Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

PubMed

Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

2018-04-01

Guidelines from the NCCN ® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The effect of increasing doses of saw palmetto fruit extract on serum prostate specific antigen: analysis of the CAMUS randomized trial.

PubMed

Andriole, Gerald L; McCullum-Hill, Christie; Sandhu, Gurdarshan S; Crawford, E David; Barry, Michael J; Cantor, Alan

2013-02-01

Saw palmetto extracts are used to treat lower urinary tract symptoms in men despite level I evidence that saw palmetto is ineffective in reducing these lower urinary tract symptoms. We determined whether higher doses of saw palmetto as studied in the CAMUS (Complementary and Alternative Medicine for Urologic Symptoms) trial affect serum prostate specific antigen levels. The CAMUS trial was a randomized, placebo controlled, double-blind, multicenter, North American trial conducted between June 5, 2008 and October 10, 2012, in which 369 men older than 45 years with an AUA symptom score of 8 to 24 were randomly assigned to placebo or dose escalation of saw palmetto, which consisted of 320 mg for the first 24 weeks, 640 mg for the next 24 weeks and 960 mg for the last 24 weeks of this 72-week trial. Serum prostate specific antigen levels were obtained at baseline and at weeks 24, 48 and 72, and were compared between treatment groups using the pooled t test and Fisher's exact test. Serum prostate specific antigen was similar at baseline for the placebo (mean ± SD 1.93 ± 1.59 ng/ml) and saw palmetto groups (2.20 ± 1.95, p = 0.16). Changes in prostate specific antigen during the study were similar, with a mean change in the placebo group of 0.16 ± 1.08 ng/ml and 0.23 ± 0.83 ng/ml in the saw palmetto group (p = 0.50). In addition, no differential effect on serum prostate specific antigen was observed between treatment arms when the groups were stratified by baseline prostate specific antigen. Saw palmetto extract does not affect serum prostate specific antigen more than placebo, even at relatively high doses. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate Cancer Screening: MedlinePlus Health Topic

MedlinePlus

... unusual. Another test is the prostate-specific antigen (PSA) blood test. Your PSA level may be high if you have prostate ... Research) Prostate Cancer Screening: Should You Get a PSA Test? (Mayo Foundation for Medical Education and Research) ...

Prostate specific antigen velocity does not aid prostate cancer detection in men with prior negative biopsy.

PubMed

Vickers, Andrew J; Wolters, Tineke; Savage, Caroline J; Cronin, Angel M; O'Brien, M Frank; Roobol, Monique J; Aus, Gunnar; Scardino, Peter T; Hugosson, Jonas; Schröder, Fritz H; Lilja, Hans

2010-09-01

Prostate specific antigen velocity has been proposed as a marker to aid in prostate cancer detection. We determined whether prostate specific antigen velocity could predict repeat biopsy results in men with persistently increased prostate specific antigen after initial negative biopsy. We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer and who underwent 1 or more subsequent prostate biopsies after an initial negative finding. We evaluated whether prostate specific antigen velocity improved predictive accuracy beyond that of prostate specific antigen alone. Of the 2,579 repeat biopsies 363 (14%) were positive for prostate cancer, of which 44 (1.7%) were high grade (Gleason score 7 or greater). Prostate specific antigen velocity was statistically associated with cancer risk but had low predictive accuracy (AUC 0.55, p <0.001). There was some evidence that prostate specific antigen velocity improved AUC compared to prostate specific antigen for high grade cancer. However, the small increase in risk associated with high prostate specific antigen velocity (from 1.7% to 2.8% as velocity increased from 0 to 1 ng/ml per year) had questionable clinical relevance. Men with prior negative biopsy are at lower risk for prostate cancer at subsequent biopsies with high grade disease particularly rare. We found little evidence to support prostate specific antigen velocity to aid in decisions about repeat biopsy for prostate cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Reassessment of the risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer treated using radical prostatectomy.

PubMed

Narita, Shintaro; Mitsuzuka, Koji; Tsuchiya, Norihiko; Koie, Takuya; Kawamura, Sadafumi; Ohyama, Chikara; Tochigi, Tatsuo; Yamaguchi, Takuhiro; Arai, Yoichi; Habuchi, Tomonori

2015-11-01

To assess the risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. We retrospectively reviewed the medical records of 1268 men with prostate cancer treated using radical prostatectomy without neoadjuvant therapy. The association between various risk factors and biochemical recurrence was then statistically evaluated. The Kaplan-Meier method, log-rank tests and Cox proportional hazards models were used for statistical analysis. In the intermediate-risk group, 96 patients (14.5%) experienced biochemical recurrence during a median follow up of 41 months. In the intermediate-risk group, preoperative prostate-specific antigen level, prostate volume and prostate-specific antigen density were significant preoperative risk factors for biochemical recurrence, whereas other factors including age, primary Gleason 4, clinical stage >T2 and percentage of positive biopsies were not. In multivariate analysis, higher preoperative prostate-specific antigen level and density, and a smaller prostate volume were independent risk factors for biochemical recurrence in the intermediate-risk group. Biochemical recurrence-free survival of patients in the intermediate-risk group with a higher prostate-specific antigen level and density (≥15 ng/mL, ≥0.6 ng/mL/cm(3), respectively), and lower prostate volume (≤10 mL) was comparable with that of high-risk group individuals (P = 0.632, 0.494 and 0.961, respectively). Preoperative prostate-specific antigen, prostate volume and prostate-specific antigen density are significant risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. Using these variables, a subset of the intermediate-risk patients can be identified as having equivalent outcomes to high-risk patients. © 2015 The Japanese Urological Association.

Prostate-specific antigen-based prostate cancer screening: Past and future.

PubMed

Alberts, Arnout R; Schoots, Ivo G; Roobol, Monique J

2015-06-01

Prostate-specific antigen-based prostate cancer screening remains a controversial topic. Up to now, there is worldwide consensus on the statement that the harms of population-based screening, mainly as a result of overdiagnosis (the detection of clinically insignificant tumors that would have never caused any symptoms), outweigh the benefits. However, worldwide opportunistic screening takes place on a wide scale. The European Randomized Study of Screening for Prostate Cancer showed a reduction in prostate cancer mortality through prostate-specific antigen based-screening. These population-based data need to be individualized in order to avoid screening in those who cannot benefit and start screening in those who will. For now, lacking a more optimal screening approach, screening should only be started after the process of shared decision-making. The focus of future research is the reduction of unnecessary testing and overdiagnosis by further research to better biomarkers and the value of the multiparametric magnetic resonance imaging, potentially combined in already existing prostate-specific antigen-based multivariate risk prediction models. © 2015 The Japanese Urological Association.

Impact of obesity on the predictive accuracy of prostate-specific antigen density and prostate-specific antigen in native Korean men undergoing prostate biopsy.

PubMed

Kim, Jae Heon; Doo, Seung Whan; Yang, Won Jae; Lee, Kwang Woo; Lee, Chang Ho; Song, Yun Seob; Jeon, Yoon Su; Kim, Min Eui; Kwon, Soon-Sun

2014-10-01

To evaluate the impact of obesity on the biopsy detection of prostate cancer. We retrospectively reviewed data of 1182 consecutive Korean patients (≥50 years) with serum prostate-specific antigen levels of 3-10 ng/mL who underwent initial extended 12-cores biopsy from September 2009 to March 2013. Patients who took medications that were likely to influence the prostate-specific antigen level were excluded. Receiver operating characteristic curves were plotted for prostate-specific antigen and prostate-specific antigen density predicting cancer status among non-obese and obese men. A total of 1062 patients (mean age 67.1 years) were enrolled in the analysis. A total of 230 men (21.7%) had a positive biopsy. In the overall study sample, the area under the receiver operator characteristic curve of serum prostate-specific antigen for predicting prostate cancer on biopsy were 0.584 and 0.633 for non-obese and obese men, respectively (P = 0.234). However, the area under the curve for prostate-specific antigen density in predicting cancer status showed a significant difference (non-obese 0.696, obese 0.784; P = 0.017). There seems to be a significant difference in the ability of prostate-specific antigen density to predict biopsy results between non-obese and obese men. Obesity positively influenced the overall ability of prostate-specific antigen density to predict prostate cancer. © 2014 The Japanese Urological Association.

Estimate of population coverage with the prostate specific antigen (PSA) test to screen for prostate cancer in a metropolitan area of northern Italy.

PubMed

Russo, A; Autelitano, M; Bellini, A; Bisanti, L

2002-01-01

The use of the prostate specific antigen (PSA) test in the period 1999-2000 in a population of 311 822 men, aged 40 years or more, resident in Milan, Italy, was examined. Data were drawn from the outpatient database of the local health information system. A total of 139 350 PSA tests were used in 83 943 subjects. Overall, 26.9% of the male population aged 40 or older, with no history of prostate cancer, received a PSA test in the 2 year study period. For subjects older than 50 the rate rose to 34%. Results show a high coverage of the male population in northern Italy with screening using the PSA test for prostate cancer.

Novel Prostate Cancer Pathway Modeling using Boolean Implication

DTIC Science & Technology

2012-09-01

cause of cancer deaths in men. Diagnosis and pathogenesis of this disease is poorly understood. Prostate specific antigen (PSA) test is still the... specific database, I combined 14 different datasets (global prostate cancer database, total n=891) that are in Affymetrix U133A (n=456), U133A 2.0...immunohistochemistry and flow cytometry are limited by the availability of antigen - specific monoclonal antibodies and by the small number of parallel

Should I Get Screened for Prostate Cancer?

MedlinePlus

... about being screened for prostate cancer with a prostate specific antigen (PSA) test. Before making a decision, men should ... Task Force Prostate Cancer Screening Final Recommendation Understanding Prostate Changes: A Health ... Cancer Institute) What Is Screening? ...

Do Ultrasensitive Prostate Specific Antigen Measurements Have a Role in Predicting Long-Term Biochemical Recurrence-Free Survival in Men after Radical Prostatectomy?

PubMed

Sokoll, Lori J; Zhang, Zhen; Chan, Daniel W; Reese, Adam C; Bivalacqua, Trinity J; Partin, Alan W; Walsh, Patrick C

2016-02-01

In this study we evaluate an ultrasensitive prostate specific antigen assay in patients with prostate cancer after radical prostatectomy to predict long-term biochemical recurrence-free survival. A total of 754 men who underwent radical prostatectomy and had an undetectable prostate specific antigen after surgery (less than 0.1 ng/ml) were studied. Prostate specific antigen was measured in banked serum specimens with an ultrasensitive assay (Hybritech® PSA, Beckman Coulter Access® 2) using a cutoff of 0.01 ng/ml. Prostate specific antigen was also measured in 44 men after cystoprostatectomy who had no pathological evidence of prostate cancer with the Hybritech assay and with the Quanterix AccuPSA™ assay. Of the 754 men 17% (131) experienced biochemical recurrence (median 4.0 years). Those men without biochemical recurrence (83%, 623) had a minimum of 5 years of followup (median 11). Prostate specific antigen was less than 0.01 ng/ml in 93.4% of men with no biochemical recurrence, whereas 30.5% of men with biochemical recurrence had a prostate specific antigen of 0.01 ng/ml or greater. On multivariate analysis postoperative prostate specific antigen at a 0.01 ng/ml cutoff, pathological stage and Gleason score, and surgical margins were significant independent predictors of biochemical recurrence risk. Kaplan-Meier estimates for mean biochemical recurrence-free survival were 15.2 years (95% CI 14.9-15.6) for prostate specific antigen less than 0.01 ng/ml and 10.0 years (95% CI 8.4-11.5) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Biochemical recurrence-free rates 11 years after surgery were 86.1% (95% CI 83.2-89.0) for prostate specific antigen less than 0.01 ng/ml and 48.9% (95% CI 37.5-60.3) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Prostate specific antigen concentrations in 44 men after cystoprostatectomy were all less than 0.03 ng/ml, with 95.4% less than 0.01 ng/ml. In men with a serum prostate specific antigen less than 0.1 ng/ml after radical prostatectomy a tenfold lower cutoff (0.01 ng/ml) stratified biochemical recurrence-free survival and was a significant independent predictor of biochemical recurrence, as were pathological features. Prostate specific antigen concentrations in men without pathological evidence of prostate cancer suggest that a higher prostate specific antigen concentration (0.03 ng/ml) in the ultrasensitive range may be needed to define the detection threshold. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[New Radiopharmaceuticals Based on Prostate-Specific Inhibitors of Membrane Antigen for Diagnostics and Therapy of Metastatic Prostate Cancer].

PubMed

Vlasova, O P; German, K E; Krilov, V V; Petriev, V M; Epstein, N B

2015-01-01

About 10.7% cases of prostate cancer were registered in Russia in 2011 (40,000 patients). More than half of cancer cases were revealed in advanced (III-IV) stages when metastases inevitably developed quickly. Clinical problem of early diagnostics and treatment of metastatic prostate cancer is still not solved. Anatomical imaging techniques have low sensitivity and specificity for the detection of this disease. Metabolic visualization methods which use prostate specific antigen (PSA) as a marker are also ineffective. This article describes prostate-specific membrane antigens (PSMA) that are proposed as a marker for diagnostics and therapy of prostate cancer. The most promising PSMA-based radiopharmaceutical agent for diagnostics has been developed and clinically tested in the European countries. These pharmaceuticals are based on small peptide molecules modified with urea, and have the highest affinity to PSMA. Favorable phannacokinetics, rapid accumulation in the tumor and rapid excretion from the body are beneficial features of these pharmaceuticals.

Prostate brachytherapy - discharge

MedlinePlus

... chap 84. Read More Prostate brachytherapy Prostate cancer Prostate-specific antigen (PSA) blood test Radical prostatectomy Review Date 2/21/2017 Updated by: Jennifer Sobol, DO, Urologist with the Michigan ... Cancer Browse the Encyclopedia A.D.A.M., ...

Relative value of race, family history and prostate specific antigen as indications for early initiation of prostate cancer screening.

PubMed

Vertosick, Emily A; Poon, Bing Ying; Vickers, Andrew J

2014-09-01

Many guidelines suggest earlier screening for prostate cancer in men at high risk, with risk defined in terms of race and family history. Recent evidence suggests that baseline prostate specific antigen is strongly predictive of the long-term risk of aggressive prostate cancer. We compared the usefulness of risk stratifying early screening by race, family history and prostate specific antigen at age 45 years. Using estimates from the literature we calculated the proportion of men targeted for early screening using family history, black race or prostate specific antigen as the criterion for high risk. We calculated the proportion of prostate cancer deaths that would occur in those men by age 75 years. Screening based on family history involved 10% of men, accounting for 14% of prostate cancer deaths. Using black race as a risk criterion involved 13% of men, accounting for 28% of deaths. In contrast, 44% of prostate cancer deaths occurred in the 10% of men with the highest prostate specific antigen at age 45 years. In no sensitivity analysis for race and family history did the ratio of risk group size to number of prostate cancer deaths in that risk group approach that of prostate specific antigen. Basing decisions for early screening on prostate specific antigen at age 45 years provided the best ratio between men screened and potential cancer deaths avoided. Given the lack of evidence that race or family history affects the relationship between prostate specific antigen and risk, prostate specific antigen based risk stratification would likely include any black men or men with a family history who are destined to experience aggressive disease. Differential screening based on risk should be informed by baseline prostate specific antigen. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0595 TITLE: Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate Cancer...Sep 2016 - 14 Sep 2017 4. TITLE AND SUBTITLE Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate

Pathological Outcome following Radical Prostatectomy in Men with Prostate Specific Antigen Greater than 10 ng/ml and Histologically Favorable Risk Prostate Cancer.

