Free Prostate Research Articles

Can Mean Platelet Volume Serve as a Marker for Prostatitis?

Aim: The aim of the study was to compare the yield of mean platelet volume (MPV), total prostate specific antigen (tPSA), free prostate specific antigen (fPSA), f/t PSA ratio and complex prostate specific antigen (cPSA) in patients with prostatitis.Material and method: The study was designed in the Kayseri Education and Research Hospital. Ninety-six patients with prostatitis were enrolled retrospectively into the study. Laboratory data were obtained from the computerized patient database. We evaluated the correlation between tPSA, fPSa, f/t PSA ratio, cPSA, MPV and extent and aggressiveness of inflammation in the surgical specimens of patients who underwent surgery for benign prostatic hyperplasia (BPH). Inflammation in the prostatic tissues was scored for extent and aggressivity of inflammation using the grading system designed by Irani et al.Results: The total PSA, fPSa, f/t PSA ratio, cPSA and pre- and post-treatment MPV values of each group did not differ (p>0.05) (Table 1). Also there was no correlation between the histopathological grades and the MPV, tPSA, fPSA, f/t PSA ratio and cPSA of patients. However, MPV values significantly decreased after treatment in all grades of prostatitis (p<0.001).Conclusion: MPV values may be used as an inflammation marker in patients with prostatitis.

Role of magnetic Fe3O4 graphene oxide in chemiluminescent aptasensors capable of sensing tumor markers in human serum

Using π–π stacking interaction between magnetic Fe3O4 graphene oxide nanoparticles and impurities (e.g., biomolecules, free prostate specific antigen (PSA) aptamer-conjugated TEX615 that does not bind with PSA) in human serum, a rapid aptasensor with 1,1′-oxalyldiimidazole chemiluminescence (ODI-CL) detection was developed for the quantification of PSA, a tumor marker. The complexes, PSA bound with PSA aptamer-conjugated TEX615, were formed in human serum while the mixture (1 : 1 volume ratio) of PSA in 25% human serum diluted in Tris–HCl buffer (pH 7.5) and PSA aptamer-conjugated TEX615 in Tris–HCl buffer was incubated for 30 minutes. After the incubation, the impurities capable of reducing the efficiency of the aptasensor were removed using magnetic Fe3O4 graphene oxide nanoparticles. With the addition of ODI CL reagents (e.g., ODI, H2O2), finally, PSA in each sample was quantified within 1 second. The sensitivity of the aptasensor with good accuracy, precision, and recovery was as good as those of enzyme immunoassays with absorbance and chemiluminescence detections operated using time-consuming procedures such as multiple-time incubation and washing and expensive and intractable antibodies.

Serum levels of cancer biomarkers in diabetic and non-diabetic proteinuric patients: a preliminary study

Cancer biomarkers (CBs) can be used in early detection of several cancers as well as in detection of recurrence and following response to treatment. We aimed to investigate the levels of CBs in proteinuric patients with primary glomerular disease (PGD) and diabetes mellitus, and compare them with healthy controls. One hundred and two patients with untreated PGD, 62 proteinuric patients with diabetic nephropathy, and 84 healthy controls were enrolled. Levels of cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3), carcinoembriogenic antigen (CEA), α-fetoprotein (AFP), total prostate specific antigen (TPSA), free prostate specific antigen (FPSA) and carbohydrate antigen 19-9 (CA 19-9) were measured. Compared to healthy controls, levels of CA 125, CA 15-3 and CA 19-9 were higher in patients with PGD and diabetic patients (all p<0.05), while levels of TPSA, FPSA, AFP and CEA were lower (all p<0.05). There was no correlation between levels of cancer biomarkers and serum fibrinogen and serum amyloid A protein levels (all p>0.05). Both urinary protein excretion rate and serum albumin levels were correlated with all CBs (all p<0.05). CBs levels seem to be changed in different proteinuric patients. This condition should be kept in mind when evaluating CBs levels in proteinuric patients.

