Prostate Cancer and Prostatic Diseases (PROSTATE CANCER P D )

Publisher: Nature Publishing Group

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Covers current developments relating to all aspects of prostate cancer research.

Impact factor 2.83

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    Impact factor
  • 5-year impact
    2.26
  • Cited half-life
    5.10
  • Immediacy index
    0.48
  • Eigenfactor
    0.00
  • Article influence
    0.77
  • Website
    Prostate Cancer and Prostatic Diseases website
  • Other titles
    Prostate cancer and prostatic diseases (Online)
  • ISSN
    1365-7852
  • OCLC
    42458934
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

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Nature Publishing Group

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:The diffusion of minimally invasive radical prostatectomy (MIRP) in the United States may have led to adverse patient outcomes due to rapid surgeon adoption and collective inexperience. We hypothesized that throughout the early period of minimally invasive surgery, MIRP patients had inferior outcomes as compared with those who had open radical prostatectomy (ORP).Methods:We used the Surveillance, Epidemiology and End Results-Medicare dataset and identified men who had ORP and MIRP for prostate cancer from 2003-2009. Study endpoints were receipt of subsequent cancer treatment, and evidence of postoperative voiding dysfunction, erectile dysfunction (ED) and bladder outlet obstruction. We used proportional hazards regression to estimate the impact of surgical approach on each endpoint, and included an interaction term to test for modification of the effect of surgical approach by year of surgery.Results:ORP (n=5362) and MIRP (n=1852) patients differed in their clinical and demographic characteristics. Controlling for patient characteristics and surgeon volume, there was no difference in subsequent cancer treatments (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76-1.05), although MIRP was associated with a higher risk of voiding dysfunction (HR 1.31, 95% CI 1.20-1.43) and ED (HR 1.43, 95% CI 1.31-1.56), but a lower risk of bladder outlet obstruction (HR 0.86, 95% CI 0.75-0.97). There was no interaction between approach and year for any outcome. When stratifying the analysis by year, MIRP consistently had higher rates of ED and voiding dysfunction with no substantial improvement over time.Conclusions:MIRP patients had adverse urinary and sexual outcomes throughout the diffusion of minimally invasive surgery. This may have been a result of the rapid adoption of robotic surgery with inadequate surgeon preparedness.Prostate Cancer and Prostatic Disease advance online publication, 16 December 2014; doi:10.1038/pcan.2014.49.
    Prostate Cancer and Prostatic Diseases 12/2014;
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    ABSTRACT: Background:To examine whether diagnostic biopsy (B1), for patients on active surveillance (AS) for prostate cancer, performed at an outside referral centre (external) compared with our in-house tertiary center (internal), increased the risk of re-classification on the second (confirmatory) biopsy (B2).Methods:Patients on AS were identified from our tertiary center database (1997-2012) with PSA<10, Gleason sum (GS) ⩽6, clinical stage ⩽cT2, ⩽3 positive cores, <50% of single core involved, age ⩽75 years and having a B2. Patients who had <10 cores at B1 and delay in B2 >24 mo were excluded. Depending on center where B1 was performed, men were dichotomized to internal or external groups. All B2 were performed internally. Multivariate logistic regression examined if external B1 was a predictor of re-classification at B2.Results:A total of 375 patients were divided into external (n=71, 18.9%) and internal groups (n=304, 81.1%). At B2, more men in the external group re-classified (26.8%) compared with the internal group (13.8%)(P=0.008). On multivariate analysis, external B1 predicted grade-related re-classification (odds ratio (OR) 4.14, confidence interval (CI) 2.01-8.54, P<0.001) and volume-related re-classification (OR 3.43, CI 1.87-6.25, P<0.001). Other significant predictors for grade-related re-classification were age (OR 2.13 per decade, CI 1.32-3.57, P<0.001), PSA density (OR 2.56 per unit, CI 1.44-4.73, P<0.001), maximum % core involvement (OR 1.04 per percentage point, CI 1.01-1.09, P=0.02) and time between B1 and B2 (OR 1.43 per 6 months, CI 1.21-1.71, P<0.001).Conclusion:At our institution, patients on AS who had their initial B1 performed externally were more likely to have adverse pathological features and re-classify on internal B2.Prostate Cancer and Prostatic Disease advance online publication, 9 December 2014; doi:10.1038/pcan.2014.48.
