Significant Predictors Of Prostate Cancer Research Articles

Development, validation and comparison of two nomograms predicting prostate cancer at initial 12-core biopsy

Our aim was to establish, validate and compare two nomograms in an Iranian population for the first time using clinical, laboratory and transrectal ultrasonography (TRUS) findings for predicting prostate cancer at initial biopsy. Data were collected on a total of 916 men referred for an initial prostate biopsy in our center in a 7-year period. Variables analyzed included age, prostate-specific antigen (PSA), free/total PSA (%fPSA), digital rectal examination (DRE) findings, prostate volume (PV) and presence of hypoechoic lesion on TRUS. Univariate logistic regression models were fitted to test cancer predictors. Two multivariate logistic regression models were fitted to create nomograms. Both models were internally validated. Calibration of nomograms was assessed graphically. The area under the receiver operating characteristic curve (AUC) was calculated as a scale of discrimination and predictive accuracy and also used to compare models. Prostate cancer was detected in 221/669 (33%) men. Based on univariate logistic regression, all of variables except DRE were significant predictors of prostate cancer, with highest AUC for PV (AUC 0.696, 95% CI 0.653-0.738).AUC of nomogram with and without TRUS findings and PSA alone were 0.791, 0.721 and 0.624, respectively. In internal validation, both nomograms had acceptable calibration plots. Our nomogram based on age, DRE, PSA, %fPSA and TRUS finding was significantly more accurate in predicting initial prostate biopsy outcome in men.

MP63-08 LOW SERUM DIHYDROTESTOSTERONE IS A POWERFUL PREDICTOR OF GLEASON SCORE 7-10 OF PROSTATE CANCER IN MEN WITH PROSTATE-SPECIFIC ANTIGEN LEVELS OF 3-10NG/ML

You have accessJournal of UrologyProstate Cancer: Detection & Screening III1 Apr 2014MP63-08 LOW SERUM DIHYDROTESTOSTERONE IS A POWERFUL PREDICTOR OF GLEASON SCORE 7-10 OF PROSTATE CANCER IN MEN WITH PROSTATE-SPECIFIC ANTIGEN LEVELS OF 3-10NG/ML Yasuhide Miyoshi, Susumu Umemoto, Hiroji Uemura, Yasuhiro Shibata, Seijiro Honma, and Yoshinobu Kubota Yasuhide MiyoshiYasuhide Miyoshi More articles by this author , Susumu UmemotoSusumu Umemoto More articles by this author , Hiroji UemuraHiroji Uemura More articles by this author , Yasuhiro ShibataYasuhiro Shibata More articles by this author , Seijiro HonmaSeijiro Honma More articles by this author , and Yoshinobu KubotaYoshinobu Kubota More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1945AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There has been no consensus on the role of androgen concentrations in prostate cancer detection in men with prostate-specific antigen (PSA) levels of 3-10 ng/mL. In this study, testosterone (T) and dihydrotestosterone (DHT) concentrations in blood and needle biopsy specimens of prostate were examined by a newly developed ultra sensitive LC-MS/MS method. METHODS We analyzed 197 men (mean age 68 years) with a total PSA range of 3-10 ng/ml who were subjected to initial prostate biopsy for suspected prostate cancer from November 2005 to July 2007. Those patients received systematic needle biopsy, and additionally one needle biopsy from the peripheral zone was conducted for the purpose of simultaneous determination of T and DHT. T and DHT concentrations in prostate tissues and blood, determined by LC-MS/MS method. Determination limits of this method was 0.5 pg/shot for T and 1 pg/shot for DHT. Concentration of T and DHT were expressed in pg/mg. T and DHT levels in tissue and blood were compared with pathological findings by multivariate analyses. RESULTS Median values of PSA and prostate volume measured by ultrasound were 5.7 ng/mL and 31.4cc respectively. Median values of T and DHT in blood were 3805.5 pg/mL and 364.4 pg/mL, respectively. There was a strong correlation between serum T and DHT. Median values of T and DHT in tissue were 0.53 pg/mg and 8.40 pg/mg, respectively. Prostate cancer was diagnosed in 82 (41.6%) of those patients including 43 (21.8%) patients with a Gleason score 7-10. In multivariate analysis, patient age (p<0.0001), prostate volume (p<0.0001), and blood DHT (p<0.01) were statistically significant predictors of prostate cancer with Gleason score 7-10. The areas under the curve of the receiver operating characteristic curve for age, prostate volume, and blood DHT were 0.658, 0.689, and 0.638, respectively. CONCLUSIONS Testosterone and dihydrotestosterone concentrations in blood or prostate tissue of needle biopsy were simultaneously examined by the newly developed ultra sensitive quantifying method, LC-MS/MS. We confirmed that low dihydrotestosterone levels in blood could predict prostate cancer with a Gleason score 7-10 in men with prostate-specific antigen levels of 3-10ng/mL. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e711-e712 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yasuhide Miyoshi More articles by this author Susumu Umemoto More articles by this author Hiroji Uemura More articles by this author Yasuhiro Shibata More articles by this author Seijiro Honma More articles by this author Yoshinobu Kubota More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact of lower urinary tract symptoms on prostate cancer risk among Japanese men with prostate‐specific antigen &lt;10 ng/mL and non‐suspicious digital rectal examination

