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Objective: To determine whether Prostate Imaging-Reporting and Data System version 2 (PIRADS v2) and neutrophil-to-lymphocyte ratio(NLR) improve the detection of clinically significant prostate cancer(csCaP) in men with prostate-specific antigen (PSA) <10 ng/ml at first biopsy.Methods: Univariable and multivariable binary logistic regression analysis were used to screen for independent risk factors of csCaP. The multivariable model based on the risk factors was to build the nomogram predicting csCaP and assessed by receiver operator characteristic curve analysis, calibration plot, and decision curve analysis.Results: This retrospective study included 335 men with PSA < 10 ng/ml who underwent initial biopsy. A total of 78 (23.3%) men had csCaP. The nomogram was built based on the multivariable model including age, digital rectal examination, free prostate-specific antigen, PIRADS v2, and NLR. It had high area under the curve of 0.876 and was well calibrated in internal validation. Decision curve analysis also demonstrated that it would improve the prediction of csCaP.Conclusion: PIRADS v2 and NLR improve the detection of csCaP in men with PSA < 10 ng/ml at first biopsy. Due to lack of external validation, relatively small cohort and homogenous population, the study has several limitations. Despite of this, the nomogram based on our study is a promising tool for patients to understand their risk of csCaP and for urologists to make clinical decisions. [ABSTRACT FROM AUTHOR]

Active surveillance (AS) protocols rely on rectal examination, prostate-specific antigen, imaging, and biopsy to identify disease progression. To evaluate whether an AS regimen based on magnetic resonance imaging (MRI) or clinical stage changes can detect reclassification to grade group (GG) ≥2 disease compared with scheduled systematic biopsies. We identified a cohort of men initiated on AS between January 2013 and April 2016 at a single tertiary-care center. Patients completed confirmatory testing and prostate MRI prior to enrollment, then underwent laboratory and physical evaluation every 6 mo, MRI every 18 mo, and biopsy every 3 yr. MRI results were evaluated using composite Likert/Prostate Imaging Reporting and Data System v2 scoring. MRI and clinical changes were assessed for association with disease progression. Univariable and multivariable regression models were used to predict upgrading on 3-yr biopsy. At 3 yr, of 207 men, 66 (32%) had ≥ GG2 at biopsy: 55 (83%) with GG2, 10 (15%) with GG3, and one (1.5%) with GG4. Among patients with a 3-yr MRI score of ≥3, 41% had ≥ GG2 disease, compared with 15% with an MRI score of <3 (p = 0.0002). The MRI score increased in 48 men (23%), decreased in 27 (13%), and was unchanged in 132 (64%) men. Increases in MRI score were not associated with reclassification after adjusting for the 3-yr MRI score (p = 0.9). Biopsying only for an increased MRI score or clinical stage would avoid 681 biopsies per 1000 men, at the cost of missing ≥GG2 disease in 169 patients. An AS strategy that uses MRI or clinical changes to trigger prostate biopsy avoids many biopsies but misses an unacceptable amount of clinically significant disease. Prostate biopsy for men on AS should be performed at scheduled intervals, regardless of stable imaging or examination findings. An active surveillance strategy for biopsy based only on increases in magnetic resonance imaging score or clinical stage will avoid many biopsies; however, it will miss many patients with clinically significant prostate cancer. Negative magnetic resonance imaging (MRI) on active surveillance (AS) cannot justify avoiding scheduled biopsy as the risk of clinically significant disease is too great. AS protocols should involve prostate-specific antigen, MRI, and physical examination combined with scheduled repeat biopsy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether total serum PSA, free-PSA ratio and PSA density have similar diagnostic properties for detecting prostate cancer (PCa) and clinically-significant (cs) PCa in men with normal testosterone compared to men with low testosterone with a prior negative biopsy.Methods: We conducted a retrospective analysis of 3295 men undergoing a 2-year prostate biopsy following a negative prestudy biopsy in the placebo arm of the Reduction by Dutasteride of PCa Events (REDUCE) study. Men were divided in 2 groups based on testosterone level < or ≥300 ng/dL. Diagnostic properties of total serum PSA, free-PSA ratio, and PSA density to predict PCa and csPCa, defined as Gleason score ≥7, were determined for several thresholds and plotted as receiver operator characteristic curves.Results: A total of 603 men (18.3%) had low testosterone. The prevalence of PCa and csPCa was 92 (15.3%) and 27 (4.5%), respectively, for low testosterone men compared to 458 (17.0%) and 138 (5.1%), correspondingly, for normal testosterone men. Total PSA, free-PSA ratio and PSA density showed similar sensitivity, specificity, and accuracy to predict PCa and csPCa among low testosterone men compared to normal testosterone men.Conclusion: Among subjects in a clinical trial with a prior negative biopsy, total PSA, free-PSA ratio and PSA density have comparable diagnostic characteristics for PCa screening in low and normal testosterone men. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have reported temporal and spatial trends of aggressive prostate cancer (PC) among black men who are known to have more aggressive disease. We examined these trends for highly aggressive PC at diagnosis among black and white men in Pennsylvania (PA).Methods: Men, aged ≥ 40 years, with a primary, clinical PC diagnosis were identified from the Pennsylvania Cancer Registry, 2004-2014. Joinpoint analysis was used to evaluate the temporal trend of highly aggressive PC (clinical/pathologic Gleason score ≥ 7 [4 + 3], clinical/pathologic tumor stage ≥ T3, or distant metastasis) and identify change points by race in which annual percent change (APC) was calculated. Logistic regression analyses were used to examine the association between race and highly aggressive PC, after adjusting for covariates with and without spatial dependence.Results: There were 89,133 PC cases, which included 88.7% white and 11.3% black men. The APC of highly aggressive PC was 8.7% from 2011 to 2014 among white men and 3.6% from 2007 to 2014 among black men (p values ≤ 0.01). The greatest odds of having highly aggressive PC among black compared to white men were found in counties where the black male population was ≤ 5.3%.Conclusions: Highly aggressive PC increased for both black and white men in PA between 2004 and 2014. Black men had more aggressive disease, with the greatest odds in counties where the black male population was small. The increase in highly aggressive PC may be due to less screening for PC, resulting in more advanced disease at diagnosis. [ABSTRACT FROM AUTHOR]

A cross-sectional survey was performed among partners and men who received treatment for prostate cancer to investigate whether demographic and clinical characteristics are associated with the extent of how difficult partners found it dealing with sexual side effects and the degree of having experienced sexual problems after treatment. Moreover, an aim was to determine whether sexual side effects have an impact on the relationship. A total of 171 partners were included. In all, 104 men (70.7%) experienced an increase in erectile complaints after treatment. Almost half of partners of men with an increase in erectile complaints (63.6%, n = 63) found it difficult to deal with sexual side effects and 63.5% (n = 66) experienced sexual problems. Partners with lower education levels experienced fewer sexual problems than partners with higher education levels (p < .001). Furthermore, no significant associations were found on demographic characteristics, number of comorbidities, clinical characteristics (prostate-specific antigen level; tumor, node, and metastasis staging; Gleason grading), and type of treatment. The majority of men (58.4%, n = 59) and partners (62.5%, n = 65) indicated to not have experienced the impact of sexual side effects on their relationship. [ABSTRACT FROM AUTHOR]