    Prostate Cancer and Prostatic Diseases 12/2014;
  • Prostate Cancer and Prostatic Diseases 11/2014; Accepted for publication.
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    ABSTRACT: Background:To determine the effect of statins and metformin in combination on biochemical recurrence (BCR) among diabetic men undergoing radical prostatectomy (RP).Methods:Diabetic men undergoing RP at our institution from January 1995 to March 2012 were retrospectively reviewed. Recipients of adjuvant radiation or hormonal therapy were excluded. Statin and/or metformin use was determined through review of electronic records. BCR-free survival was plotted using Kaplan-Meier analysis, and the effect of statins and metformin on BCR was assessed via a multivariate Cox proportional hazards model.Results:Seven hundred and sixty-seven men met the inclusion criteria. Seventy-six (9.9%) were users of statins only, 56 (7.3%) were users of metformin only and 42 (5.5%) were dual users. Median follow-up time was 27 months. Dual users were less likely than nonusers or users of either medication alone to have a biopsy Gleason sum of 8-10 (P=0.033), and tended towards a lower rate of pathological T stage of pT3 or higher (P=0.064). Dual users had the highest 2-year and 5-year BCR-free survival, although this was not statistically significant (P=0.205). On multivariate regression, neither statin nor metformin use alone was significantly associated with BCR-free survival. However, their interaction led to a significantly lower BCR risk than would be expected from each medication's independent effects (hazard ratio=0.2; P=0.037).Conclusions:The combination of statins and metformin in men undergoing RP for prostate cancer (PCa) may be associated with a lower BCR risk than would be predicted based on the independent effects of both medications. A synergism between these two agents is biologically plausible based on our current understanding of their diverse molecular pathways of action. The results of future clinical trials involving the use of either medication in men with PCa should be carefully assessed for confirmatory evidence of such a relationship.Prostate Cancer and Prostatic Disease advance online publication, 18 November 2014; doi:10.1038/pcan.2014.47.
    Prostate Cancer and Prostatic Diseases 11/2014;
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    ABSTRACT: Background:Partner of SLD5 1 (PSF1) is an evolutionarily conserved DNA replication factor. Previous studies have suggested that transcriptional activity of the PSF1 gene correlated with malignancy of cancer cells. The objective of the current study was to evaluate the relationship between PSF1 expression and the clinical features of prostate cancer.Methods:We determined the expression of PSF1 in 120 needle biopsy samples of prostate cancer by immunohistochemistry. We divided patients into PSF1-positive or -negative groups and analyzed the relationships between the expression of PSF1, the Gleason score, PSA level, TNM classification and prognosis.Results:Our results showed that the PSF1 expression correlated significantly with PSA values at diagnosis (P=0.0028), with tumor grade (P<0.0001), and with clinical stage (P=0.0005). Moreover, the PSF1 expression correlated significantly with overall survival (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.17-15.8; P=0.003) and progression-free survival in 99 consecutive patients with prostate cancer. Noteworthy, the prognosis of PSF1-positive cases was also worse in patients with a Gleason score of 8-10 (HR 3.7; 95% CI 1.28-13.43; P=0.0143). Limitations include that this study had a retrospective design, that patients in the study were heterogeneous and included those with early and advanced cancer, and that small tumor fragments may not be representative of the entire carcinoma.Conclusions:PSF1 is expressed in high-grade prostate cancer and may be a useful biomarker to identify patients with a poor prognosis at the time of diagnosis.Prostate Cancer and Prostatic Disease advance online publication, 18 November 2014; doi:10.1038/pcan.2014.46.
    Prostate Cancer and Prostatic Diseases 11/2014;
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    ABSTRACT: Background:The role of global DNA methylation in prostate cancer (PCa) remains largely unknown. Our aim was to summarize evidence on the role of global DNA hypomethylation in PCa development and progression.Methods:We searched PubMed through December 2013 for all studies containing information on global methylation levels in PCa tissue and at least one non-tumor comparison tissue and/or studies reporting association between global methylation levels in PCa tissue and survival, disease recurrence or at least one clinicopathological prognostic factor. We summarized results using non-parametric comparisons and P-value summary methods.Results:We included 15 studies in the review: 6 studies with both diagnostic and prognostic information, 5 studies with only diagnostic information and 4 studies with only prognostic information. Quantitative meta-analysis was not possible because of the large heterogeneity in molecular techniques, types of tissues analyzed, aims and study designs. Summary statistical tests showed association of DNA hypomethylation with PCa diagnosis (P<0.006) and prognosis (P<0.001). Restriction to studies assessing 5-methylcytosine or long interspersed nucleotide element-1 revealed results in the same direction. Analyses restricted to specific clinicopathological features showed association with the presence of metastasis and tumor stage in all tests with P<0.03, and no association with Gleason score (all tests P>0.1 except for the weighted Z-test, P=0.05).Conclusion:DNA hypomethylation was associated with PCa development and progression. However, due to the heterogeneity and small sample sizes of the included studies, along with the possibility of publication bias, this association requires additional assessment.Prostate Cancer and Prostatic Disease advance online publication, 11 November 2014; doi:10.1038/pcan.2014.45.