Prospective Multicenter Evaluation of the Beckman Coulter Prostate Health Index Using WHO Calibration

Reported prostate specific antigen values may differ substantially among assays using Hybritech® or WHO standardization. The Beckman Coulter® Prostate Health Index and [-2]proPSA are newly approved serum markers associated with prostate cancer risk and aggressiveness. We studied the influence of assay standardization on these markers. Prostate specific antigen, percent free prostate specific antigen and [-2]proPSA were measured using Hybritech calibration in 892 men from a prospective, multicenter study undergoing prostate biopsy. We calculated the Prostate Health Index using the equation, ([-2]proPSA/free prostate specific antigen) × PSA. Index performance characteristics for prostate cancer detection were then determined using recalculated WHO calibration prostate specific antigen values. The median Prostate Health Index was significantly higher in men with prostate cancer than in those with negative biopsies using WHO values (47.4 vs 39.8, p <0.001). The index offered improved discrimination of prostate cancer detection on biopsy (AUC 0.704) compared to percent free or total prostate specific antigen using the WHO calibration. The Prostate Health Index can be calculated using Hybritech or WHO standardized assays. It significantly improved prediction of the biopsy outcome over that of percent free or prostate specific antigen alone.

Value of Prostate Specific Antigen Density and Percent Free Prostate Specific Antigen for Prostate Cancer Prognosis

Limited data exist on the relationship of percent free prostate specific antigen and prostate specific antigen density with prostate cancer prognosis. Therefore, we compared percent free prostate specific antigen and prostate specific antigen density with prostate specific antigen, Gleason sum and stage to predict prostate cancer prognosis in a large cohort using a single prostate specific antigen and free prostate specific antigen assay. Between 1999 and 2007 a total of 1,656 patients with prostate cancer underwent laparoscopic radical prostatectomy at the Charité Berlin. There were 322 patients excluded from analysis for a variety of reasons. The final 1,334 patients had prostate specific antigen, free prostate specific antigen, prostate volume and complete pathological analysis available. Median followup was 60.3 months (range 0.2 to 135). Median age (63 years, range 43 to 75) did not differ between the 1,092 patients without and the 242 with biochemical recurrence (p = 0.956), but prostate volume, prostate specific antigen and percent free prostate specific antigen differed significantly (p <0.0001). While prostate specific antigen and prostate specific antigen density increased significantly in patients with Gleason less than 7, 7 and greater than 7 tumors, percent free prostate specific antigen decreased significantly (p <0.0001). Prostate specific antigen, percent free prostate specific antigen and prostate specific antigen density differed significantly between pT2 and pT3 tumors, and between patients with vs without positive surgical margins. On univariate analysis Gleason sum, pathological stage, positive surgical margin, total prostate specific antigen, percent free prostate specific antigen and prostate specific antigen density were predictors of biochemical recurrence-free survival. Multivariate Cox regression analysis identified Gleason sum, pathological stage, positive surgical margin and prostate specific antigen density as independent predictors of biochemical recurrence-free survival, while percent free prostate specific antigen and total prostate specific antigen failed to be significant. Few models for prostate cancer prognosis include prostate specific antigen density. There is substantial value in prostate specific antigen density but not in percent free prostate specific antigen for improving prostate cancer prognosis and biochemical recurrence prediction.

Simultaneous electrochemical detection of multiple tumor markers based on dual catalysis amplification of multi-functionalized onion-like mesoporous graphene sheets

In this work, a sandwich-type electrochemical immunosensor for simultaneous sensitive detection of prostate specific antigen (PSA) and free prostate specific antigen (fPSA) is fabricated. Gold nanoparticles (AuNPs) modified Prussian blue and nickel hexacyanoferrates nanoparticles were firstly prepared, respectively, and then decorated onion-like mesoporous graphene sheets (denoted as Au@PBNPs/O-GS and Au@NiNPs/O-GS) as distinguishable signal tags to label different detection antibodies. Subsequently, streptavidin and biotinylated alkaline phosphatase (bio-AP) were employed to block the possible remaining active sites. With the employment of the as prepared nanohybrids, the dual catalysis amplification can be achieved by catalysis of the ascorbic acid 2-phosphate to in situ produce AA in the presence of bio-AP, and then AA was further catalyzed by Au@PBNPs/O-GS and Au@NiNPs/O-GS nanohybrids, respectively, to obtain the higher signal responses. The experiment results show that the linear range of the proposed immunosensor for simultaneous determination of fPSA is from 0.02 to 10ngmL−1 with a detection limit of 6.7pgmL−1 and PSA is from 0.01 to 50ngmL−1 with a detection limit of 3.4pgmL−1 (S/N=3). Importantly, the proposed method offers promise for rapid, simple and cost-effective analysis of biological samples.