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

Importance: In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 13%, and the lifetime risk of dying of prostate cancer is 2.5%. The median age of death from prostate cancer is 80 years. Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease. African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men.Objective: To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on prostate-specific antigen (PSA)-based screening for prostate cancer.Evidence Review: The USPSTF reviewed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer. The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening. The reviews also examined the benefits and harms of PSA-based screening in patient subpopulations at higher risk of prostate cancer, including older men, African American men, and men with a family history of prostate cancer.Findings: Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened. Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened. Potential harms of screening include frequent false-positive results and psychological harms. Harms of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel symptoms. About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results, diagnostic harms from biopsies, and harms from treatment. The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men. How each man weighs specific benefits and harms will determine whether the overall net benefit is small. The USPSTF concludes with moderate certainty that the potential benefits of PSA-based screening for prostate cancer in men 70 years and older do not outweigh the expected harms.Conclusions and Recommendation: For men aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician. Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results that require additional testing and possible prostate biopsy; overdiagnosis and overtreatment; and treatment complications, such as incontinence and erectile dysfunction. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes, and other health needs. Clinicians should not screen men who do not express a preference for screening. (C recommendation) The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older. (D recommendation). [ABSTRACT FROM AUTHOR]

Introduction: Recommendations for prostate-specific antigen-based screening for prostate cancer are placing increasing emphasis on men aged 55-69 years. The goal of the current study is to describe patterns of population-based prostate-specific antigen testing with details about that age group.Methods: National Health Interview Surveys from 2005 to 2015 were analyzed in 2017 to estimate routine prostate-specific antigen testing in the past year from self-reported data by age group (40-54, 55-69, ≥70 years), and also by risk group, defined as African American men or men with a family history of prostate cancer versus other men. Differences between successive survey years by age and risk groups were assessed by predicted margins and rate ratios with 99% CIs, using logistic regressions.Results: Prostate-specific antigen testing among men aged 55-69 years decreased from a high of 43.1% (95% CI=40.3, 46.1) in 2008 to a low of 32.8% (95% CI=30.8, 34.7) in 2013, with no significant change in 2015 at 33.8% (95% CI=31.3, 36.4). Men aged ≥70 years had consistently high prevalence in all survey years, ranging from 51.1% in 2008 to 36.4% in 2015. African American men, men with a family history of prostate cancer, and other men showed a 5% absolute decrease over time, but this reduction was significant only in other men.Conclusions: Despite decreases, the absolute change in prostate-specific antigen testing for men aged 55-69 years was small (9.3%) over the study period. Men aged ≥70 years, for whom the benefits are unlikely to exceed the harms, continue to have consistently high testing prevalence. [ABSTRACT FROM AUTHOR]

The authors offer a systematic review of studies on the psychological interventions for prostate cancer survivors and their partners. Topics include the change in the medical and social context of prostate cancer since the introduction of prostate-specific antigen (PSA) testing, clinical questions that guided the review, and effects of psychosocial and psychosexual intervention on men with prostate cancer.

This study investigated the immunohistochemical expression of the cancer testis antigen SSX in prostate cancer. SSX expression, with varying staining intensities, was observed in 83% of cancer samples. Substantial heterogeneity of expression was observed within individual samples. SSX expression was significantly higher in Gleason score 7 than in Gleason score 6 cancer (p=0.008). Tumours demonstrating capsular invasion had higher SSX expression than did tumours without capsular invasion (p=0.005). SSX expression did not correlate significantly with prostatespecific antigen level or tumour size. Further studies are needed to investigate SSX expression in prostate cancer and its potential implications for diagnosis and immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: We examined the most recent Surveillance, Epidemiology, and End Results release to corroborate temporal trends in nonmetastatic and distant prostate cancer metastases in the United States.Methods: Surveillance, Epidemiology, and End Results was analyzed for the incidence of nonmetastatic and distant metastasis for men with prostate cancer aged 50-74 and ≥75 years during 2004-2015. Incidence ratios (IR) were calculated relative to the year prior.Results: The incidence of distant metastasis significantly increased from 451.0 to 504.0 per million (IR:1.12, 95% CI:1.01-1.24) from 2011 to 2012 and 532.3 to 586.1 per million (IR:1.10, 95% CI:1.00-1.21) from 2014 to 2015 in men aged ≥75 years. The incidence of distant metastasis did not significantly increase in men aged 55-74 over the study period.Conclusion: We demonstrate a sustained and definitive increase in prostate cancer distant metastases in men aged ≥75 years. Although our observational study design cannot pinpoint the exact cause of this increase, which is likely multifactorial, this shift reverses declines in metastases at diagnoses that followed the advent of prostate-specific antigen screening. [ABSTRACT FROM AUTHOR]

For men interested in early detection of prostate cancer, the potential impact on decisional conflict of a decision aid with or without cost compensation for the prostate-specific antigen test will be investigated. [ABSTRACT FROM AUTHOR]

This editorial provides an overview of the clinical presentation of depression in men with prostate cancer, presents potential causal mechanisms, and identifies resources for screening and treatment. [ABSTRACT FROM AUTHOR]

Purpose Prostate specific antigen has decreased performance characteristics for the detection of prostate cancer in African-American men. We evaluated urinary PCA3 and TMPRSS2:ERG in a racially diverse group of men. Materials and Methods After institutional review board approval, post-examination urine was prospectively collected before prostate biopsy. PCA3 and TMPRSS2:ERG RNA copies were quantified using transcription mediated amplification assays (Hologic, San Diego, California). Prediction models were created using standard of care variables (age, race, family history, prior biopsy, abnormal digital rectal examination) plus prostate specific antigen. Decision curve analysis was performed to compare the net benefit of PCA3 and TMPRSS2:ERG. Results Of 304 patients 182 (60%) were African-American and 139 (46%) were diagnosed with prostate cancer (69% African-American). PCA3 and TMPRSS2:ERG scores were greater in men with prostate cancer, 3 or more cores, 33.3% or more cores, greater than 50% involvement of greatest biopsy core and Epstein significant prostate cancer (p <0.01). PCA3 added to the standard of care plus prostate specific antigen model for the detection of any prostate cancer in the overall cohort (0.747 vs 0.677, p <0.0001) in African-American men only (0.711 vs 0.638, p=0.0002) and nonAfrican-American men (0.781 vs 0.732, p=0.0016). PCA3 added to the model for the prediction of high grade prostate cancer for the overall cohort (0.804 vs 0.78, p=0.0002) and African-American men only (0.759 vs 0.717, p=0.0003) but not nonAfrican-American men. Decision curve analysis demonstrated improvement with the addition of PCA3. For African-American men TMPRSS2:ERG did not improve concordance statistics for the detection of prostate cancer. Conclusions For African-American men urinary PCA3 improves the ability to predict the presence of any and high grade prostate cancer. However, the TMPRSS2:ERG urinary assay does not add significantly to standard tools. [ABSTRACT FROM AUTHOR]

Purpose The growth potential of low grade prostate cancer is unknown and yet it is potentially impactful for the practice of active surveillance. We evaluated the incidence, growth dynamics and clinical significance of changes in prostate lesions on serial transrectal ultrasound among a large cohort of men with prostate cancer managed by active surveillance. Materials and Methods This retrospective study included men with prostate cancer treated with active surveillance at UCSF (University of California-San Francisco) from 2000 to 2014 who underwent a minimum of 2 transrectal ultrasound studies. Study inclusion criteria were prostate specific antigen 20 ng/ml or less, clinical stage T2 or less and biopsy Gleason grade 3 + 4 or less. Progression end points included an increase in imaging stage, a 50% or greater increase in volume and an increase in the number of sites (sextants) with apparent lesions. The relationship between transrectal ultrasound progression and biopsy Gleason upgrade was assessed by univariate and multivariate logistic regression models. Results The 875 identified patients underwent a median of 5 transrectal ultrasound studies (IQR 3–8). Median followup was 49 months (IQR 27–81). Of the patients 345 (39%) progressed on serial transrectal ultrasound, including 51 by size, 265 by the number of lesion sites and 279 by stage. Median time to progression was 14 months. Transrectal ultrasound progression was independently associated with biopsy upgrade (OR 1.8, 95% CI 1.3–2.5, p <0.01). Conclusions Local progression on transrectal ultrasound was associated with Gleason upgrade at biopsy. These results suggest that stable imaging findings on transrectal ultrasound may allow for increased intervals between biopsies among men on active surveillance. A prospective study is required to evaluate the usefulness of such a practice. [ABSTRACT FROM AUTHOR]