PubMed

Yu, Jiwoong; Kwon, Young Suk; Kim, Sinae; Han, Christopher Sejong; Farber, Nicholas; Kim, Jongmyung; Byun, Seok Soo; Kim, Wun-Jae; Jeon, Seong Soo; Kim, Isaac Yi

2016-05-01

Active surveillance is now the treatment of choice in men with low risk prostate cancer. Although there is no consensus on which patients are eligible for active surveillance, prostate specific antigen above 10 ng/ml is generally excluded. In an attempt to determine the validity of using a prostate specific antigen cutoff of 10 ng/ml to counsel men considering active surveillance we analyzed a multi-institution database to determine the pathological outcome in men with prostate specific antigen greater than 10 ng/ml but histologically favorable risk prostate cancer. We queried a prospectively maintained database of men with histologically favorable risk prostate cancer who underwent radical prostatectomy between 2003 and 2015. The cohort was categorized into 3 groups based on prostate specific antigen level, including low-less than 10 ng/ml, intermediate-10 or greater to less than 20 and high-20 or greater. Associations of prostate specific antigen group with adverse pathological and oncologic outcomes were analyzed. Of 2,125 patients 1,327 were categorized with histologically favorable risk disease. However on multivariate analyses the rates of up staging and upgrading were similar between the intermediate and low prostate specific antigen groups. In contrast compared to the intermediate prostate specific antigen group the high group had higher incidences of up staging (p = 0.02) and upgrading to 4 + 3 or greater disease (p = 0.046). Biochemical recurrence-free survival rates revealed no pairwise intergroup differences except between the low and high groups. Patients with preoperatively elevated prostate specific antigen between 10 and less than 20 ng/ml who otherwise had histologically favorable risk prostate cancer were not at higher risk for adverse pathological outcomes than men with prostate specific antigen less than 10 ng/ml. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Semiconductor nanocrystal-aptamer bioconjugate probes for specific prostate carcinoma cell targeting

NASA Astrophysics Data System (ADS)

Shieh, Felice; Lavery, Laura; Chu, Chitai T.; Richards-Kortum, Rebecca; Ellington, Andrew D.; Korgel, Brian A.

2005-04-01

Cancer of the prostate affects approximately 1 in 11 men. Current early screening for prostate cancer utilizes digital rectal examinations to detect anomalies in the prostate gland and blood test screenings for upregulated levels of prostate specific antigen (PSA). Many of these tests are invasive and can often be inconclusive as PSA levels may be heightened due to benign factors. Prostate specific membrane antigen (PSMA), a well-characterized integral membrane protein, is expressed in virtually all prostate cancers and often correlates with cancer aggressiveness. Therefore, it may be used as an indicator of cancer growth and metastases. PSMA-specific antibodies have been identified and conjugated to fluorescent markers for cancer cell targeting; however, both the antibodies and markers possess significant limitations in their pharmaceutical and diagnostic value. Here we report the use of semiconductor nanocrystals bioconjugated to PSMA-specific aptamer recognition molecules for prostate carcinoma cell targeting. The nanocrystal/aptamer bioconjugates are small biocompatible probes with the potential for color-tunability for multicolor imaging. Ongoing in vitro and in vivo research seeks to introduce these nanoparticle bioconjugates into medical diagnostics.

Prostate Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Prostate cancer screening with the prostate-specific antigen (PSA) test or digital rectal exams has not been shown to reduce prostate cancer deaths. Get detailed information about prostate cancer screening, including potential benefits and harms, in this summary for clinicians.

Prostate Cancer: Symptoms, Diagnosis and Treatment | NIH MedlinePlus the Magazine

MedlinePlus

... The prostate is checked for growths or enlargement. Prostate-specific antigen (PSA) test —A simple blood test to measure the amount of PSA, which is a marker for tumors. Biopsy —Tissue samples are extracted from the prostate with a long needle by a specialist. They ...

A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication.

PubMed

Bellera, Carine; Proust-Lima, Cécile; Joseph, Lawrence; Richaud, Pierre; Taylor, Jeremy; Sandler, Howard; Hanley, James; Mathoulin-Pélissier, Simone

2018-04-01

Background Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure. Objective Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework. For this purpose, we monitored the prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. We focused on the assessment of the prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure. Methods We used a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. We modeled prostate-specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability was expressed as a function of prostate-specific antigens concentration. Covariates in the survival model included hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process. Results We showed positive associations between an increased prostate-specific antigens nadir, an earlier changepoint and a steeper post-nadir slope with an increased risk of failure. Importantly, we highlighted a significant benefit of hormone therapy, an effect that was not observed when the prostate-specific antigens trajectory was not accounted for in the survival model. Conclusion Our modeling strategy was particularly flexible and accounted for multiple complex features of longitudinal and survival data, including the presence of a random changepoint and a time-dependent covariate.

Molecular Characterization of Indolent Prostate Cancer

DTIC Science & Technology

2016-12-01

prostate - specific antigen (PSA) test, and treated aggressively following diagnosis, leading to the contemporary problem of prostate cancer over-diagnosis... specific purpose of comparing low- risk and high-risk prostate cancer. Figure 3 shows the mapping rates for exon, intron, and inter-genic sequences. The...FFPE specimens, for the specific comparison of low-risk and high-risk prostate cancer. 5. Identified sufficient number of biopsy cases and sections

Determining the sensitivity of transrectal ultrasonography on a consecutive series of prostate cancers in a clinical and screening setting.

PubMed

Ciatto, Stefano; Bonardi, Rita; Lombardi, Claudio; Zappa, Marco; Gervasi, Ginetta

2002-01-01

To evaluate the sensitivity at transrectal ultrasonography (TRUS) for prostate cancer. A consecutive series of 170 prostate cancers identified by matching local cancer registry and TRUS archives at the Centro per lo Studio e la Prevenzione Oncologica of Florence. TRUS sensitivity was determined as the ratio of TRUS positive to total prostate cancers occurring at different intervals from TRUS date. Univariate and multivariate analyses of sensitivity determinants were performed. Sensitivity at 6 months, 1, 2 and 3 years after the test was 94.1% (95% CI, 90-98), 89.8% (95% CI, 85-95), 80.4% (95% CI, 74-87) and 74.1% (95% CI, 68-81%), respectively. A higher sensitivity (statistically significant) of TRUS was observed only if digital rectal examination was suspicious, whereas no association to sensitivity was observed for age, prostate-specific antigen or prostate-specific antigen density. The study provided a reliable estimate of TRUS sensitivity, particularly reliable being checked against a cancer registry: observed sensitivity was high, at least of the same magnitude of other cancer screening tests. TRUS, which is known to allow for considerable diagnostic anticipation and is more specific than prostate-specific antigen, might still be considered for its contribution to a screening approach.

Recognition of prostate-specific antigenic peptide determinants by human CD4 and CD8 T cells.

PubMed

Corman, J M; Sercarz, E E; Nanda, N K

1998-11-01

It is now becoming accepted that one is not tolerant to all the determinants of self proteins: the T cell repertoire directed to some sequences in self proteins is intact and can be activated. When a self protein is exclusively expressed by tumour cells, the T cell repertoire directed to the particular self antigen can potentially be activated to attack the tumour: this would amount to induction of a beneficial autoimmune response. Prostate cancer offers a unique opportunity for activation of a tumour-specific immune response owing to the exclusive synthesis of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) by prostatic tissue and prostate tumour cells. In this study we examine the CD4 and CD8 T cell repertoires specific for peptides of PSA and PSM in normal human male individuals, using short-term, peptide antigen-driven CD4 and CD8 T cell lines. We show that short-term, CD4 T cell lines derived from six HLA-DR4 individuals showed strong proliferative responses to six of 10 tested peptides of PSA, selected as to contain a DR4 binding motif. Short-term, CD8 T cell lines from three HLA-A1 individuals showed specific cytolytic activity for autologous targets loaded with five of five tested peptides of PSA and PSM, selected to possess an HLA-A1 binding motif. One of the peptides chosen is termed a 'dual-motif' peptide, as it encodes determinants for both CD4 and CD8 T cells. These results, indicating the existence of CD4 and CD8 T cells against determinants of the self proteins, PSA and PSM, in healthy male individuals reveal the potential of the T cell repertoire from the typical prostate cancer patient to eradicate prostate tumours upon being appropriately activated.

Biomarkers in localized prostate cancer

PubMed Central

Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

2016-01-01

Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer. PMID:26768791

Incidental Detection of Type B2 Thymoma on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT Imaging.

PubMed

Krishnaraju, Venkata Subramanian; Basher, Rajender Kumar; Singh, Harmandeep; Singh, Shrawan Kumar; Bal, Amanjit; Mittal, Bhagwant Rai

2018-05-01

Ga-labeled prostate-specific membrane antigen is a novel radiotracer for imaging of prostate cancer. We report a hormonally treated patient with prostate carcinoma, presenting with lower urinary tract symptoms and rising prostate-specific antigen levels, who underwent Ga-labeled prostate-specific membrane antigen PET/CT for suspected recurrence. No tracer avid lesion was noted in the prostate gland and locoregional area. However, intense tracer avid heterogeneously enhancing soft tissue lesion with cystic areas and coarse calcifications was seen in the anterior mediastinum. PET/CT-guided biopsy from the mediastenal lesion revealed type B2 thymoma.

Identification of threshold prostate specific antigen levels to optimize the detection of clinically significant prostate cancer by magnetic resonance imaging/ultrasound fusion guided biopsy.

PubMed

Shakir, Nabeel A; George, Arvin K; Siddiqui, M Minhaj; Rothwax, Jason T; Rais-Bahrami, Soroush; Stamatakis, Lambros; Su, Daniel; Okoro, Chinonyerem; Raskolnikov, Dima; Walton-Diaz, Annerleim; Simon, Richard; Turkbey, Baris; Choyke, Peter L; Merino, Maria J; Wood, Bradford J; Pinto, Peter A

2014-12-01

Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate-specific antigen (PSA) blood test

MedlinePlus

... very early. But there is debate over the value of the PSA test for detecting prostate cancer. No single answer fits all men. Before having the test, talk to your provider about the pros and cons of having a PSA test. Ask ...

Prostate-specific antigen and acute myocardial infarction: a possible new intriguing scenario.

PubMed

Patanè, Salvatore; Marte, Filippo

2009-05-29

Prostate-specific antigen (PSA) has been identified as a member of the human kallikrein family of serine proteases and it is an established marker for detection of prostate cancer. Apparently spurious result has been reported in a work about mean serum PSA concentration during acute myocardial infarction with mean serum PSA concentration significantly lower on day 2 than either day 1 or day 3 and it has been reported that these preliminary results could reflect several factors, such as antiinfarctual treatment, reduced physical activity or an acute-phase response. Elevation of prostate-specific antigen has also been reported during acute myocardial infarction in three patients and in another one also after transurethral resection of the prostate (TURP) and without histological diagnosis of prostate cancer. In our report we present three cases of diminution of serum PSA concentration during acute myocardial infarction. Our report extends the evaluation of PSA during acute myocardial infarction. It seems that when elevation of prostate-specific antigen occurs during acute myocardial infarction, coronary lesions are frequent and often more severe than when diminution of prostate-specific antigen occurs during acute myocardial infarction. It opens a possible new intriguing scenario of the role of the prostate-specific antigen in acute myocardial infarction.

Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques.

PubMed

Au, Bryan C; Lee, Chyan-Jang; Lopez-Perez, Orlay; Foltz, Warren; Felizardo, Tania C; Wang, James C M; Huang, Ju; Fan, Xin; Madden, Melissa; Goldstein, Alyssa; Jaffray, David A; Moloo, Badru; McCart, J Andrea; Medin, Jeffrey A

2016-02-19

Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA)-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months-the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an "off-the-shelf" anti-cancer vaccine that could be made at large scale and injected into patients-even on an out-patient basis.

Long-Term Trial Results Show No Mortality Benefit from Annual Prostate Cancer Screening

Cancer.gov

Thirteen year follow-up data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial show higher incidence but similar mortality among men screened annually with the prostate-specific antigen (PSA) test and digital rectal examination

Heterobivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2014-11-01

Prostate-Specific Membrane Antigen ( PSMA ) and Hepsin PRINCIPAL INVESTIGATOR: Youngjoo Byun, Ph. D. CONTRACTING ORGANIZATION: Korea...Simultaneous Targeting Prostate-Specific Membrane Antigen ( PSMA ) and Hepsin 5b. GRANT NUMBER W81XWH-10-1-0189 5c. PROGRAM ELEMENT NUMBER 6...heterobivalent conjugates of PSMA /hepsin-binding ligands labeled with optical dyes or radionuclides. The sensitivity and accuracy of prostate cancer

Biomarkers for prostate cancer detection and progression: Beyond prostate-specific antigen.

PubMed

Berney, Daniel M

2010-04-01

Prostate cancer is a major health problem with an incompletely understood pathogenesis and etiology. The advent of the prostate-specific antigen (PSA) test in the 1980s caused a revolution in how the disease was detected, but the evidence for PSA as a screening test is deficient. Biomarkers have been investigated, both for detection and discrimination of indolent from aggressive cancers. Refinements to the PSA test have been proposed but for practical and evidence-based reasons none have translated through to widespread clinical use. Of the novel biomarkers, the most promising is the prostate cancer antigen 3 (PCA3) test. New biomarkers to predict aggressive disease are even more contentious. The pathological grade of tumor remains the most powerful biomarker of prognosis. Other proven variables include tumor extent on biopsy and serum PSA. Tissue biomarkers have proven unhelpful due to a variable and biased literature with multiple methodological flaws, but Ki-67 probably shows more promise than any other current tissue biomarker. The recent discovery of a family of fusion genes in the prostate has led to considerable discussion on their prognostic role. Dissection of the genetic basis of the disease may lead to discoveries that will enhance our understanding and aid the search for prognostically valuable biomarkers. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2012-09-01

micrometastases that may be targeted with radioimmunotherapy. Prostate specific membrane antigen (PSMA) is the single, most well-established, highly restricted...Radiolabeled anti- prostate specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu-J591) for nonmetastatic castration-resistant prostate cancer...rationale for systemic salvage targeted anti- prostate specific membrane antigen radioimmunotherapy. Adv Urol 2012, Article ID 921674, doi:10.1155

Prostatectomy - Series (image)

MedlinePlus

... result from a blood test called a PSA (prostate-specific antigen), and/or a digital rectal exam. The digital rectal exam checks the rear surface of the prostate gland for any abnormalities. A lump or hardness ...

Prostate-Specific Antigen (PSA) Test

MedlinePlus

... incidence of prostate cancer than men in the control group but the same rate of deaths from the ... the PLCO trial who were assigned to the control group had nevertheless undergone PSA screening. This analysis suggested ...

Synchronous Detection of Male Breast Cancer and Prostatic Cancer in a Patient With Suspected Prostatic Carcinoma on 68Ga-PSMA PET/CT Imaging.

PubMed

Kumar, Rajender; Mittal, Bhagwant Rai; Bhattacharya, Anish; Singh, Harmandeep; Singh, Shrawan Kumar

2018-06-01

The male breast cancer is very less common as compared with the female breast cancer. We report a case of 64-year-old man who presented with the history of lower urinary tract symptoms. The digital rectal examination revealed hard and nodular prostate, and serum prostate-specific antigen level was 23.4 ng/mL. Ga-labeled prostate-specific membrane antigen PET/CT revealed prostate-specific membrane antigen-expressing lesions in the prostate, axillary tail of the right breast, and axillary lymph nodes. Histology from prostate revealed prostate carcinoma, whereas fine-needle aspiration from the breast revealed invasive ductal carcinoma of the breast.

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

PubMed

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

2008-12-01

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

Epithelial Plasticity in Castration-Resistant Prostate Cancer: Biology of the Lethal Phenotype

DTIC Science & Technology

2012-07-01

mCRPC, with metastatic progres- sion by prostate - specific antigen (PSA; 2 consecutive rises over nadir separated by more than 1 week) or radiologic...Abbreviations: CRPC, castration-resistant prostate cancer; PSA, prostate specific antigen . Armstrong et al. Mol Cancer Res; 9(8) August 2011 Molecular... antigen , which we found did correlate with PSA outcomes and high risk disease among men with localized prostate cancer who were undergoing radical

Incidental Metastatic Melanoma Identified on 68Ga-Prostate-Specific Membrane Antigen PET/CT for Metastatic Prostate Cancer.

PubMed

Snow, Hayden A; Hofman, Michael S; Mitchell, Catherine A; Gyorki, David E; Smith, Myles J F

2018-07-01

A 78-year-old man with a history of surgically treated prostate cancer and melanoma underwent Ga-prostate-specific membrane antigen (PSMA) PET/CT for biochemical recurrence of his prostate cancer. This revealed locoregionally recurrent prostate cancer and a separate PSMA-avid nodule in his left arm. Subsequent F-FDG PET/CT and excision confirmed this to be an in-transit melanoma metastasis. Prostate-specific membrane antigen PET/CT has become a widely used and valuable tool in the assessment of prostate cancer, particularly biochemically recurrent. Uptake of PSMA has been described in a multitude of different benign and malignant conditions, but it has only rarely been documented in melanoma.

Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

NASA Astrophysics Data System (ADS)

Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

2016-05-01

Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

Herniated Thoracic Spleen Mimicking Lung Metastasis on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT in a Patient With Prostate Cancer.

PubMed

Malik, Dharmender; Basher, Rajender K; Sood, Apurva; Devana, Sudheer Kumar; Bhattacharya, Anish; Mittal, Bhagwant Rai

2017-06-01

We report a case of clinically asymptomatic patient of prostate cancer who was previously subjected to radical prostatectomy presenting with a rising serum prostate-specific antigen level of 6.6 ng/mL. Whole-body PET/CT with Ga-labeled prostate-specific membrane antigen ligand was performed to assess for disease recurrence, which revealed an intense tracer uptake in a soft tissue mass in left hemithorax mimicking lung metastasis; which later turned out to be splenic tissue.

The roles of prostate-specific antigen (PSA) density, prostate volume, and their zone-adjusted derivatives in predicting prostate cancer in patients with PSA less than 20.0 ng/mL.

PubMed

Shen, P; Zhao, J; Sun, G; Chen, N; Zhang, X; Gui, H; Yang, Y; Liu, J; Shu, K; Wang, Z; Zeng, H

2017-05-01

The aim of this study was to develop nomograms for predicting prostate cancer and its zonal location using prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives. A total of 928 consecutive patients with prostate-specific antigen (PSA) less than 20.0 ng/mL, who underwent transrectal ultrasound-guided transperineal 12-core prostate biopsy at West China Hospital between 2011 and 2014, were retrospectively enrolled. The patients were randomly split into training cohort (70%, n = 650) and validation cohort (30%, n = 278). Predicting models and the associated nomograms were built using the training cohort, while the validations of the models were conducted using the validation cohort. Univariate and multivariate logistic regression was performed. Then, new nomograms were generated based on multivariate regression coefficients. The discrimination power and calibration of these nomograms were validated using the area under the ROC curve (AUC) and the calibration curve. The potential clinical effects of these models were also tested using decision curve analysis. In total, 285 (30.7%) patients were diagnosed with prostate cancer. Among them, 131 (14.1%) and 269 (29.0%) had transition zone prostate cancer and peripheral zone prostate cancer. Each of zone-adjusted derivatives-based nomogram had an AUC more than 0.75. All nomograms had higher calibration and much better net benefit than the scenarios in predicting patients with or without different zones prostate cancer. Prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives have important roles in detecting prostate cancer and its zonal location for patients with PSA 2.5-20.0 ng/mL. To the best of our knowledge, this is the first nomogram using these parameters to predict outcomes of 12-core prostate biopsy. These instruments can help clinicians to increase the accuracy of prostate cancer screening and to avoid unnecessary prostate biopsy. © 2017 American Society of Andrology and European Academy of Andrology.

Prostate Specific Membrane Antigen Positron Emission Tomography May Improve the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging in Localized Prostate Cancer.

PubMed

Rhee, H; Thomas, P; Shepherd, B; Gustafson, S; Vela, I; Russell, P J; Nelson, C; Chung, E; Wood, G; Malone, G; Wood, S; Heathcote, P

2016-10-01

Positron emission tomography using ligands targeting prostate specific membrane antigen has recently been introduced. Positron emission tomography imaging with (68)Ga-PSMA-HBED-CC has been shown to detect metastatic prostate cancer lesions at a high rate. In this study we compare multiparametric magnetic resonance imaging and prostate specific membrane antigen positron emission tomography of the prostate with whole mount ex vivo prostate histopathology to determine the true sensitivity and specificity of these imaging modalities for detecting and locating tumor foci within the prostate. In a prospective clinical trial setting 20 patients with localized prostate cancer and a planned radical prostatectomy were recruited. All patients underwent multiparametric magnetic resonance imaging and positron emission tomography before surgery, and whole mount histopathology slides were directly compared to the images. European Society of Urogenital Radiology guidelines for reporting magnetic resonance imaging were used as a template for regional units of analysis. The uropathologist and radiologists were blinded to individual components of the study, and the final correlation was performed by visual and deformable registration analysis. A total of 50 clinically significant lesions were identified from the whole mount histopathological analysis. Based on regional analysis the sensitivity, specificity, positive predictive value and negative predictive value for multiparametric magnetic resonance imaging were 44%, 94%, 81% and 76%, respectively. With prostate specific membrane antigen positron emission tomography the sensitivity, specificity, positive predictive value and negative predictive value were 49%, 95%, 85% and 88%, respectively. Prostate specific membrane antigen positron emission tomography yielded a higher specificity and positive predictive value. A significant proportion of cancers are potentially missed and underestimated by both imaging modalities. Prostate specific membrane antigen positron emission tomography may be used in addition to multiparametric magnetic resonance imaging to help improve local staging in those patients undergoing retropubic radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Heterobivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2011-04-01

specific membrane antigen (PSMA), showed promise in the clinic for identifying candidates for salvage radiotherapy. (4, 5) Because of the important...removed benzyl group to afford the Lys- Urea-Glu 14 in 85% yield. Compound 14 was conjugated with the suberic acid bis-(N- hydroxysuccinimide ( DSS ) in...directed against human and mouse prostate-specific membrane antigen. Prostate 2004; 61: 1-11. 4. Chang SS, Heston WD. The clinical role of prostate

Combination therapy for biochemically recurrent prostate cancer tested in new trial | Center for Cancer Research

Cancer.gov

Prostate-specific antigen (PSA) is an enzyme released by the prostate gland and is found in abnormally high concentrations in the blood of men with prostate cancer. “Biochemical recurrence” is when PSA levels continue to rise after initial treatment for prostate cancer, such as surgery or radiation. Marijo Bilusic, M.D., of the Genitourinary Malignancies Branch is leading the

Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses.

PubMed

Ferraro, Bernadette; Cisper, Neil J; Talbott, Kendra T; Philipson-Weiner, Lindsey; Lucke, Colleen E; Khan, Amir S; Sardesai, Niranjan Y; Weiner, David B

2011-01-01

Prostate cancer (PCa) remains a significant public health problem. Current treatment modalities for PCa can be useful, but may be accompanied by deleterious side effects and often do not confer long-term control. Accordingly, additional modalities, such as immunotherapy, may represent an important approach for PCa treatment. The identification of tissue-specific antigens engenders PCa an attractive target for immunotherapeutic approaches. Delivery of DNA vaccines with electroporation has shown promising results for prophylactic and therapeutic targets in a variety of species including humans. Application of this technology for PCa immunotherapy strategies has been limited to single antigen and epitope targets. We sought to test the hypothesis that a broader collection of antigens would improve the breadth and effectiveness of a PCa immune therapy approach. We therefore developed highly optimized DNA vaccines encoding prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) as a dual antigen approach to immune therapy of PCa. PSA-and PSMA-specific cellular immunogenicity was evaluated in a mouse model for co-delivery and single antigen vaccination. Mice received 2 immunizations spaced 2 weeks apart and immunogenicity was evaluated 1 week after the second vaccination. Both the PSA and PSMA vaccines induced robust antigen-specific IFNγ responses by ELISpot. Further characterization of cellular immunogenicity by flow cytometry indicated strong antigen-specific TNFα production by CD4+ T cells and IFNγ and IL-2 secretion by both CD4+ and CD8+ T cells. There was also a strong humoral response as determined by PSA-specific seroconversion. These data support further study of this novel approach to immune therapy of PCa.

Gender Identity Disparities in Cancer Screening Behaviors.

PubMed

Tabaac, Ariella R; Sutter, Megan E; Wall, Catherine S J; Baker, Kellan E

2018-03-01

Transgender (trans) and gender-nonconforming adults have reported reduced access to health care because of discrimination and lack of knowledgeable care. This study aimed to contribute to the nascent cancer prevention literature among trans and gender-nonconforming individuals by ascertaining rates of breast, cervical, prostate, and colorectal cancer screening behaviors by gender identity. Publicly available de-identified data from the 2014-2016 Behavioral Risk Factor Surveillance System surveys were utilized to evaluate rates of cancer screenings by gender identity, while controlling for healthcare access, sociodemographics, and survey year. Analyses were conducted in 2017. Weighted chi-square tests identified significant differences in the proportion of cancer screening behaviors by gender identity among lifetime colorectal cancer screenings, Pap tests, prostate-specific antigen tests, discussing prostate-specific antigen test advantages/disadvantages with their healthcare provider, and up-to-date colorectal cancer screenings and Pap tests (p<0.036). Weighted logistic regressions found that although some differences based on gender identity were fully explained by covariates, trans women had reduced odds of having up-to-date colorectal cancer screenings compared to cisgender (cis) men (AOR=0.20) and cis women (AOR=0.24), whereas trans men were more likely to ever receive a sigmoidoscopy/colonoscopy as compared to cis men (AOR=2.76) and cis women (AOR=2.65). Trans women were more likely than cis men to have up-to-date prostate-specific antigen tests (AOR=3.19). Finally, trans men and gender-nonconforming individuals had reduced odds of lifetime Pap tests versus cis women (AOR=0.14 and 0.08, respectively), and gender-nonconforming individuals had lower odds of discussing prostate-specific antigen tests than cis men (AOR=0.09; all p<0.05). The findings indicate that gender identity disparities in cancer screenings persist beyond known sociodemographic and healthcare factors. It is critical that gender identity questions are included in cancer and other health-related surveillance systems to create knowledge to better inform healthcare practitioners and policymakers of appropriate screenings for trans and gender-nonconforming individuals. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

CD8+ T-cell responses rapidly select for antigen-negative tumor cells in the prostate.

PubMed

Bak, S Peter; Barnkob, Mike Stein; Wittrup, K Dane; Chen, Jianzhu

2013-12-01

Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8(+) T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell-treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8(+) T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells. ©2013 AACR.

Prostate-Specific Antigen (PSA) Bounce After Dose-Escalated External Beam Radiation Therapy Is an Independent Predictor of PSA Recurrence, Metastasis, and Survival in Prostate Adenocarcinoma Patients.

PubMed

Romesser, Paul B; Pei, Xin; Shi, Weiji; Zhang, Zhigang; Kollmeier, Marisa; McBride, Sean M; Zelefsky, Michael J

2018-01-01

To evaluate the difference in prostate-specific antigen (PSA) recurrence-free, distant metastasis-free, overall, and cancer-specific survival between PSA bounce (PSA-B) and non-bounce patients treated with dose-escalated external beam radiation therapy (DE-EBRT). During 1990-2010, 1898 prostate adenocarcinoma patients were treated with DE-EBRT to ≥75 Gy with ≥5 years follow-up. Patients receiving neoadjuvant/concurrent androgen-deprivation therapy (n=1035) or with fewer than 4 PSA values obtained 6 months or more after post-EBRT completion (n=87) were excluded. The evaluable 776 patients were treated (median, 81.0 Gy). Prostate-specific antigen bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. Prostate-specific antigen relapse was defined as post-radiation therapy PSA nadir + 2 ng/mL. Median follow-up was 9.2 years (interquartile range, 6.9-11.3 years). One hundred twenty-three patients (15.9%) experienced PSA-B after DE-EBRT at a median of 24.6 months (interquartile range, 16.1-38.5 months). On multivariate analysis, younger age (P=.001), lower Gleason score (P=.0003), and higher radiation therapy dose (P=.0002) independently predicted PSA-B. Prostate-specific antigen bounce was independently associated with decreased risk for PSA relapse (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.33-0.85; P=.008), distant metastatic disease (HR 0.34; 95% CI 0.12-0.94; P=.04), and all-cause mortality (HR 0.53; 95% CI 0.29-0.96; P=.04) on multivariate Cox analysis. Because all 50 prostate cancer-specific deaths in patients without PSA-B were in the non-bounce cohort, competing-risks analysis was not applicable. A nonparametric competing-risks test demonstrated that patients with PSA-B had superior cancer-specific survival compared with patients without PSA-B (P=.004). Patients treated with dose-escalated radiation therapy for prostate adenocarcinoma who experience posttreatment PSA-B have improved PSA recurrence-free survival, distant metastasis-free survival, overall survival, and cancer-specific survival outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Gastric Metastasis of Prostate Cancer as an Unusual Presentation Using 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Solis Lara, Hugo Enrique; Villarreal Del Bosque, Natalia; Sada Treviño, Miguel Antonio; Yamamoto Ramos, Masao; Argueta Ruiz, Rocío Del Carmen

2018-05-01

A 79-year-old man with prostate cancer underwent Ga prostate-specific membrane antigen (Ga-PSMA) dual-time-point PET/CT scan to evaluate tumor activity due to early satiety, unquantified weight loss, and elevation of prostate-specific antigen (PSA), demonstrating thickening of the gastric wall with intense tracer uptake. The immunohistochemistry of gastric biopsy showed CDX2 and CK20: negative; CK7, focal positive; PSA, positive, which confirmed metastatic disease. Metastatic disease was also found in bones, right lung, and retroperitoneal and pelvic lymphadenopathies.

Age-related reference intervals for free and total prostate-specific antigen in a Singaporean population.

PubMed

Saw, S; Aw, T C

2000-11-01

Cancer of the prostate is the sixth most frequently found cancer in Singapore. Prostate-specific antigen (PSA) is the most clinically useful tumour marker available today for the diagnosis and management of prostate cancer. To enhance the value of PSA as a screening test we developed age-specific intervals for our ethnic population. The measurement of free PSA was included in the study to calculate the free:total ratio which enhances the differential diagnosis of prostate cancer from benign prostatic hyperplasia or prostatitis. The total PSA upper limits of 10-year intervals, beginning at 30-years-old, were 1.4, 1.7, 2.3, 4.0, 6.3 and 6.6 microg/l. Free PSA cut-off limits were 0.4, 0.5, 0.5, 1.0, 1.5 and 1.6 microg/l. The free:total ratio of PSA was not age dependent. Abbott AxSym standardised their calibration material for both free and total PSA assays with the Stanford 90:10 reference material. This laboratory has implemented these age-specific reference intervals and are currently following up their pick-up rate in the detection of prostate cancer.

Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the Prostate-Specific Antigen Era

PubMed Central

2014-01-01

Background The role of lycopene in prostate cancer prevention remains controversial. We examined the associations between dietary lycopene intake and prostate cancer, paying particular attention to the influence of prostate-specific antigen screening, and evaluated tissue biomarkers in prostate cancers in relation to lycopene intake. Methods Among 49898 male health professionals, we obtained dietary information through questionnaires and ascertained total and lethal prostate cancer cases from 1986 through January 31, 2010. Cox regression was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Tissue microarrays and immunohistochemistry were used to assess tumor biomarker expression in a subset of men. Two-sided χ2 tests were used to calculate the P values. Results Higher lycopene intake was inversely associated with total prostate cancer and more strongly with lethal prostate cancer (top vs bottom quintile: HR = 0.72; 95% CI = 0.56 to 0.94; P trend = .04). In a restricted population of screened participants, the inverse associations became markedly stronger (for lethal prostate cancer: HR = 0.47; 95% CI = 0.29 to 0.75; P trend = .009). Comparing different measures of dietary lycopene, early intake, but not recent intake, was inversely associated with prostate cancer. Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential. Conclusions Dietary intake of lycopene was associated with reduced risk of lethal prostate cancer and with a lesser degree of angiogenesis in the tumor. Because angiogenesis is a strong progression factor, an endpoint of lethal prostate cancer may be more relevant than an endpoint of indolent prostate cancer for lycopene in the era of highly prevalent prostate-specific antigen screening. PMID:24463248

Synergistic co-targeting of prostate-specific membrane antigen and androgen receptor in prostate cancer.

