosis accuracy (sensitivity = 88.9% and specificity = 100%), which indicate the promising results of the presented computer-aided diagnostic system. PMID:29804518

SU-G-TeP1-01: A Simulation Study to Investigate Maximum Allowable Deformations of Implant Geometry Before Plan Objectives Are Violated in Prostate HDR Brachytherapy

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

Babier, A; Joshi, C; Cancer Center of Southeastern Ontario, Kingston General Hospital, Kingston, Ontario

Purpose: In prostate HDR brachytherapy dose distributions are highly sensitive to changes in prostate volume and catheter displacements. We investigate the maximum deformations in implant geometry before planning objectives are violated. Methods: A typical prostate Ir-192 HDR brachytherapy reference plan was calculated on the Oncentra planning system, which used CT images from a tissue equivalent prostate phantom (CIRS Model 053S) embedded inside a pelvis wax phantom. The prostate was deformed and catheters were displaced in simulations using a code written in MATLAB. For each deformation dose distributions were calculated, based on TG43 methods, using the MATLAB code. The calculations weremore » validated through comparison with Oncentra calculations for the reference plan, and agreed within 0.12%SD and 0.3%SD for dose and volume, respectively. Isotropic prostate volume deformations of up to +34% to −27% relative to its original volume, and longitudinal catheter displacements of 7.5 mm in superior and inferior directions were simulated. Planning objectives were based on American Brachytherapy Society guidelines for prostate and urethra volumes. A plan violated the planning objectives when less than 90% of the prostate volume received the prescribed dose or higher (V{sub 100}), or the urethral volume receiving 125% of prescribed dose or higher was more than 1 cc (U{sub 125}). Lastly, the dose homogeneity index (DHI=1-V{sub 150}/V{sub 100}) was evaluated; a plan was considered sub-optimal when the DHI fell below 0.62. Results and Conclusion: Planning objectives were violated when the prostate expanded by 10.7±0.5% or contracted by 11.0±0.2%; objectives were also violated when catheters were displaced by 4.15±0.15 mm and 3.70±0.15 mm in the superior and inferior directions, respectively. The DHI changes did not affect the plan optimality, except in the case of prostate compression. In general, catheter displacements have a significantly larger impact on plan optimality than prostate volume changes.« less

Sexual (dys)function after radiotherapy for prostate cancer: a review.

PubMed

Incrocci, Luca; Slob, A Koos; Levendag, Peter C

2002-03-01

Prostate cancer has become the most common nonskin malignant neoplasm in older men in Western countries. As treatment efficacy has improved, issues related to posttherapy quality of life and sexual functioning have become more important. We discuss the various methods used to evaluate erectile and sexual dysfunction and the definition of potency. The etiologies of erectile dysfunction after external beam radiotherapy and brachytherapy for prostate cancer are also reviewed. The literature is summarized, and comparative studies of radiation and surgery are surveyed briefly. Rates of erectile dysfunction vary from 6 to 84% after external beam radiotherapy and from 0 to 51% after brachytherapy. In most of the studies, the analysis is retrospective, the definition of erectile dysfunction is not clear, only one question about sexual functioning is asked, and nonvalidated instruments are used. The etiology of erectile dysfunction after radiation for prostate cancer is not completely understood. Because erectile function is only one component of sexual function, it is necessary to assess sexual desire, satisfaction, frequency of intercourse, and other such factors when evaluating the effects of therapy. Patients should be offered sexual counseling and informed about the availability of effective treatments for erectile dysfunction, such as sildenafil, intracavernosal injection, and vacuum devices.

Prostatic calculi influence the antimicrobial efficacy in men with chronic bacterial prostatitis

PubMed Central

Zhao, Wei-Ping; Li, Yong-Tao; Chen, Jun; Zhang, Zhi-Gen; Jiang, Hai; Xia, Dan; Wang, Shuo; Wang, Ping

2012-01-01

We studied the efficacy of culture-specific antibiotic therapy for chronic bacterial prostatitis (CBP) patients with or without prostatic calculi. This study included 101 patients (21–62 years old) who met the consensus criteria for CBP (National Institutes of Health category II). According to the results of transrectal ultrasonography (TRUS), all patients were divided into two groups: Group 1, CBP with prostatic calculi, n=39; Group 2, CBP without prostatic calculi, n=62. All patients received optimal antimicrobial therapy for 4 weeks and followed up for a minimum of 3 months (range: 3–8 months). In addition to expressed prostatic secretions (EPS) and urine culture, all patients were asked to complete the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the subjective global assessment (SGA). The microbiological eradication rate at the end of treatment were 32/39 (82.1%) and 54/62 (87.1%), while the rates for continued eradication at the end of study were 17/39 (43.6%) and 45/62 (72.6%) in Group 1 and Group 2 (P<0.01), respectively. We observed a decrease in the total NIH-CPSI score median values from 24 to 19 in Group 1 and from 24 to 11 in Group 2. The pain subscore (P<0.01), urinary sunscore (P<0.05) and quality of life (QoL; P<0.05) as well as the total NIH-CPSI score (P<0.01) were significantly improved after antimicrobial treatment in Group 2 compared to Group 1. Response, defined as a decrease of the NIH-CPSI total score by at least 50%, was seen in Group 1 versus Group 2 in 38.5% and 58.1% (P<0.01), respectively. Our results showed that prostatic calculi influence the antimicrobial efficacy in men with CBP. There was a noticeable decrease in the cure rate of CBP patients with prostatic calculi due to relapse after antimicrobial therapy. PMID:22796735

Prostatic calculi influence the antimicrobial efficacy in men with chronic bacterial prostatitis.

PubMed

Zhao, Wei-Ping; Li, Yong-Tao; Chen, Jun; Zhang, Zhi-Gen; Jiang, Hai; Xia, Dan; Wang, Shuo; Wang, Ping

2012-09-01

We studied the efficacy of culture-specific antibiotic therapy for chronic bacterial prostatitis (CBP) patients with or without prostatic calculi. This study included 101 patients (21-62 years old) who met the consensus criteria for CBP (National Institutes of Health category II). According to the results of transrectal ultrasonography (TRUS), all patients were divided into two groups: Group 1, CBP with prostatic calculi, n=39; Group 2, CBP without prostatic calculi, n=62. All patients received optimal antimicrobial therapy for 4 weeks and followed up for a minimum of 3 months (range: 3-8 months). In addition to expressed prostatic secretions (EPS) and urine culture, all patients were asked to complete the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the subjective global assessment (SGA). The microbiological eradication rate at the end of treatment were 32/39 (82.1%) and 54/62 (87.1%), while the rates for continued eradication at the end of study were 17/39 (43.6%) and 45/62 (72.6%) in Group 1 and Group 2 (P<0.01), respectively. We observed a decrease in the total NIH-CPSI score median values from 24 to 19 in Group 1 and from 24 to 11 in Group 2. The pain subscore (P<0.01), urinary sunscore (P<0.05) and quality of life (QoL; P<0.05) as well as the total NIH-CPSI score (P<0.01) were significantly improved after antimicrobial treatment in Group 2 compared to Group 1. Response, defined as a decrease of the NIH-CPSI total score by at least 50%, was seen in Group 1 versus Group 2 in 38.5% and 58.1% (P<0.01), respectively. Our results showed that prostatic calculi influence the antimicrobial efficacy in men with CBP. There was a noticeable decrease in the cure rate of CBP patients with prostatic calculi due to relapse after antimicrobial therapy.