Background: We propose to improve the prognostic assessment after radical prostatectomy (RP) by dividing high-risk prostate cancer (hrPCa) (according to the d'Amico classification) into subgroups combining 1, 2 or 3 criteria of aggressiveness (cT2c-T3a, PSA >20 ng/ml, Gleason score (GS) > 7).Methods: Data from 4795 hrPCa patients who underwent RP in two French university hospitals from 1991 to 2013 were analyzed. Subgroups were formed to determine whether an increasing number (1, 2 or 3) of criteria of tumor aggressiveness was associated with poorer oncological results and early biochemical recurrence (BCR) (PSA > 0.2 ng/ml). These results were compared using Fisher's exact test and BCR was compared according to the Kaplan-Meier method.Results: Eight hundred fifteen patients were treated by RP for hrPCa (8 %). Four hundred eleven patients (79.5 %) presented 1 RF (Risk Factor), 93 (18.0 %) 2 RF and 13 (2.5 %) 3 RF. Lymph node invasion and positive margin rates were 12.4 and 44.1 %, respectively. The prognostic sub-stratification based on these 3 factors was significantly predictive for adverse pathologic features and for oncologic outcomes. BCR free survival was respectively 56.4, 27.06 and 18.46 % for 1RF, 2RF and 3RF (p < 0.0001). However, no predominant negative criterion was found.Conclusion: Oncologic results after RP are heterogenous within the hrPCa risk group. Sub-stratification based on three well-defined criteria leads to a better identification of the most aggressive cancers. On the other hand, RP provides both effective cancer control and satisfactory survival rates in patients with only one risk factor. [ABSTRACT FROM AUTHOR]

Objective: To collect disease-specific and generic preference values for three populations.Methods: Prostate cancer-specific health states were developed with attributes that varied across five health domains: sexual function, urinary function, bowel function, pain, and fear of the future. Men with prostate cancer, men at risk for prostate cancer, and a sample of the general population assigned value to 18 disease-specific health states using standard gamble (SG) methodology. Study participants also completed the Health Utilities Index (HUI) to obtain generic, community-based preference values to capture their current health rating.Results: A total of 136 participants were enrolled (n = 43 prostate cancer; n = 40 at risk for prostate cancer; n = 49 general population). Mean HUI mark 3 current health ratings: men with prostate cancer 0.75 ± 0.260; men at risk for prostate cancer 0.77 ± 0.238; general population 0.84 ± 0.178. Mean SG preference values ranged from 0.46 to 0.85 among men with prostate cancer, 0.37 to 0.75 among men at risk for prostate cancer, and 0.32 to 0.81 among the general population group.Conclusions: In general, preference values for disease-specific health states using the patient perspective were higher than those for the general population. Generic preference values calculated from the HUI were higher than disease-specific preference values calculated from the SG. The higher values calculated from the HUI, from all three perspectives, indicate that a generic measure may not be sensitive enough to capture the disutility of prostate cancer symptoms, specifically sexual dysfunction, urinary dysfunction, and bowel dysfunction, which are being directly measured in the disease-specific health states. [ABSTRACT FROM AUTHOR]

The article discusses the Beckman Coulter Prostate Health Index (phi), an in vitro diagnostic multivariate index assay incorporating immunoassay measurements of prostate-specific antigen (PSA), free PSA, and the free PSA isoform [-2]proPSA (p2PSA) in serum. Topics include the approval of phi in 2012 by the U.S. Food and Drug Administration to detect prostate cancer in men 50 years or older, how the phi score is interpreted, and specimen handling instructions from the manufacturer for p2PSA.

A commentary is presented on a research by the U.S. Preventive Services Task Force (USPSTF) which arrived at the conclusion that the net benefit of prostate-specific antigen (PSA)-based screening for prostate cancer in men aged 55 to 69 years is small for some men. Topics covered include reason for the decision of the USPSTF to change its recommendation from D to C for men aged 55 to 69 years, and USPSTF approach in reassessing the benefits and harms of PSA-based screening for prostate cancer.

Prostate cancer remains a significant public health concern among men in the U.S. and worldwide. Epidemiologic studies have generally produced inconclusive results for dietary risk factors for prostate cancer, including consumption of red and processed meats. We aimed to update a previous meta-analysis of prospective cohorts of red and processed meats and prostate cancer with the inclusion of new and updated cohort studies, as well as evaluate meat cooking methods, heme iron, and heterocyclic amine (HCA) intake exposure data. A comprehensive literature search was performed and 26 publications from 19 different cohort studies were included. Random effects models were used to calculate summary relative risk estimates (SRREs) for high vs. low exposure categories. Additionally, meta-regression analyses and stratified intake analyses were conducted to evaluate dose-response relationships. The SRREs for total prostate cancer and total red meat consumption, fresh red meat consumption, and processed meat consumption were 1.02 (95% CI: 0.92-1.12), 1.06 (95% CI: 0.97-1.16), and 1.05 (95% CI: 1.01-1.10), respectively. Analyses were also conducted for the outcomes of non-advanced, advanced, and fatal prostate cancer when sufficient data were available, but these analyses did not produce significant results. No significant SRREs were observed for any of the meat cooking methods, HCA, or heme iron analyses. Dose-response analyses did not reveal significant patterns of associations between red or processed meat and prostate cancer. In conclusion, the results from our analyses do not support an association between red meat or processed consumption and prostate cancer, although we observed a weak positive summary estimate for processed meats. [ABSTRACT FROM AUTHOR]

Background:To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.Methods:Retrospective analysis of 531 bone scans of 312 clinically CRPC patients with no known metastases at baseline treated with a variety of primary treatment types in the SEARCH database. The association of patients' demographics, pathological features, PSA levels and kinetics with risk of a positive scan was tested using generalized estimating equations.Results:A total of 149 (28%) scans were positive. Positive scans were associated with younger age (odds ratio (OR)=0.98; P=0.014), higher Gleason scores (relative to Gleason 2-6, Gleason 3+4: OR=2.03, P=0.035; Gleason 4+3 and 8-10: OR=1.76, P=0.059), higher prescan PSA (OR=2.11; P<0.001), shorter prescan PSA doubling time (PSADT; OR=0.53; P<0.001), higher PSA velocity (OR=1.74; P<0.001) and more remote scan year (OR=0.92; P=0.004). Scan positivity was 6, 14, 29 and 57% for men with PSA<5, 5-14.9, 15-49.9 and ⩾50 ng ml−1, respectively (P-trend <0.001). Men with PSADT ⩾15, 9-14.9, 3-8.9 and <3 months had a scan positivity of 11, 22, 34 and 47%, correspondingly (P-trend <0.001). Tables were constructed using PSA and PSADT to predict the likelihood of a positive bone scan.Conclusions:PSA levels and kinetics were associated with positive bone scans. We developed tables to predict the risk of positive bone scans by PSA and PSADT. Combining PSA levels and kinetics may help select patients with CRPC for bone scans. [ABSTRACT FROM AUTHOR]

Purpose We evaluated the ability of PHI to discriminate aggressive prostate cancer from indolent or no cancer in a biopsy naïve population. Materials and Methods Two independent prospective cohorts of 561 and 395 subjects, respectively, with no prior prostate biopsy who were enrolled at different clinical sites were used to validate the results. We compared the diagnostic specificity of PHI to prebiopsy total and percent free prostate specific antigen using prostate biopsy results. We also determined the optimal PHI threshold to discriminate aggressive prostate cancer (Gleason score 7 or greater) from indolent or no prostate cancer (Gleason score 6 or less). Results In the primary cohort higher PHI values were significantly associated with Gleason score 7 or greater. The AUC to detect aggressive prostate cancer was 0.815. At 95% sensitivity PHI specificity was 36.0% vs 17.2% and 19.4% for total and percent free prostate specific antigen, respectively. At 95% sensitivity for detecting aggressive prostate cancer the optimal PHI cutoff was 24, which would help avoid 41% of unnecessary biopsies. A cutoff of 24 led to 36% biopsies avoided with few aggressive cancers missed. These results were confirmed in the validation cohort. Conclusions The PHI detected aggressive prostate cancer with better specificity than total and percent free prostate specific antigen in a biopsy naïve population. It could be a useful tool to decrease unnecessary prostate biopsies. [ABSTRACT FROM AUTHOR]