PubMed

Murga, Jose D; Moorji, Sameer M; Han, Amy Q; Magargal, Wells W; DiPippo, Vincent A; Olson, William C

2015-02-15

Antibody-drug conjugates (ADCs) are an emerging class of cancer therapies that have demonstrated favorable activity both as single agents and as components of combination regimens. Phase 2 testing of an ADC targeting prostate-specific membrane antigen (PSMA) in advanced prostate cancer has shown antitumor activity. The present study examined PSMA ADC used in combination with potent antiandrogens (enzalutamide and abiraterone) and other compounds. Antiproliferative activity and expression of PSMA, prostate-specific antigen and androgen receptor were evaluated in the prostate cancer cell lines LNCaP and C4-2. Cells were tested for susceptibility to antiandrogens or other inhibitors, used alone and in combination with PSMA ADC. Potential drug synergy or antagonism was evaluated using the Bliss independence method. Enzalutamide and abiraterone demonstrated robust, statistically significant synergy when combined with PSMA ADC. Largely additive activity was observed between the antiandrogens and the individual components of the ADC (free drug and unmodified antibody). Rapamycin also synergized with PSMA ADC in certain settings. Synergy was linked in part to upregulation of PSMA expression. In androgen-dependent LNCaP cells, enzalutamide and abiraterone each inhibited proliferation, upregulated PSMA expression, and synergized with PSMA ADC. In androgen-independent C4-2 cells, enzalutamide and abiraterone showed no measurable antiproliferative activity on their own but increased PSMA expression and synergized with PSMA ADC nonetheless. PSMA expression increased progressively over 3 weeks with enzalutamide and returned to baseline levels 1 week after enzalutamide removal. The findings support exploration of clinical treatment regimens that combine potent antiandrogens and PSMA-targeted therapies for prostate cancer. © 2014 Wiley Periodicals, Inc.

Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.

PubMed

Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K; Marck, Brett T; Matsumoto, Alvin M

2011-07-01

Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older, hypogonadal men with symptomatic benign prostatic hyperplasia. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate Cancer Relevant Antigens and Enzymes for Targeted Drug Delivery

PubMed Central

Barve, Ashutosh; Jin, Wei; Cheng, Kun

2014-01-01

Chemotherapy is one of the most widely used approaches in combating advanced prostate cancer, but its therapeutic efficacy is usually insufficient due to lack of specificity and associated toxicity. Lack of targeted delivery to prostate cancer cells is also the primary obstacles in achieving feasible therapeutic effect of other promising agents including peptide, protein, and nucleic acid. Consequently, there remains a critical need for strategies to increase the selectivity of anti-prostate cancer agents. This review will focus on various prostate cancer-specific antigens and enzymes that could be exploited for prostate cancer targeted drug delivery. Among various targeting strategies, active targeting is the most advanced approach to specifically deliver drugs to their designated cancer cells. In this approach, drug carriers are modified with targeting ligands that can specifically bind to prostate cancer-specific antigens. Moreover, there are several specific enzymes in the tumor microenvironment of prostate cancer that can be exploited for stimulus-responsive drug delivery systems. These systems can specifically release the active drug in the tumor microenvironment of prostate cancer, leading to enhanced tumor penetration efficiency. PMID:24878184

Prostatic specific antigen. From its early days until becoming a prostate cancer biomarker.

PubMed

Dellavedova, T

2016-01-01

Prostate-specific antigen (PSA) has been since the mid 80's the most commonly used biomarker for measuring current and future risk of prostate cancer, for its early detection and to measure response to treatments and detecting recurrence in all stages of the disease. PSA's early development came along with progress in the field of immunology, which allowed detection and study of antigens from different tissues and fluids when injecting them into rabbits to promote immune response. Rubin Flocks in 1960 was the first to investigate and discover prostate-specific antigens in benign and malignant tissue. Some years later, Hara, a Japanese forensic investigator, found 'gamma seminoprotein', that he used to detect human semen in rape cases. However, his work published in Japanese did not reach the Englishspeaking scientific community. In 1970 Ablin discovered both in prostatic fluid and tissue what he called "prostate-specific antigen", but he didn't characterize or describe it. Investigators Li and Beling, and Sensabaugh, approached the current PSA, but they were limited by available technology at that time. Dr T Ming Chu led a research team on prostate cancer in New York, USA and published their results in 1979. He finally received the patent for the discovery of "human purified prostate antigen" in 1984. Due to this work, the Food and Drug Administration (FDA), in USA, approved the use of PSA for monitoring recurrence after treatment. It was later known that PSA was not prostate-specific since it was produced in other tissues and fluids, but it was recognized that it was human species-specific. Works by Papsidero and Stamey showed new indications and utilities for PSA, but it was Catalona who first used it as a marker for prostate cancer in 1991. Thanks to these advances FDA authorized in 1994 the clinical use of PSA for early detection of prostate cancer.

76 FR 40736 - NIH State-of-the-Science Conference on the Role of Active Surveillance in the Management of Men...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... blood test that measures prostate-specific antigen (PSA), a tumor marker. More than half of cancers detected with PSA screening are localized (confined to the prostate), not aggressive at diagnosis, and... which PSA levels are closely monitored, prostate biopsies may be repeated, and eventual treatment is...

A population-based study on the association between educational length, prostate-specific antigen testing and use of prostate biopsies.

PubMed

Nordström, Tobias; Bratt, Ola; Örtegren, Joakim; Aly, Markus; Adolfsson, Jan; Grönberg, Henrik

2016-01-01

The aim of this study was to determine whether educational length affects prostate-specific antigen (PSA) testing and the time to prostate biopsy for men with raised PSA values. Using register data on all men in Stockholm County in 2013 (n = 1,052,841), the limited-duration point prevalence of PSA testing and time between test and prostate biopsy or repeat testing were analysed. Patterns of follow-up were assessed using Kaplan-Meier product limit estimators and Cox proportional hazard models. Educational length was categorized as short (≤ 9 years), intermediate (10-12 years) or long (≥ 13 years). PSA testing increased with educational length in all age groups. Among men aged 50-69 years, 61% with long and 54% with short education had had a PSA test within the preceding 10 years (p < 0.001). In men with PSA 4-10 ng/ml, 40% [95% confidence interval (CI) 38-41] with long and 27% (95% CI 26-29) with short education underwent a prostate biopsy within 12 months. After adjusting for PSA level and age, educational length was still associated with the chance of having a prostate biopsy in men with PSA 4-10 ng/ml (hazard ratio 1.22, 95% CI 1.12-1.31), but not in men with higher PSA values. PSA testing increased with educational length. Men with long education were more likely to have a prostate biopsy after an increased PSA value below 10 ng/ml than men with short education. These differences may contribute to the worse prostate cancer outcomes observed among men with lower socioeconomic status.

Prostate-specific antigen testing in inner London general practices: are those at higher risk most likely to get tested?

PubMed

Nderitu, Paul; Van Hemelrijck, Mieke; Ashworth, Mark; Mathur, Rohini; Hull, Sally; Dudek, Alexandra; Chowdhury, Simon

2016-07-12

To investigate the association between factors influencing prostate-specific antigen (PSA) testing prevalence including prostate cancer risk factors (age, ethnicity, obesity) and non-risk factors (social deprivation and comorbidity). A cross-sectional database of 136 inner London general practices from 1 August 2009 to 31 July 2014. Men aged ≥40 years without prostate cancer were included (n=150 481). Logistic regression analyses were used to estimate the association between PSA testing and age, ethnicity, social deprivation, body mass index (BMI) and comorbidity while adjusting for age, benign prostatic hypertrophy, prostatitis and tamsulosin or finasteride use. PSA testing prevalence was 8.2% (2013-2014), and the mean age was 54 years (SD 11). PSA testing was positively associated with age (OR 70-74 years compared to 40-44 years: 7.34 (95% CI 6.82 to 7.90)), ethnicity (black) (OR compared to white: 1.78 (95% CI 1.71 to 1.85)), increasing BMI and cardiovascular comorbidity. Testing was negatively associated with Chinese ethnicity and with increasing social deprivation. PSA testing among black patients was higher compared to that among white patients, which differs from lower testing rates seen in previous studies. PSA testing was positively associated with prostate cancer risk factors and non-risk factors. Association with non-risk factors may increase the risk of unnecessary invasive diagnostic procedures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

68Ga-Labeled Anti-Prostate-Specific Membrane Antigen Peptide as Marker for Androgen Deprivation Therapy Response in Prostate Cancer.

PubMed

Schlenkhoff, Carl Diedrich; Gaertner, Florian; Essler, Markus; Hauser, Stefan; Ahmadzadehfar, Hojjat

2016-05-01

Prostate cancer was diagnosed in a 71-year-old man with an elevated prostate-specific antigen. The CT of the abdomen showed multiple para-aortal lymph nodes, and thus, a Ga anti-prostate-specific membrane antigen (PSMA-11) PET/CT was initiated, which showed, aside from the prostate cancer and multiple iliacal and para-aortal lymph node metastases, an increased tracer uptake in a lymph node left cervical. According to this advanced disease, a palliative therapy with GnRH agonist was initiated. A second PSMA-11 PET/CT was performed 4 months later, which showed a very good response; thus, additional radiation of the pelvis and the draining lymphatic system was performed.

Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements.

PubMed

McJimpsey, Erica L

2016-02-25

The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves.

Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements

NASA Astrophysics Data System (ADS)

McJimpsey, Erica L.

2016-02-01

The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves.

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

PubMed

Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

2011-02-01

To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

Prostate-specific membrane antigen-directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells.

PubMed

Lee, Seung S; Roche, Philip Jr; Giannopoulos, Paresa N; Mitmaker, Elliot J; Tamilia, Michael; Paliouras, Miltiadis; Trifiro, Mark A

2017-03-01

Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigen-positive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.

A large, benign prostatic cyst presented with an extremely high serum prostate-specific antigen level.

PubMed

Chen, Han-Kuang; Pemberton, Richard

2016-01-08

We report a case of a patient who presented with an extremely high serum prostate specific antigen (PSA) level and underwent radical prostatectomy for presumed prostate cancer. Surprisingly, the whole mount prostatectomy specimen showed only small volume, organ-confined prostate adenocarcinoma and a large, benign intraprostatic cyst, which was thought to be responsible for the PSA elevation. 2016 BMJ Publishing Group Ltd.

Echo-Planar Imaging Based J-Resolved Spectroscopic Imaging for Improved Metabolite Detection in Prostate Cancer

DTIC Science & Technology

2013-10-01

Scope: A major outcome is expected to be on improved detection ( specificity ) in differentiating malignant from benign prostate cancer using a novel...Digital Rectal Examination, prostate specific antigen , Four Dimensional (4D) Echo-Planar J-Resolved Spectroscopic Imaging (EP-JRESI); Citrate, Choline... prostate biopsy ranged from 3 to 8, while prostate - specific antigen varied from 2.8 to 20.6 ng/mL (mean of 6.84 ng/mL). A Siemens 3T MRI Scanner with

Prostate-specific antigen kallikrein: from prostate cancer to cardiovascular system.

PubMed

Patanè, Salvatore; Marte, Filippo

2009-05-01

Prostate-specific antigen (PSA), considered only an established marker for the detection of prostate cancer, has been identified as a member (hK3) of the human kallikrein family of serine proteases and now, it is known that PSA is not specific to prostate, semen, and gender. Increased PSA serum levels have been reported also in cardiovascular patients and both elevated as well as diminished PSA have been reported during acute myocardial infarction (AMI). Preliminary observations have concluded that when elevation of prostate-specific antigen occurs during AMI, it seems to relate to a higher occurrence of major adverse cardiac events and that coronary lesions are frequent and often more severe than when a diminution of PSA occurs. Large studies need to be done to confirm these preliminary results but the journey of PSA could be longer than expected.

Pre-screening Discussions and Prostate-Specific Antigen Testing for Prostate Cancer Screening

PubMed Central

Li, Jun; Zhao, Guixiang; Hall, Ingrid J.

2015-01-01

Introduction For many men, the net benefit of prostate cancer screening with prostate-specific antigen (PSA) tests may be small. Many major medical organizations have issued recommendations for prostate cancer screening, stressing the need for shared decision making before ordering a test. The purpose of this study is to better understand associations between discussions about benefits and harms of PSA testing and uptake of the test among men aged ≥40 years. Methods Associations between pre-screening discussions and PSA testing were examined using self-reported data from the 2012 Behavioral Risk Factor Surveillance System. Unadjusted prevalence of PSA testing was estimated and AORs were calculated using logistic regression in 2014. Results The multivariate analysis showed that men who had ever discussed advantages of PSA testing only or discussed both advantages and disadvantages were more likely, respectively, to report having had a test within the past year than men who had no discussions (p<0.001). In addition, men who had only discussed the disadvantages of PSA testing with their healthcare providers were more likely (AOR=2.75, 95% CI=2.00, 3.79) to report getting tested than men who had no discussions. Conclusions Discussions of the benefits or harms of PSA testing are positively associated with increased uptake of the test. Given the conflicting recommendations for prostate cancer screening and increasing importance of shared decision making, this study points to the need for understanding how pre-screening discussions are being conducted in clinical practice and the role played by patients’ values and preferences in decisions about PSA testing. PMID:25997905

Pre-screening Discussions and Prostate-Specific Antigen Testing for Prostate Cancer Screening.

PubMed

Li, Jun; Zhao, Guixiang; Hall, Ingrid J

2015-08-01

For many men, the net benefit of prostate cancer screening with prostate-specific antigen (PSA) tests may be small. Many major medical organizations have issued recommendations for prostate cancer screening, stressing the need for shared decision making before ordering a test. The purpose of this study is to better understand associations between discussions about benefits and harms of PSA testing and uptake of the test among men aged ≥40 years. Associations between pre-screening discussions and PSA testing were examined using self-reported data from the 2012 Behavioral Risk Factor Surveillance System. Unadjusted prevalence of PSA testing was estimated and AORs were calculated using logistic regression in 2014. The multivariate analysis showed that men who had ever discussed advantages of PSA testing only or discussed both advantages and disadvantages were more likely, respectively, to report having had a test within the past year than men who had no discussions (p<0.001). In addition, men who had only discussed the disadvantages of PSA testing with their healthcare providers were more likely (AOR=2.75, 95% CI=2.00, 3.79) to report getting tested than men who had no discussions. Discussions of the benefits or harms of PSA testing are positively associated with increased uptake of the test. Given the conflicting recommendations for prostate cancer screening and increasing importance of shared decision making, this study points to the need for understanding how pre-screening discussions are being conducted in clinical practice and the role played by patients' values and preferences in decisions about PSA testing. Published by Elsevier Inc.

Prostate-Specific Membrane Antigen Expression in Adrenocortical Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Aggarwal, Sameer; Passah, Averilicia; Behera, Abhishek; Arora, Geetanjali; Bal, Chandrasekhar; Tripathi, Madhavi

2018-06-01

We present here a case of metastatic adrenocortical carcinoma with bilateral lung nodules. The patient had been treated with mitotane therapy initially and then was later referred for chemotherapy. There was progression of disease noted on the F-FDG PET/CT. Ga prostate-specific membrane antigen (PSMA) PET/CT was planned to explore the possibility of future treatment with Lu-DKFZ-PSMA-617. It revealed peripheral increased uptake of Ga-HBED-CC-PSMA equal to liver uptake.

Significance of serum total prostate specific antigen and digital rectal examination in the diagnosis of prostate cancer.

PubMed

Abdrabo, Abdelkarim A; Fadlalla, Adil I; Fadl-Elmula, Imad M

2011-11-01

To assess the significance of serum total prostate specific antigen (tPSA) and digital rectal examination (DRE) in the diagnosis of prostate cancer (PC). One hundred and eighteen patients with serum tPSA ranging between 2.5 and 10 ng/ml with lower urinary tract symptoms presented at the Urology Clinic of Soba University Hospital, Khartoum, Sudan from August 2008 and January 2010 were included in the study. Serum tPSA was measured using enzyme immunoassay method, and accordingly, the patients were classified into 2 groups: patients that had tPSA between 2.5-4.0 ng/ml; and patients that had tPSA between 4.1-10 ng/ml. The DRE was performed on all patients by a qualified urologist, and were recorded as a group with suspicion of PC, and a group with no suspicion of PC. All patients underwent transrectal sextant prostate biopsy. The DRE alone showed 63.8% sensitivity and 68% specificity with 46.9% positive predictive value (PPV) for the diagnosis of PC. The tPSA test revealed 91.6% sensitivity and 24% specificity with PPV of 34%. However, when combining DRE and tPSA, the sensitivity reached 100% and the specificity increased to 92% with PPV of 49%. Combining DRE and tPSA test increases the sensitivity, specificity, and PPV of PC detection.

Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer.