To investigate the association between lower urinary tract symptoms status and prostate cancer risk at initial extended biopsy. Between 2005 and 2011, the International Prostate Symptom Score was completed on 1467 consecutive men with prostate-specific antigen <10 ng/mL and non-suspicious digital rectal examination. After excluding 308 men treated with alpha-blockers, the remaining 1159 men were enrolled in the present study. Lower urinary tract symptoms status was divided into absent or mild (International Prostate Symptom Score scores of 0-7) and moderate or severe lower urinary tract symptoms (International Prostate Symptom Score scores of 8-35). The risks of prostate cancer diagnosis and high-grade (Gleason score ≥4 + 3) prostate cancer diagnosis in relation to lower urinary tract symptoms status was evaluated using logistic regression. A stratified analysis based on prostate volume (<30 cc, 30-50 cc and >50 cc) was also carried out. Of 1159 patients, 421 (36.3%) had a positive biopsy and 590 (51.0%) had moderate or severe lower urinary tract symptoms. On multivariate analysis, absent or mild lower urinary tract symptoms had a significant and positive impact on the risk of prostate cancer and high-grade disease (odds ratio 1.64 and 1.70, P = 0.0007 and 0.0121, respectively). Furthermore, the aforementioned findings for prostate cancer detection did not change throughout every prostate volume subgroup. In contrast, in men with prostate volume ≤50 cc, but not in those with prostate volume >50 cc, prostate-specific antigen or %free prostate-specific antigen remained as a significant predictor of prostate cancer. In men with elevated prostate-specific antigen, absent or mild lower urinary tract symptoms are positively associated with prostate cancer and high-grade disease regardless of the prostate volume. This finding is especially useful in men with enlarged prostates.

1451 THE ASSOCIATION BETWEEN MALE PATTERN BALDNESS AND SECOND TO FORTH FINGER RATIO WITH PROSTATE CANCER- A PROSPECTIVE COHORT STUDY