Purpose Prostate specific antigen screening is controversial, as a large number of men must be screened annually to achieve a benefit. We sought to determine whether baseline prostate specific antigen could reliably predict subsequent risk of prostate cancer and risk of consequential prostate cancer. Materials and Methods A multiethnic cohort of 2,923 prostate cancer-free men was recruited between 2000 and 2012, and followed for a median of 7.5 years. Baseline prostate specific antigen was stratified into 6 strata and relative hazards of prostate cancer detection for each prostate specific antigen stratum were estimated, adjusting for ethnicity, family history and age. Results During followup 289 patients were diagnosed with prostate cancer. Men with baseline prostate specific antigen in the lowest stratum (0.1 to 1.0 ng/ml) were at greatly reduced risk for prostate cancer during followup. This half of the cohort with prostate specific antigen 1.0 ng/ml or less were at 3.4% (95% CI 2.1, 4.5) 10-year risk of prostate cancer and 90% of the cancers were low risk. By comparison the other half were at 15% to 39% risk of cancer detection with a 39% risk in the highest stratum (3 to 10 ng/ml). Conclusions Optimal prostate specific antigen screening frequency for men with a prostate specific antigen level of 0.1 to 1.0 ng/ml may be up to every 10 years. This approach has the potential to dramatically reduce the cost of screening, decreasing over detection of inconsequential tumors, while maintaining detection of tumors for which treatment has been proven to reduce prostate cancer mortality. [ABSTRACT FROM AUTHOR]

Prostate cancer and chronic lymphocytic leukemia (CLL) are relatively common malignancies associated with advanced age. Although immunotherapy-based strategies are used to treat both, currently, there is no overlap in specific therapies. Sipuleucel-T is an active cellular immunotherapy that improves overall survival for patients with metastatic castration resistant prostate cancer (mCRPC) but is not typically associated with a decline in prostate-specific antigen (PSA) following administration. We report the case of a 78-year-old man with mCRPC and Rai stage 0 CLL who sustained a 12-month decline in both PSA and white blood cell (WBC) count following treatment with APC8015-2 (an investigational form of sipuleucel-T), as part of the phase II ProACT clinical trial. Two years later, the patient received commercial sipuleucel-T and again was noted to have a decline in PSA. Exploratory analysis did not clearly identify any peripheral immune markers associated with response. This case report suggests that treatment with sipuleucel-T can rarely lead to PSA decline, may have dual activity against both prostate cancer and CLL, and that these findings warrant further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer is a serious public health issue affecting more and more men. Using PSA and periodic urologic exams more and patients are diagnosed in an early stage and may benefit from a curative treatment. Retropubic radical prostatectomy, external beam radiation therapy and brachytherapy are the curative options. Materials and method: The experience of a single surgical team from Central Military Hospital representing 50 cases was analyzed in terms of PSA level at diagnose moment, preoperative and postoperative staging, preoperative and postoperative Gleason score, intraoperative complications and also precocious and late postoperative complications and oncologic outcomes. Besides those aspects, we have analysed surgery related parameters. Results: Favorable outcomes were obtained in most cases with mild to moderate intraoperative complications (blood loss), early postoperative complications (hematuria, urinary tract infection, lymph drainage) or late postoperative complications (erectile dysfunction and urinary incontinence). Conclusions: Radical prostatectomy remains the gold standard treatment for patient with localized prostate cancer and in some cases for local advanced prostate cancer. It provides good oncological outcome with manageable complications. [ABSTRACT FROM AUTHOR]

Introduction: It is unknown whether a normal range, diagnostic serum prostate specific antigen (PSA) level's influence on prostate cancer specific mortality (PCSM) is dependent upon digital rectal examination (DRE) findings. Methods: Between 2004 and 2007, 9081 men diagnosed with non-palpable (T1c, N =1710) or palpable (T2-T4, N =7371) and non-metastatic prostate cancer (PC) were identified from surveillance, epidemiology, and end results data, selected based on pre-treatment PSA < 2.5 ng/ml. A multivariable competing risks regression model evaluated whether DRE findings interacted with PSA level in predicting risk of PCSM. Results: After median follow-up of 2.83 years, 118 of 548 deaths (21.5%) were due to PC. Increasing diagnostic PSA was associated with increased risk of PCSM (AHR = 3.52; 95% CI: 1.25-9.89; P = .017) in men with T1c, Gleason score 7-10 PC, but decreased PCSM risk (AHR = 0.66; 95% CI: 0.52-0.83; P < .001) for men with T2-T4 PC and any Gleason score. Discussion: For men with diagnostic PSA level <2.5 ng/ml and palpable PC, risk of early PCSM increases by 34% for a 1 point decrease in PSA from 2. This suggests the existence of clinically detectable, low PSA secreting disease with an elevated risk of early PCSM, highlighting the importance of the DRE in men with PC and normal range, diagnostic PSA. [ABSTRACT FROM AUTHOR]

Background:Polyphenol-rich foods such as pomegranate, green tea, broccoli and turmeric have demonstrated anti-neoplastic effects in laboratory models involving angiogenesis, apoptosis and proliferation. Although some have been investigated in small, phase II studies, this combination has never been evaluated within an adequately powered randomised controlled trial.Methods:In total, 199 men, average age 74 years, with localised prostate cancer, 60% managed with primary active surveillance (AS) or 40% with watchful waiting (WW) following previous interventions, were randomised (2:1) to receive an oral capsule containing a blend of pomegranate, green tea, broccoli and turmeric, or an identical placebo for 6 months.Results:The median rise in PSA in the food supplement group (FSG) was 14.7% (95% confidence intervals (CIs) 3.4-36.7%), as opposed to 78.5% in the placebo group (PG) (95% CI 48.1-115.5%), difference 63.8% (P=0.0008). In all, 8.2% of men in the FSG and 27.7% in the PG opted to leave surveillance at the end of the intervention (χ2 P=0.014). There were no significant differences within the predetermined subgroups of age, Gleason grade, treatment category or body mass index. There were no differences in cholesterol, blood pressure, blood sugar, C-reactive protein or adverse events.Conclusions:This study found a significant short-term, favourable effect on the percentage rise in PSA in men managed with AS and WW following ingestion of this well-tolerated, specific blend of concentrated foods. Its influence on decision-making suggests that this intervention is clinically meaningful, but further trials will evaluate longer term clinical effects, and other makers of disease progression. [ABSTRACT FROM AUTHOR]