Withania coagulans Extract Induces Cell Apoptosis and Inhibits COX-2 Expression in a Rat Model of Benign Prostatic Hyperplasia

PubMed Central

Sarbishegi, Maryam; Khajavi, Ozra; Arab, Mohammad Reza

2016-01-01

Background Phytotherapy is a popular treatment option in cases of benign prostatic hyperplasia (BPH), with many different herbal products being used for the treatment of this condition. Withania coagulans (WC) is an herbal medicine that has shown anti-tumoral, anti-inflammatory, and antioxidant effects. Objectives This study examined the effect of Withania coagulans extract (WCE) on prostatic cell apoptosis and cyclooxygenase-2 (COX-2) expression in cases of benign prostatic hyperplasia (BPH) in rats. Methods Forty Wistar rats were equally divided into five groups: control, sham, BPH, BPH + WCE, and BPH + CLX (celecoxib) as a positive control group. The induction of BPH was achieved via the subcutaneous injection of 3 mg/kg of testosterone propionate (TP) daily for 28 days. The animals received WCE, celecoxib, or distilled water by oral gavage accompanied by the TP injection. After four weeks, the prostate glands of the rats were weighed to measure the prostatic index (PI). The ventral lobes of the prostates were dissected and processed with paraffin blocks in order to study the number of mast cells. A TUNEL analysis was performed to evaluate the cell apoptosis, while the expression of COX-2 was examined using immunohistochemistry. Results BPH was obvious in the ventral lobe of the prostate, and the administration of WCE markedly decreased the PI and the number of mast cells (P < 0.001) in the BPH rats. Additionally, the WCE treatment induced prostatic cell apoptosis when compared to the BPH group. Furthermore, following the WCE treatment, the expression of COX-2 in the prostatic tissues was significantly decreased when compared to the BPH groups. Conclusions According to the results of this study, WCE was effective in the treatment of BPH in rats. It may therefore have beneficial effects in the treatment of patients with BPH. PMID:27878112

Beef Tallow, but Not Perilla or Corn Oil, Promotion of Rat Prostate and Intestinal Carcinogenesis by 3,2‐Dimethyl‐4‐aminobiphenyl

PubMed Central

Mori, Toshio; Imaida, Katsumi; Tamano, Seiko; Sano, Masashi; Takahashi, Satoru; Asamoto, Makoto; Takeshita, Masazumi; Ueda, Hiroshi

2001-01-01

The modifying effects of three kinds of fat (corn oil, beef tallow or perilla oil, each at 20% in the diet) on F344 rat prostate carcinogenesis induced by 3,2‐dimethyl‐4‐aminobiphenyl (DMAB) were investigated. Non‐invasive carcinomas of the ventral prostate were induced by DMAB alone and invasive carcinomas of the other prostate lobes and seminal vesicles by DMAB and testosterone propionate (TP). Eight groups of F344 rats were initiated with 50 mg/kg body weight of DMAB at 2‐week intervals for the first 20 weeks, four also receiving TP, extended until week 60. The animals received basal chow powder diet or one of three high fat diets throughout the experiment (60 weeks). One further group served as a non‐carcinogen‐treated control maintained on basal chow powder diet. Beef tallow significantly increased the development of ventral prostate carcinomas with DMAB alone (from 15 to 45%, P<0.05), while perilla oil reduced the incidence of prostatic intraepithelial neoplasia (PIN) in the ventral lobe of rats given DMAB + TP (from 70 to 10%, P<0.01), but not in those given DMAB alone. No other effects of high fats were observed regarding PIN or invasive cancers of the dorsolateral and anterior prostate or seminal vesicles. A satellite experiment demonstrated that all high fat diets for 4 weeks increased the 5‐bromo‐2‐deoxyuridine (BrdU) labeling index of prostate epithelial cells, suggesting that a high fat intake, irrespective of the fatty acid composition, may accelerate cell kinetics in the prostate. Of the three high fat diets, beef tallow was also found to increase intestinal carcinogenesis. Thus, the present data revealed carcinogenesis in the prostate and intestine to be promoted by beef tallow. PMID:11676852

Measurement of serum isoform [-2]proPSA derivatives shows superior accuracy to magnetic resonance imaging in the diagnosis of prostate cancer in patients with a total prostate-specific antigen level of 2-10 ng/ml.

PubMed

Furuya, Kazuhiro; Kawahara, Takashi; Narahara, Masaki; Tokita, Takashi; Fukui, Sachi; Imano, Masashi; Mitome, Taku; Ito, Yusuke; Izumi, Koji; Osaka, Kimito; Yokomizo, Yumiko; Hayashi, Narihiko; Hasumi, Hisashi; Nawata, Shintaro; Kawano, Tsuyoshi; Yao, Masahiro; Uemura, Hiroji

2017-08-01

More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer. The subjects were 50 consecutive men with a PSA level of 2.0-10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer. In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%). PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer.

The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats

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

Wang, Chao; Luo, Fei; Zhou, Ying

Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression ofmore » androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression. - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.« less

Targeted Elimination of PCDH-PC Expressing Prostate Cancer Cells for Control of Hormone-Resistant Prostate Cancer

DTIC Science & Technology

2008-11-01

or antisense oligonucleotides ( ASOs ) might be useful in preventing the development of castration- recurrent prostate cancer in prostate cancer...patients. To this end, we have created functional shRNA vectors and ASOs capable of suppressing PCDH-PC expression and we have also created a monoclonal...electrophoresed on an SDS-PAGE gel and blotted onto a filter. The filter was probed with an anti-myc antibody. The levels of myc-tagged PCDH-PC protein

Targeted Elimination of PCDH-PC Expressing Prostate Cancer Cells for Control of Hormone-Resistant Prostate Cancer

DTIC Science & Technology

2009-11-01

expression knockout by shRNAs or antisense oligonucleotides ( ASOs ) might be useful in preventing the development of castration-recurrent prostate...cancer in prostate cancer patients. To this end, we have created functional shRNA vectors and ASOs capable of suppressing PCDH-PC expression and we have...containing PCDH-PC cDNA. Cell extracts were prepared 48 hrs after co-transfection and were electrophoresed on an SDS-PAGE gel and blotted onto a

Regulation of Prostate Development and Benign Prostatic Hyperplasia by Autocrine Cholinergic Signaling via Maintaining the Epithelial Progenitor Cells in Proliferating Status.

PubMed

Wang, Naitao; Dong, Bai-Jun; Quan, Yizhou; Chen, Qianqian; Chu, Mingliang; Xu, Jin; Xue, Wei; Huang, Yi-Ran; Yang, Ru; Gao, Wei-Qiang

2016-05-10

Regulation of prostate epithelial progenitor cells is important in prostate development and prostate diseases. Our previous study demonstrated a function of autocrine cholinergic signaling (ACS) in promoting prostate cancer growth and castration resistance. However, whether or not such ACS also plays a role in prostate development is unknown. Here, we report that ACS promoted the proliferation and inhibited the differentiation of prostate epithelial progenitor cells in organotypic cultures. These results were confirmed by ex vivo lineage tracing assays and in vivo renal capsule recombination assays. Moreover, we found that M3 cholinergic receptor (CHRM3) was upregulated in a large subset of benign prostatic hyperplasia (BPH) tissues compared with normal tissues. Activation of CHRM3 also promoted the proliferation of BPH cells. Together, our findings identify a role of ACS in maintaining prostate epithelial progenitor cells in the proliferating state, and blockade of ACS may have clinical implications for the management of BPH. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Clinicopathological, functional, and immediate oncologic outcome assessment in men aged≤50 years with prostate cancer after robotic prostatectomy.