Development and Internal Validation of a Prostate Health Index Based Nomogram for Predicting Prostate Cancer at Extended Biopsy

We developed and validated a Prostate Health Index (Beckman Coulter, Brea, California) based nomogram to predict prostate cancer at extended prostate biopsy. The study population consisted of 729 patients who were scheduled for prostate biopsy following suspicious digital rectal examination and/or increased prostate specific antigen. Total and free prostate specific antigen, percent free-to-total prostate specific antigen, [-2]proPSA and the prostate health index [([-2]proPSA/free prostate specific antigen) × √total prostate specific antigen)] were determined. Logistic regression models were fitted to test prostate cancer predictors. Predictive accuracy estimates of biopsy outcome predictions were quantified. Regression coefficients were used to create a decision making tool to predict prostate cancer. A calibration plot was used to evaluate the extent of overestimating or underestimating the observed prostate cancer rate. Decision curve analysis provided an estimate of the net benefit obtained using the prostate health index based nomogram. Overall 280 of 729 patients (38.4%) were diagnosed with prostate cancer at extended prostate biopsy. On accuracy analyses prostate health index emerged as the most informative predictor of prostate cancer (AUC 0.70) compared to established predictors, such as total prostate specific antigen (0.51) and percent free-to-total prostate specific antigen (0.62). Including the prostate health index in a multivariable logistic regression model based on patient age, prostate volume, digital rectal examination and biopsy history significantly increased predictive accuracy by 7% from 0.73 to 0.80 (p <0.001). Nomogram calibration was good. Decision curve analysis showed that using the prostate health index based nomogram resulted in the highest net benefit. The prostate health index based nomogram can assist clinicians in the decision to perform biopsy by providing an accurate estimation of an individual risk of prostate cancer.

Serum Index Test %[-2]proPSA and Prostate Health Index are More Accurate than Prostate Specific Antigen and %fPSA in Predicting a Positive Repeat Prostate Biopsy

We tested the hypothesis that serum isoform [-2]proPSA derivatives %p2PSA and Prostate Health Index are accurate predictors of prostate cancer in men scheduled for repeat biopsy. The study was an observational prospective evaluation of a clinical cohort of men with 1 or 2 previous negative prostate biopsies, with persistent suspicion of prostate cancer. They were enrolled in the study to determine the diagnostic accuracy of %p2PSA using the formula, (p2PSA pg/ml)/(free prostate specific antigen ng/ml × 1,000)]× 100, and Beckman-Coulter Prostate Health Index using the formula, (p2PSA/free prostate specific antigen) × √total prostate specific antigen), and to compare it with the accuracy of established prostate cancer serum tests (total prostate specific antigen, free prostate specific antigen and percent free prostate specific antigen). Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. Prostate cancer was found in 71 of 222 (31.9%) subjects. %p2PSA and Prostate Health Index were the most accurate predictors of disease. %p2PSA significantly outperformed total prostate specific antigen, free prostate specific antigen, percent free prostate specific antigen and p2PSA in the prediction of prostate cancer (p ≤0.01), but not Prostate Health Index (p = 0.094). Prostate Health Index significantly outperformed total prostate specific antigen and p2PSA (p ≤0.001) but not free prostate specific antigen (p = 0.109) and free/total prostate specific antigen (p = 0.136). In multivariable logistic regression models %p2PSA and Prostate Health Index achieved independent predictor status, and significantly increased the accuracy of multivariable models including prostate specific antigen and prostate volume with or without percent free prostate specific antigen and prostate specific antigen density by 8% to 11% (p ≤0.034). At a %p2PSA cutoff of 1.23, 153 (68.9%) biopsies could have been avoided, missing prostate cancer in 6 patients. At a Prostate Health Index cutoff of 28.8, 116 (52.25%) biopsies could have been avoided, missing prostate cancer in 6 patients. Serum %p2PSA and Prostate Health Index are more accurate than standard reference tests in predicting repeat prostate biopsy outcome, and could avoid unnecessary repeat biopsies.