    Prostate Cancer and Prostatic Diseases 11/2014;
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    ABSTRACT: BACKGROUND:Multiple phase-2 trials in men with biochemically-recurrent prostate cancer (BRPC) have assessed the impact of nonhormonal agents on PSA kinetics. We have previously demonstrated that changes in PSA kinetics correlate with metastasis-free survival; however, it is unknown whether these changes also correlate with overall survival (OS).METHODS:We performed a combined retrospective analysis of 146 men with BRPC treated on phase-2 trials using one of four investigational drugs: lenalidomide (n=60), marimastat (n=39), ATN-224 (n=22) and imatinib (n=25). We examined factors influencing OS, including within-subject changes in PSA kinetics (PSA slope, PSA doubling time and PSA velocity), before and 6 months after treatment initiation.RESULTS:After a median follow-up of 83.1 months, 49 of 146 men had died. In univariate Cox regression analysis, two factors were associated with OS: baseline PSA velocity and change in PSA velocity on therapy. In a landmark multivariable model, stratified by study (which controlled for age, Gleason score, type of local therapy and use of androgen-deprivation therapy prior to metastases), baseline PSA velocity and increase in PSA velocity on therapy remained independent predictors of OS. Median OS for men with an increase in PSA velocity on treatment was 115.4 months and was not reached for men with a decrease in PSA velocity (hazard ratio=0.47, 95% confidence interval 0.25-0.88; P=0.02).CONCLUSIONS:This hypothesis-generating study suggests that within-subject changes in PSA velocity after initiation of nonhormonal therapy may correlate with OS in men with BRPC. If validated in prospective trials, change in PSA velocity may represent a reasonable intermediate end point for screening new agents in these patients.Prostate Cancer and Prostatic Disease advance online publication, 11 November 2014; doi:10.1038/pcan.2014.44.
    Prostate Cancer and Prostatic Diseases 11/2014;
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    ABSTRACT: Background:To examine the impact of race on treatment regret among men with recurrent prostate cancer after surgery or radiation.Methods:The prospective Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry was used to study a cohort of 484 men with biochemically recurrent prostate cancer after radical prostatectomy, external beam radiation or brachytherapy. Multivariable logistic regression was used to model the association between race and treatment regret and to determine whether there was an interaction between race and sexual problems after treatment with regards to treatment regret.Results:Black men (N=78) were significantly more likely to have treatment regret when compared with non-black men (N=406; 21.8% versus 12.6%) on univariable analysis (odds ratio (OR) 1.94; 95% confidence interval 1.05-3.56; P=0.03). On multivariable analysis, black race trended towards but was no longer significantly associated with an increase in treatment regret (adjusted OR (AOR) 1.84 (0.95-3.58); P=0.071). There was an interaction between race and sexual problems after treatment (Pinteraction=0.02) such that among those without sexual problems, black men had more treatment regret than non-black men (26.7% versus 8.4%: AOR 4.68 (1.73-12.63); P=0.002), whereas among those with sexual problems, there was no difference in treatment regret between black and non-black men (18.8% versus 17.3%: AOR 1.04 (0.44-2.46); P=0.93).Conclusions:Among men with recurrent prostate cancer after surgery or radiation, black men were nearly twice as likely to experience treatment regret. Treating physicians should ensure that patients are fully apprised of the pros and cons of all treatment options to reduce the risk of subsequent regret.Prostate Cancer and Prostatic Disease advance online publication, 28 October 2014; doi:10.1038/pcan.2014.42.