PubMed

Samadi, David B; Sebrow, Dov; Hobbs, Adele R; Bernstein, Adrien N; Brajtbord, Jonathan; Lavery, Hugh J; Jazayeri, Seyed Behzad

2017-01-01

To define the pathologic and functional outcomes of men 50 years of age and younger with prostate cancer in a contemporary robotic cohort, this study was designed. Patients undergoing robotic-assisted laparoscopic prostatectomy from April 2002 to April 2012 (n = 2,495) formed the base population for the current analyses. The patients were dichotomized according to their age≤50 (n = 271) and>50-year-old (n = 2,224). Clinicopathological and health-related quality-of-life outcomes were recorded and analyzed for differences. Propensity score matching was used when assessing urinary and sexual function outcome. Baseline prostate-specific antigen and clinical stage were similar between men older than 50 years and those younger. Younger patients had less severe disease (D׳Amico risk and Gleason scores) and smaller prostates. Young men had higher rates of erectile function at all time points, including baseline (94% vs. 83% at 12mo, P <0.01). Continence was similar at all time points except for 6 months, where younger patients experienced a faster return than older patients and then remained constant, while older patients continued to improve (96% vs. 89%, P<0.01). After matching process, the difference in erectile function at 6-month follow-up was lost. Most men aged 50 years and younger who received robotic-assisted laparoscopic prostatectomy had clinically significant prostate cancer. Although histopathologic and short-term oncologic outcomes were nearly identical when compared to older patients, younger men had a more rapid and superior return of erectile function. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function: a systematic review.

PubMed

Frieben, Ryan W; Lin, Hao-Cheng; Hinh, Peter P; Berardinelli, Francesco; Canfield, Steven E; Wang, Run

2010-07-01

A systematic review of randomized controlled trials and cohort studies was conducted to evaluate data for the effects of minimally invasive procedures for treatment of symptomatic benign prostatic hyperplasia (BPH) on male sexual function. The studies searched were trials that enrolled men with symptomatic BPH who were treated with laser surgeries, transurethral microwave therapy (TUMT), transurethral needle ablation of the prostate (TUNA), transurethral ethanol ablation of the prostate (TEAP) and high-intensity frequency ultrasound (HIFU), in comparison with traditional transurethral resection of the prostate (TURP) or sham operations. A total of 72 studies were identified, of which 33 met the inclusion criteria. Of the 33 studies, 21 were concerned with laser surgeries, six with TUMT, four with TUNA and two with TEAP containing information regarding male sexual function. No study is available regarding the effect of HIFU for BPH on male sexual function. Our analysis shows that minimally invasive surgeries for BPH have comparable effects to those of TURP on male erectile function. Collectively, less than 15.4% or 15.2% of patients will have either decrease or increase, respectively, of erectile function after laser procedures, TUMT and TUNA. As observed with TURP, a high incidence of ejaculatory dysfunction (EjD) is common after treatment of BPH with holmium, potassium-titanyl-phosphate and thulium laser therapies (> 33.6%). TUMT, TUNA and neodymium:yttrium aluminum garnet visual laser ablation or interstitial laser coagulation for BPH has less incidence of EjD, but these procedures are considered less effective for BPH treatment when compared with TURP.

The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function: a systematic review

PubMed Central

Frieben, Ryan W.; Lin, Hao-Cheng; Hinh, Peter P.; Berardinelli, Francesco; Canfield, Steven E.; Wang, Run

2010-01-01

A systematic review of randomized controlled trials and cohort studies was conducted to evaluate data for the effects of minimally invasive procedures for treatment of symptomatic benign prostatic hyperplasia (BPH) on male sexual function. The studies searched were trials that enrolled men with symptomatic BPH who were treated with laser surgeries, transurethral microwave therapy (TUMT), transurethral needle ablation of the prostate (TUNA), transurethral ethanol ablation of the prostate (TEAP) and high-intensity frequency ultrasound (HIFU), in comparison with traditional transurethral resection of the prostate (TURP) or sham operations. A total of 72 studies were identified, of which 33 met the inclusion criteria. Of the 33 studies, 21 were concerned with laser surgeries, six with TUMT, four with TUNA and two with TEAP containing information regarding male sexual function. No study is available regarding the effect of HIFU for BPH on male sexual function. Our analysis shows that minimally invasive surgeries for BPH have comparable effects to those of TURP on male erectile function. Collectively, less than 15.4% or 15.2% of patients will have either decrease or increase, respectively, of erectile function after laser procedures, TUMT and TUNA. As observed with TURP, a high incidence of ejaculatory dysfunction (EjD) is common after treatment of BPH with holmium, potassium-titanyl-phosphate and thulium laser therapies (> 33.6%). TUMT, TUNA and neodymium:yttrium aluminum garnet visual laser ablation or interstitial laser coagulation for BPH has less incidence of EjD, but these procedures are considered less effective for BPH treatment when compared with TURP. PMID:20473318

Imaging of Prostate Cancer Using Gallium-68-Labeled Bombesin.

PubMed

Sonni, Ida; Baratto, Lucia; Iagaru, Andrei

2017-04-01

Nuclear medicine can play an important role in evaluating prostate cancer combining anatomical and functional information with hybrid techniques. Various PET radiopharmaceuticals have been used for targeting specific biological markers in prostate cancer. Research is ideally oriented towards the development of radiopharmaceuticals targeting antigens overexpressed in prostate cancer, as opposed to normal prostate tissue. In this regard, gastrin-releasing peptide receptors (GRPR) are excellent candidates. Bombesin analogues targeting the GRPR have been investigated. Gallium-68 ( 68 Ga) is an interesting PET radioisotope due to several advantages, such as availability, ease of radiochemistry, half-life, and costs. The focus of this review is on 68 Ga-labeled bombesin analogues in prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Questions and answers on prostate multiparameter magnetic resonance imaging: Everything a urologist should know.

PubMed

Catalá, V; Salas, D; Esquena, S; Mateu, S; Algaba, F; Palou, J; de la Torre, P

2016-01-01

For many years, the detection of prostate cancer (PC) and the management of its therapy have been based primarily on prostate-specific antigen, rectal examination and prostate biopsy. However, these parameters have known limitations. Multiparametric magnetic resonance imaging (mpMRI) for prostate cancer has undergone extensive development in recent years, providing morphological and functional information. The aim of this study is to present an updated review of the scope and limitations of prostatic mpMRI for PC, in the framework of a multidisciplinary vision. We conducted a literature review (in PubMed) of articles referencing "mpMRI/staging/ PC/detection/active surveillance/therapy planning/post-therapy". We included 4 systematic reviews and other articles published in high impact-factor journals within the field of radiology and urology. MpMRI provides morphological and functional information concerning PC. This information is integrated into the Prostate Imaging Report and Date System, classifying the probability of clinically significant carcinoma on a scale from 1 to 5. The usefulness of mpMRI is currently being established for patients with high prostate-specific antigen levels and prior negative prostate biopsy; tumour staging in selected cases; assessment of patients who are candidates for active surveillance; the planning of focal treatments; and the assessment of tumour persistence and recurrence. MpMRI currently fills a relevant role in the diagnosis and therapeutic decision-making of PC. More widespread use of the technique requires a cost/benefit analysis. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Estrogenic Environmental Chemicals and Drugs: Mechanisms for Effects on the Developing Male Urogenital System

PubMed Central

Taylor, Julia A.; Richter, Catherine A.; Ruhlen, Rachel L.; vom Saal, Frederick S.