Abstract: Background: Using transrectal saturation prostate biopsy (SPBx) as an initial strategy remains a controversial topic. Objective: To compare SPBx with extended prostate biopsy (EPBx) as an initial biopsy template in a large sequential cohort study. Design, setting, and participants: We reviewed 438 men with initial SPBx and 3338 men who underwent initial EPBx between January 2002 and October 2011. Intervention: Office-based SPBx under periprostatic local anesthesia. Outcome measurements and statistical analysis: The yield of SPBx was compared with EPBx. Multivariable logistic regression models addressed cancer detection (CD) and cancer characteristics. Results and limitations: Overall CD was 51.6% and 42.6% in men who underwent initial SPBx and EPBx, respectively. Multivariate analysis confirmed that SPBx was an independent predictor factor correlated with the CD (odds ratio [OR]: 1.66; 95% confidence interval [CI], 1.30–1.92). Stratified by prostate-specific antigen (PSA) values, CD was higher in SPBx compared with EPBx, 47.1% versus 32.8% (OR: 2.00; 95% CI, 1.19–3.38) in patients with a PSA <4 ng/ml and 50.9% versus 42.9% in patients with a PSA from 4 ng/ml to 9.9 ng/ml (OR: 1.62; 95% CI, 1.20–2.20). By contrast, SPBx did not increase CD in men with a PSA >10 ng/ml (60.0% vs 61%; OR: 1.42; 95% CI, 0.70–2.89). There was no significant difference in the detection of insignificant cancer (p = 0.223) or low-risk cancer (p = 0.077) between the two biopsy schemes. The limitation of our study is its retrospective nature and inhomogeneity. Conclusions: Compared with EPBx, SPBx significantly increases CD as an initial biopsy strategy in men with a PSA <10 ng/ml without a significant increase in the detection of insignificant cancer. These findings suggest that SPBx may merit further investigation as an initial biopsy strategy in men with a PSA <10 ng/ml in hopes of avoiding repeat biopsy for missed malignancy during the initial biopsy. [Copyright &y& Elsevier]

Introduction: For men with elevated prostate-specific antigen (PSA), appropriate management after negative prostate biopsy remains controversial. After determining PSA kinetics, subsequent follow-up was considered. Patients and Methods: A total of 115 cases with negative repeat biopsy were followed by evaluating PSA kinetics and ratio of percent free PSA (F/T) and by performing second repeat biopsy. Results: Eighteen cancer cases were diagnosed. Shorter PSA doubling times and faster velocities were found in cancer cases compared with cases without cancer. We observed a clear decrease in F/T among cancer cases. Conclusions: To avoid unnecessary repeat biopsies, cases with a suspicion of cancer after negative biopsy can be divided into two groups: one that requires additional biopsies and one with an average change in PSA of <1 ng/ml/year and no change in F/T, which is recommended for surveillance as stable disease without biopsy over a specified time period. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To describe the results of 3 rounds of diagnostic testing and linkage to the Dutch Cancer Registry for men with an initial prostate cancer antigen 3 (PCA3) score ≥100. Methods: Within an earlier reported comparative study of PCA3 vs prostate-specific antigen in a prescreened population, 90 men with a PCA3 score ≥100 were identified and underwent biopsy, 28 prostate cancers (PCs) were found, 62 men remained at risk of a diagnosis of PC. All men were offered repeat testing; 6 PCs were found in 20 men at rebiopsy. Men with at least 1 negative biopsy (n = 56) were invited to undergo magnetic resonance imaging (MRI) studies and MRI-guided biopsies if indicated. Linkage to the Dutch Cancer Registry after 2.8 years of follow-up was performed for men with negative biopsies. Results: Of the 56 men at risk, 28 agreed to participate in further testing. They were offered MRI studies; only 7 men agreed, and in 2, suspicious lesions were found and biopsies carried out. Only 1 PC was diagnosed and classified as T1c, Gleason 3 + 3 = 6. The overall findings of 3 rounds of testing and of linkage to the cancer registry show that eventually 35 PCs were detected in 90 men with PCA3 scores ≥100 (positive predictive value 38.9%). Conclusion: Finding no PC despite extended diagnostic efforts in many men with initial PCA3 scores ≥100 is unexpected and might be clinically relevant. [Copyright &y& Elsevier]

Background and Purpose. Life expectancy data could identify men with favorable post-radiation prostate-specific antigen (PSA) failure kinetics unlikely to require androgen deprivation therapy (ADT). Materials and Methods. Of 206menwith unfavorable-risk prostate cancer in a randomized trial of radiation versus radiation and ADT, 53 experienced a PSA failure and were followed without salvage ADT. Comorbidity, age and established prognostic factors were assessed for relationship to death using Cox regression analyses. Results. The median age at failure, interval to PSA failure, and PSA doubling time were 76.6 years (interquartile range [IQR]: 71.8-79.3), 49.1 months (IQR: 37.7-87.4), and 25 months (IQR: 13.1-42.8), respectively. After a median follow up of 4.0 years following PSA failure, 45% of men had died, none from prostate cancer and no one had developed metastases. Both increasing age at PSA failure (HR: 1.14; 95% CI: 1.03-1.25; p = 0.008) and the presence of moderate to severe comorbidity (HR: 12.5; 95% CI: 3.81-41.0; p < 0.001) were significantly associated with an increased risk of death. Conclusions. Men over the age of 76 with significant comorbidity and a PSA doubling time >2 years following post-radiation PSA failure appear to be good candidates for observation without ADT intervention. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have evaluated the risk profile of prostate-specific antigen (PSA)- detected T1cN0M0 prostate cancer, defined as tumors diagnosed by needle biopsy because of elevated PSA levels without other clinical signs of disease. However, some men with stageT1cN0M0 prostate cancer may have high-risk disease (HRD), thus experiencing inferior outcomes as predicted by a risk group stratification model. Methods:We identified men diagnosed with stage T1cN0M0 prostate cancer from 2004 to 2008 reported to the surveillance, epidemiology, and end results (SEER) program. Multivari-ate logistic regression was used to model the probability of intermediate-risk-disease (IRD) (PSA<10 ng/ml but <20 ng/ml and/or GS 7), and high-risk-disease (HDR) (PSA⩾20 ng/ml, and/or GS⩾8), relative to low-risk disease (LRD) (PSA<10 ng/ml and GS⩽6), adjusting for age, race, marital status, median household income, and area of residence. Results: A total of 70,345 men with PSA-detected T1cN0M0 prostate cancer were iden-tified. Of these, 47.6, 35.9, and 16.5% presented with low-, intermediate-, and high-risk disease, respectively. At baseline (50 years of age), risk was higher for black men than for whites for HRD (OR 3.31, 95% CI 2.85-3.84). The ORs for age (per year) for HRD relative to LRD were 1.09 (95% CI 1.09-1.10) for white men, and as 1.06 (95% CI 1.05-1.07) for black men. Further, among a subgroup of men with lowPSA (<10 ng/ml)T1cN0M0 prostate cancer, risk was also higher for black man than for white men at baseline (50 years of age) (OR 2.70, 95% CI 2.09-3.48).The ORs for age (per year) for HRD relative to LRD were 1.09 (95% CI 1.09-1.10) for white men, and as 1.06 (95% CI 1.05-1.07) for black men. Conclusion: A substantial proportion of men with PSA-detected prostate cancer as reported to the SEER program had HRD. Black race and older age were associated with a greater likelihood of HRD. [ABSTRACT FROM AUTHOR]