    Prostate Cancer and Prostatic Diseases 10/2014;
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    ABSTRACT: BACKGROUND:The significance of lymphovascular invasion (LVI) remains controversial, and the association of LVI with biochemical relapse was investigated in men treated with radical prostatectomy according to pathological results.METHODS:Data from 1268 patients undergoing radical prostatectomy between 2000 and 2009 were retrospectively reviewed. Clinicopathological variables were compared between LVI-negative and LVI-positive patients. Multivariate analyses by Cox proportional hazard model and Kaplan-Meier method were performed to identify risk factors for biochemical relapse in all patients, patients with pT2N0 and pT2N0 negative resection margin (RM).RESULTS:LVI information was available in 1160 cases, and LVI was seen in 121 cases (10.4%). Clinicopathological variables were significantly worse in LVI-positive patients than in LVI-negative patients. On multivariate analyses, PSA⩾10 ng ml(-1), pathological Gleason score ⩾8, pathological T stage ⩾3, lymph node metastasis, positive RM and LVI were independent predictors for biochemical relapse in all patients. In patients with pT2N0, PSA⩾10 ng ml(-1), pathological Gleason score ⩾8, positive RM and LVI were independent predictors for biochemical relapse. In patients with pT2N0 negative RM, LVI and pathological Gleason score ⩾8 were independent predictors for biochemical relapse (LVI; hazard ratio 3.809, 95% confidence interval 1.900-7.635, P-value<0.001, Gleason score ⩾8; hazard ratio 2.189, 95% confidence interval 1.199-3.999, P-value=0.011). With a median follow-up of 50 months, 5-year biochemical relapse-free survival in patients with pT2N0 negative RM was 95.7% in those with negative LVI in comparison to 85.3% in those with positive LVI (P<0.001, log rank).CONCLUSIONS:LVI was consistently a significant predictor for biochemical relapse after radical prostatectomy in not only all patients but also in patients with pT2N0 and pT2N0 negative RM. These results strongly support the significance of LVI as a predictor for biochemical relapse.Prostate Cancer and Prostatic Disease advance online publication, 21 October 2014; doi:10.1038/pcan.2014.40.
    Prostate Cancer and Prostatic Diseases 10/2014;
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    ABSTRACT: Background:During the last 30 years, there has been a major shift in initial staging in prostate cancer (CaP) in Western countries, with the incidence of metastases at diagnosis decreasing from over 50% in the 1970s to currently less than 10%. Yet, CaP is still the second cause of cancer death in men. We used two monthly curated databases of patients with castration-resistant prostate cancer (CRPC) to describe the natural history of patients dying of CaP in the modern era.Methods:The outcome of 190 men with metastatic CRPC treated from 2008 to 2011 was studied. The characteristics of the patients who died from CaP (n=113 patients, 61%) were analyzed.Results:All 113 patients who died of CaP were assessable for the presence of metastases at diagnosis. Sixty-three patients (56%) had detectable metastases at diagnosis: 67%, 11% and 43% had bone, visceral and lymph node metastases, respectively. The median time to CRPC was 16 months and median overall survival (OS) was 5.2 years.Among the patients with localized CaP at diagnosis (n=50, 44%), 46% had T stage⩾3 and 38% had a Gleason score⩾8. Overall, 64% of patients were classified as having a high-risk CaP. Only 26% who died from CaP had a Gleason score⩽6. Median OS was 8.8 years.Conclusions:In the modern era, approximately half of the patients who die from CaP have metastases at diagnosis. The paradigm of progression from localized disease to metastasis and eventually death is only represented in the other half, although possible initial screening and staging errors ought to be taken into consideration. More efforts are needed to conduct trials in patients with newly diagnosed metastatic CaP.Prostate Cancer and Prostatic Disease advance online publication, 14 October 2014; doi:10.1038/pcan.2014.35.