2011-01-01

Development and differentiation of the prostate from the fetal urogenital sinus (UGS) is dependent on androgen action via androgen receptors (AR) in the UGS mesenchyme. Estrogens are not required for prostate differentiation but do act to modulate androgen action. In mice exposure to exogenous estrogen during development results in permanent effects on adult prostate size and function, which is mediated through mesenchymal estrogen receptor (ER) alpha. For many years estrogens were thought to inhibit prostate growth because estrogenic drugs studied were administered at very high concentrations that interfered with normal prostate development. There is now extensive evidence that exposure to estrogen at very low concentrations during the early stages of prostate differentiation can stimulate fetal/neonatal prostate growth and lead to prostate disease in adulthood. Bisphenol A (BPA) is an environmental endocrine disrupting chemical that binds to both ER receptor subtypes as well as to AR. Interest in BPA has increased because of its prevalence in the environment and its detection in over 90% of people in the USA. In tissue culture of fetal mouse UGS mesenchymal cells, BPA and estradiol stimulated changes in the expression of several genes. We discuss here the potential involvement of estrogen in regulating signaling pathways affecting cellular functions relevant to steroid hormone signaling and metabolism and to inter- and intra-cellular communications that promote cell growth. The findings presented here provide additional evidence that BPA and the estrogenic drug ethinylestradiol disrupt prostate development in male mice at administered doses relevant to human exposures. PMID:21827855

Telocytes play a key role in prostate tissue organisation during the gland morphogenesis.

PubMed

Sanches, Bruno D A; Maldarine, Juliana S; Zani, Bruno C; Tamarindo, Guilherme H; Biancardi, Manoel F; Santos, Fernanda C A; Rahal, Paula; Góes, Rejane M; Felisbino, Sérgio L; Vilamaior, Patricia S L; Taboga, Sebastião R

2017-12-01

Telocytes are CD34-positive interstitial cells, known to exert several functions, one of which is a role in tissue organisation, previously demonstrated by telocytes in the myocardium. The existence of telocytes in the prostate has recently been reported, however, there is a lack of information regarding the function of these cells in prostate tissue, and information regarding the possible role of these cells in prostatic development. This study used immunofluorescence techniques in prostate tissue and prostatic telocytes in culture to determine the relationship between telocytes and prostate morphogenesis. Furthermore, immunofluorescent labelling of telocytes was performed on prostate tissue at different stages of early postnatal development. Initially, CD34-positive cells are found at the periphery of the developing alveoli, later in the same region, c-kit-positive cells and cells positive for both factors are verified and CD34-positive cells were predominantly observed in the interalveolar stroma and the region surrounding the periductal smooth muscle. Fluorescence assays also demonstrated that telocytes secrete TGF-β1 and are ER-Beta (ERβ) positive. The results suggest that telocytes play a changing role during development, initially supporting the differentiation of periductal and perialveolar smooth muscle, and later, producing dense networks that separate alveoli groups and form a barrier between the interalveolar region and periurethral smooth muscle. We conclude that telocytes play a relevant role in prostate tissue organisation during postnatal development. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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.

A dosimetric comparison of {sup 169}Yb versus {sup 192}Ir for HDR prostate brachytherapy

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

Lymperopoulou, G.; Papagiannis, P.; Sakelliou, L.

2005-12-15

For the purpose of evaluating the use of {sup 169}Yb for prostate High Dose Rate brachytherapy (HDR), a hypothetical {sup 169}Yb source is assumed with the exact same design of the new microSelectron source replacing the {sup 192}Ir active core by pure {sup 169}Yb metal. Monte Carlo simulation is employed for the full dosimetric characterization of both sources and results are compared following the AAPM TG-43 dosimetric formalism. Monte Carlo calculated dosimetry results are incorporated in a commercially available treatment planning system (SWIFT{sup TM}), which features an inverse treatment planning option based on a multiobjective dose optimization engine. The qualitymore » of prostate HDR brachytherapy using the real {sup 192}Ir and hypothetical {sup 169}Yb source is compared in a comprehensive analysis of different prostate implants in terms of the multiobjective dose optimization solutions as well as treatment quality indices such as Dose Volume Histograms (DVH) and the Conformal Index (COIN). Given that scattering overcompensates for absorption in intermediate photon energies and distances in the range of interest to prostate HDR brachytherapy, {sup 169}Yb proves at least equivalent to {sup 192}Ir irrespective of prostate volume. This has to be evaluated in view of the shielding requirements for the {sup 169}Yb energies that are minimal relative to that for {sup 192}Ir.« less

The Problems with the Kappa Statistic as a Metric of Interobserver Agreement on Lesion Detection Using a Third-reader Approach When Locations Are Not Prespecified.

PubMed

Shih, Joanna H; Greer, Matthew D; Turkbey, Baris

2018-03-16

To point out the problems with Cohen kappa statistic and to explore alternative metrics to determine interobserver agreement on lesion detection when locations are not prespecified. Use of kappa and two alternative methods, namely index of specific agreement (ISA) and modified kappa, for measuring interobserver agreement on the location of detected lesions are presented. These indices of agreement are illustrated by application to a retrospective multireader study in which nine readers detected and scored prostate cancer lesions in 163 consecutive patients (n = 110 cases, n = 53 controls) using the guideline of Prostate Imaging Reporting and Data System version 2 on multiparametric magnetic resonance imaging. The proposed modified kappa, which properly corrects for the amount of agreement by chance, is shown to be approximately equivalent to the ISA. In the prostate cancer data, average kappa, modified kappa, and ISA equaled 30%, 55%, and 57%, respectively, for all lesions and 20%, 87%, and 87%, respectively, for index lesions. The application of kappa could result in a substantial downward bias in reader agreement on lesion detection when locations are not prespecified. ISA is recommended for assessment of reader agreement on lesion detection. Published by Elsevier Inc.

Automatic CT simulation optimization for radiation therapy: A general strategy.

PubMed

Li, Hua; Yu, Lifeng; Anastasio, Mark A; Chen, Hsin-Chen; Tan, Jun; Gay, Hiram; Michalski, Jeff M; Low, Daniel A; Mutic, Sasa

2014-03-01

In radiation therapy, x-ray computed tomography (CT) simulation protocol specifications should be driven by the treatment planning requirements in lieu of duplicating diagnostic CT screening protocols. The purpose of this study was to develop a general strategy that allows for automatically, prospectively, and objectively determining the optimal patient-specific CT simulation protocols based on radiation-therapy goals, namely, maintenance of contouring quality and integrity while minimizing patient CT simulation dose. The authors proposed a general prediction strategy that provides automatic optimal CT simulation protocol selection as a function of patient size and treatment planning task. The optimal protocol is the one that delivers the minimum dose required to provide a CT simulation scan that yields accurate contours. Accurate treatment plans depend on accurate contours in order to conform the dose to actual tumor and normal organ positions. An image quality index, defined to characterize how simulation scan quality affects contour delineation, was developed and used to benchmark the contouring accuracy and treatment plan quality within the predication strategy. A clinical workflow was developed to select the optimal CT simulation protocols incorporating patient size, target delineation, and radiation dose efficiency. An experimental study using an anthropomorphic pelvis phantom with added-bolus layers was used to demonstrate how the proposed prediction strategy could be implemented and how the optimal CT simulation protocols could be selected for prostate cancer patients based on patient size and treatment planning task. Clinical IMRT prostate treatment plans for seven CT scans with varied image quality indices were separately optimized and compared to verify the trace of target and organ dosimetry coverage. Based on the phantom study, the optimal image quality index for accurate manual prostate contouring was 4.4. The optimal tube potentials for patient sizes of 38, 43, 48, 53, and 58 cm were 120, 140, 140, 140, and 140 kVp, respectively, and the corresponding minimum CTDIvol for achieving the optimal image quality index 4.4 were 9.8, 32.2, 100.9, 241.4, and 274.1 mGy, respectively. For patients with lateral sizes of 43-58 cm, 120-kVp scan protocols yielded up to 165% greater radiation dose relative to 140-kVp protocols, and 140-kVp protocols always yielded a greater image quality index compared to the same dose-level 120-kVp protocols. The trace of target and organ dosimetry coverage and the γ passing rates of seven IMRT dose distribution pairs indicated the feasibility of the proposed image quality index for the predication strategy. A general strategy to predict the optimal CT simulation protocols in a flexible and quantitative way was developed that takes into account patient size, treatment planning task, and radiation dose. The experimental study indicated that the optimal CT simulation protocol and the corresponding radiation dose varied significantly for different patient sizes, contouring accuracy, and radiation treatment planning tasks.