Major clinical trials using prostate-specific antigen (PSA) as the screening test to detect localized early-stage prostate cancer and to attempt to change its natural history with early intervention have yielded conflicting interpretations. The US Prostate, Lung, Colorectal, and Ovarian (US PLCO) cancer screening trial concluded that PSA-based screening conferred no meaningful survival benefit, whereas the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the GOTEBORG clinical trial (GOTEBORG) trials claimed statistically significant life-saving benefits. These divergent outcomes have not provided physicians with clarity on the best evidence-based treatment. To determine the extent to which these divergent outcomes are clinically meaningful, we evaluated these data and those of a long-term prospective cohort study in the context of the clinically documented harms of androgen deprivation therapy (ADT). We noted the unheralded fact that in both European trials far more patients received hormonal treatment in the control than the prostatectomy arm, whereas hormonal therapy in the US trial was balanced between arms. We examined this imbalance in ADT treatment and prostate cancer–related deaths in the contexts of contamination, stage migration, and attribution of cause of death, all of which impinge on data interpretation. The ERSPC and GOTEBORG data are compatible with the hypothesis that ADT treatment contributes differentially to an increase in prostate cancer deaths in control patients. If so, the claim of a reduction in prostate cancer deaths in the screened cohort requires reappraisal. The conventional interpretation that PSA screening and radical treatment intervention are the major contributors to the results of these two studies needs more rigorous scientific scrutiny, as does the role of ADT treatment of nonmetastatic disease. [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: We hypothesized the prostate-specific antigen (PSA) “grey zone” in Chinese men was higher than the traditional value (4.0–10.0 ng/ml) since incidence of prostate cancer (CaP) in Chinese men was relative low. We then assessed the efficiencies of transition zone PSA density (TZPSAD) in the diagnosis of CaP in Chinese men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml. Materials and methods: Men had a prostatic biopsy for detecting CaP from November 1999 to August 2009 were retrospectively retrieved from our computer center. Those had a document of transrectal ultrasound transition zone measurement with a PSA of 4.0–20.0 ng/ml were included. Receiver-operating characteristic (ROC) curve was used to analyze the efficiencies of PSA and TZPSAD in the diagnosis of CaP. Results: A total of 189 men were included in the study. Of these men, 78 and 111 had a PSA of 4.0–10.0 and 10.1–20.0 ng/ml, respectively. The rate of CaP in men with a PSA of 4.0–10.0 ng/ml was not statistically significantly different compared with those with a PSA of 10.1–20.0 ng/ml (20.5% vs. 21.6%, P = 0.854). The areas under the ROC curve (AUCs) in diagnosis of CaP for PSA and TZPSAD were 0.569 and 0.702 in men with a PSA of 4.0–10.0 ng/ml and 0.463 and 0.730 in men with a PSA of 10.1–20.0 ng/ml, respectively. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 4.0–10.0 ng/ml was 0.370 ng/ml/ml, the sensitivity of which equaled 68.8%, specificity 72.6%. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 10.1–20.0 ng/ml was 0.500 ng/ml/ml. Its sensitivity equaled 70.8%, specificity 70.1%. Conclusions: Using TZPSAD can improve the efficiency of PSA in diagnosis of CaP and decreases the unnecessary prostatic biopsy in men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml in Chinese men. [Copyright &y& Elsevier]

Abstract: Purpose: To determine the outcomes of prostate seed implantation in men with prostate volume (PV) of 100cc or greater (PV100). Methods: A total of 2051 men with localized prostate cancer were treated with permanent prostate brachytherapy of whom 34 (1.7%) had PV100 (mean, 126.2; range, 100–205cc). The PV100 patients were older (mean, 69 vs. 66 years; p =0.031), had higher initial prostate-specific antigen level (20.4 vs. 9.6 ng/mL, p <0.001), and received a lower dose (182 vs. 194Gy2 biologic equivalent dose, p =0.032). There were no differences in clinical stage, Gleason score, and baseline International Prostate Symptom Score. The mean followup time was 6.7 years (range, 2–18). Biochemical freedom from failure (bFFF) was defined using the Phoenix definition. Results: The BFFF at 10 years was no different between PV100 and smaller glands (82.4% vs. 84.5%, p =0.71). At last followup, mean International Prostate Symptom Score for PV100 increased from 8.5 to 9.1 against 7.4 to 9.2 for smaller glands (p =0.935). Urinary retention rates were higher for PV100 (6/34, 17.6% vs. 148/2017, 7.3%; odds ratio, 2.71; 95% confidence interval, 1.1–6.6; p =0.038). Postimplant transurethral resection of the prostate was performed in none of the 34 patients with PV100 against 66 of the 2017 patients (3.3%, p <0.001). Long-term radiation proctitis for PV100 were 1 of 34 (2.9%) against 82 of 2017 (4.1%, p =0.741). Rectourethral fistula occurred in 4 patients (0.19%), that is, 1 of 34 (2.9%) in PV100 group and 3 of 2017 (0.1%, p <0.001). Conclusion: This study demonstrates the feasibility of implanting patients with PV100. Very large PV does not influence bFFF. Although urinary retention rates were higher, the long-term urinary symptoms were no different between the two groups. Requirement for transurethral resection of the prostate was no higher in patients with PV100. Radiation proctitis rates were similar for both. [Copyright &y& Elsevier]

What's known on the subject? and What does the study add? There are two randomized controlled trials showing that radiotherapy can be beneficial for men with locally advanced prostate cancer. The present study confirms the importance of curative treatment for men with high-risk prostate cancer., Objective To investigate the influence of curative treatment on cause-specific mortality in men diagnosed with prostate cancer ( PCa) with serum prostate-specific antigen ( PSA) levels between 20 and 100 ng/ mL., Materials and Methods Patients with PCa ( T1-4, N0/ N1/ NX, M0/ MX), PSA 20-100 ng/ mL and age ≤75 years were identified in the National Prostate Cancer Register of Sweden., Data on co-morbidity diagnoses were obtained from the National Patient Register and cause of death from the Cause of Death Register., Following adjustment for age at diagnosis, co-morbidity burden, Gleason score, T-category, PSA level and cause-specific mortality in relation to treatment were estimated using Cox regression analysis., Result A total of 11 380 men were diagnosed with PCa between 1996 and 2008 and fulfilled the inclusion criteria., The cumulative 10-year PCa-specific mortality was 36% for patients receiving only palliative treatment and 13% for those treated with curative intent., For the 8462 (74%) patients with PSA levels from 20 to 50 ng/ mL at diagnosis, the hazard ratio for death from PCa was 0.23 (95% confidence interval 0.19-0.27) for those treated with curative intent compared with those given palliative treatment after adjusting for age, co-morbidity, T category, PSA level and Gleason score. The corresponding hazard ratio was 0.22 (95% confidence interval 0.17-0.30) for patients with PSA levels from 51 to 100 ng/ mL., Conclusion Treatment with curative intent for men with high-risk PCa was associated with reduced cause-specific mortality and should be considered even when serum PSA exceeds 20 ng/ mL. [ABSTRACT FROM AUTHOR]

Study Type - Diagnostic (inception cohort) Level of Evidence 2b What's known on the subject? and What does the study add? In spite of its low specificity, PSA is the most widely used screening test for prostate cancer (PCa), and is considered the main cause of the stage migration recently observed. The ratio of free to total PSA (%fPSA) has been shown to increase PSA accuracy in cancer detection; however, few screening studies have systematically evaluated its role in cancer detection rates in men with PSA levels <4.0 ng/mL and normal DRE. The present study supports a possible role of %fPSA as an adjunct to screening in men with total PSA 2.5-4.0 ng/mL and normal DRE, with a marked increase in cancer detection rates in a large Brazilian PCa screening study. We believe that %fPSA maybe a useful refinement to biopsy indications in men with low PSA levels. OBJECTIVE To evaluate the role of the free to total prostate-specific antigen ratio (%fPSA) in identifying prostate cancer (PCa) in men with a prostate-specific antigen (PSA) level of 2.5-3.9 ng/mL and a normal digital rectal examination (DRE)., PATIENTS AND METHODS A prospective PCa screening study was conducted, which included 17 571 men aged ≥45 years, across six Brazilian states, where men were recalled for further evaluation in the case of either a suspicious DRE and/or PSA ≥4.0 ng/mL, or PSA 2.5-3.9 ng/mL and %fPSA ≤15., We evaluated the impact of a %fPSA ≤15 on cancer detection rates and the clinical and pathological stage of tumours in men with a normal DRE and PSA 2.5-3.9 ng/mL., RESULTS When suspicious DRE and/or PSA ≥4.0 ng/mL were considered as criteria to prompt further evaluation, the cancer detection rate was 3.1%. When %fPSA ≤15 in men with total PSA levels of 2.5-3.9 ng/mL were considered as criteria, the PCa detection rate increased to 3.7%. Considering %fPSA ≤15 in men with PSA 2.5-3.9 ng/mL and normal DRE, the positive predictive value of biopsy was 31.1%., Clinical stage was more favourable among men with PSA 2.5-3.9 ng/mL, normal DRE, and %fPSA ≤15 compared with men with normal DRE and PSA ≥4.0 ng/mL ( P= 0.02)., Among those who underwent radical prostatectomy, pathological stage and the proportion of insignificant tumours were similar between men with PSA 2.5-3.9 ng/mL, normal DRE findings and %fPSA ≤15, and men with PSA ≥4.0 ng/mL., CONCLUSIONS The use of %fPSA ≤15 as a biopsy indication in men with normal DRE and PSA 2.5-4.0 ng/mL in a PCa screening programme, increased cancer detection rates. Tumours in this subset of patients had similar pathological characteristics., Using %fPSA ≤15 to indicate biopsy in men with PSA 2.5-3.9 ng/mL is a useful adjunct to PCa screening. [ABSTRACT FROM AUTHOR]