The value of percentage free prostate specific antigen (PSA) in the detection of prostate cancer among patients with intermediate levels of total PSA (4.0–10.0 ng/mL) in Nigeria

ObjectivesTo assess the value of percentage free prostate-specific antigen (%fPSA) in the detection of prostate cancer among Nigerian men with an intermediate total PSA level (4–10ng/mL), and to show if the optimum threshold for biopsy is different from Caucasian values when the widely used (six-core, digitally directed) prostate biopsy protocol in Nigerians is applied. Patients and methodsThe study included 105 patients aged >50years, with a palpably benign prostate gland and intermediate levels of total PSA (4–10ng/mL). These patients had a free PSA assay and a transrectal digitally directed six-core biopsy of the prostate. The %fPSA was calculated and the optimum threshold value for detecting prostate cancer was determined. ResultsThe mean (SD) age of the patients was 64.4 (6.6) years and their mean (SD) total PSA level was 6.6 (1.7)ng/mL. Of these men 14 (13.3%) had cancer of the prostate detected by the prostate biopsy. The %fPSA level related directly to sensitivity values but inversely to the specificity and the positive predictive values. The best threshold of %fPSA for detecting cancer in these men was <40%, with a sensitivity of 100%, specificity of 93.4% and a positive predictive value of 70% (P<0.05). ConclusionsIn evaluating Nigerian patients with a palpably benign prostate gland and within the intermediate total PSA range, when digitally directed biopsy protocol is adopted, a %fPSA threshold of <40% will detect significant percentage of those with prostate cancer, with a minimal number of unnecessary biopsies. This value differs from that reported in western studies in which transrectal ultrasonography-directed biopsy was used.

Does antibiotherapy prevent unnecessary prostate biopsies in patients with high PSA values?

IntroductionWe investigated if antibiotherapy has any role on total prostate specific antigen (tPSA), free prostate specific antigen (fPSA) and fPSA/tPSA ratio in patients with tPSA higher than 2.5ng/ml. We also analyzed if it has any relation with prostate cancer diagnosis rate. Material and methodsA total of 108 patients older than 50 years of age with lower urinary system symptoms and tPSA>2.5ng/ml were included in this study. Antibiotherapy was given to all the cases for three weeks. After that, transrectal ultrasound-guided prostate biopsies were taken from all the patients. Before and after antibiotherapy, “The International Prostate Symptom Score” (IPSS) and “National Institutes of Health Chronic Prostatitis Symptom Index” (NIH-CPSI) questionnaires are performed and serum tPSA, fPSA and fPSA/tPSA values are obtained. ResultstPSA, fPSA and fPSA/tPSA ratio alterations prior to and after antibiotherapy did not show any statistically significant difference (p>0.05). When prostate adenocarcinoma was excluded, a statistically significant decrease was found in IPSS and NIH-CPSI scores for all cases. ConclusionsAntibiotherapy given to patients with prostate specific antigen (PSA) levels higher than threshold value has not led to significant change in prostate needle biopsy decision. Prostate biopsy should be considered without trying antibiotherapy in patients with high PSA values if a suspicion of prostatitis does not exist.