Prostasomes--their effects on human male reproduction and fertility.

PubMed

Burden, H P; Holmes, C H; Persad, R; Whittington, K

2006-01-01

The prostate is a glandular male accessory sex organ vital for normal fertility. It provides the prostatic component of seminal plasma which nourishes and protects sperm following ejaculation. Prostasomes are small (40-500 nm) membrane-bound vesicles produced by epithelial cells lining the prostate acini and are a component of prostatic secretions. Although the existence of these particles has been known for many years, their full function and relevance to reproductive health are largely unknown. Proteomic studies have shown a wide range of proteins (enzymes, structural proteins and novel, unannotated proteins) present in or on the surface of prostasomes providing them with a diverse nature. Interestingly prostasomes are able to fuse with sperm, this event and the associated transfer of proteins lies at the heart of many of their proposed functions. Sperm motility is increased by the presence of prostasomes and their fusion prevents premature acrosome reactions. Prostasomes have been shown to aid protection of sperm within the female reproductive tract because of immunosuppressive, antioxidant and antibacterial properties. Clinically these functions imply a role for prostasomes in male factor infertility. However, the very functions that promote fertility may have negative connotations in later life; recent work has suggested that prostasomes are involved in prostate cancer. Clearly more work is needed to clarify the role of these novel particles and their impact on men's health.

Quality of Life, Psychological Functioning, and Treatment Satisfaction of Men Who Have Undergone Penile Prosthesis Surgery Following Robot-Assisted Radical Prostatectomy.

PubMed

Pillay, Brindha; Moon, Daniel; Love, Christopher; Meyer, Denny; Ferguson, Emma; Crowe, Helen; Howard, Nicholas; Mann, Sarah; Wootten, Addie

2017-12-01

Penile prosthesis surgery is last-line treatment to regaining erectile function after radical prostatectomy (RP) for localized prostate cancer. To assess quality of life, psychological functioning, and treatment satisfaction of men who underwent penile implantation after RP; the psychosocial correlates of treatment satisfaction and sexual function after surgery; and the relation between patients' and partners' ratings of treatment satisfaction. 98 consecutive patients who underwent penile implantation after RP from 2010 and 2015 and their partners were invited to complete a series of measures at a single time point. Of these, 71 patients and 43 partners completed measures assessing sexual function, psychological functioning, and treatment satisfaction. Proportions of patients who demonstrated good sexual function and satisfaction with treatment and clinical levels of anxiety and depression were calculated. Hierarchical regression analyses were conducted to determine psychosocial factors associated with patient treatment satisfaction and sexual function and patient-partner differences in treatment satisfaction. Patients completed the Expanded Prostate Cancer Index Composite Short Form (EPIC-26), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Prostate Cancer-Related Quality of Life Scale, Self-Esteem and Relationship Questionnaire (SEAR), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Partners completed the GAD-7, PHQ-9, EDITS (partner version), and SEAR. 94% of men reported satisfaction with treatment (EDITS score > 50). 77% of men reported good sexual function (EPIC-26 score > 60). Lower depression scores were associated with higher sexual confidence and sexual intimacy, and these were correlated with better treatment satisfaction and sexual function. Patients experienced higher sexual relationship satisfaction (median score = 90.6) than their partners (median score = 81.2), but there was no difference in treatment satisfaction between groups. Higher patient treatment satisfaction was more likely to be reported for couples whose depression scores were more similar. It is important to provide preoperative penile implant counseling and encourage patients to seek postoperative counseling if needed. This is one of the first Australian-based studies comprehensively assessing treatment satisfaction and psychosocial health of men after penile prosthesis surgery after RP. This was a retrospective cross-sectional study, so there is a possibility of recall bias, and causal associations could not be determined. Men in this Australian series who underwent penile prosthesis surgery after RP generally reported good sexual function and treatment satisfaction. Nevertheless, patient and partner mental health influenced their reported experience of the treatment. Pillay B, Moon D, Love C, et al. Quality of Life, Psychological Functioning, and Treatment Satisfaction of Men Who Have Undergone Penile Prosthesis Surgery Following Robot-Assisted Radical Prostatectomy. J Sex Med 2017;14:1612-1620. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

PubMed

Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

2015-02-01

Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Recurrence of Lower Urinary Tract Symptoms Following Prostate Artery Embolization for Benign Hyperplasia: Single Center Experience Comparing Two Techniques

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

Carnevale, Francisco Cesar, E-mail: francisco.carnevale@criep.com.br; Moreira, Airton Mota; Harward, Sardis Honoria

PurposeTo compare recurrence of lower urinary tract symptoms (LUTS) recurrence at 12 months following original prostate artery embolization (oPAE) or “proximal embolization first, then embolize distal” (PErFecTED) PAE for benign prostatic hyperplasia (BPH).Materials and Methods105 consecutive patients older than 45 years, with prostate size greater than 30 cm{sup 3}, International Prostate Symptom Score (IPSS) ≥ 8, quality of life (QoL) index ≥ 3, and refractory status or intolerance of medical management were prospectively enrolled between June 2008 and August 2013. The study was IRB-approved, and all patients provided informed consent. Patients underwent oPAE or PErFecTED PAE and were followed for at least 12 months. Technical success was definedmore » as bilateral embolization and clinical success (non-recurrence) was defined as removal of the Foley catheter in patients with urinary retention, IPSS < 8 and QoL index < 3 at 12 months of follow-up. Nonparametric statistics were used to compare the study groups due to the size of the study population and distributions of clinical data.Results97 patients had 12-month data and were categorized as oPAE without recurrence (n = 46), oPAE with recurrence (n  = 13), PErFecTED without recurrence (n  = 36), or PErFecTED with recurrence (n  = 2). Recurrence was significantly more common in oPAE patients (χ{sup 2}, p = 0.026). Unilateral embolization was significantly associated with recurrence among patients who underwent oPAE (χ{sup 2}, p = 0.032).ConclusionsBoth oPAE and PErFecTED PAE are safe and effective methods for treatment of LUTS, but PErFecTED PAE is associated with a significantly lower rate of symptom recurrence.« less

BPH: a tell-tale sign of prostate cancer? Results from the Prostate Cancer and Environment Study (PROtEuS).