You have accessJournal of UrologyProstate Cancer: Detection and Screening II1 Apr 20121451 THE ASSOCIATION BETWEEN MALE PATTERN BALDNESS AND SECOND TO FORTH FINGER RATIO WITH PROSTATE CANCER- A PROSPECTIVE COHORT STUDY David Margel, Seetha Venkateswaran, Abbas Darwish, Antonio Finelli, John Trachtenberg, Karen Chadwick, and Neil Fleshner David MargelDavid Margel Toronto, Canada More articles by this author , Seetha VenkateswaranSeetha Venkateswaran Toronto, Canada More articles by this author , Abbas DarwishAbbas Darwish Toronto, Canada More articles by this author , Antonio FinelliAntonio Finelli Toronto, Canada More articles by this author , John TrachtenbergJohn Trachtenberg Toronto, Canada More articles by this author , Karen ChadwickKaren Chadwick Toronto, Canada More articles by this author , and Neil FleshnerNeil Fleshner Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1945AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgens play a role in the development of androgenic alopecia, commonly known as male pattern baldness. The ratio of the lengths of index and ring fingers (2D:4D) is also a marker of exposure to sex hormones, with low 2D:4D being indicative of high prenatal androgen action. Retrospective case control studies have demonstrated an association between male pattern baldness and 2D:4D ratio and prostate cancer. The aim of this study was to validate these findings in a prospective cohort. METHODS Upon approval from our local ethical review board we prospectively enrolled 196 consecutive patients referred to a prostate biopsy. Finger lengths were measured using a digital vernier calliper, and the 2D:4D ratio was calculated. Male pattern baldness was assessed on a scale of 0-4 using the standardized Norwood classification (0= no balding, 1= frontal balding, 2= Mild vortex, 3=moderate vortex and 4=severe vortex). We performed all measurements prior to the biopsy thus blinded to the pathology outcome. We performed a univariable and multivariable analysis to associate 2D:4D ratio and male pattern baldness with prostate cancer diagnosis at biopsy. The multivariable model included the two main predictors (male pattern baldness and 2D:4D ratio) as well age, digital rectal examination (normalvs abnormal) and PSA. RESULTS The median (IQR) age and PSA of our cohort was 64 (59-70) and 5.8 (4.1-8.4), respectively. Overall 109 patients (55%) were diagnosed with prostate cancer. On univariable analysis male pattern baldness was associated with prostate cancer (p for trend=0.03). However 2D:4D ratio was not. On multivariable analysis male pattern baldness remained a significant predictor of prostate cancer. Furthermore, we noted a dose response effect- the more severe balding patterns were more strongly associated with prostate cancer (Frontal balding OR 2.0 (95%CI 1.1-6.6); mild vortex OR 2.1 (95%CI 1.5-5.2); moderate vortex OR 2.5 (95%CI 1.2-7.1); severe vortex OR 2.9 (95%CI 1.1-4.3). CONCLUSIONS In a prospective cohort we found that male pattern baldness was an independent predictor of prostate cancer. Further studies are needed in order to assess whether the inclusion of male pattern baldness can contribute to existing models to predict prostate cancer prior to biopsy. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e588 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Margel Toronto, Canada More articles by this author Seetha Venkateswaran Toronto, Canada More articles by this author Abbas Darwish Toronto, Canada More articles by this author Antonio Finelli Toronto, Canada More articles by this author John Trachtenberg Toronto, Canada More articles by this author Karen Chadwick Toronto, Canada More articles by this author Neil Fleshner Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

2065 INVERSE ASSOCIATION BETWEEN THE PRESENCE OF HISTOLOGICAL INFLAMMATION IN NEEDLE BIOPSY SPECIMENS AND THE POSITIVE BIOPSY FINDINGS FOR PROSTATE CANCER IN MEN WITH SERUM PROSTATE-SPECIFIC ANTIGEN LEVEL OF 10 - 50 NG/ML

You have accessJournal of UrologyProstate Cancer: Detection and Screening IV1 Apr 20122065 INVERSE ASSOCIATION BETWEEN THE PRESENCE OF HISTOLOGICAL INFLAMMATION IN NEEDLE BIOPSY SPECIMENS AND THE POSITIVE BIOPSY FINDINGS FOR PROSTATE CANCER IN MEN WITH SERUM PROSTATE-SPECIFIC ANTIGEN LEVEL OF 10 - 50 NG/ML Tomoaki Terakawa, Hideaki Miyake, Iori Sakai, and Masato Fujisawa Tomoaki TerakawaTomoaki Terakawa Akashi, Japan More articles by this author , Hideaki MiyakeHideaki Miyake Kobe, Japan More articles by this author , Iori SakaiIori Sakai Kobe, Japan More articles by this author , and Masato FujisawaMasato Fujisawa Kobe, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2230AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The utility of prostate-specific antigen (PSA) is occasionally lessened by an abnormal elevation under several unusual conditions, including inflammatory changes of the prostate. Although acute bacterial prostatitis results in the remarkable elevation of serum PSA, the effect of asymptomatic inflammation within the prostate on serum PSA level has not been well characterized. The objective of this study was to analyze the impact of the presence of histologically inflammation in needle biopsy specimens on the detection of prostate cancer in men with comparatively high serum PSA level. METHODS This study included 286 consecutive patients with serum PSA ranging from 10 - 50 ng/ml who initially underwent transrectal systematic biopsy of the prostate. A single pathologist reviewed all the biopsy specimens, and moderate or severe inflammation in the biopsy specimens according to the report by De Marzo (Am J Pathol 1999; 155: 1985-1992) was defined as the presence of histological inflammation. RESULTS In this series, 172 patients (60.1%, Group A) were diagnosed as having prostate cancer, and the remaining 114 (39.9%, Group B) were negative for malignant lesion in the biopsy specimens. There was a significant difference in the incidence of histological inflammation between the Group A (40.7%) and the Group B (73.7%). Prostate volume, transition zone (TZ) volume and the incidence of histological inflammation in Group A was significantly smaller than those in Group B, while PSA density and PSA density of the TZ in Group A were significantly greater than those in Group B. Univariate analysis identified prostate volume, TZ volume, PSA density, PSA density of the TZ and histological inflammation as significant predictors of prostate cancer, among which only PSA density and histological inflammation were appeared to be independently associated with the detection of prostate cancer on multivariate analysis. Furthermore, combined consideration of these two independent factors could differentiate prostate cancer from benign disease in the biopsy specimens with 87.2% sensitivity, 63.2% specificity, 78.1% positive predictive value and 76.6% negative predictive value. CONCLUSIONS These findings suggest that it would be possible to avoid unnecessary repeat biopsy using PSA density and the presence of histological inflammation in biopsy specimens in patients with continuously elevated serum PSA after initial biopsy. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e833 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomoaki Terakawa Akashi, Japan More articles by this author Hideaki Miyake Kobe, Japan More articles by this author Iori Sakai Kobe, Japan More articles by this author Masato Fujisawa Kobe, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Detection of Prostate Cancer in an Ethnically Diverse, Disadvantaged Population With Multiple Prostate Specific Antigen Measurements Before Biopsy