    Prostate Cancer and Prostatic Diseases 10/2014;
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    ABSTRACT: Background:With the increasing use of robotic surgery in the United States, the comparative effectiveness and differences in reimbursement of minimally invasive radical prostatectomy (MIRP) and open prostatectomy (ORP) in privately insured patients are unknown. Therefore, we sought to assess the differences in perioperative outcomes and hospital reimbursement in a privately insured patient population who were surgically treated for prostate cancer.Methods:Using a large private insurance database, we identified 17 610 prostate cancer patients who underwent either MIRP or ORP from 2003 to 2010. The primary outcomes were length of stay (LOS), perioperative complications, 90-day readmissions rates and hospital reimbursement. Multivariable regression analyses were used to evaluate for differences in primary outcomes across surgical approaches.Results:Overall, 8981 (51.0%) and 8629 (49.0%) surgically treated prostate cancer patients underwent MIRP and ORP, respectively. The proportion of patients undergoing MIRP markedly rose from 11.9% in 2003 to 72.5% in 2010 (P<0.001 for trend). Relative to ORP, MIRP was associated with a shorter median LOS (1.0 day vs 3.0 days; P<0.001) and lower adjusted odds ratio of perioperative complications (OR: 0.82; P<0.001). However, the 90-day readmission rates of MIRP and ORP were similar (OR: 0.99; P=0.76). MIRP provided higher adjusted mean hospital reimbursement compared with ORP (US$19 292 vs US$17 347; P<0.001).Conclusions:Among privately insured patients diagnosed with prostate cancer, robotic surgery rapidly disseminated with over 70% of patients undergoing MIRP by 2009-2010. Although MIRP was associated with shorter LOS and modestly better perioperative outcomes, hospitals received higher reimbursement for MIRP compared with ORP.Prostate Cancer and Prostatic Disease advance online publication, 14 October 2014; doi:10.1038/pcan.2014.38.
    Prostate Cancer and Prostatic Diseases 10/2014;
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    ABSTRACT: BACKGROUND:The introduction of laser therapies for the management of bladder outlet obstruction in men with BPH has challenged the gold standard treatment, TURP. We sought to compare the changing clinical characteristics of patients undergoing TURP and laser vaporization of the prostate (LVP) over time.METHODS:The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for men who underwent TURP and LVP from 2007 to 2012. Patient demographics, clinical and intraoperative characteristics and 30-day postoperative outcomes were analyzed.RESULTS:In all, 12 645 men met inclusion criteria, of whom 65% underwent TURP and 35% underwent LVP. Overall, men undergoing TURP were more likely to be scheduled as an emergency (3% vs 1%, P<0.001), have shorter operative times (53 vs 56 min, P<0.001), longer hospital stays (2.4 vs 1.0 days, P<0.001), more frequent blood transfusions (2.1% vs 0.6%, P<0.001) and more postoperative complications including: pneumonia (0.5% vs 0.3%, P=0.02), septic shock (0.3% vs 0.1%, P=0.045), and reoperation within 30 days (2.2% vs 1.4%, P=0.06). However, between 2007 and 2012, there was a significant trend for men undergoing TURP to have increased functional independence (93-96%, P<0.01) and American Society of Anesthesiology (ASA) Physical Class I categorization (0.6-5.1%, P<0.001). In contrast, over the same time period, there was a trend for men undergoing LVP to be significantly older (71-73 years, P<0.001) and have an increased hospital stay (0.50 days to 1.30 days, P=0.03).CONCLUSIONS:Statistically significant differences in clinical characteristics of patients undergoing TURP and LVP have historically existed. However, since 2007, the characteristics of patients undergoing LVP and TURP have changed significantly. Further studies are required to compare these patient characteristics with specific urologic variables and to evaluate clinically significant changes in these cohorts.Prostate Cancer and Prostatic Disease advance online publication, 14 October 2014; doi:10.1038/pcan.2014.39.
    Prostate Cancer and Prostatic Diseases 10/2014;
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    ABSTRACT: BACKGROUND:Men with biochemical recurrence (BCR) of prostate cancer are typically observed or treated with androgen-deprivation therapy. Non-hormonal, non-toxic treatments to slow the rise of PSA are desirable. We studied a combination herbal supplement, Prostate Health Cocktail (PHC), in prostate cancer cell lines and in a population of men with BCR.METHODS:PC3, LAPC3 and LNCaP cells were incubated with increasing concentrations of PHC suspension. Men previously treated for prostate cancer with surgery, radiation or both with rising PSA but no radiographic metastases were treated with three capsules of PHC daily; the primary end point was 50% PSA decline. Circulating tumor cells (CTCs) were identified using parylene membrane filters.RESULTS:PHC showed a strong dose-dependent anti-proliferative effect in androgen-sensitive and independent cell lines in vitro and suppression of androgen receptor expression. Forty eligible patients were enrolled in the clinical trial. Median baseline PSA was 2.8 ng ml(-1) (1.1-84.1) and 15 men (38%) had a PSA decline on study (1-55% reduction); 25 (62%) had rising PSA on study. The median duration of PSA stability was 6.4 months. Two patients had grade 2/3 transaminitis; the only other grade 2 toxicities were hyperglycemia, hypercalcemia and flatulence. There were no significant changes in testosterone or dihydrotestosterone. CTCs were identified in 19 men (47%).CONCLUSIONS:Although the primary end point was not met, PHC was well tolerated and was associated with PSA declines and stabilization in a significant number of patients. We believe this is the first report of detecting CTCs in men with BCR prostate cancer. Randomized studies are needed to better define the effect of PHC in men with BCR.Prostate Cancer and Prostatic Disease advance online publication, 23 September 2014; doi:10.1038/pcan.2014.37.