PubMed

Boehm, Katharina; Valdivieso, Roger; Meskawi, Malek; Larcher, Alessandro; Sun, Maxine; Sosa, José; Blanc-Lapierre, Audrey; Weiss, Deborah; Graefen, Markus; Saad, Fred; Parent, Marie-Élise; Karakiewicz, Pierre I

2015-12-01

In a population-based case-control study (PROtEuS), we examined the association between prostate cancer (PCa) and (1) benign prostatic hypertrophy (BPH) history at any time prior to PCa diagnosis, (2) BPH-history reported at least 1 year prior to interview/diagnosis (index date) and (3) exposure to BPH-medications. Cases were 1933 men with incident prostate cancer diagnosed across Montreal French hospitals between 2005 and 2009. Population controls were 1994 men from the same age distribution and residential area. In-person interviews collected socio-demographic characteristics and medical history, e.g., BPH diagnosis, duration and treatment, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. A BPH-history was associated with an increased risk of PCa (OR 1.37 [95 % CI 1.16-2.61]), more pronounced for low-grade PCa (Gleason ≤6: OR 1.54 [1.26-1.87]; Gleason ≥7: OR 1.05 [0.86-1.27]). The association was not significant when BPH-history diagnosis was more than 1 year prior to index date, except for low-grade PCa (OR 1.29 [1.05-1.60]). Exposure to 5α reductase inhibitors (5α-RI) resulted in a decreased risk of overall PCa (OR 0.62 [0.42-0.92]), particularly for intermediate- to high-grade PCa (Gleason ≤6: OR 0.70 [0.43-1.14]; Gleason ≥7: OR 0.43 [0.26-0.72]). Adjusting for PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. BPH-history was associated with an increased PCa risk, which disappeared, when BPH-history did not include BPH diagnosis within the previous year. Our results also suggest that 5α-RI exposure exerts a protective effect on intermediate and high-grade PCa.

Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.

PubMed

Ahearn, Thomas U; Tchrakian, Nairi; Wilson, Kathryn M; Lis, Rosina; Nuttall, Elizabeth; Sesso, Howard D; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei A; Finn, Stephen; Shui, Irene M

2016-06-01

Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression. We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. A validated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. Participants were followed up or cancer-specific mortality or development of metastatic disease. On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0). Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.

Statin use and fatal prostate cancer: a matched case-control study.

PubMed

Marcella, Stephen W; David, Alice; Ohman-Strickland, Pamela A; Carson, Jeffery; Rhoads, George G

2012-08-15

Statins are some of the most commonly prescribed medications in medical practice, and prostate cancer is the most common malignancy among men. Although there has been no consistent evidence that statins affect cancer incidence, including prostate cancer, several reports suggest they may decrease the rate of advanced prostate cancer. However, no study to date has specifically examined statin use and prostate cancer mortality. The authors conducted this population-based case-control investigation to examine this association. This was a matched case-control study. Cases were residents of New Jersey ages 55 to 79 years who died from prostate cancer between 1997 and 2000. The cases were matched individually to population-based controls by 5-year age group and race. Medication data were obtained identically for cases and controls from blinded medical chart review. Conditional logistic regression was used to adjust for confounders. In total, 718 cases were identified, and cooperation was obtained from 77% of their spouses (N = 553). After a review of medical records, 387 men were eligible, and 380 were matched to a control. The unadjusted odds ratio was 0.49 (95% confidence interval, 0.34-0.70) and decreased to 0.37 (P < .0001) after adjusting for education, waist size, body mass index, comorbidities, and antihypertensive medication. There was little difference between lipophilic and hydrophilic statins, but more risk reduction was noted for high-potency statins (73%; P < .0001) compared with low-potency statins (31%; P = .32). Statin use was associated with substantial protection against prostate cancer death, adding to the epidemiologic evidence for an inhibitory effect on prostate cancer. Copyright © 2011 American Cancer Society.

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

PubMed Central

Vos, Larissa J; Janoski, Michele; Wachowicz, Keith; Yahya, Atiyah; Boychak, Oleksandr; Amanie, John; Pervez, Nadeem; Parliament, Matthew B; Pituskin, Edith; Fallone, B Gino; Usmani, Nawaid

2016-01-01

AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods. PMID:27158428

Androgen receptor and chemokine receptors 4 and 7 form a signaling axis to regulate CXCL12-dependent cellular motility.

PubMed

Hsiao, Jordy J; Ng, Brandon H; Smits, Melinda M; Wang, Jiahui; Jasavala, Rohini J; Martinez, Harryl D; Lee, Jinhee; Alston, Jhullian J; Misonou, Hiroaki; Trimmer, James S; Wright, Michael E

2015-03-31

Identifying cellular signaling pathways that become corrupted in the presence of androgens that increase the metastatic potential of organ-confined tumor cells is critical to devising strategies capable of attenuating the metastatic progression of hormone-naïve, organ-confined tumors. In localized prostate cancers, gene fusions that place ETS-family transcription factors under the control of androgens drive gene expression programs that increase the invasiveness of organ-confined tumor cells. C-X-C chemokine receptor type 4 (CXCR4) is a downstream target of ERG, whose upregulation in prostate-tumor cells contributes to their migration from the prostate gland. Recent evidence suggests that CXCR4-mediated proliferation and metastasis of tumor cells is regulated by CXCR7 through its scavenging of chemokine CXCL12. However, the role of androgens in regulating CXCR4-mediated motility with respect to CXCR7 function in prostate-cancer cells remains unclear. Immunocytochemistry, western blot, and affinity-purification analyses were used to study how androgens influenced the expression, subcellular localization, and function of CXCR7, CXCR4, and androgen receptor (AR) in LNCaP prostate-tumor cells. Moreover, luciferase assays and quantitative polymerase chain reaction (qPCR) were used to study how chemokines CXCL11 and CXCL12 regulate androgen-regulated genes (ARGs) in LNCaP prostate-tumor cells. Lastly, cell motility assays were carried out to determine how androgens influenced CXCR4-dependent motility through CXCL12. Here we show that, in the LNCaP prostate-tumor cell line, androgens coordinate the expression of CXCR4 and CXCR7, thereby promoting CXCL12/CXCR4-mediated cell motility. RNA interference experiments revealed functional interactions between AR and CXCR7 in these cells. Co-localization and affinity-purification experiments support a physical interaction between AR and CXCR7 in LNCaP cells. Unexpectedly, CXCR7 resided in the nuclear compartment and modulated AR-mediated transcription. Moreover, androgen-mediated cell motility correlated positively with the co-localization of CXCR4 and CXCR7 receptors, suggesting that cell migration may be linked to functional CXCR4/CXCR7 heterodimers. Lastly, CXCL12-mediated cell motility was CXCR7-dependent, with CXCR7 expression required for optimal expression of CXCR4 protein. Overall, our results suggest that inhibition of CXCR7 function might decrease the metastatic potential of organ-confined prostate cancers.

Lectin-Like Oxidized LDL Receptor-1 Is an Enhancer of Tumor Angiogenesis in Human Prostate Cancer Cells

PubMed Central

González-Chavarría, Iván; Cerro, Rita P.; Parra, Natalie P.; Sandoval, Felipe A.; Zuñiga, Felipe A.; Omazábal, Valeska A.; Lamperti, Liliana I.; Jiménez, Silvana P.; Fernandez, Edelmira A.; Gutiérrez, Nicolas A.; Rodriguez, Federico S.; Onate, Sergio A.; Sánchez, Oliberto; Vera, Juan C.; Toledo, Jorge R.