We assessed the predictive effect of prostate specific antigen velocity for men with a minimum of 3 pre-biopsy prostate specific antigen measurements in a racially diverse population. We identified 795 patients who underwent 3 or more prostate specific antigen tests before prostate biopsy. Prostate specific antigen velocity was calculated by linear regression and used to assess associations with the risk of prostate cancer overall and of high grade prostate cancer (Gleason score 7-10). We created ROC curves and determined the AUC for several models, including only prostate specific antigen velocity or the last prostate specific antigen measurement before biopsy, to predict prostate cancer and high grade prostate cancer. The risk of prostate cancer and high grade prostate cancer increased linearly with increasing prostate specific antigen velocity quartiles (each p trend<0.001). Older patients were more likely to be diagnosed with prostate cancer, given the same prostate specific antigen velocity. In black and Hispanic patients there were strong linear associations between increasing prostate specific antigen velocity and the risk of prostate cancer overall and high grade prostate cancer. ROC curves incorporating prostate specific antigen velocity to predict prostate cancer and high grade prostate cancer varied significantly by race. The AUC of models in black and Hispanic patients was significantly higher than in white patients (0.62 and 0.64, respectively, vs 0.47, p=0.03). Prostate specific antigen velocity is a significant predictor of prostate cancer and high grade prostate cancer in men with 3 or more prostate specific antigen tests before prostate biopsy. Black and Hispanic patients appear to be at increased risk for prostate cancer at higher prostate specific antigen velocity, as are men older than 60 years. Further studies should confirm these results and create age and race specific guidelines to assess prostate specific antigen velocity.

Abstract A32: A urinary mRNA profile to increase the specificity of PSA and reduce the number of unnecessary biopsies

Abstract Background: Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. Methods: We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (&amp;gt;4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings with PSAD to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic “gray zone” (4–10 ng/ml) on a target subset of 82 men with no prior biopsy. Results: By univariate analysis, we found that the PSMA, PSGR, PCA3 and PSAD scores were significant predictors of PCa. Using a multiplex model, the area under the multireceiver operating characteristic curve was 0.80 versus 0.89 in the diagnostic gray zone. Fixing the sensitivity at 96%, we obtained a specificity of 40% and 62% in the gray zone. By this approach it would be possible to save approximately 35% of unnecessary biopsies with a sensitivity of 95%. Conclusions: Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Citation Format: Marina Rigau, Tatiana Altadill, Andreas Doll, Tamara Sequeiros, Mireia Olivan, Marta Garcia, Alex Sanchez, Melania Montes, Israel Ortega, Juan Morote, Jaume Reventos. A urinary mRNA profile to increase the specificity of PSA and reduce the number of unnecessary biopsies [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A32.

A Three‐Gene panel on urine increases PSA specificity in the detection of prostate cancer

Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy.