PubMed

Brawer, M K; Cheli, C D; Neaman, I E; Goldblatt, J; Smith, C; Schwartz, M K; Bruzek, D J; Morris, D L; Sokoll, L J; Chan, D W; Yeung, K K; Partin, A W; Allard, W J

2000-05-01

Determining serum total prostate specific antigen (PSA) has proved to be a valuable diagnostic aid for detecting prostatic carcinoma, although the lack of specificity has limited its usefulness. Studies indicate that the use of percent free PSA would improve specificity while maintaining sensitivity. Since complexed PSA represents the major proportion of measurable PSA in serum, we determined whether it represents a single test alternative to the use of percent free PSA for the early detection of prostate cancer. Archival serum was obtained from 385 men with no evidence of malignancy on biopsy and 272 with biopsy confirmed prostate cancer. We determined the concentration and proportion of total, complexed and free PSA. Receiver operating characteristics analysis using total PSA results from all samples (range 0.32 to 117 ng./ml.) indicated that the areas under the curve for complexed PSA alone as well as the free-to-total and complexed-to-total PSA ratios were similar and significantly greater than those for total PSA alone. Within the range of 85% to 95% sensitivity receiver operating characteristics analysis revealed that the specificity of complexed PSA was higher than that of total PSA and equivalent to that of the free-to-total PSA ratio. We noted a similar improvement in specificity in the 4 to 10 ng./ml. total PSA range. Using published cutoff values for complexed, total and percent free PSA when total PSA was in the 4 to 10 ng./ml. range the sensitivity and specificity of complexed and percent free PSA were similar. Within the 4 to 10 ng./ml. total PSA range the population of patients with no evidence of malignancy and complexed PSA below the upper limit was different with respect to total PSA from that with no evidence of malignancy and free PSA greater than 25%. The measurement of complexed PSA represents an alternative to the use of percent free PSA, although the patient populations identified by the 2 tests are different.

Emerging Vaccine Therapy Approaches for Prostate Cancer

PubMed Central

Sonpavde, Guru; Slawin, Kevin M; Spencer, David M; Levitt, Jonathan M

2010-01-01

Prostate cancer vaccines attempt to induce clinically relevant, cancer-specific systemic immune responses in patients with prostate cancer and represent a new class of targeted, nontoxic therapies. With a growing array of vaccine technologies in preclinical or clinical development, autologous antigen-presenting cell vaccines loaded with the antigen, prostate acid phosphatase, and poxvirus vaccines targeting prostate-specific antigen have recently demonstrated a significant survival benefit in randomized trials of patients with metastatic castration-resistant prostate cancer, whereas others have failed to demonstrate any benefit. The combination of vaccines with chemotherapy, radiotherapy, and other biologic agents is also being evaluated. Efforts to optimize vaccine approaches and select ideal patient populations need to continue to build on these early successes. PMID:20428291

A Multiplex Cancer/Testis Antigen-Based Biomarker Panel to Predict the Aggressive Phenotype of Prostate Cancer

DTIC Science & Technology

2016-09-01

US (Siegel et al., 2014). The introduction of the prostate specific antigen ( PSA ) test has greatly aided to the early detection of PCa. Detectable...levels of PSA are the earliest sign of recurrent disease after radical prostatectomy (RP) (Pound et al., 1999). Besides its sensitiveness, it is...estimated that 23-44% of patients submitted to RP will progress with detectable PSA levels and will never present recurrence (Draisma et al., 2009). Thus

Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers.

PubMed

Zhang, S; Zhang, H S; Reuter, V E; Slovin, S F; Scher, H I; Livingston, P O

1998-02-01

Defining the expression of tumor-associated antigens on primary and metastatic prostate cancer is the crucial first step in selecting appropriate targets for immune attack. In this study, the distribution of the tumor-associated antigens GM2, Tn, sTn, Thompson-Friedenreich antigen (TF), Globo H, Le(y), MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC7, carcinoembryonic antigen, beta chain of human chorionic gonadotropin (hCG beta), HER2/neu, PSMA, and KSA on primary and metastatic prostate cancer and 16 types of normal tissues was compared by immunohistochemistry, using a panel of well-characterized monoclonal antibodies. Our results show that GM2, KSA, and MUC2 were strongly expressed on 8 or 9 of 9 metastatic prostate cancer biopsy specimens and, with PSMA, hCG beta, TF, Tn, and sTn, on 8 or more of 11 primary prostate cancer specimens. Tn, MUC1, and PSMA were expressed on 4-6 of 9 metastatic specimens. The remaining antigens were expressed on no more than three of nine metastatic specimens. Normal tissues were also tested with all antibodies. With regard to the eight antigens most widely expressed on prostate cancers, PSMA was not expressed significantly on any of the normal tissues except prostate epithelium. Tn, sTn, hCG beta, and MUC2 were detected on up to 3 of 10 types of normal epithelia. GM2, TF, MUC1, and KSA were more broadly distributed on normal epithelia, all primarily at the secretory borders. STn, KSA, and hCG beta were also detected in the testis, and GM2 was expressed on gray matter of brain. From the 30 antigens that we have screened, this study provides the basis for selecting GM2, TF, Tn, sTn, hCG beta, MUC1, MUC2, KSA, and PSMA as target antigens for specific immunotherapy of prostate cancer.

Discoveries and application of prostate-specific antigen, and some proposals to optimize prostate cancer screening.

PubMed

Tokudome, Shinkan; Ando, Ryosuke; Koda, Yoshiro

2016-01-01

The discoveries and application of prostate-specific antigen (PSA) have been much appreciated because PSA-based screening has saved millions of lives of prostate cancer (PCa) patients. Historically speaking, Flocks et al first identified antigenic properties in prostate tissue in 1960. Then, Barnes et al detected immunologic characteristics in prostatic fluid in 1963. Hara et al characterized γ-semino-protein in semen in 1966, and it has been proven to be identical to PSA. Subsequently, Ablin et al independently reported the presence of precipitation antigens in the prostate in 1970. Wang et al purified the PSA in 1979, and Kuriyama et al first applied an enzyme-linked immunosorbent assay for PSA in 1980. However, the positive predictive value with a cutoff figure of 4.0 ng/mL appeared substantially low (∼30%). There are overdiagnoses and overtreatments for latent/low-risk PCa. Controversies exist in the PCa mortality-reducing effects of PSA screening between the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. For optimizing PCa screening, PSA-related items may require the following: 1) adjustment of the cutoff values according to age, as well as setting limits to age and screening intervals; 2) improving test performance using doubling time, density, and ratio of free: total PSA; and 3) fostering active surveillance for low-risk PCa with monitoring by PSA value. Other items needing consideration may include the following: 1) examinations of cell proliferation and cell cycle markers in biopsy specimens; 2) independent quantification of Gleason grading; 3) developing ethnicity-specific staging nomograms based on tumor stage, PSA value, and Gleason score; 4) delineation of the natural history; 5) revisiting the significance of the androgen/testosterone hypothesis; and 6) devoting special attention to individuals with a certain genetic predisposition. Finally, considering the uncertainty that exists in medicine, risk communication on PSA-based screening is indeed due.

High serum dihydrotestosterone examined by ultrasensitive LC-MS/MS as a predictor of benign prostatic hyperplasia or Gleason score 6 cancer in men with prostate-specific antigen levels of 3-10 ng/mL.

PubMed

Miyoshi, Y; Uemura, H; Suzuki, K; Shibata, Y; Honma, S; Harada, M; Kubota, Y

2017-03-01

There has been no consensus on the role of serum androgen concentrations in prostate cancer detection in men with prostate-specific antigen levels of 3-10 ng/mL. In this study, testosterone and dihydrotestosterone concentrations in blood were examined by a newly developed method using ultrasensitive liquid chromatography with two serially linked mass spectrometers (LC-MS/MS). We investigated the correlation between serum androgen levels and Gleason scores at biopsy. We analyzed data of 157 men with a total prostate-specific antigen range of 3-10 ng/mL who underwent initial systematic prostate needle biopsy for suspected prostate cancer between April 2000 and July 2003. Peripheral blood testosterone and dihydrotestosterone concentrations were determined by LC-MS/MS. Blood levels of testosterone and dihydrotestosterone were compared with pathological findings by multivariate analyses. Median values of prostate-specific antigen and prostate volume measured by ultrasound were 5.7 ng/mL and 31.4 cm 3 , respectively. Benign prostatic hyperplasia was diagnosed in 97 patients (61.8%), and prostate cancer was diagnosed in 60 (38.2%) patients, including 31 (19.7%) patients with a Gleason score of 6 and 29 (18.5%) patients with a Gleason score of 7-10. Median values of testosterone and dihydrotestosterone in blood were 3798.7 and 371.7 pg/mL, respectively. There was a strong correlation between serum testosterone and dihydrotestosterone. In multivariate analysis, age, prostate volume, and serum dihydrotestosterone were significant predictors of benign prostatic hyperplasia or prostate cancer with a Gleason score of 6. The area under the receiver operating characteristics curve for age, prostate volume, and serum dihydrotestosterone were 0.67, 0.67, and 0.67, respectively . We confirmed that high dihydrotestosterone blood levels can predict benign prostatic hyperplasia or prostate cancer with a Gleason score of 6 in men with prostate-specific antigen levels of 3-10 ng/mL. © 2016 American Society of Andrology and European Academy of Andrology.

Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice.

PubMed

Karan, Dev

2017-10-13

We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad 5 -PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells. In this study, we further characterized the use of the bivalent vaccine (Ad 5 -PSA+PSCA) in a transgenic mouse model expressing human PSA in the mouse prostate. We demonstrated the expression of PSA analyzed at the mRNA level (by RT-PCR) and protein level (by immunohistochemistry) in the prostate lobes harvested from the PSA-transgenic (PSA-Tg) mice. We established that the administration of the bivalent vaccine in surgifoam to the PSA-Tg mice induces strong PSA-specific effector CD8 + T cells as measured by IFN-γ secretion and in vitro cytotoxic T-cell assay. Furthermore, the use of surgifoam with Ad 5 -PSA+PSCA vaccine allows multiple boosting vaccinations with a significant increase in antigen-specific CD8 + T cells. These observations suggest that the formulation of the bivalent prostate cancer vaccine (Ad 5 -PSA+PSCA) with surgifoam bypasses the neutralizing antibody response, thus allowing multiple boosting. This formulation is also helpful for inducing an antigen-specific immune response in the presence of self-antigen, and maintains long-term effector CD8 + T cells. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Antibody Responses to Prostate-Associated Antigens in Patients with Prostatitis and Prostate Cancer

PubMed Central

Maricque, Brett B.; Eickhoff, Jens C.; McNeel, Douglas G.

2010-01-01

Background An important focus of tumor immunotherapy has been the identification of appropriate antigenic targets. Serum-based screening approaches have led to the discovery of hundreds of tumor-associated antigens recognized by IgG. Our efforts to identify immunologically recognized proteins in prostate cancer have yielded a multitude of antigens, however prioritizing these antigens as targets for evaluation in immunotherapies has been challenging. In this report, we set out to determine whether the evaluation of multiple antigenic targets would allow the identification of a subset of antigens that are common immunologic targets in patients with prostate cancer. Methods Using a phage immunoblot approach, we evaluated IgG responses in patients with prostate cancer (n=126), patients with chronic prostatitis (n=45), and men without prostate disease (n=53). Results We found that patients with prostate cancer or prostatitis have IgG specific for multiple common antigens. A subset of 23 proteins was identified to which IgG were detected in 38% of patients with prostate cancer and 33% patients with prostatitis versus 6% of controls (p<0.001 and p=0.003, respectively). Responses to multiple members were not higher in patients with advanced disease, suggesting antibody immune responses occur early in the natural history of cancer progression. Conclusions These findings suggest an association between inflammatory conditions of the prostate and prostate cancer, and suggest that IgG responses to a panel of commonly recognized prostate antigens could be potentially used in the identification of patients at risk for prostate cancer or as a tool to identify immune responses elicited to prostate tissue. PMID:20632317

Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen.

PubMed

O'Rourke, Dennis J; DiJohnson, Daniel A; Caiazzo, Robert J; Nelson, James C; Ure, David; O'Leary, Michael P; Richie, Jerome P; Liu, Brian C-S

2012-03-22

Serum prostate specific antigen (PSA) concentrations lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures to specific cancer targets which might be able to differentiate prostate cancer from BPH in patients with increased serum PSA. To identify autoantibody signatures as biomarkers, a native antigen reverse capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nanoparticle slides to capture native antigens from prostate cancer cells. Prostate cancer patient serum samples (n=41) and BPH patient samples (collected starting at the time of initial diagnosis) with a mean follow-up of 6.56 y without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined. Using our microarray platform, we identified autoantibody signatures capable of distinguishing between prostate cancer and BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95% at 80% specificity) compared to AUC of 0.5 for serum concentration PSA (sensitivity of 12.2% at 80% specificity). Our preliminary results showed that we were able to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with increased serum PSA. Copyright © 2011 Elsevier B.V. All rights reserved.

Radiation Effects on the Immune Response to Prostate Cancer

DTIC Science & Technology

2008-02-01

as an alternative treatment since the discovery of prostate tumor-associated antigens (TAA) and of corresponding tumor-specific T cells in prostate...class I and co-stimulatory molecules, which could promote T cell filtration into tumors and T cell activation. On the other hand, we recently showed...immunotherapy (IT) has gained in popularity by finding some patients have specific T cell response to prostate tumor-associated antigens such as

Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements

PubMed Central

McJimpsey, Erica L.

2016-01-01

The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves. PMID:26911983

Measurement of serum isoform [-2]proPSA derivatives shows superior accuracy to magnetic resonance imaging in the diagnosis of prostate cancer in patients with a total prostate-specific antigen level of 2-10 ng/ml.

PubMed

Furuya, Kazuhiro; Kawahara, Takashi; Narahara, Masaki; Tokita, Takashi; Fukui, Sachi; Imano, Masashi; Mitome, Taku; Ito, Yusuke; Izumi, Koji; Osaka, Kimito; Yokomizo, Yumiko; Hayashi, Narihiko; Hasumi, Hisashi; Nawata, Shintaro; Kawano, Tsuyoshi; Yao, Masahiro; Uemura, Hiroji

2017-08-01

More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer. The subjects were 50 consecutive men with a PSA level of 2.0-10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer. In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%). PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer.

Bone Marrow-derived Mesenchymal Stem Cells (MSCs) as a Selective Delivery Vehicle for a PSA-Activated Protoxin for Advanced Prostate Cancer

DTIC Science & Technology

2014-04-01

other groups are seeking to develop MSCs as vectors to deliver prostate - specific antigen (PSA)-activated prodrugs (Denmeade et al. 2003) and protoxins...Denmeade SR, Jakobsen CM, Janssen S, Khan SR, Garrett ES, Lilja H, Christensen SB & Isaacs JT 2003 Prostate - specific antigen -activated thapsigargin...cells derived from benign prostatic hyperplasia specimens possess stem cell like property. Prostate 67 1265–1276. (doi:10.1002/ pros .20599) Lin G, Yang R

A single microfocus (5% or less) of Gleason 6 prostate cancer at biopsy--can we predict adverse pathological outcomes?

PubMed

Thong, Alan E; Shikanov, Sergey; Katz, Mark H; Gofrit, Ofer N; Eggener, Scott; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2008-12-01

Patients with Gleason score 6 microfocal prostate cancer, defined as 5% or less in 1 biopsy core, are often considered to have favorable disease. Few studies have addressed clinical parameters that predict pathological upgrading or up staging at radical prostatectomy. From a prospective database of 1,271 consecutive robot assisted laparoscopic prostatectomies performed from 2003 to 2008 patients with Gleason score 6 microfocal prostate cancer were identified. Adverse pathological outcome was defined as any upgrading and/or up staging on prostatectomy pathological findings. Multivariate logistic regression was used to evaluate the ability of patient age, clinical stage, the total number of biopsy cores, preoperative prostate specific antigen, prostate volume and pathological prostate specific antigen density to predict adverse pathological outcomes. A total of 192 patients with a median age of 59 years (range 42 to 73) were identified with Gleason score 6 prostate cancer involving 5% or less of 1 biopsy core, including 177 (92%) with clinical T1c disease. Mean +/- SD preoperative prostate specific antigen was 6.0 +/- 3.9 ng/ml (range 0.8 to 35). Overall 42 patients (22%) had adverse pathological outcomes, including upgrading in 35 (18%) and up staging in 16 (8%). Multivariate logistic regression revealed that age more than 65 years and pathological prostate specific antigen density greater than 0.20 ng/ml/gm were predictive of an increased risk of adverse pathological results (p = 0.0081 and 0.0169, respectively). While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.