Purpose: Radical prostatectomy has decreased prostate cancer specific mortality in men with clinically localized prostate cancer. We report oncological outcomes of the longest running series of nerve sparing radical retropubic prostatectomy on the 30th anniversary of the inaugural operation. Materials and Methods: A total of 4,478 men underwent anatomical radical retropubic prostatectomy, as performed by a single surgeon (PCW), at the Johns Hopkins Medical Institutions from 1982 to 2011, without neoadjuvant or adjuvant therapy. During a median followup of 10 years (range 1 to 29), we examined progression-free, metastasis-free and cancer specific survival. Results: The overall 25-year progression-free, metastasis-free and cancer specific survival rates were 68%, 84% and 86%, respectively, although there were significant differences in treatment outcomes between men treated in the pre-PSA and PSA eras. In each era, there were significant differences in progression-free, metastasis-free and cancer specific survival by D''Amico risk groups. In multivariable models considering prostatectomy features, pathological stage and grade were significantly associated with the risk of metastatic progression and disease specific mortality. Conclusions: Excellent prostate cancer specific survival was demonstrated up to 30 years after surgery. Clinical risk categories and pathological tumor features were significant predictors of long-term disease specific outcomes, supporting their ongoing use in risk stratification and management decisions. Anatomical radical retropubic prostatectomy continues to represent the gold standard in the surgical management of clinically localized prostate cancer to which alternate treatment options should be compared. [Copyright &y& Elsevier]

Purpose: The detection of prostate cancer relies primarily on abnormal digital rectal examination or increased serum prostate specific antigen concentration. However, low positive predictive values result in many men with increased prostate specific antigen and/or suspicious digital rectal examination having a negative biopsy. We investigated the value of the PCA3 (prostate cancer gene 3) urine test in predicting the likelihood of diagnosis of cancer before biopsy. Materials and Methods: We performed a prospective, community based clinical trial to evaluate PCA3 score before any biopsy. This trial was conducted at 50 urology practices in the United States. Samples were obtained from 1,962 men with increased serum prostate specific antigen (greater than 2.5 ng/ml) and/or abnormal digital rectal examination before transrectal prostate needle biopsy. Study samples (urinary PCA3 and biopsies) were processed and analyzed by a central laboratory. Sensitivity-specificity analyses were conducted. Results: A total of 1,913 urine samples (97.5%) were adequate for PCA3 testing. Of 802 cases diagnosed with prostate cancer 222 had high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation and were suspicious for cancer, whereas 889 cases were benign. The traditional PCA3 cutoff of 35 reduced the number of false-positives from 1,089 to 249, a 77.1% reduction. However, false-negatives (missed cancers) increased significantly from 17 to 413, an increase of more than 2,300%. Lowering the PCA3 cutoff to 10 reduced the number of false-positives 35.4% and false-negatives only increased 5.6%. Conclusions: Urinary PCA3 testing in conjunction with prostate specific antigen has the potential to significantly decrease the number of unnecessary prostate biopsies. [ABSTRACT FROM AUTHOR]

Purpose: Active surveillance is increasingly recommended to reduce overtreatment in men with favorable risk prostate cancer. A repeat confirmatory biopsy has become the standard recommendation for these men to increase the precision of this risk attribution. We investigate the usefulness of this approach by comparing the current practice standard, repeat transrectal ultrasound biopsy, with template prostate mapping. Materials and Methods: A total of 124 men who were attributed a favorable risk prostate cancer status based on transrectal ultrasound guided biopsy and who were considering a policy of active surveillance underwent combined transrectal ultrasound biopsy and template prostate mapping as a confirmatory strategy. Maximum Gleason grade and disease burden were compared between the 2 confirmatory tests. Results: Depending on the definition used between 8% and 22% of men had prostate cancer reclassified as clinically important by repeat transrectal ultrasound biopsy whereas template guided prostate mapping reclassified the disease in 41% to 85% of the men. Repeat transrectal ultrasound biopsy failed to detect up to 80% of clinically important cancers detected by the reference standard. The sensitivity of repeat transrectal ultrasound biopsy to identify clinically important disease varied from 9% to 24% with the negative predictive value ranging from 23% to 60%. Conclusions: When applied to a population of men initially deemed to have favorable risk prostate cancer, transrectal ultrasound biopsy will miss a large proportion of clinically important cancers compared to template guided prostate mapping. The usefulness of repeat transrectal ultrasound biopsy in ruling out clinically important prostate cancer needs to be reconsidered. [Copyright &y& Elsevier]

Purpose: We examined the effect of 5α-reductase inhibitor therapy on prostate cancer detection in men with persistently increased or fluctuating prostate specific antigen and prior negative prostate cancer biopsy. Materials and Methods: A total of 276 men with prostate specific antigen greater than 4 ng/ml (208) or a prostate specific antigen velocity change of 0.75 ng/ml (68) and a normal digital rectal examination who had previously undergone biopsy a minimum of 2 times with prostate cancer not detected were given 5 mg finasteride (154) or dutasteride (122) daily. In phase 1, 97 patients had prostate specific antigen measured at 6 and 12 months with repeat transrectal ultrasonography and biopsy (12 cores) performed at 1 year. In phase 2, 179 patients underwent biopsy triggered by a change in nadir prostate specific antigen of more than 0.4 ng/ml. Results: In phase 1 at 1 year prostate specific antigen had decreased by 2.4 ng/ml (−46.7%), and prostate volume had decreased 7.1 ml (−17.9%). Prostate cancer was detected in 27 of 97 (27.8%) patients and the mean minimum prostate specific antigen velocity from a nadir of 0.4 ng/ml was 0.6 ng/ml. In phase 2, 48 of 179 (26.8%) men underwent repeat biopsy at a mean of 14.6 months. Of these 48 men 26 (54.1%) were found to have prostate cancer. Of the 26 men in whom prostate cancer was detected 20 (76.9%) were found to have Gleason score 7 or greater disease. Conclusions: The magnitude of change in serum prostate specific antigen after 5α-reductase inhibitor therapy may be useful in diagnosing prostate cancer in patients with persistently increased or fluctuating prostate specific antigen and prior negative prostate biopsy. [Copyright &y& Elsevier]

. Thomas J-A II, Gerber L, Moreira DM, Hamilton RJ, Bañez LL, Castro-Santamaria R, Andriole GL, Isaacs WB, Xu J, Freedland SJ (Durham VA Medical Center, Durham, NC, USA; Duke University School of Medicine, Durham, NC, USA; The Author Smith Institute for Urology, New Hyde Park, NY, USA; Memorial Sloan-Kettering Cancer Center, New York, NY, USA; GlaxoSmithKline, Research Triangle Park, NC, USA; Washington University School of Medicine, St. Louis, MO, USA; Johns Hopkins Hospital, Baltimore, MD, USA; Wake Forest University, Winston-Salem, NC, USA; and Duke University School of Medicine, Durham, NC, USA). Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1). J Intern Med 2012; 272: 85-92. Background. To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases. Methods. Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5-10.0 ng mL−1 and a negative prestudy biopsy. Among men undergoing at least one on-study biopsy with complete data ( n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics. Results. A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22-1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73-1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38-2.15) ( P-interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72-3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84-1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region. Conclusions. In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification. [ABSTRACT FROM AUTHOR]