2010 “PROSTATE PAL” - EMPOWERING PATIENTS TO MONITOR UROLOGIC HEALTH WITH MOBILE TECHNOLOGY

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Surgical Therapy and New Technology II1 Apr 20122010 “PROSTATE PAL” - EMPOWERING PATIENTS TO MONITOR UROLOGIC HEALTH WITH MOBILE TECHNOLOGY Benjamin Herrick, Cameron Banga, Michael Phelps, and Ronald Yap Benjamin HerrickBenjamin Herrick Lebanon, NH More articles by this author , Cameron BangaCameron Banga Hobart, IN More articles by this author , Michael PhelpsMichael Phelps Hobart, IN More articles by this author , and Ronald YapRonald Yap Concord, NH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2173AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The mobile technology revolution provides an opportunity for patients to better monitor their urologic health. We report the construction and initial usage data regarding the free prostate health Apple iOS app, “Prostate Pal”. METHODS A voiding diary, AUA symptom score tracker, and PSA tracker were programmed into a solitary Apple iOS based app. The Apple Software Development Kit was used with programming in Objective C 2.0. The app was accepted by the Apple app review team and distributed without charge on the App Store. Google Analytics was used to track usage data from January 1, 2011 through November 10, 2011. RESULTS During the study period, 1569 unique visitors used the mobile application a total of 3550 times. The top 3 visiting countries were: USA (1629 visits/45.9%), Brazil (306 visits/8.6%), and UK (207 visits/5.8%). In the application, section page views were as follows: voiding diary 4333 pages (44.5%), AUA score 2843 pages (29.2%), and PSA tracker 2555 pages (26.3%). CONCLUSIONS It is feasible to create a mobile urologic app for widespread distribution on the Apple App Store. Though predominant visits were from the USA, usage data also demonstrates international interest in this app. Users were most interested in the voiding diary functionality. As mobile technology becomes more widespread and standard, healthcare apps have the potential to improve doctor/patient communication and patient care. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e811-e812 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benjamin Herrick Lebanon, NH More articles by this author Cameron Banga Hobart, IN More articles by this author Michael Phelps Hobart, IN More articles by this author Ronald Yap Concord, NH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Association Between Smoking Status, and Free, Total and Percent Free Prostate Specific Antigen

There are scant data available on the relationship between smoking and total prostate specific antigen, free prostate specific antigen and percent-free prostate specific antigen. Given the high prevalence of smoking and the frequency of prostate specific antigen screening, it is important to determine any association between smoking and prostate specific antigen values using nationally representative data. Included in the final study population were 3,820 men 40 years old or older who participated in the 2001-2006 NHANES (National Health and Nutrition Examination Survey) and met the eligibility criteria for prostate specific antigen testing. The distributions of total, free and percent free prostate specific antigen were estimated by sociodemographic and clinical characteristics. Multivariate linear regression models were fit to determine the adjusted relationship between smoking and total and percent free prostate specific antigen while simultaneously controlling for these characteristics. For all ages combined the median total and free prostate specific antigen levels were 0.90 (0.81-0.90) and 0.26 (0.25-0.28) ng/ml, respectively. Multivariate linear regression analysis showed that total prostate specific antigen was 7.9% and 12.2% lower among current and former smokers, respectively, than among never smokers. High body mass index and diabetes were also statistically significantly associated with a lower total prostate specific antigen. Approximately a third of the men had a percent free prostate specific antigen less than 25%. Current smokers had a significantly lower percent free prostate specific antigen than former smokers. Our finding that smoking is inversely associated with total prostate specific antigen may have potential implications for the interpretation of prostate specific antigen levels in men who are current or former smokers. Given the high prevalence of smoking, obesity and diabetes, additional research on the combined effect of these health risk factors is warranted.

Long-term quality of life in disadvantaged men with prostate cancer on androgen-deprivation therapy

To explore the effects of androgen-deprivation therapy (ADT) on general, disease-specific and hormone-specific health-related quality of life (HRQOL) among minority men. Men enrolled in a state-funded program, providing free prostate cancer treatment for underserved men, were recruited, if they had received at least 3 months of continuous ADT and/or other forms of primary treatment. HRQOL was assessed with validated measures including the RAND Medical Outcomes Study 12-item Health Short Form Survey (SF-12), the UCLA Prostate Cancer Index Survey and the Expanded Prostate Cancer Index Composite Survey. Repeated measures analysis was performed to evaluate the association between clinical and sociodemographic covariates with HRQOL. We enrolled 322 men, including 94 on ADT and 228 who received other forms of treatment. When controlling for patient characteristics, men receiving ADT had poorer outcomes relative to sexual function (P<0.01), sexual bother (P<0.01), hormonal function (P<0.01) and hormonal bother (P=0.02). ADT use was significantly associated with worsening sexual function (P<0.01) and sexual bother (P=0.01) over two years compared with non-ADT users. Analysis also demonstrated significant differences between whites, Hispanics and Others (African American (n=43, 16%), Asian (n=13, 5%), multiracial (n=1, 0.4%), Native American (n=1, 0.4%) and other (n=9, 3%)) relative to urinary bother (P=0.01), urinary function (P=0.01) and hormonal bother (P=0.03). ADT users had better urinary function and less bother than non-ADT users among the Other group, while the opposite was true for whites and Hispanics. For hormonal bother, ADT use was associated with worse outcomes across all three race/ethnicity groups; however, Hispanics were less bothered by their hormonal symptoms than whites or Others. Men of disadvantaged backgrounds on hormone therapy for prostate cancer experience declines in sexual and hormonal HRQOL. Whites and non-whites on ADT have significantly different HRQOL outcomes.