2014-01-01

Altered expression and function of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been associated with several diseases such as endothelial dysfunction, atherosclerosis and obesity. In these pathologies, oxLDL/LOX-1 activates signaling pathways that promote cell proliferation, cell motility and angiogenesis. Recent studies have indicated that olr1 mRNA is over-expressed in stage III and IV of human prostatic adenocarcinomas. However, the function of LOX-1 in prostate cancer angiogenesis remains to be determined. Our aim was to analyze the contribution of oxLDL and LOX-1 to tumor angiogenesis using C4-2 prostate cancer cells. We analyzed the expression of pro-angiogenic molecules and angiogenesis on prostate cancer tumor xenografts, using prostate cancer cell models with overexpression or knockdown of LOX-1 receptor. Our results demonstrate that the activation of LOX-1 using oxLDL increases cell proliferation, and the expression of the pro-angiogenic molecules VEGF, MMP-2, and MMP-9 in a dose-dependent manner. Noticeably, these effects were prevented in the C4-2 prostate cancer model when LOX-1 expression was knocked down. The angiogenic effect of LOX-1 activated with oxLDL was further demonstrated using the aortic ring assay and the xenograft model of tumor growth on chorioallantoic membrane of chicken embryos. Consequently, we propose that LOX-1 activation by oxLDL is an important event that enhances tumor angiogenesis in human prostate cancer cells. PMID:25170920

Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

DTIC Science & Technology

2013-09-01

objective is to develop dendrimer -based theranostic agent with prostate cancer specificity and positron emission tomography imaging capability that...The goal of this project is to construct dendrimer nanoconjuate containing a prostate specific cell permeation peptide, peptide therapeutic(s) and...bifunctional chelator for PET imaging. Dr. Simanek’s laboratory will make dendrimers that bear functional handles for conjugation with imaging

Role of PSMA in Aberrant Cell Cycle Progression in Prostate Cancer

DTIC Science & Technology

2004-12-01

playing a role in nutrient uptake, and a peptidase involved in signal transduction in prostate epithelial cells. Insights into possible functions of PSMA...should improve the diagnostic and therapeutic values of this clinically important molecule. prostate cancer; receptor; peptidase ; endocytosis 2 OVERVIEW... peptidase activities hydrolyze gamma-peptide bonds between N-acetylaspartate and glutamate in the abundant neuropeptide N-acetylaspartylglutamate

Surgical anatomy of the prostate in the era of radical robotic prostatectomy.

PubMed

Walz, Jochen; Graefen, Markus; Huland, Hartwig

2011-05-01

New insights in the anatomy of the prostate and the surrounding tissue evolve the technique of radical prostatectomy for the treatment of prostate cancer. Regarding the course of the erectile nerves along the prostate, recent studies confirmed the presence of parasympathetic pro-erectile nerve fibers at the anterolateral aspect of the prostate. Another study of intraoperative electrostimulation of those nerves confirmed an increase in intracavernosal pressure by stimulations between the 1 and 3 o'clock position. Therefore, it is very likely that these anterior nerve fibers have an effect on erectile function. Regarding the urethral sphincter in the male, a study showed no attachment of the external sphincter to the levator ani muscle, probably resulting in an absence of a levator ani support to the continence mechanism. The male urinary sphincter seems to be in isolation responsible for urinary continence. The nerve fibers at the anterolateral aspect of the prostate seem to participate in erectile function, which renders the concept of a high anterior release during nerve sparing beneficial. The isolated urinary sphincter mechanism results in the need to conserve as much urethral length as possible during radical prostatectomy to avoid urinary incontinence.

Epidermal growth factor receptor signaling promotes metastatic prostate cancer through microRNA-96-mediated downregulation of the tumor suppressor ETV6.

PubMed

Tsai, Yuan-Chin; Chen, Wei-Yu; Siu, Man Kit; Tsai, Hong-Yuan; Yin, Juan Juan; Huang, Jiaoti; Liu, Yen-Nien

2017-01-01

It has been suggested that ETV6 serves as a tumor suppressor; however, its molecular regulation and cellular functions remain unclear. We used prostate cancer as a model system and demonstrated a molecular mechanism in which ETV6 can be regulated by epidermal growth factor receptor (EGFR) signaling through microRNA-96 (miR-96)-mediated downregulation. In addition, EGFR acts as a transcriptional coactivator that binds to the promoter of primary miR-96 and transcriptionally regulates miR-96 levels. We analyzed two sets of clinical prostate cancer samples, confirmed association patterns that were consistent with the EGFR-miR-96-ETV6 signaling model and demonstrated that the reduced ETV6 levels were associated with malignant prostate cancer. Based on results derived from multiple approaches, we identified the biological functions of ETV6 as a tumor suppressor that inhibits proliferation and metastasis in prostate cancer. We present a molecular mechanism in which EGFR activation leads to the induction of miR-96 expression and suppression of ETV6, which contributes to prostate cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PRKC-ζ Expression Promotes the Aggressive Phenotype of Human Prostate Cancer Cells and Is a Novel Target for Therapeutic Intervention

PubMed Central

Yao, Sheng; Bee, Alix; Brewer, Daniel; Dodson, Andrew; Beesley, Carol; Ke, Youqiang; Ambroisine, Laurence; Fisher, Gabrielle; Møller, Heinrich; Dickinson, Tim; Gerard, Patricia; Lian, Lu-Yu; Risk, Janet; Lane, Brian; Smith, Paul; Reuter, Victor; Berney, Daniel; Gosden, Christine; Scardino, Peter; Cuzick, Jack; Djamgoz, Mustafa B.A.; Cooper, Colin; Foster, Christopher S.

2010-01-01

We show protein kinase C–zeta (PKC-ζ) to be a novel predictive biomarker for survival from prostate cancer (P < 0.001). We also confirm that transcription of the PRKC-ζ gene is crucial to the malignant phenotype of human prostate cancer. Following siRNA silencing of PRKC-ζ in PC3-M prostate cancer cells, stable transfectant cell line si-PRKC-ζ-PC3-MT1-6 is phenotypically nonmalignant in vitro and in vivo. Genome-wide expression analysis identified 373 genes to be differentially expressed in the knockdown cells and 4 key gene networks to be significantly perturbed during phenotype modulation. Functional interconnection between some of the modulated genes is revealed, although these may be within different regulatory pathways, emphasizing the complexity of their mutual interdependence. Genes with altered expression following PRKC-ζ knockdown include HSPB1, RAD51, and ID1 that we have previously described to be critical in prostatic malignancy. Because expression of PRKC-ζ is functionally involved in promoting the malignant phenotype, we propose PKC-ζ as a novel and biologically relevant target for therapeutic intervention in prostate cancer. PMID:21779455

Recent advances in prostate development and links to prostatic diseases

PubMed Central

Powers, Ginny L.

2013-01-01

The prostate is a branched ductal-acinar gland that is part of the male reproductive tract. Prostate development depends upon the integration of steroid hormone signals, paracrine interactions between the stromal and epithelial tissue layers, and the actions of cell autonomous factors. Several genes and signalling pathways are known to be required for one or more steps of prostate development including epithelial budding, duct elongation, branching morphogenesis, and/or cellular differentiation. Recent progress in the field of prostate development has included the application of genome-wide technologies including serial analysis of gene expression (SAGE), expression profiling microarrays, and other large scale approaches to identify new genes and pathways that are essential for prostate development. The aggregation of experimental results into online databases by organized multi-lab projects including the Genitourinary Developmental Molecular Atlas Project (GUDMAP) has also accelerated the understanding of molecular pathways that function during prostate development and identified links between prostate anatomy and molecular signaling. Rapid progress has also recently been made in understanding the nature and role of candidate stem cells in the developing and adult prostate. This has included the identification of putative prostate stem cell markers, lineage tracing, and organ reconstitution studies. However, several issues regarding their origin, precise nature, and possible role(s) in disease remain unresolved. Nevertheless, several links between prostatic developmental mechanisms and the pathogenesis of prostatic diseases including benign prostatic hyperplasia and prostate cancer have led to recent progress on targeting developmental pathways as therapeutic strategies for these diseases. PMID:23335485

MicroRNA-613 represses prostate cancer cell proliferation and invasion through targeting Frizzled7