Summary: Cancer is a growth process and it is natural that we should be concerned with how the routinely used marker of prostate cancer tumour burden – PSA – changes over time. Such change is measured by PSA velocity or PSA doubling time, described in general as “PSA kinetics”. However, it turns out that calculation of PSA velocity and doubling time is far from straightforward. More than 20 different methods have been proposed, and many of these give quite divergent results. There is clear evidence that PSA kinetics are critical for understanding prognosis in advanced or relapsed prostate cancer. However, PSA kinetics have no value for men with an untreated prostate: neither PSA velocity nor doubling time have any role in diagnosing prostate cancer or providing a prognosis for men before treatment. [ABSTRACT FROM AUTHOR]

To quantify the downstream impact of PSA testing on cancer characteristics and utilization of cancer therapies among men aged 70 or older, we utilized patients diagnosed with prostate cancer in 2004-2005 in the Surveillance, Epidemiology and End Results (SEER)-Medicare and their Medicare claims before their cancer diagnosis during 2000-2005. Among men in the highest testing group (4-6 PSA tests), 75% were diagnosed with low- or intermediate-risk of disease, but 77% received treatments within 180 days of cancer diagnosis. More than 45% of newly diagnosed patients in 2004-2005 had 4-6 PSA tests before their cancer diagnosis during 2000-2005. Men in the high testing group were 3.57 times more likely to receive cancer treatments (either surgery, radiation or hormonal therapy) when compared with men who had no previous PSA testing during the same time period. Among men aged 75+ diagnosed with low-risk cancer, men in the high testing group were 78% more likely to receive treatment than those who had no previous PSA testing. In conclusion, given the lack of evidence of effective treatment for elderly patients diagnosed with low- and intermediate-risk prostate cancer and our inability to distinguish indolent from aggressive cancer, more frequent PSA testing among elderly population may exacerbate the risk of overdiagnosis and overtreatment. [ABSTRACT FROM AUTHOR]

The article discusses a study which determined the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. Statistical analysis showed the significant increase in the risk of prostate cancer among healthy men who received vitamin E dietary supplements. According to data, 620 men in the vitamin E group and 575 men in the selenium group developed prostate cancer, compared with 529 men in the placebo group. Data indicate the frequency of use of prostate-specific antigen (PSA) and digital rectal examination, as well as the rate of prostate cancer detection in all the treatment groups.

Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? It has been reported that patients with Gleason 6 prostate cancer detected in a single microfocal positive core may actually harbour more aggressive disease. Meanwhile, several studies analyzing cases of single microfocal prostate cancer included a significant number of patients with serum PSA ≥ 10 ng/mL. Also, significant proportions of currently available published data on actual pathological characteristics of prostate cancer with favourable biopsy features were obtained from patients who underwent prostate biopsies performed in non-systematic fashion at different institutions and/or via non-contemporary scheme, such as sextant biopsy. Although PSA density can be considered an independent predictor of pathologically insignificant tumour among the patients with PSA ≤ 10 ng/mL and only a single microfocal tumour detected via multi (≥12)-core biopsy, clinical and biopsy-related parameters currently available have limited value in predicting pathologically insignificant or unfavourable prostate cancer in such patients. OBJECTIVE • To examine potential predictors of pathological outcomes for a single microfocal (≤3 mm) positive prostate cancer detected via contemporary biopsy scheme in patients presenting with prostate-specific antigen (PSA) ≤10 ng/mL. PATIENTS AND METHODS • We reviewed the data of 119 patients who had prebiopsy PSA ≤ 10 ng/mL and a single microfocal (≤3 mm) Gleason ≤6 prostate cancer identified via multicore (≥12) biopsy and who subsequently underwent radical prostatectomy (RP). • We assessed the rates of insignificant prostate cancer (organ-confined and pathological Gleason ≤6 with tumour volume <0.5 mL) and unfavourable prostate cancer (upstaging and/or upgrading) by analysing pathological findings. • Potential preoperative predictors of insignificant or unfavourable prostate cancer were analysed. Multivariable models for predicting insignificant and unfavourable tumours were devised and evaluated. RESULTS • Overall rates of insignificant and unfavourable prostate cancer were 44.5% and 24.4%, respectively. In multivariate analysis, only PSA density was an independent predictor of insignificant prostate cancer. • Predictive accuracies of multivariable models for predicting insignificant prostate cancer did not exceed 68.2%. No significant predictor for pathologically unfavourable tumour was found in multivariate analysis. • All versions of the multivariable model devised for prediction of unfavourable tumour showed predictive accuracies ≤66.9%. CONCLUSION • Although PSA density can be considered an independent predictor of pathologically insignificant tumour among patients with PSA ≤10 ng/mL and only a single microfocal tumour detected via multicore (≥12) biopsy, the clinical and biopsy-related parameters that are currently available have limited value in predicting pathologically insignificant or unfavourable prostate cancer in such patients. [ABSTRACT FROM AUTHOR]

Abstract: Prostate cancer (PCa) is one of the most common types of cancer in men in the United States and is the second leading cause of cancer related death in men. Clinically, secreted prostate specific antigen (PSA) has gained recognition because of its proteolytic activity being directly linked to PCa cell proliferation leading to disease initiation and progression. Using phage display technology, we identified four distinct cyclical peptides. These peptides apart from differences in their amino acid sequence, elicited minimal cross reactive antibody responses against each other. One of the four peptides analyzed produced an antibody response that recognizes the PSA protein. We demonstrate that the synthetic PSA peptide mimics identified in our study are immunologically active and produce neutralizing activity and this has relevance and utility for prostate cancer disease progression. [Copyright &y& Elsevier]

Objective: To test the hypothesis that there is no significant difference in the rate of prostate cancer (PCa) detection rate between the transrectal and transperineal approach in men undergoing a saturation (24-core) prostate rebiopsy. Methods: We evaluated 472 consecutive men who underwent a 24-core prostate rebiopsy at 2 tertiary referral centers. Of these, 70% (332) underwent a transrectal biopsy, and 30% (140) underwent a transperineal biopsy. Propensity score was used to match 280 patients with homogeneous characteristics; those represented the final study cohort. Univariable and multivariable logistic regression analyses were used to address the relationship between biopsy approach and PCa detection rate. Covariates consisted of age at biopsy, prostate-specific antigen, total prostate volume, digital rectal examination findings, histologic findings on previous biopsy, and the number of previous negative biopsy sets. Results: Overall, PCa detection rate was 28.6%. There was no statistically significant difference in PCa detection rate between the transrectal and transperineal approach (31.4% vs 25.7%, respectively; P = .3). The type of approach was not an independent predictor of PCa detection rate at multivariable analyses (odds ratio = 0.61, P = .1). Conclusions: Transrectal and transperineal prostate saturation biopsies have a similar PCa detection rate in men undergoing a saturation rebiopsy. Both approaches can be offered to men undergoing a prostate rebiopsy without undermining the rate of PCa detection. [ABSTRACT FROM AUTHOR]

The article highlights a study on prostate-specific antigen (PSA) velocity, which is the rate of PSA level increases that is being used to determine when to conduct biopsy for prostate cancer. Using data from the Prostate Cancer Prevention Trial (PCPT), it was concluded that using PSA velocity, as the National Comprehensive Cancer Network (NCCN) guidelines suggest, would lead to many unnecessary biopsies. The guidelines require biopsy for men whose PSA is rising more than 0.35 ng/mL per year.