The Role of Self-Efficacy in Quality of Life for Disadvantaged Men With Prostate Cancer

Self-efficacy is associated with increased participation in treatment decision making and improved health related quality of life. We examined the influence of perceived efficacy in patient-physician interactions on health related quality of life among low income, uninsured men with prostate cancer during a 2-year period. We analyzed data derived on participants enrolled in a state funded program providing free prostate cancer treatment and care to indigent men. We used validated instruments to measure patient self-efficacy (confidence in interacting with physicians), and the general and prostate specific health related quality of life outcomes of urinary, sexual and bowel bother, symptom distress, psychological well-being and vitality. We performed repeated measures analysis with general linear mixed modeling to estimate the association of sociodemographic and clinical covariates with health related quality of life. Our cohort included a total of 472 observations in 99 men. Self-efficacy had a measurable effect on subjective measurements of general and disease specific health related quality of life. Men with the lowest self-efficacy had inferior mean health related quality of life scores across all outcomes. Low self-efficacy was significantly associated with worse bowel bother and general symptom distress during the 2-year study period. Similar health related quality of life outcomes trajectories were observed across self-efficacy categories. Of disadvantaged men with clinically localized prostate cancer those with the lowest self-efficacy in physician interactions fared worst across all measured domains of health related quality of life. Interventions to improve patient-physician communication in this population may provide physicians with a supplemental method by which to address health perceptions, mitigate symptom experience and improve health outcomes.

Changes in Prostate Specific Antigen in Hypogonadal Men After 12 Months of Testosterone Replacement Therapy: Support for the Prostate Saturation Theory

We measured prostate specific antigen after 12 months of testosterone replacement therapy in hypogonadal men. Data were collected from the TRiUS (Testim® Registry in the United States), an observational registry of hypogonadal men on testosterone replacement therapy (849). Participants were Testim naïve, had no prostate cancer and received 5 to 10 gm Testim 1% (testosterone gel) daily. A total of 451 patients with prostate specific antigen and total testosterone values were divided into group A (197 with total testosterone less than 250 ng/dl) and group B (254 with total testosterone 250 ng/dl or greater). The groups differed significantly in free testosterone and sex hormone-binding globulin, but not in age or prostate specific antigen. In group A but not group B prostate specific antigen correlated significantly with total testosterone (r=0.20, p=0.005), free testosterone (r=0.22, p=0.03) and sex hormone-binding globulin (r=0.59, p=0.002) at baseline. After 12 months of testosterone replacement therapy, increase in total testosterone (mean±SD) was statistically significant in group A (+326±295 ng/dl, p<0.001; final total testosterone 516±28 ng/dl) and group B (+154±217 ng/dl, p<0.001; final total testosterone 513±20 ng/dl). After 12 months of testosterone replacement therapy, increase in prostate specific antigen was statistically significant in group A (+0.19±0.61 ng/ml, p=0.02; final prostate specific antigen 1.26±0.96 ng/ml) but not in group B (+0.28±1.18 ng/ml, p=0.06; final prostate specific antigen 1.55±1.72 ng/ml). The average percent prostate specific antigen increase from baseline was higher in group A (21.9%) than in group B (14.1%). Overall the greatest prostate specific antigen was observed after 1 month of treatment and decreased thereafter. Patients with baseline total testosterone less than 250 ng/dl were more likely to have an increased prostate specific antigen after testosterone replacement therapy than those with baseline total testosterone 250 ng/dl or greater, supporting the prostate saturation hypothesis. Clinicians should be aware that severely hypogonadal patients may experience increased prostate specific antigen after testosterone replacement therapy.