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

Ren, Wei; Department of Urology, Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710068; Li, Chan

A growing number of studies have indicated that microRNAs (miRNAs) are critical regulators of carcinogenesis and cancer progression and may serve as potential therapeutic tools for cancer therapy. Frizzled7 (Fzd7), the most important receptor of the Wnt signaling pathway, is extensively involved in cancer development and progression. However, the role of Fzd7 in prostate cancer remains unclear. In this study, we aimed to explore the expression of Fzd7 in prostate cancer and test whether modulating Fzd7 expression by miR-613 would have an impact on prostate cancer cell proliferation and invasion. We found that Fzd7 was highly expressed in prostate cancermore » cell lines. Through bioinformatics analysis, Fzd7 was predicted as a target gene of miR-613, which was validated by dual-luciferase reporter assays, real-time quantitative polymerase chain reaction and Western blot analysis. By gain of function experiments, we showed that overexpression of miR-613 significantly suppressed prostate cancer cell proliferation and invasion. Furthermore, miR-613 overexpression markedly downregulated the Wnt signaling pathway. Through a rescue experiment, we showed that overexpression of Fzd7 could abrogate the inhibitory effect of miR-613 on cell proliferation and invasion as well as Wnt signaling. Additionally, these results were further strengthened by data showing that miR-613 was significantly downregulated in prostate cancer tissues, exhibiting an inverse correlation with Fzd7 expression. In conclusion, our study suggests that miR-613 functions as a tumor suppressor, partially through targeting Fzd7, and is a potential therapeutic target for prostate cancer. - Highlights: • Fzd7 was highly expressed in prostate cancer. • Fzd7 was predicted as a target gene of miR-613. • MiR-613 negatively regulated prostate cancer by Fzd7. • MiR-613 inversely correlated with Fzd7 in prostate cancer.« less

68Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients.

PubMed

Liu, Chen; Liu, Teli; Zhang, Ning; Liu, Yiqiang; Li, Nan; Du, Peng; Yang, Yong; Liu, Ming; Gong, Kan; Yang, Xing; Zhu, Hua; Yan, Kun; Yang, Zhi

2018-05-02

The purpose of this study was to investigate the performance of 68 Ga-PSMA-617 PET/CT in predicting risk stratification and metastatic risk of prostate cancer. Fifty newly diagnosed patients with prostate cancer as confirmed by needle biopsy were continuously included, 40 in a train set and ten in a test set. 68 Ga-PSMA-617 PET/CT and clinical data of all patients were retrospectively analyzed. Semi-quantitative analysis of PET images provided maximum standardized uptake (SUVmax) of primary prostate cancer and volumetric parameters including intraprostatic PSMA-derived tumor volume (iPSMA-TV) and intraprostatic total lesion PSMA (iTL-PSMA). According to prostate cancer risk stratification criteria of the NCCN Guideline, all patients were simplified into a low-intermediate risk group or a high-risk group. The semi-quantitative parameters of 68 Ga-PSMA-617 PET/CT were used to establish a univariate logistic regression model for high-risk prostate cancer and its metastatic risk, and to evaluate the diagnostic efficacy of the predictive model. In the train set, 30/40 (75%) patients had high-risk prostate cancer and 10/40 (25%) patients had low-to-moderate-risk prostate cancer; in the test set, 8/10 (80%) patients had high-risk prostate cancer while 2/10 (20%) had low-intermediate risk prostate cancer. The univariate logistic regression model established with SUVmax, iPSMA-TV and iTL-PSMA could all effectively predict high-risk prostate cancer; the AUC of ROC were 0.843, 0.802 and 0.900, respectively. Based on the test set, the sensitivity and specificity of each model were 87.5% and 50% for SUVmax, 62.5% and 100% for iPSMA-TV, and 87.5% and 100% for iTL-PSMA, respectively. The iPSMA-TV and iTL-PSMA-based predictive model could predict the metastatic risk of prostate cancer, the AUC of ROC was 0.863 and 0.848, respectively, but the SUVmax-based prediction model could not predict metastatic risk. Semi-quantitative analysis indexes of 68 Ga-PSMA-617 PET/CT imaging can be used as "imaging biomarkers" to predict risk stratification and metastatic risk of prostate cancer.

Finasteride Reduces the Risk of Low-Grade Prostate Cancer in Men 55 and Older

MedlinePlus

... the researchers gathered using data from the Social Security Death Index (SSDI) from the time the trial ... Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & Copyright Syndication Services Website Linking U.S. Department ...

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

PubMed

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

2015-01-01

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

Influence of prostatic calculi on lower urinary tract symptoms in middle-aged men.

PubMed

Kim, Woong Bin; Doo, Seung Whan; Yang, Won Jae; Song, Yun Seob

2011-08-01

To investigate the incidence and echographic patterns of prostatic calculi, and to determine whether the presence of prostatic calculi is an associated factor for moderate lower urinary tract symptom (LUTS) in middle-aged men. Between October 2007 and June 2010, 1575 consecutive ostensibly healthy Korean men aged 40-59 years visited the health promotion center for a routine check-up and were enrolled. All men had a complete history, physical examination, and an international prostate symptom score (IPSS) questionnaire. Based on the echo patterns of the prostatic calculi by transrectal ultrasound, the men were divided in 3 groups-no calculi; type A calculi (discrete, small echoes); and type B calculi (large masses of multiple echoes, much coarser). In total, 1563 men were included. Measurable calcifications in the prostate gland were found in 799 men (51.1%). Small calculi (type A) were found in 615 men (39.3%) and large calculi (type B) were found in 184 men (11.8%). In the multivariate analysis, old age (>50 years), obesity (body mass index >25 kg/m(2)), and large calculi (type B) were significant associated factors for higher IPSS ≥8. The likelihood of IPSS being ≥8 was related to large calculi group with a 1.784-fold increase in risk over no and small calculi (P <.001). The presence of large prostatic calculi is a significant associated factor of moderate LUTS, whereas there was no statistical difference in IPSS analyzed between the no calculi and small calculi group. Copyright © 2011 Elsevier Inc. All rights reserved.

Prostate-specific antigen testing in inner London general practices: are those at higher risk most likely to get tested?

PubMed

Nderitu, Paul; Van Hemelrijck, Mieke; Ashworth, Mark; Mathur, Rohini; Hull, Sally; Dudek, Alexandra; Chowdhury, Simon

2016-07-12

To investigate the association between factors influencing prostate-specific antigen (PSA) testing prevalence including prostate cancer risk factors (age, ethnicity, obesity) and non-risk factors (social deprivation and comorbidity). A cross-sectional database of 136 inner London general practices from 1 August 2009 to 31 July 2014. Men aged ≥40 years without prostate cancer were included (n=150 481). Logistic regression analyses were used to estimate the association between PSA testing and age, ethnicity, social deprivation, body mass index (BMI) and comorbidity while adjusting for age, benign prostatic hypertrophy, prostatitis and tamsulosin or finasteride use. PSA testing prevalence was 8.2% (2013-2014), and the mean age was 54 years (SD 11). PSA testing was positively associated with age (OR 70-74 years compared to 40-44 years: 7.34 (95% CI 6.82 to 7.90)), ethnicity (black) (OR compared to white: 1.78 (95% CI 1.71 to 1.85)), increasing BMI and cardiovascular comorbidity. Testing was negatively associated with Chinese ethnicity and with increasing social deprivation. PSA testing among black patients was higher compared to that among white patients, which differs from lower testing rates seen in previous studies. PSA testing was positively associated with prostate cancer risk factors and non-risk factors. Association with non-risk factors may increase the risk of unnecessary invasive diagnostic procedures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/