Prostate-specific Antigen Mass Density--A Measure Predicting Prostate Cancer Volume and Accounting for Overweight and Obesity-related Prostate-specific Antigen Hemodilution.

PubMed

Kryvenko, Oleksandr N; Diaz, Mireya; Matoso, Andres; Kates, Max; Cohen, Jason; Swanson, Gregory P; Epstein, Jonathan I

2016-04-01

To test prostate-specific antigen mass density (PSAMD) as a predictor of total tumor volume (TTV) at radical prostatectomy (RP). We conducted a detailed pathologic analysis of 469 RP from men with NCCN low-risk prostate cancer who had Gleason score of 3 + 3 = 6 (grade group 1) at RP. We then compared the ability of PSA, PSA density (PSAD), PSA mass (PSAM-absolute amount of PSA in patient's circulation), and PSAM density (PSAM divided by prostate weight without seminal vesicles) to predict TTV at RP. PSAM was calculated by multiplying plasma volume (estimated body surface [weight, kg(0.425) × height, m(0.72) × 0.007184] × 1.67) by PSA. Performance of the above measures in different BMI categories was assessed. Kruskal-Wallis test was used to compare the means and Spearman's rank correlation coefficient to assess the correlations. The 469 men were normal weight (n = 129), overweight (n = 253), and obese (n = 87). Mean age of the patients' was 57.4 years and PSA of 4.53 ng/ml. Increase of prostate weight with body mass index (BMI) was reflected in PSAM (both P <.001) but not in other measures. BMI did not correlate with TTV and PSA. Among PSA, PSAD, PSAM, and PSAMD, PSAMD had the highest correlation with TTV (r = 0.336; P <.001). Prostate weight had stronger (negative) association with PSAMD (r = -0.394; <.001) than TTV. PSAMD is the biochemical measure with the best correlation with TTV at RP. Unlike other measures, it is not affected by BMI-related hemodilution. Thresholds should be established to use this more objective measure clinically in surveillance algorithms and in planning radical prostatectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum antibodies to huntingtin interacting protein-1: a new blood test for prostate cancer.

PubMed

Bradley, Sarah V; Oravecz-Wilson, Katherine I; Bougeard, Gaelle; Mizukami, Ikuko; Li, Lina; Munaco, Anthony J; Sreekumar, Arun; Corradetti, Michael N; Chinnaiyan, Arul M; Sanda, Martin G; Ross, Theodora S

2005-05-15

Huntingtin-interacting protein 1 (HIP1) is frequently overexpressed in prostate cancer. HIP1 is a clathrin-binding protein involved in growth factor receptor trafficking that transforms fibroblasts by prolonging the half-life of growth factor receptors. In addition to human cancers, HIP1 is also overexpressed in prostate tumors from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model. Here we provide evidence that HIP1 plays an important role in mouse tumor development, as tumor formation in the TRAMP mice was impaired in the Hip1null/null background. In addition, we report that autoantibodies to HIP1 developed in the sera of TRAMP mice with prostate cancer as well as in the sera from human prostate cancer patients. This led to the development of an anti-HIP1 serum test in humans that had a similar sensitivity and specificity to the anti-alpha-methylacyl CoA racemase (AMACR) and prostate-specific antigen tests for prostate cancer and when combined with the anti-AMACR test yielded a specificity of 97%. These data suggest that HIP1 plays a functional role in tumorigenesis and that a positive HIP1 autoantibody test may be an important serum marker of prostate cancer.

Disability and Preventive Cancer Screening: Results from the 2001 California Health Interview Survey

PubMed Central

Ramirez, Anthony; Farmer, Gail C.; Grant, David; Papachristou, Theodora

2005-01-01

Objective. We sought to evaluate preventive cancer screening compliance among adults with disability in California. Methods. We used data from the 2001 California Health Interview Survey to compare disabled and nondisabled adults for differences in preventive cancer screening behaviors. Compliance rates for cancer screening tests (mammography, Papanicolaou test, prostate-specific antigen, sigmoidoscopy/colonoscopy, and fecal occult blood test) between the 2 subpopulations were evaluated. Results. Women with disabilities were 17% (Papanicolaou tests) and 13% (mammograms) more likely than women without disabilities to report noncompliance with cancer screening guidelines. Interactions between disability and reports of a doctor recommendation on cervical cancer screening were significant; women with disabilities had a lower likelihood of receiving a recommendation. Men with disabilities were 19% less likely than men without disabilities to report a prostate-specific antigen test within the last 3 years. Conclusions.secondary to structural and/or clinical factors underpinning the differences found. PMID:16195509

Simultaneous targeting of prostate stem cell antigen and prostate-specific membrane antigen improves the killing of prostate cancer cells using a novel modular T cell-retargeting system.

PubMed

Arndt, Claudia; Feldmann, Anja; Koristka, Stefanie; Cartellieri, Marc; Dimmel, Maria; Ehninger, Armin; Ehninger, Gerhard; Bachmann, Michael

2014-09-01

Recently, we described a novel modular platform technology in which T cell-recruitment and tumor-targeting domains of conventional bispecific antibodies are split to independent components, a universal effector module (EM) and replaceable monospecific/monovalent target modules (TMs) that form highly efficient T cell-retargeting complexes. Theoretically, our unique strategy should allow us to simultaneously retarget T cells to different tumor antigens by combining the EM with two or more different monovalent/monospecific TMs or even with bivalent/bispecific TMs, thereby overcoming limitations of a monospecific treatment such as the selection of target-negative tumor escape variants. In order to advance our recently introduced prostate stem cell antigen (PSCA)-specific modular system for a dual-targeting of prostate cancer cells, two additional TMs were constructed: a monovalent/monospecific TM directed against the prostate-specific membrane antigen (PSMA) and a bivalent/bispecific TM (bsTM) with specificity for PSMA and PSCA. The functionality of the novel dual-targeting strategies was analyzed by performing T cell activation and chromium release assays. Similar to the PSCA-specific modular system, the novel PSMA-specific modular system mediates an efficient target-dependent and -specific tumor cell lysis at low E:T ratios and picomolar Ab concentrations. Moreover, by combination of the EM with either the bispecific TM directed to PSMA and PSCA or both monospecifc TMs directed to either PSCA or PSMA, dual-specific targeting complexes were formed which allowed us to kill potential escape variants expressing only one or the other target antigen. Overall, the novel modular system represents a promising tool for multiple tumor targeting. © 2014 Wiley Periodicals, Inc.

A case report of prostate cancer metastasis to the stomach resembling undifferentiated-type early gastric cancer.

PubMed

Inagaki, Chiaki; Suzuki, Takuto; Kitagawa, Yoshiyasu; Hara, Taro; Yamaguchi, Taketo

2017-08-07

Occurrence of metastatic cancer to the stomach is rare, particularly in patients with prostate cancer. Gastric metastasis generally presents as a solitary and submucosal lesion with a central depression. We describe a case of gastric metastasis arising from prostate cancer, which is almost indistinguishable from the undifferentiated-type gastric cancer. A definitive diagnosis was not made until endoscopic resection. On performing both conventional and magnifying endoscopies, the lesion appeared to be slightly depressed and discolored area and it could not be distinguished from undifferentiated early gastric cancer. Biopsy from the lesion was negative for immunohistochemical staining of prostate-specific antigen, a sensitive and specific marker for prostate cancer. Thus, false initial diagnosis of an early primary gastric cancer was made and endoscopic submucosal dissection was performed. Pathological findings from the resected specimen aroused suspicion of a metastatic lesion. Consequently, immunostaining was performed. The lesion was positive for prostate-specific acid phosphatase and negative for prostate-specific antigen, cytokeratin 7, and cytokeratin 20. Accordingly, the final diagnosis was a metastatic gastric lesion originating from prostate cancer. In this patient, the definitive diagnosis as a metastatic lesion was difficult due to its unusual endoscopic appearance and the negative stain for prostate-specific antigen. We postulate that both of these are consequences of hormonal therapy against prostate cancer.

The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer.

PubMed

Navarro-Pelayo Láinez, M M; Rodríguez-Fernández, A; Gómez-Río, M; Vázquez-Alonso, F; Cózar-Olmo, J M; Llamas-Elvira, J M

2014-11-01

prostate cancer is the most frequent solid malignant tumor in Western Countries. Positron emission tomography/x-ray computed tomography imaging with radiolabeled choline analogues is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. a MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer» and «Choline-PET/CT». Other search terms were «Biochemical failure» and/or «Staging» and/or «PSA kinetics». English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. according to available data, radiolabeled choline analogues plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Impact of Body Mass Index, Age, Prostate Volume, and Genetic Polymorphisms on Prostate-specific Antigen Levels in a Control Population.

PubMed

Cornu, Jean-Nicolas; Cancel-Tassin, Geraldine; Cox, David G; Roupret, Morgan; Koutlidis, Nicolas; Bigot, Pierre; Valeri, Antoine; Ondet, Valerie; Gaffory, Cécile; Fournier, Georges; Azzouzi, Abdel-Rahmene; Cormier, Luc; Cussenot, Olivier

2016-07-01

Prostate-specific antigen (PSA) is still the cornerstone of prostate cancer (PCa) screening and diagnosis in both research and current clinical practice. Inaccuracy of PSA is partly due to the influence of a number of genetic, clinical, and biological factors modifying PSA blood levels. In the present study, we detailed the respective influence of each factor among age, body mass index (BMI), prostate volume, and five single-nucleotide polymorphisms-rs10788160 (10q26), rs10993994 (10q11), rs11067228 (12q24), rs17632542 (19q13.33), and rs2928679 (8p21)-on PSA values in a cohort of 1374 men without PCa. Our results show that genetic factors, when risk variants are combined, influence PSA levels with an effect size similar to that of BMI. Taken together, the respective correlations of clinical parameters and genetic parameters would make it possible to correct and adjust PSA values more effectively in each individual. These results establish the basis to understand and implement a more personalised approach for the interpretation of PSA blood levels in the context of PCa screening and diagnosis. Prostate-specific antigen (PSA) values in an individual may vary according to genetic predisposition. The effect size of this variation can be significant, comparable with those resulting from clinical characteristics. Personalised PSA testing should take this into account. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Body mass index influences prostate cancer risk at biopsy in Japanese men.

PubMed

Masuda, Hitoshi; Kagawa, Makoto; Kawakami, Satoru; Numao, Noboru; Matsuoka, Yoh; Yokoyama, Minato; Yamamoto, Shinya; Yonese, Junji; Fukui, Iwao; Kihara, Kazunori

2013-07-01

To determine the relationship between body mass index and prostate cancer risk at biopsy in Japanese men, and to compared the risk with that of Caucasian men. We retrospectively evaluated 3966 men with prostate-specific antigen levels from 2.5 to 19.9 ng/mL who underwent an initial extended prostate biopsy. Using logistic regression, odds ratios of each body mass index category for risk of prostate cancer and high-grade disease (Gleason score ≥4 + 3) were estimated after controlling for age, prostate-specific antigen, %free prostate-specific antigen, prostate volume, digital rectal examination findings, family history of prostate cancer and the number of biopsy cores. Patients were divided into six categories according to their body mass index (kg/m(2) ) as follows: <21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9 and ≥30.0. A significant positive association was observed between body mass index and prostate cancer risk at biopsy, with an increased risk observed in men whose body mass index was ≥27.0 compared with the reference group. A significantly increased risk starting at body mass index ≥25.0 was found in high-grade disease. In contrast to our results, there has been no reported increase in the risk of prostate cancer at biopsy in Caucasians within the overweight range (body mass index of 25.0-29.9 based on World Health Organization classification). Japanese men within the overweight body mass index range who have an elevated prostate-specific antigen level also have a significant risk of harboring prostate cancer, especially high-grade disease. Overweight Japanese might be at greater prostate cancer risk at biopsy than overweight Caucasians. © 2012 The Japanese Urological Association.

Genetics Home Reference: prostate cancer

MedlinePlus

... prostate cancer Genetic Testing Registry: Prostate cancer aggressiveness quantitative trait locus on chromosome 19 Genetic Testing Registry: ... OMIM (25 links) PROSTATE CANCER PROSTATE CANCER AGGRESSIVENESS QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 19 PROSTATE CANCER ANTIGEN ...

Clinical outcomes of prostate cancer patients in Yokosuka City, Japan: A comparative study between cases detected by prostate-specific antigen-based screening in Yokosuka and those detected by other means.

PubMed

Sakai, Naoki; Taguri, Masataka; Kobayashi, Kazuki; Noguchi, Sumio; Ikeda, Shigeru; Koh, Hideshige; Satomi, Yoshiaki; Furuhata, Akihiko

2015-08-01

To investigate whether prostate-specific antigen-based screening reduced the prostate cancer mortality rate in Yokosuka, Japan. We carried out a cohort study, in which we compared clinical outcomes between patients detected by prostate-specific antigen-based screening (S group n = 524) versus those detected by other means (NS group n = 1044). Clinical and pathological factors were evaluated using Cox regression analyses and the Kaplan-Meier method. A total of 1.5% (8/524) of patients in the S group and 6.7% (70/1044) of those in the NS group died from prostate cancer during follow up. A total of 8.0% (42/524) of patients in the S group and 11.4% (119/1044) in the NS group died from other causes. The 10-year cancer specific survival rates of the S and NS groups were 97% and 86%, respectively (P < 0.001). The median age was significantly lower in the S group than the NS group: 71 and 73 years, respectively (P < 0.001). The rate of Gleason score 8-10 was significantly lower in the S group than the NS group: 9.7% and 16.7%, respectively (P < 0.001). The rate of patients with metastasis or prostate-specific antigen 100 ng/mL or more was significantly lower in the S group than the NS group: 7.8% and 23.0%, respectively (P < 0.001). On multivariate analysis, Gleason score 8-10 compared with Gleason score 6 was independently associated with cancer-specific survival (hazard ratio 4.808, 95% confidence interval 1.044-22.14, P = 0.044). Prostate-specific antigen-based population screening in Yokosuka City might help to reduce the prostate cancer mortality rate. © 2015 The Japanese Urological Association.

Prospective evaluation of magnetic resonance imaging guided in-bore prostate biopsy versus systematic transrectal ultrasound guided prostate biopsy in biopsy naïve men with elevated prostate specific antigen.

PubMed

Quentin, Michael; Blondin, Dirk; Arsov, Christian; Schimmöller, Lars; Hiester, Andreas; Godehardt, Erhard; Albers, Peter; Antoch, Gerald; Rabenalt, Robert

2014-11-01

Magnetic resonance imaging guided biopsy is increasingly performed to diagnose prostate cancer. However, there is a lack of well controlled, prospective trials to support this treatment method. We prospectively compared magnetic resonance imaging guided in-bore biopsy with standard systematic transrectal ultrasound guided biopsy in biopsy naïve men with increased prostate specific antigen. We performed a prospective study in 132 biopsy naïve men with increased prostate specific antigen (greater than 4 ng/ml). After 3 Tesla functional multiparametric magnetic resonance imaging patients were referred for magnetic resonance imaging guided in-bore biopsy of prostate lesions (maximum 3) followed by standard systematic transrectal ultrasound guided biopsy (12 cores). We analyzed the detection rates of prostate cancer and significant prostate cancer (greater than 5 mm total cancer length or any Gleason pattern greater than 3). A total of 128 patients with a mean ± SD age of 66.1 ± 8.1 years met all study requirements. Median prostate specific antigen was 6.7 ng/ml (IQR 5.1-9.0). Transrectal ultrasound and magnetic resonance imaging guided biopsies provided the same 53.1% detection rate, including 79.4% and 85.3%, respectively, for significant prostate cancer. Magnetic resonance imaging and transrectal ultrasound guided biopsies missed 7.8% and 9.4% of clinically significant prostate cancers, respectively. Magnetic resonance imaging biopsy required significantly fewer cores and revealed a higher percent of cancer involvement per biopsy core (each p <0.01). Combining the 2 methods provided a 60.9% detection rate with an 82.1% rate for significant prostate cancer. Magnetic resonance imaging guided in-bore and systematic transrectal ultrasound guided biopsies achieved equally high detection rates in biopsy naïve patients with increased prostate specific antigen. Magnetic resonance imaging guided in-bore biopsies required significantly fewer cores and revealed a significantly higher percent of cancer involvement per biopsy core. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate-specific membrane antigen-targeted liposomes specifically deliver the Zn(2+) chelator TPEN inducing oxidative stress in prostate cancer cells.