1910 A MULTIPLEX MODEL OF COMBINING POSITIVE AND NEGATIVE MARKERS IN URINE FOR EARLY DIAGNOSIS OF PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Detection and Screening1 Apr 20111910 A MULTIPLEX MODEL OF COMBINING POSITIVE AND NEGATIVE MARKERS IN URINE FOR EARLY DIAGNOSIS OF PROSTATE CANCER Da-Long Cao, Xu-Dong Yao, Ding-Wei Ye, Yao Zhu, and Hai-Liang Zhang Da-Long CaoDa-Long Cao Shanghai, China, People's Republic of More articles by this author , Xu-Dong YaoXu-Dong Yao Shanghai, China, People's Republic of More articles by this author , Ding-Wei YeDing-Wei Ye Shanghai, China, People's Republic of More articles by this author , Yao ZhuYao Zhu Shanghai, China, People's Republic of More articles by this author , and Hai-Liang ZhangHai-Liang Zhang Shanghai, China, People's Republic of More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2048AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Newly emerged multiplex urine-based test outperforms single biomarker (e.g. prostate-specific antigen, PSA) in prostate cancer (PCa) diagnostics, whereas its combined mode has to be fully optimized. Our endeavor is directed to determine whether a strategy of integrating positive and negative makers in urine could optimize a multiplex model for diagnosing PCa. METHODS Using quantitative PCR and western blot, expression patterns of prostate cancer antigen 3 (PCA3, positive marker) and Annexin A3 (negative marker) were measured in urine samples from 86 untreated patients with PCa and 45 patients with no evidence of malignancy, confirmed by 10 core prostate biopsies. Multivariate logistic regression analysis using Akaike information criterion-based backward selection was used to generate a final panel. The diagnostic performance of each single marker and the final panel were assessed using receiver-operating characteristic (ROC) analysis and special bootstrap software. RESULTS Univariate and multivariate logistic regression analysis revealed that PCA3, Annexin A3 and a panel including these biomarkers were significant predictors of PCa in both groups of all patients and patients with PSA 4–10 ng/ml (all p<0.05). By ROC analysis, the areas under the curves (AUCs) of the panel in these two cohorts were 0.829 and 0.782, respectively, which outperform that of any single biomarker (serum PSA: 0.566 and 0.511; PCA3: 0.739 and 0.733; Annexin A3: 0.728 and 0.716; respectively). CONCLUSIONS These results showed that integrating positive and negative makers has effect on optimizing a panel for predicting PCa. Further validation experiments and optimization for the strategy of constructing multiplex urine-based test are awaited before it reaches the clinic. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e763-e764 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Da-Long Cao Shanghai, China, People's Republic of More articles by this author Xu-Dong Yao Shanghai, China, People's Republic of More articles by this author Ding-Wei Ye Shanghai, China, People's Republic of More articles by this author Yao Zhu Shanghai, China, People's Republic of More articles by this author Hai-Liang Zhang Shanghai, China, People's Republic of More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

637 A THREE-GENE PANEL ON URINE INCREASES PSA SPECIFICITY IN THE DETECTION OF PROSTATE CANCER

BACKGROUND. Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. METHODS. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic ‘‘gray zone’’ (4–10 ng/ml) on a target subset of 82 men with no prior biopsy. RESULTS. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiveroperating characteristic curve was 0.74 versus 0.82 in the diagnostic ‘‘gray zone.’’ Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. CONCLUSIONS. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Prostate # 2011 Wiley-Liss, Inc.

PSGR and PCA3 as biomarkers for the detection of prostate cancer in urine

Several studies have demonstrated the usefulness of monitoring an RNA transcript in urine, such as PCA3, for prostate cancer (PCa) diagnosis. PCa screening would benefit from additional biomarkers of higher specificity and could be used in conjunction with prostate-specific antigen (PSA) testing, in order to better determine biopsy candidates. We used urine sediments after prostate massage (PM) from 215 consecutive patients, who presented for prostate biopsy. We tested whether prostate-specific G-protein coupled receptor (PSGR), a biomarker previously described to be over-expressed in PCa tissue, could also be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings with prostate cancer gene 3 (PCA3), the current gold standard for PCa diagnosis in urine, to test if a combination of both biomarkers could improve the sensitivity of PCA3 alone. By univariate analysis we found that PSGR and PCA3 were significant predictors of PCa. Receiver operator characteristic curve analysis and its multivariate extension, multivariate ROC (MultiROC), were used to assess the outcome predictive values of the individual and the paired biomarkers. We obtained the following area under the curve values: PSA (0.602), PSGR (0.681), PCA3 (0.656), and PSGRvPCA3 (0.729). Then, we tested whether a combination of PSGR and PCA3 could improve specificity by fixing the sensitivity at 95%. We obtained specificities of 15% (PSGR), 17% (PCA3), and 34% (PSGRvPCA3). A multiplexed model including PSGR and PCA3 improves the specificity for the detection of PCa, especially in the area of high sensitivity. This could be clinically useful for determining which patients should undergo biopsy.