Clinical Evaluation of the PCA3 Assay in Guiding Initial Biopsy Decisions

We evaluated the clinical utility of the PCA3 assay in guiding initial biopsy decisions in prostate cancer. A European, prospective, multicenter study enrolled men with a serum total prostate specific antigen of 2.5 to 10 ng/ml scheduled for initial biopsy. After digital rectal examination first catch urine was collected. PCA3 scores were determined using the PROGENSA(®) PCA3 assay and compared to biopsy outcome. The diagnostic accuracy of PCA3 was compared to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen. In 516 men the positive biopsy rate was 40%. An increasing PCA3 score corresponded with an increasing probability of a positive biopsy. The mean PCA3 score was higher in men with a positive vs a negative biopsy (69.6 vs 31.0, median 50 vs 18, p <0.0001). The PCA3 score was independent of age, total prostate specific antigen and prostate volume. The PCA3 score (cutoff of 35) had a sensitivity of 64% and specificity of 76%. ROC analysis showed a significantly higher AUC for the PCA3 score vs total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen. The PCA3 score was significantly higher in men with biopsy Gleason score 7 or greater vs less than 7, greater than 33% vs 33% or fewer positive cores and significant vs indolent prostate cancer. Inclusion of PCA3 in multivariable models increased their predictive accuracy by up to 5.5%. The PROGENSA PCA3 assay can aid in guiding biopsy decisions. It is superior to total prostate specific antigen, prostate specific antigen density and %free prostate specific antigen in predicting initial biopsy outcome, and may be indicative of prostate cancer aggressiveness.

A Multicenter Study of [-2]Pro-Prostate Specific Antigen Combined With Prostate Specific Antigen and Free Prostate Specific Antigen for Prostate Cancer Detection in the 2.0 to 10.0 ng/ml Prostate Specific Antigen Range

Prostate specific antigen and free prostate specific antigen have limited specificity to detect clinically significant, curable prostate cancer, leading to unnecessary biopsy, and detection and treatment of some indolent tumors. Specificity to detect clinically significant prostate cancer may be improved by [-2]pro-prostate specific antigen. We evaluated [-2]pro-prostate specific antigen, free prostate specific antigen and prostate specific antigen using the formula, ([-2]pro-prostate specific antigen/free prostate specific antigen × prostate specific antigen(1/2)) to enhance specificity to detect overall and high grade prostate cancer. We enrolled 892 men with no history of prostate cancer, normal rectal examination, prostate specific antigen 2 to 10 ng/ml and 6-core or greater prostate biopsy in a prospective multi-institutional trial. We examined the relationship of serum prostate specific antigen, free-to-total prostate specific antigen and the prostate health index with biopsy results. Primary end points were specificity and AUC using the prostate health index to detect overall and Gleason 7 or greater prostate cancer on biopsy compared with those of free-to-total prostate specific antigen. In the 2 to 10 ng/ml prostate specific antigen range at 80% to 95% sensitivity the specificity and AUC (0.703) of the prostate health index exceeded those of prostate specific antigen and free-to-total prostate specific antigen. An increasing prostate health index was associated with a 4.7-fold increased risk of prostate cancer and a 1.61-fold increased risk of Gleason score greater than or equal to 4 + 3 = 7 disease on biopsy. The AUC of the index exceeded that of free-to-total prostate specific antigen (0.724 vs 0.670) to discriminate prostate cancer with Gleason 4 or greater + 3 from lower grade disease or negative biopsy. Prostate health index results were not associated with age and prostate volume. The prostate health index may be useful in prostate cancer screening to decrease unnecessary biopsy in men 50 years old or older with prostate specific antigen 2 to 10 ng/ml and negative digital rectal examination with minimal loss in sensitivity.

On chip immuno-affinity profiling of cancer- and benign hyperplasia-associated free prostate specific antigen.