PubMed

Stuart, Christopher H; Singh, Ravi; Smith, Thomas L; D'Agostino, Ralph; Caudell, David; Balaji, K C; Gmeiner, William H

2016-05-01

To evaluate the potential use of zinc chelation for prostate cancer therapy using a new liposomal formulation of the zinc chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN). TPEN was encapsulated in nontargeted liposomes or liposomes displaying an aptamer to target prostate cancer cells overexpression prostate-specific membrane antigen. The prostate cancer selectivity and therapeutic efficacy of liposomal (targeted and nontargeted) and free TPEN were evaluated in vitro and in tumor-bearing mice. TPEN chelates zinc and results in reactive oxygen species imbalance leading to cell death. Delivery of TPEN using aptamer-targeted liposomes results in specific delivery to targeted cells. In vivo experiments show that TPEN-loaded, aptamer-targeted liposomes reduce tumor growth in a human prostate cancer xenograft model.

INITIAL SYMPTOMATIC PITUITARY METASTASIS IN A PATIENT WITH PROSTATE FOAMY GLAND CARCINOMA: TAILORING SAFE AND EFFECTIVE THERAPY.

PubMed

Prpić, Marin; Fröbe, Ana; Zadravec, Dijana; Pažanin, Leo; Jakšić, Blanka; Bolanča, Ante; Kusić, Zvonko

2015-06-01

Metastases to pituitary gland are unusual and mostly asymptomatic, presenting with local symptoms in one of ten patients, and only 3%-5% of them are of prostate origin. Here we report and evaluate the effectiveness and safety of multimodal treatment in a patient with pituitary metastasis of a prostate foamy gland carcinoma. A 78-year-old male patient presented with blurred vision and headache without a previous history of malignancy. Magnetic resonance imaging scans revealed a large sellar mass, with infiltration of the surrounding structures. Maximal transsphenoidal reduction of pituitary metastasis was performed, with a histologic finding of metastatic prostate foamy gland adenocarcinoma. Evaluation of the prostate specific antigen revealed a very high level (1461 ng/mL) and foamy gland carcinoma was found on prostate needle biopsy. The patient received 3D conformal external beam radiotherapy with 6 MV photons to the sellar and parasellar region with a tumor dose of 44 Gy, followed by androgen deprivation therapy. Follow up magnetic resonance imaging done after radiotherapy showed shrinkage of the tumor process, with rapid prostate specific antigen decline to 0.3 ng/mL. The visual function was fully established and headache resolved. On the last follow up 14 months after the diagnosis, the patient was alive and free from clinical signs of disease. Tailored treatment, including limited radiotherapy in a higher palliative dose, in a patient with foamy gland symptomatic pituitary metastatic disease resulted in good local and systemic control of the disease. In older male patients with clinical and/or radiologic characteristics suggestive of metastatic pituitary disease, the prostate specific antigen test should be included as part of the work-up.

Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0-10.0 ng/ml.

PubMed

Chen, Rui; Huang, Yiran; Cai, Xiaobing; Xie, Liping; He, Dalin; Zhou, Liqun; Xu, Chuanliang; Gao, Xu; Ren, Shancheng; Wang, Fubo; Ma, Lulin; Wei, Qiang; Yin, Changjun; Tian, Ye; Sun, Zhongquan; Fu, Qiang; Ding, Qiang; Zheng, Junhua; Ye, Zhangqun; Ye, Dingwei; Xu, Danfeng; Hou, Jianquan; Xu, Kexin; Yuan, Jianlin; Gao, Xin; Liu, Chunxiao; Pan, Tiejun; Sun, Yinghao

2015-01-01

The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies. Consecutive patients with a prostate-specific antigen (PSA) level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis. The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60-69, 70-79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0-10.0 ng/ml to detect 90% of all PCa. The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.

Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0–10.0 ng/ml

PubMed Central

Xie, Liping; He, Dalin; Zhou, Liqun; Xu, Chuanliang; Gao, Xu; Ren, Shancheng; Wang, Fubo; Ma, Lulin; Wei, Qiang; Yin, Changjun; Tian, Ye; Sun, Zhongquan; Fu, Qiang; Ding, Qiang; Zheng, Junhua; Ye, Zhangqun; Ye, Dingwei; Xu, Danfeng; Hou, Jianquan; Xu, Kexin; Yuan, Jianlin; Gao, Xin; Liu, Chunxiao; Pan, Tiejun; Sun, Yinghao

2015-01-01

Objective The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies. Methods Consecutive patients with a prostate-specific antigen (PSA) level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis. Results The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60–69, 70–79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0–10.0 ng/ml to detect 90% of all PCa. Conclusions The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population. PMID:26091007

Informed Decision Making About Prostate Cancer Testing in Predominantly Immigrant Black Men: A Randomized Controlled Trial

PubMed Central

Lepore, Stephen J.; Wolf, Randi L.; Basch, Charles E.; Godfrey, Melissa; McGinty, Emma; Shmukler, Celia; Ullman, Ralph; Thomas, Nigel; Weinrich, Sally

2012-01-01

Background Decision support interventions have been developed to help men clarify their values and make informed decisions about prostate cancer testing, but they seldom target high-risk black and immigrant men. Purpose This study evaluated the efficacy of a decision support intervention focused on prostate cancer testing in a sample of predominantly immigrant black men. Methods Black men (N = 490) were randomized to tailored telephone education about prostate cancer testing or a control condition. Results Post-intervention, the intervention group had significantly greater knowledge, lower decision conflict, and greater likelihood of talking with their physician about prostate cancer testing than the control group. There were no significant intervention effects on prostate specific antigen testing, congruence between testing intention and behavior, or anxiety. Conclusions A tailored telephone decision support intervention can promote informed decision making about prostate cancer testing in black and predominantly immigrant men without increasing testing or anxiety. Clinical trial Registered in clinicaltrials.gov (NCT01415375) PMID:22825933

[Age peculiarities in prostate cancer detection based on the prostate-specific antigen and its alterations control].

PubMed

Ponkratov, S V; Kheyfets, V Kh; Kagan, O F

2017-01-01

Data on epidemiology of a prostate cancer are presented in article, high prevalence and body height of a case rate cause relevance of researches on this oncopathology. It is shown that the number augmentation for the first time of the taped cases is bound including to the program of a screening of inspection of men by determination of level of prostates-specific antigen (PSA). Modern diagnostic methods of identification of modifications of PSA, possessing larger sensitivity and specificity concerning a prostate cancer are lit. The attention to change of level of PSA depending on age is focused that needs to be considered at diagnostics of malignant neoplasms of a prostate.

[The role of a single PCA3 test before a first negative prostate biopsy: 5-year follow-up].

PubMed

Bernardeau, S; Charles, T; Fromont-Hankard, G; Irani, J

2017-04-01

We report a 5-year follow-up of a cohort of patients who underwent a first prostate biopsy following a prostate cancer antigen 3 (PCA3) test. We reviewed consecutive patients who had in 2008 a single urinary PCA3 test using the Gen-Probe ® assay before a first prostate biopsy for a prostate-specific antigen (PSA) between 3 and 20ng/mL and/or a suspicious digital rectal examination. PCA3 performances were analyzed in 2008 and then in 2013 after taking into account the results of repeat biopsies. At initial biopsy in 2008, among the 125 patients study cohort, prostate cancer was diagnosed in 47 patients (37.6%). Abnormal digital rectal exam, PSA density, prostate volume and PCA3 score were significantly associated with prostate cancer diagnosis. PCA3 area under the curve of the receiver operating curve was 0.67 [95%CI: 0.57-0.76] with an optimal threshold of PCA3 in this sample of 24 units. During the 5-year follow-up, among the 78 patients with a negative prostate biopsy in 2008, 23 (29.5%) had a repeat prostate biopsy of whom 14 were diagnosed with prostate cancer. PCA3 score measured in 2008 was associated with prostate cancer diagnosis (P=0.002). All 9 patients with a negative repeat prostate biopsy had a PCA3 score below the cut-off while this was the case in only 2 patients among the 14 with a positive repeat prostate biopsy. The results of a single PCA3 test before a first prostate biopsy seems to be a useful aid in deciding whether to perform a repeat biopsy. 4. Copyright © 2017. Published by Elsevier Masson SAS.

Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

DTIC Science & Technology

2005-10-01

Reiter RE, Lilly MB: Gene expression profiling in R- flurbiprofen -treated prostate cancer: Identification of prostate stem cell antigen as a... flurbiprofen -regulated gene. (submitted, 2006). 51. Holder SL, Zemskova M, Bremner R, Neidigh J, Lilly MB: Identification of specific, cell-permeable...profiling in R- flurbiprofen - treated prostate cancer: Identification of prostate stem cell antigen as a flurbiprofen - regulated gene. (poster

Prostate-specific Antigen (PSA) Density and Free to Total PSA Ratio in Diagnosing Prostate Cancer with Prostate-Specific Antigen Levels of 4.0 ng/ml or Less.

PubMed

Liu, Xin; Tang, Jie; Fei, Xiang; Li, Qiu-Yang

2015-11-01

We aimed to value the usefulness of free to total prostate-specific antigen and Prostate-specific antigen (PSA) density for prostate cancer in the patients with PSA levels of 4.0 ng/ml or less. A total of 343 subjects with PSA levels of 4.0 ng/ml or less were biopsied. All patients were divided into four groups according to the PSA levels: 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml. The reliability of cancer detection in relation to the f/t PSA ratio and PSAD were estimated. Overall, 65 people were diagnosed with prostate cancer. The detection rate was 16.28%、17.17%, 21.82%, 25.00% in subjects with PSA levels of 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml, respectively. The f/t PSA ratio was significantly lower in patients with prostate cancer and PSA levels of 2.1 to 4.0 ng/ml (P<0.05). The PSAD had no statistical significance between the two groups. Routine prostate biopsy should be undertaken if the f/t PSA ratio less than 15% with /without abnormal DRE/TRUS findings.

Prostate Stem Cell Antigen DNA Vaccination Breaks Tolerance to Self-antigen and Inhibits Prostate Cancer Growth

PubMed Central

Ahmad, Sarfraz; Casey, Garrett; Sweeney, Paul; Tangney, Mark; O'Sullivan, Gerald C

2009-01-01

Prostate stem cell antigen (PSCA) is a cell surface antigen expressed in normal human prostate and over expressed in prostate cancer. Elevated levels of PSCA protein in prostate cancer correlate with increased tumor stage/grade, with androgen independence and have higher expression in bone metastases. In this study, the PSCA gene was isolated from the transgenic adenocarcinoma mouse prostate cell line (TRAMPC1), and a vaccine plasmid construct was generated. This plasmid PSCA (pmPSCA) was delivered by intramuscular electroporation (EP) and induced effective antitumor immune responses against subcutaneous TRAMPC1 tumors in male C57 BL/6 mice. The pmPSCA vaccination inhibited tumor growth, resulting in cure or prolongation in survival. Similarly, the vaccine inhibited metastases in PSCA expressing B16 F10 tumors. There was activation of Th-1 type immunity against PSCA, indicating the breaking of tolerance to a self-antigen. This immunity was tumor specific and was transferable by adoptive transfer of splenocytes. The mice remained healthy and there was no evidence of collateral autoimmune responses in normal tissues. EP-assisted delivery of the pmPSCA evoked strong specific responses and could, in neoadjuvant or adjuvant settings, provide a safe and effective immune control of prostate cancer, given that there is significant homology between human and mouse PSCA. PMID:19337234

How Precisely Can Prostate Cancer Be Managed?

PubMed Central

2016-01-01

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

Development of a PET Prostate-Specific Membrane Antigen Imaging Agent: Preclinical Translation for Future Clinical Application

DTIC Science & Technology

2016-10-01

small-molecule peptidomimetic imaging agents labeled with positron emitting fluorine- 18 . These data will enable the filing of an exploratory IND...outcome. 15. SUBJECT TERMS Prostate Cancer, Prostate Specific Membrane Antigen (PSMA), Fluorine- 18 , Molecular Imaging, Radiotracer, Automated...Synthesis, Phosphoramidate, Inhibitor, Peptide Mimic, Peptidomimetic 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a

PROSTVAC® targeted immunotherapy candidate for prostate cancer.

PubMed

Shore, Neal D

2014-01-01

Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

Prostate cancer gene 3 and multiparametric magnetic resonance can reduce unnecessary biopsies: decision curve analysis to evaluate predictive models.

PubMed

Busetto, Gian Maria; De Berardinis, Ettore; Sciarra, Alessandro; Panebianco, Valeria; Giovannone, Riccardo; Rosato, Stefano; D'Errigo, Paola; Di Silverio, Franco; Gentile, Vincenzo; Salciccia, Stefano

2013-12-01

To overcome the well-known prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasound-guided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Copyright © 2013 Elsevier Inc. All rights reserved.

A national survey of medical students' beliefs and knowledge in screening for prostate cancer.

PubMed

Marcella, Stephen; Delnevo, Cristine D; Coughlin, Steven S

2007-01-01

Today's medical students are being educated at a time when there are no evidence-based guidelines for prostate cancer screening. To examine medical students' knowledge and beliefs concerning prostate cancer screening and specific determinants for their beliefs. One thousand six hundred and forty four students were sampled at 20 medical schools using a web-based, cross-sectional survey. Basic knowledge and beliefs about prostate cancer testing, epidemiology, and therapy were ascertained. Four of 8 knowledge items were answered incorrectly by 50% or more of students. Seven of 8 students believe that early diagnosis from screening can improve survival from prostate cancer. Second- and third-year students were more likely than fourth-year students to believe that the digital rectal exam (DRE) and the prostate-specific antigen test were accurate, adjusted odds ratio (AOR) 1.8; 95% confidence interval (CI), 1.2 to 2.7 and 1.7; 1.3 to 2.2 for second and third years, respectively, for the DRE. Black and Hispanic students were no more likely than white students to agree that early screening diagnosis improves survival, but blacks were more likely to agree with screening black or Hispanic men (AOR 7.8; 95% CI, 5.3 to 11.4 and 3.2; 2.2 to 4.7, respectively). More knowledgeable students were less likely to believe in the benefit of early detection and the accuracy of the prostate-specific antigen (AOR 0.3; 95%CI, 0.2 to 0.5). Medical students generally are very optimistic about the benefits of screening for prostate cancer. Increased knowledge about prostate cancer is associated with a more conservative view of screening. Other predictors are independent of this knowledge.

The influence of PSA-RNA yield on the analysis of expressed prostatic secretions (EPS) for prostate cancer diagnosis.

PubMed

Whelan, Christopher; Crocitto, Laura; Kawachi, Mark; Chan, Kevin; Smith, David; Wilson, Timothy; Smith, Steven

2013-02-01

In patients with prostate cancer, luminal prostate-specific antigen (PSA) enters the circulation because the basement membrane and glandular epithelium are damaged. Given that excess mobilization of prostate cells during prostatic massage can influence normalization in diagnostic testing, we studied PSA mRNA levels in expressed prostatic secretions (EPS) from patients undergoing biopsy for prostate cancer to determine if prostate cells are preferentially mobilized from patients with prostate cancer during prostatic massage. Quantitative Reverse-Transcription PCR (qRT-PCR) was used to measure the RNA levels of GAPDH, PSA, TMPRSS2:ERG and PCA3 in EPS specimens obtained from patients undergoing biopsy for prostate cancer. The level of PSA mRNA is significantly elevated in EPS specimens obtained from patients with a subsequent diagnosis of prostate cancer. This correlation influenced diagnostic testing results from EPS in two ways. First, when used as an exclusion parameter it appears to improve the diagnostic performance of TMPRSS2:ERG in EPS. Second, when used as a normalization parameter it appears to decrease the performance of these same tests. When comparing the results of mRNA based prostate cancer diagnostics in EPS it will be essential to consider PSA mRNA as a prostate specific gene and not a housekeeping gene.

Prostate-specific antigen screening and mortality from prostate cancer.

PubMed

Marcella, Stephen W; Rhoads, George G; Carson, Jeffrey L; Merlino, Frances; Wilcox, Homer

2008-03-01

There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55-79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2-29.2% of cases and 21.8-26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality.