Detection rate and factors predictive the presence of prostate cancer in patients undergoing ultrasonography-guided transperineal saturation biopsies of the prostate

To assess the prostate cancer detection rate and predictive factors for prostate cancer after transrectal ultrasonography (TRUS)-guided transperineal saturation re-biopsies of the prostate, using a 24-core scheme. We evaluated 143 consecutive patients undergoing TRUS-guided transperineal saturation re-biopsy of the prostate using a 24-core scheme. The inclusion criteria were a previous negative biopsy and a prostate-specific antigen (PSA) level of > or =10.0 ng/mL, or of 4.0-10.0 ng/mL with a free/total ratio of <20% or an abnormal digital rectal examination or previous high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP). The mean (sd) age of the patients was 66.5 (6.1) years and the median (interquartile range) PSA level was 9.0 (6.1-12.8) ng/mL. The number of previous biopsies was one in 59% of patients, two in 26% and three or more in 15%. We detected prostate cancer in 26%, ASAP in 5.6% and HGPIN in 2.1%. The cancer detection rate was 47%, 25.5% and 14% for prostate volumes of <40, 40-60 and > or =60 mL, respectively (P = 0.002). On a multivariate analysis the total prostate volume (40-60 vs <40 mL, hazard ratio 5.683; >60 vs <40 mL, hazard ratio 6.965; P = 0.01) was the only significant predictor of prostate cancer at saturation biopsy. TRUS-guided transperineal saturation re-biopsy of the prostate using a 24-core scheme resulted in a high cancer detection rate also in patients who had had two or more previous biopsies. The total prostate volume was the only predictor of prostate cancer.

Short-term Prostate-Specific Antigen Velocity Measurement before Prostate Biopsy

Purpose: We investigated whether a short-term follow-up prostate-specific antigen (PSA) measurement before prostate biopsy is useful in predicting the presence of prostate cancer. Materials and Methods: From January 2004 to May 2008, 670 patients underwent transrectal ultrasound-guided prostate biopsy. The initial PSA (PSA1) was measured at the first outpatient visit. The second PSA (PSA2) was measured the evening before prostate biopsy. Only the patients with a PSA1 between 2.5 and 20 ng/ml and an interval between PSA1 and PSA2 of between 7 and 90 days were included in this study. The short-term PSA velocity (PSAVm) was defined as {(PSA2−PSA1/interval (days)}x30. Prostate volume (PV), PSA1, PSA2, and PSAVm were compared between the patients with prostate cancer and those with benign histology. Results: Of the 362 patients who fulfilled the entry criteria, 365 prostate biopsies were performed. The PSAVm differed significantly between patients with prostate cancer and those with benign histology (p=0.021). In patients with a PSA1 of 10-20 ng/ml, age, PV, PSA1, PSA2, and PSAVm were significantly different between patients with prostate cancer and those with benign histology, whereas in patients with a PSA1 of 2.5-10 ng/ml, only PV was significantly different. In multivariate logistic regression analysis excluding PSA1 and PSA2, PSAVm was a significant predictor of prostate cancer overall and in patients with a PSA1 of 10-20 ng/ml, but not in patients with a PSA1 of 2.5-10 ng/ml. Conclusions: PSAVm was significantly different between the benign group and the prostate cancer group. But, this difference was mainly the result of a falsely elevated PSA, and PSAVm was not a significant predictor of prostate cancer when the PSA1 was 2.5-10 ng/ml. (Korean J Urol 2009;50: 553-559) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate Cancer