    Prostate Cancer and Prostatic Diseases 09/2014;
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    ABSTRACT: Background:Chronic inflammation and obesity may contribute to the genesis or progression of BPH and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single-nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4 and RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG and TCF7L2), with BPH.Methods:BPH cases (N=568) and age-frequency matched controls (N=568) were selected from among adult male CLUE II cohort participants who responded in 2000 to a mailed questionnaire. BPH was defined as BPH surgery, use of BPH medications or symptomatic BPH (American Urological Association Symptom Index Score ⩾15). Controls were men who had not had BPH surgery, did not use BPH medications and whose symptom score was ⩽7. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.Results:None of the candidate SNPs was statistically significantly associated with BPH. However, we could not rule out possible weak associations for CRP rs1205 (1082C>T), ADIPOQ rs1501299 (276C>A), PPARG rs1801282 (-49C>G) and TCF7L2 rs7903146 (47833T>C). After summing risk alleles, men with ⩾4 had an increased BPH risk compared with those with ⩽1 (OR, 1.78; 95% CI, 1.10-2.89; Ptrend=0.006).Conclusions:SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH.Prostate Cancer and Prostatic Disease advance online publication, 16 September 2014; doi:10.1038/pcan.2014.36.
    Prostate Cancer and Prostatic Diseases 09/2014;
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    ABSTRACT: Background:Controversial data on the association of single-nucleotide polymorphisms (SNPs, rs3787016G>A and rs10773338G>A) in long non-coding RNA (lncRNA) with prostate cancer risk were emerged. Considering possible genetic differences among populations, we conducted the present study to clarify these discrepancies and re-validate these results in an eastern Chinese population and thus provide clues for new therapeutic targets of prostate cancer.Methods:Genotypes of these two SNPs from 1015 ethnic Han Chinese patients with prostate cancer and 1032 cancer-free controls were determined by Taqman assays. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations.Results:The association of rs3787016 A variant genotypes with a significantly higher prostate cancer risk were found (adjusted OR=1.418, 95% CI=1.090-1.844 for AA vs GG). Stratification analysis indicated that the risk of rs3787016 variant AG/AA genotypes was more evident in younger subjects, ever smoking, patients with Gleason score ⩾7(4+3) and highly aggressive status. All these risks were not present for rs10773338G>A.Conclusions:These findings suggested that lncRNA SNPs may contribute to prostate cancer risk in an eastern Chinese population. Larger and well-designed studies with different ethnic populations are warranted to validate our findings.Prostate Cancer and Prostatic Disease advance online publication, 16 September 2014; doi:10.1038/pcan.2014.34.