Prostate specific antigen (PSA) exhibits pronounced heterogeneity in both primary structure and glycan composition, resulting in the existence of different molecular forms. Investigation of PSA structure is a demanding task facing limitations due to inadequate sensitivity of analytical techniques and low concentrations of the different forms. This study aimed to profile free PSA (fPSA), especially lower molecular mass species lacking detailed classification, in normal seminal plasma and in sera from subjects with benign hyperplasia (BPH) or cancer of the prostate (PCa) as samples of known clinical relevance. fPSA forms were separated from complex proteomes on chips with immobilized anti-fPSA antibody followed by detection using surface-enhanced laser desorption/ionization time of flight mass spectrometry. At least 39 fPSA-immunoreactive species, ranging from 3–29 kDa were detected in seminal plasma. General fPSA profiles in seminal plasma and sera were similar, but differed in the abundance and presence of particular peaks/clusters of the lower molecular mass species. No striking difference in fPSA forms was observed between BPH and PCa samples, but some distinct peaks varied in intensity and frequency within or between groups. Obtained data verify fPSA heterogeneity that might be important for better exploration of all their molecular and marker potentials.

Prospective Evaluation of Operating Characteristics of Prostate Cancer Detection Biomarkers

We assessed the independent predictive values of the serum markers free prostate specific antigen, proenzyme prostate specific antigen, neuroendocrine marker and Dickkopf-1 compared to serum prostate specific antigen and other standard risk factors for early prostate cancer detection. From the prospectively collected SABOR cohort 250 prostate cancer cases, and 250 mean age matched and proportion of African-American race/ethnicity matched controls were selected who had a prior available prostate specific antigen and digital rectal examination. Serum samples were obtained, and free prostate specific antigen, [-2]proenzyme prostate specific antigen, Dickkopf-1 and neuroendocrine marker were measured. AUC, sensitivities and specificities were calculated, and multivariable logistic regression was used to assess the independent predictive value compared to prostate specific antigen, digital rectal examination, family history, prior biopsy history, race/ethnicity and age. The AUCs (95% CI) were 0.76 (0.71, 0.8) for free prostate specific antigen, 0.72 (0.67, 0.76) for [-2]proenzyme prostate specific antigen, 0.76 (0.72, 0.8) for %free prostate specific antigen, 0.61 (0.56, 0.66) for %[-2]proenzyme prostate specific antigen, 0.73 (0.68, 0.77) for prostate health index, 0.53 (0.48, 0.58) for Dickkopf-1 and 0.53 (0.48, 0.59) for neuroendocrine marker. In the 2 to 10 ng/ml prostate specific antigen range the AUCs (95% CI) were 0.58 (0.49, 0.67) for free prostate specific antigen, 0.53 (0.44, 0.62) for [-2]proenzyme prostate specific antigen, 0.67 (0.59, 0.75) for %free prostate specific antigen, 0.57 (0.49, 0.65) for %[-2]proenzyme prostate specific antigen and 0.59 (0.51, 0.67) for phi. Only %free prostate specific antigen retained independent predictive value compared to the traditional risk factors. Free prostate specific antigen retained independent diagnostic usefulness for prostate cancers detected through prostate specific antigen and digital rectal examination screening. Prostate specific antigen isoforms are highly correlated with prostate specific antigen. Future research is needed to identify new markers associated with prostate cancer through different mechanisms.

Multi-gene biomarker panel for reference free prostate cancer diagnosis: determination and independent validation

Identification of biomarkers that can accurately and reliably diagnose prostate cancer is clinically highly desirable. A novel classification method, K-closest resemblance was applied to several high-quality transcriptomic datasets of prostate cancer leading to the discovery of a panel of eight gene biomarkers that can detect prostate cancer with over 96% specificity and sensitivity in leave-one-out cross-validation. Independent validation on clinical samples confirmed the discriminatory power of this gene panel, yielding over 95% accuracy of diagnosis based on receiver-operating characteristic curve analyses. Different levels of validation of the proposed biomarker panel have shown that it allows extremely accurate diagnosis of prostate cancer. Application of this panel can possibly add a fast and objective tool to the pathologist’s arsenal following further clinical testing.