Prostate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data from multiple prostate cancer studies, we identified GOLM1 (Golgi membrane protein 1, Golm 1) as consistently up-regulated in clinically localized prostate cancer. This observation was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and validated at the protein level by immunoblot assay and immunohistochemistry. Prostate epithelial cells were identified as the cellular source of GOLM1 expression using laser capture microdissection. Immunohistochemical staining localized the GOLM1 signal to the subapical cytoplasmic region, typical of a Golgi distribution. Surprisingly, GOLM1 immunoreactivity was detected in the supernatants of prostate cell lines and in the urine of patients with prostate cancer. The mechanism by which intact GOLM1 might be released from cells has not yet been elucidated. GOLM1 transcript levels were measured in urine sediments using quantitative PCR on a cohort of patients presenting for biopsy or radical prostatectomy. We found that urinary GOLM1 mRNA levels were a significant predictor of prostate cancer. Further, GOLM1 outperformed serum prostate-specific antigen (PSA) in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.622 for GOLM1 (P = .0009) versus 0.495 for serum PSA (P = .902). Our data indicating the up-regulation of GOLM1 expression and its appearance in patients' urine suggest GOLM1 as a potential novel biomarker for clinically localized prostate cancer.

DEVELOPMENT OF A NOMOGRAM FOR PREDICTING HIGH- GRADE PROSTATE CANCER ON BIOPSY: THE SIGNIFICANCE OF SERUM TESTOSTERONE LEVELS

BACKGROUND: A screening method that focuses on the early detection of high-grade prostate cancer is required. In this study, two sets of nomograms were developed, one to predict the presence of prostate cancer, and the other to predict the presence of high-grade prostate cancer (defined as Gleason Score > or =7). PATIENTS AND METHODS: Prostate biopsies were obtained from 396 men with an abnormal serum level of prostate-specific antigen (PSA). Using factors including age, PSA, follicle stimulating hormone (FSH), serum teststerone level and prostate volume of the transitional zone (TZ), nomograms were created that incorporated these factors. External validations were performed involving 174 males, including 103 normal and 71 prostate cancer cases from our institution. RESULTS: Out of the 396 patients referred for prostate biopsy, 146 were found to have prostate cancer. On logistic regression analysis, age, PSA, prostate volume of the TZ and FSH were significant predictors of prostate cancer, while serum PSA, and testosterone levels were significant predictors of high-grade prostate cancer. The pretreatment testosterone level was found to be a significant biomarker for predicting the pathological features. CONCLUSION: The testosterone level might be a useful biomarker to be included in conventional PSA screening programs to further improve the efficacy of detecting potentially lethal carcinomas.

A First-Generation Multiplex Biomarker Analysis of Urine for the Early Detection of Prostate Cancer

Although prostate-specific antigen (PSA) serum level is currently the standard of care for prostate cancer screening in the United States, it lacks ideal specificity and additional biomarkers are needed to supplement or potentially replace serum PSA testing. Emerging evidence suggests that monitoring the noncoding RNA transcript PCA3 in urine may be useful in detecting prostate cancer in patients with elevated PSA levels. Here, we show that a multiplex panel of urine transcripts outperforms PCA3 transcript alone for the detection of prostate cancer. We measured the expression of seven putative prostate cancer biomarkers, including PCA3, in sedimented urine using quantitative PCR on a cohort of 234 patients presenting for biopsy or radical prostatectomy. By univariate analysis, we found that increased GOLPH2, SPINK1, and PCA3 transcript expression and TMPRSS2:ERG fusion status were significant predictors of prostate cancer. Multivariate regression analysis showed that a multiplexed model, including these biomarkers, outperformed serum PSA or PCA3 alone in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.758 for the multiplexed model versus 0.662 for PCA3 alone (P = 0.003). The sensitivity and specificity for the multiplexed model were 65.9% and 76.0%, respectively, and the positive and negative predictive values were 79.8% and 60.8%, respectively. Taken together, these results provide the framework for the development of highly optimized, multiplex urine biomarker tests for more accurate detection of prostate cancer.

High Yield of Saturation Prostate Biopsy for Patients with Previous Negative Biopsies and Small Prostates