    Prostate Cancer and Prostatic Diseases 09/2014;
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    ABSTRACT: Background:Bicalutamide is a widely used, relatively non-toxic anti-androgen, particularly when used in combination with androgen deprivation. In men on combined androgen blockade (CAB), the typical dose is 50 mg per day. For men receiving monotherapy with bicalutamide anti-androgen, the dose is 150 mg per day. The objective was to determine the PSA response rate to increasing bicalutamide to 150 mg per day in men who develop castrate-resistant prostate cancer (CRPC) on CAB with goserelin acetate and bicalutamide 50 mg per day.Methods:A national, multicentre, phase 2, open-label study in men on CAB with a rising PSA>2.0. The primary end point of the trial was PSA response at 12 months, defined as a decline by 50% or more compared with baseline value. Partial response was defined as a PSA decline of 10-49%. Secondary end points were duration of PSA response, change in slope of serum PSA, change in ratio of free PSA: total PSA at 3 months, 6 months and 12 months as compared with baseline; duration of the bicalutamide withdrawal response after discontinuation; the rate of cardiovascular events; and toxicity. The study was initially planned to accrue 100 patients, but was closed early due to diminishing accrual.Results:Sixty-four patients were accrued; 61 patients received trial treatment and constituted the intention-to-treat (ITT) cohort. 70% were M0. Among 59 evaluable ITT patients, 13 (22%) patients had a >50% PSA decline, 5 (8%) had a decline between 10 and 50%, 4 (7%) had stabilization and 37 (63%) had PSA progression. The median duration was 3.7 months (95% confidence interval of 0.92-6.21 months).Conclusion:In patients with early biochemical failure on CAB with bicalutamide 50 mg, an increase in dose to 150 mg of bicalutamide resulted in a PSA response of ⩾50% in 22% of patients. Toxicity was mild. Bicalutamide dose intensification may benefit a subset of patients with CRPC. We believe this relatively inexpensive approach warrants further evaluation.Prostate Cancer and Prostatic Disease advance online publication, 2 September 2014; doi:10.1038/pcan.2014.24.
    Prostate Cancer and Prostatic Diseases 09/2014;
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    ABSTRACT: Background:To evaluate the safety and clinical feasibility of focal irreversible electroporation (IRE) of the prostate.Methods:We assessed the toxicity profile and functional outcomes of consecutive patients undergoing focal IRE for localised prostate cancer in two centres. Eligibility was assessed by multi-parametric magnetic resonance imaging (mpMRI) and targeted and/or template biopsy. IRE was delivered under transrectal ultrasound guidance with two to six electrodes positioned transperineally within the cancer lesion. Complications were recorded and scored accordingly to the NCI Common Terminology Criteria for Adverse Events; the functional outcome was physician reported in all patients with at least 6 months follow-up. A contrast-enhanced MRI 1 week after the procedure was carried out to assess treatment effect with a further mpMRI at 6 months to rule out evidence of residual visible cancer.Results:Overall, 34 patients with a mean age of 65 years (s.d.=±6) and a median PSA of 6.1 ng ml(-1) (interquartile range (IQR)= 4.3-7.7) were included. Nine (26%), 24 (71%) and 1 (3%) men had low, intermediate and high risk disease, respectively (D'Amico criteria). After a median follow-up of 6 months (range 1-24), 12 grade 1 and 10 grade 2 complications occurred. No patient had grade >/= 3 complication. From a functional point of view, 100% (24/24) patients were continent and potency was preserved in 95% (19/20) men potent before treatment. The volume of ablation was a median 12 ml (IQR=5.6-14.5 ml) with the median PSA after 6 months of 3.4 ng ml(-1) (IQR=1.9-4.8 ng ml(-1)). MpMRI showed suspicious residual disease in six patients, of whom four (17%) underwent another form of local treatment.Conclusions:Focal IRE has a low toxicity profile with encouraging genito-urinary functional outcomes. Further prospective development studies are needed to confirm the functional outcomes and to explore the oncological potential.Prostate Cancer and Prostatic Disease advance online publication, 2 September 2014; doi:10.1038/pcan.2014.33.
    Prostate Cancer and Prostatic Diseases 09/2014;
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    ABSTRACT: Background:Prostate cancer (PCa) patients are often over-treated because of the lack of biomarkers needed to distinguish the lethal from the indolent form of PCa. YWHAZ was recently identified as a potential therapeutic target in castration-resistant PCa (CRPC). Therefore, this study focused on determining the prognostic significance of YWHAZ in localized PCa.Methods:YWHAZ expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded tissue from 213 men who underwent radical prostatectomy. Kaplan-Meier analysis and Cox proportional-hazards models were used to assess the prognostic value of YWHAZ intensity.Results:High YWHAZ expression was strongly associated with high Gleason score at the time of diagnosis (P<0.001) and PSA relapse (P=0.001). Importantly, patients with high expression of YWHAZ had a higher risk of CRPC development (P=0.002) and reduced survival time (P=0.002).Conclusions:Our findings indicate that YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors, which might benefit from earlier adjuvant or YWHAZ-targeted therapy.Prostate Cancer and Prostatic Disease advance online publication, 26 August 2014; doi:10.1038/pcan.2014.32.
    Prostate Cancer and Prostatic Diseases 08/2014;