Men with previously negative prostate biopsies but continued suspicion for carcinoma present a diagnostic dilemma often managed by saturation prostate biopsy (SPB). We sought to determine the patient characteristics for which repeat biopsy by SPB provides the greatest utility for prostate cancer detection. The records of the men at the state hospital and affiliated Veterans Affairs Medical Center with previously negative prostate biopsy findings who had then undergone SPB were reviewed. The predictors of cancer were analyzed, and those that were significant were included in a multivariate logistic regression model. A total of 82 men underwent SPB from November 2001 to March 2006. Their mean age was 61 years (range 43 to 76), and 44 (54%) were white, 37 (45%) were African American, and 1 (1%) was Asian. The mean prostate-specific antigen level at SPB was 9.1 ng/mL (range 1.0 to 34). The number of prior biopsies was one in 43 patients (52%) and two or more in 39 patients (47%). The prostate volume averaged 53 cm(3) (range 12 to 200). SPB included a median of 24 cores (range 24 to 40). Of the 82 patients, 16 (19.5%) were diagnosed with cancer, of whom 10 (63%) elected to undergo radical prostatectomy. The only significant predictors of prostate cancer were the prostate-specific antigen level (P = 0.009) and prostate volume. The cancer detection rate was 57% for patients with a prostate volume less than 37 cm(3) and 7% for those with larger glands, and the difference was significant on multivariate analysis (odds ratio 31, 95% confidence interval 6 to 158, P <0.0001). The results of our study have shown that SPB is an effective diagnostic tool with a high yield for men with persistent suspicion for prostate cancer, prior negative biopsy findings, and a prostate volume less than 37 cm(3).

Is interval from an initial biopsy a significant predictor of prostate cancer at repeat biopsies?

Background: Currently, there are no clear criteria for indicating repeat biopsies in patients with negative results at an initial biopsy of the prostate. The aim of the present study is to determine the clinical and pathological parameters which predict prostate cancer at repeat biopsies with special attention to the interval between biopsies in addition to prostate specific antigen (PSA) and its derivatives. Methods: We reviewed 100 patients who underwent an initial biopsy that proved negative for prostate cancer and required repeat biopsies between November 1996 and November 2003. Clinical parameters such as age, PSA and its derivatives, interval between biopsies, number of cores taken and initial biopsy histology were analyzed. Results: In total, 31 patients (31.0%) were found to have prostate cancer, 18 (25.7%) of 70 patients by the second biopsy and 13 (46.4%) of 28 patients by the third biopsy. Two patients underwent the fourth biopsy, which revealed no prostate cancer. The patients with a positive biopsy had a significantly longer interval between the biopsies than the patients with a negative biopsy (P = 0.0036). Furthermore, in both univariate and multivariate logistic regression analysis, only the interval between the biopsies proved to be an independent predictor of positive results at repeat biopsies (P = 0.0094 and 0.0019). Conclusions: Only the biopsy interval was a significant predictor of prostate cancer at repeat biopsies in both univariate and multivariate analysis.

Re: Is interval from an initial biopsy a significant predictor of prostate cancer at repeat biopsies?

Re: Is interval from an initial biopsy a significant predictor of prostate cancer at repeat biopsies?

Nuclear magnetic resonance spectroscopy of expressed prostatic secretions: Metabolite citrate and derivatives are potential markers of prostate cancer

4623 Background: Nuclear magnetic resonance spectroscopy (NMRS) along with a novel method for determining absolute concentrations of metabolites were utilized to analyze expressed prostatic secretions (EPS) from men with prostate cancer (PCa) and from healthy controls. Methods: Flash frozen EPS samples from 66 men (40 with PCa and 26 controls) were analyzed by high-resolution 1H-NMR spectroscopy using a Bruker 500 MHz DRX NMR spectrometer with a 1-mm microprobe. The total number of scans per fully relaxed 1H-NMR spectrum was n = 40 with water suppression. Absolute concentrations of endogenous metabolites (citrate, spermine, myo-inositol, lactate, alanine, phosphocholine, glutamate, acetate, hydroxybutyrate) were quantified using trimethylsilyl-propionic acid as an external standard reference. Stepwise multivariable logistic regression (LR) was used to model the risk of PCa based upon the levels of the measured metabolites. Results: The average age of the EPS donors was 54.7 ± 9.8 years. The median Gleason score for the men with PCa was 6 (range 5–9). The Wilcoxon rank sum test indicated that citrate, spermine, inositol, citrate/spermine, and citrate/lactate were all significant predictors of PCa (p &lt; .001). The LR models indicated that the absolute concentration of citrate was highly predictive of PCa with lower concentrations resulting in a higher risk of cancer. The area under the receiver operating characteristic curve (AUROC) for citrate alone was 0.79 (95% CI 0.75–0.83). Using relative concentrations (metabolite ratios) in a two-variable LR model, citrate/spermine and citrate/lactate were also predictive of PCa with an AUROC of 0.76 (95% CI 0.71–0.81). Conclusions: The results suggest that absolute concentration of citrate and its derivatives in EPS as measured by NMRS have promising potential as accurate markers of prostate cancer. No significant financial relationships to disclose.