Prostate-Specific Antigen Screening and Mortality from Prostate Cancer

PubMed Central

Rhoads, George G.; Carson, Jeffrey L.; Merlino, Frances; Wilcox, Homer

2008-01-01

Background There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. Objective The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. Design, setting, and participants This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55–79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Results Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2–29.2% of cases and 21.8–26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. Conclusions PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality. PMID:18172740

A Preliminary Analysis of Calcifying Particles in the Serum and Prostates of Patients with Prostatic Inflammation

NASA Technical Reports Server (NTRS)

Jones, Jeffrey A.; Carlson, Grant; Kajander, E. Olavi; Warmflash, David; Taylor, Karen; Ayala, Gustavo; Shoskes, Daniel; Everett, Meg; Feedback, Dan; Ciftcioglu, Neva

2006-01-01

Chronic diseases of the prostate such as benign prostatic hyperplasia (BPH) & chronic pelvic pain syndrome (CPPS) have associated findings of chronic inflammation, despite a lack of causal relationship. Numerous attempts to define an infectious agent responsible for the clinical findings have been inconsistent. The possibility of an infectious agent, that has not been uncovered with routine culturing methods, forms the basis for this study. Serum from 940 healthy Finnish men were compared with serum from 40 Crohn's, 40 path dx prostatitis, & 40 with path dx carcinoma, using an enzyme-linked immunosorbant assay (ELISA), to detect antigens specific to Nanobacteria(NB) utilizing monoclonal antibodies (Ab) 5/3 and 8D10. This ELISA has not been validated for detecting NB-associated with clinical prostatic disease, yet cross-reactivity with other bacterial species is low. Immunohistochemistry was performed on de-paraffinized prostatic tissue slides, de-calcified with EDTA and stained with the DAKO Catalyzed Signal Amplification kit, employing 8D10 as the primary (target/antigen-detecting) Ab. The mean (plus or minus SD) & median concentrations of NB antigen (U/50 L) were 379.59 (plus or minus 219.28) & 640.00 for patients with prostatitis (BPH) vs 3.31 (plus or minus 3.55) & 2.94 for prostate adenocarcinoma, 1.88 (plus or minus 2.94) & 0.80 for Crohn's disease, & 7.43 (plus or minus 25.57) & 0.00 for patients with no clinical prostatic disease. Unpaired t-tests revealed statistically significant differences between the prostatitis (BPH) sera & each of the other groups with p less than 0.005, but no differences between the other groups themselves. Preliminary studies with immunohistochemistry & 3-D confocal microscopy reveal 16/24 tissue sections + for NB Ag in BPH vs. only 2/22 tissue sections with prostate cancer. The preliminary findings of this serum screening study suggest that NB antigen may be commonly found in the serum of patients with the pathological diagnosis of prostatitis. Preliminary immunohistologic studies, suggest that NB may be found within the gland itself at a higher rate in patients with BPH relative to patients with adenocarcinoma, however confirmatory studies with a more specific ELISA technique, primary cultures, & with larger numbers of patients in a prospective design are required to determine if 1) NB are a causative organism for clinical hyperplastic and inflammatory disease, & if 2) serological testing can be used to discriminate patients with nanobacterial-associated prostatic disease.

MD-miniRNA could be a more accurate biomarker for prostate cancer screening compared with serum prostate-specific antigen level.

PubMed

Xue, Dong; Zhou, Cui-Xing; Shi, Yun-Bo; Lu, Hao; He, Xiao-Zhou

2015-05-01

Prostate cancer and prostatic hyperplasia detection remains a great challenge, lacking of effective non-invasive and specific diagnostic biomarkers. In the current study, we aimed to identify the relative expression of plasma MD-miniRNA and its diagnostic performance in differentiating prostate cancer and prostatic hyperplasia patients from healthy controls, compared with serum prostate-specific antigen (PSA) level. All of the clinical participants (63 prostate cancer patients, 32 prostatic hyperplasia patients, and 50 healthy controls) were obtained from the Third Affiliated Hospital of Suzhou University in China between January 2013 and April 2014. Clinical characteristics were well matched. Plasma samples were extracted to test the relative expression of MD-miniRNA using the method of qRT-PCR. SPSS 22.0 statistical software package was used to analyze the data and GraphPad Prism 6.0 was used to generate the graphs. Relativity expression of plasma MD-miniRNA was significantly upregulated in prostate cancer, compared with prostatic hyperplasia patients and healthy controls. Serum PSA level revealed similar differences among these groups. MD-miniRNA presented a relatively high diagnostic accuracy with AUC of 0.86 (95 % CI 0.80-0.93) in differentiating prostate cancer patients from healthy controls. Simultaneously, MD-miniRNA was able to discriminate prostate cancer patients from prostatic hyperplasia controls with AUC of 0.79 (95 % CI 0.70-0.88). In addition, MD-miniRNA displayed a better diagnostic performance than PSA level. However, the panel of these two biomarkers revealed the best diagnostic performance, compared with either single biomarker. Results of this study showed that plasma MD-miniRNA could serve as a promising and noninvasive biomarker for diagnosing prostate cancer. Further large-scale studies are needed to confirm its clinical diagnosis accuracy.

Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

PubMed

Abugharib, Ahmed; Jackson, William C; Tumati, Vasu; Dess, Robert T; Lee, Jae Y; Zhao, Shuang G; Soliman, Moaaz; Zumsteg, Zachary S; Mehra, Rohit; Feng, Felix Y; Morgan, Todd M; Desai, Neil; Spratt, Daniel E

2017-03-01

Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival. Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R 2 = 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R 2 = 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes

ClinicalTrials.gov

2016-07-03

Prostate Cancer; Local Anesthesia; Prostate-Specific Antigen/Blood; Biopsy/Methods; Image-guided Biopsy/Methods; Prostatic Neoplasms/Diagnosis; Prostate/Pathology; Prospective Studies; Humans; Male; Ultrasonography, Interventional/Methods

Management of Men with Prostate-specific Antigen Failure After Prostate Radiotherapy: The Case Against Early Androgen Deprivation.

PubMed

Brand, Douglas; Parker, Chris

2018-04-01

In men with prostate-specific antigen failure after radical radiotherapy, androgen deprivation therapy should be delayed until the site of recurrence is known to allow consideration of curative treatment options, to delay androgen deprivation therapy-related morbidity, and to enable earlier access to abiraterone and docetaxel. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Prostate-Specific Membrane Antigen-Negative Metastases-A Potential Pitfall in Prostate-Specific Membrane Antigen PET.

PubMed

Noto, Benjamin; Auf der Springe, Katharina; Huss, Sebastian; Allkemper, Thomas; Stegger, Lars

2018-06-01

Ga-PSMA-11 PET/CT was performed in a 74-year-old man because of biochemical recurrence of prostate cancer following radiation therapy of the prostate gland 24 months earlier. Besides focal nuclide accumulation in the prostate gland suggestive of local recurrence, PET scan revealed no further pathologic uptake. However, CT showed multiple pulmonic nodules suggestive of metastases. Thoracotomy and pathologic examination revealed the nodules to be prostate cancer metastasis. Furthermore, immunohistochemical staining with PSMA antibodies demonstrated a virtual lack of PSMA expression. This case demonstrates the possibility of PSMA-negative metastases of prostate cancer an important pitfall that should be known to physicians interpreting PSMA PET.

Current strategies for monitoring men with localised prostate cancer lack a strong evidence base: observational longitudinal study.

PubMed

Metcalfe, C; Tilling, K; Davis, M; Lane, J A; Martin, R M; Kynaston, H; Powell, P; Neal, D E; Hamdy, F; Donovan, J L

2009-08-04

The UK National Institute for Health and Clinical Excellence (NICE) guidance recommends conservative management of men with 'low-risk' localised prostate cancer, monitoring the disease using prostate-specific antigen (PSA) kinetics and re-biopsy. However, there is little evidence of the changes in PSA level that should alert to the need for clinical re-assessment. This study compares the alerts resulting from PSA kinetics and a novel longitudinal reference range approach, which incorporates age-related changes, during the monitoring of 408 men with localised prostate cancer. Men were monitored by regular PSA tests over a mean of 2.9 years, recording when a man's PSA doubling time fell below 2 years, PSA velocity exceeded 2 ng ml(-1) per year, or when his upper 10% reference range was exceeded. Prostate-specific antigen doubling time and PSA velocity alerted a high proportion of men initially but became unresponsive to changes with successive tests. Calculating doubling time using recent PSA measurements reduced the decline in response. The reference range method maintained responsiveness to changes in PSA level throughout the monitoring. The increasing unresponsiveness of PSA kinetics is a consequence of the underlying regression model. Novel methods are needed for evaluation in cohorts currently being managed by monitoring. Meanwhile, the NICE guidance should be cautious.

Feasibility of minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen: feasibility and 1-year outcomes.

PubMed

Do, Minh; Ragavan, Narasimhan; Dietel, Anja; Liatsikos, Evangelos; Anderson, Chris; McNeill, Alan; Stolzenburg, Jens-Uwe

2012-10-01

Urologists are cautious to offer minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen (and therefore anticipated to have locally advanced or metastatic disease) because of concerns regarding lack of complete cure after minimally invasive radical prostatectomy and of worsening of continence if adjuvant radiotherapy is used. A retrospective review of our institutional database was carried out to identify patients with PSA ≥20 ng/mL who underwent minimally invasive radical prostatectomy between January 2002 and October 2010. Intraoperative, pathological, functional and short-term oncological outcomes were assessed. Overall, 233 patients met study criteria and were included in the analysis. The median prostate-specific antigen and prostate size were 28.5 ng/mL and 47 mL, respectively. Intraoperative complications were the following: rectal injury (0.86%) and blood transfusion (1.7%). Early postoperative complications included prolonged (>6 days) catheterization (9.4%), hematoma (4.7%), deep venous thrombosis (0.86%) and lymphocele (5.1%). Late postoperative complications included cerebrovascular accident (0.4%) and anastomotic stricture (0.8%). Pathology revealed poorly differentiated cancer in 48.9%, pT3/pT4 disease in 55.8%, positive margins in 28.3% and lymph node disease in 20.2% of the cases. Adverse pathological findings were more frequent in patients with prostate-specific antigen >40 ng/mL and (or) in those with locally advanced disease (pT3/pT4). In 62.2% of the cases, adjuvant radiotherapy was used. At 1-year follow up, 80% of patients did not show evidence of biochemical recurrence and 98.8% of them had good recovery of continence. Minimally invasive radical prostatectomy might represent a reasonable option in prostate cancer patients with high prostate-specific antigen as a part of a multimodality treatment approach. © 2012 The Japanese Urological Association.

[Development of a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse tanscription polymerase chain reaction (qRT-PCR)].

PubMed

Pavlov, K A; Shkoporov, A N; Khokhlova, E V; Korchagina, A A; Sidorenkov, A V; Grigor'ev, M É; Pushkar', D Iu; Chekhonin, V P

2013-01-01

The wide introduction of prostatic specific antigen (PSA) determination into clinical practice has resulted in a larger number of prostate biopsies, while the lower age threshold for PSA has led to a larger number of unnecessary prostate biopsies. Hence, there is a need for new biomarkers that can detect prostate cancer. PCA3 is a noncoding messenger ribonucleic acid (mRNA) that is expressed exclusively in prostate cells. The aim of the study has been to develop a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of the study, a laboratory diagnostic test system prototype has been designed, an application methodology has been developed and specificity and sensitivity data of the method has been assessed. The diagnostic system has demonstrated its ability to detect significantly elevated levels of PCA 3/KLK 3 in samples from prostate cancer (PCa) patients compared with those from healthy men. The findings have shown relatively high diagnostic sensitivity, specificity and negative-predictive values for an early non-invasive screening of prostate cancer

Integrating Molecular Imaging Approaches to Monitor Prostate Targeted Suicide and Anti-angiogenic Gene Therapy

DTIC Science & Technology

2005-02-01

tissue-specific expression of prostate-specific antigen. Cancer Res. 57: 495–499. 11. Schuur, E. R ., Henderson, G . A., Kmetec, L. A., Miller, J. D...Lamparski, H. G ., and Henderson, D. R . (1996). Prostate-specific antigen expression is regulated by an up- stream enhancer. J. Biol. Chem. 271: 7043...5: 223–232. 29. Blasberg, R . G ., and Tjuvajev, J. G . (1999). Herpes simplex virus thymidine kinase as a marker/reporter gene for PET imaging of gene

Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Approach to Treatment of Prostate Cancer

DTIC Science & Technology

2008-10-01

NOTES 14. ABSTRACT We determined that cell lysates prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition...to the known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the...appeared to be superior to prostate lysate antigen-loaded canine autologous dendritic cells when both were injected subcutaneously near the popliteal lymph

Expression of the gastrin-releasing peptide receptor, the prostate stem cell antigen and the prostate-specific membrane antigen in lymph node and bone metastases of prostate cancer.

PubMed

Ananias, Hildo J K; van den Heuvel, Marius C; Helfrich, Wijnand; de Jong, Igle J

2009-07-01

Cell membrane antigens like the gastrin-releasing peptide receptor (GRPR), the prostate stem cell antigen (PSCA), and the prostate-specific membrane antigen (PSMA), expressed in prostate cancer, are attractive targets for new therapeutic and diagnostic applications. Therefore, we investigated in this study whether these antigens are expressed in metastasized prostate cancer. Formalin-fixed, paraffin-embedded specimens of 15 patients with uni- or bilateral lymph node metastases of prostate cancer (totaling 21 cases) and 17 patient-cases of bone metastases were processed for immunohistochemistry with anti-GRPR, anti-PSCA, and anti-PSMA antibodies. A pathologist blinded to clinical and pathological data scored the immunoreactivity for these antibodies on a four-point scale (0 = no staining; 1+ = weak staining; 2+ = moderate staining; 3+ = strong staining) and documented the distribution pattern. GRPR staining in lymph node metastases was seen in 85.7% of cases (18 of 21 cases), PSCA in 95.2% (20/21), and PSMA in 100% (21/21). GRPR in bone metastases was seen in 52.9% of cases (9/17), PSCA in 94.1% (16/17), and PSMA in 100% (17/17). We have shown for the first time that GRPR is expressed in the vast majority of lymph node metastases and in 52.9% of bone metastases of prostate cancer. PSCA and PSMA are both highly expressed in lymph node and bone metastases. Although PSCA and PSMA are mostly expressed in prostate cancer metastases, GRPR offers an interesting alternative target as it can be targeted relatively easy with peptide-based (radio)pharmaceuticals. (c) 2009 Wiley-Liss, Inc.

Length of positive surgical margin after radical prostatectomy as a predictor of biochemical recurrence.

PubMed

Shikanov, Sergey; Song, Jie; Royce, Cassandra; Al-Ahmadie, Hikmat; Zorn, Kevin; Steinberg, Gary; Zagaja, Gregory; Shalhav, Arieh; Eggener, Scott

2009-07-01

Length and location of positive surgical margins are independent predictors of biochemical recurrence after open radical prostatectomy. We assessed their impact on biochemical recurrence in a large robotic prostatectomy series. Data were collected prospectively from 1,398 men undergoing robotic radical prostatectomy for clinically localized prostate cancer from 2003 to 2008 at a single institution. The associations of preoperative prostate specific antigen, pathological Gleason score, pathological stage and positive surgical margin parameters (location, length and focality) with biochemical recurrence rate were evaluated. Margin status and length were measured by a single uropathologist. Biochemical recurrence was defined as serum prostate specific antigen greater than 0.1 ng/ml on 2 consecutive tests. Cox regression models were constructed to evaluate predictors of biochemical recurrence. Of 1,398 consecutive patients who underwent robotic prostatectomy positive margins were present in 243 (17%) (11% of pathological T2 and 41% of T3). Preoperative prostate specific antigen, pathological stage, Gleason score, margin status, and margin length as a continuous and categorical variable (less than 1, 1 to 3, more than 3 mm) were independent predictors of biochemical recurrence. Patients with negative margins and those with a positive margin less than 1 mm had similar rates of biochemical recurrence (log rank test p = 0.18). Surgical margin location was not independently associated with biochemical recurrence. Margin status and length are independent predictors of biochemical recurrence following robotic radical prostatectomy. Although longer followup and validation studies are necessary for confirmation, patients with a positive margin less than 1 mm appear to have similar recurrence rates as those with negative margins.

A single-chain fragment against prostate specific membrane antigen as a tool to build theranostic reagents for prostate cancer.

PubMed

Frigerio, B; Fracasso, G; Luison, E; Cingarlini, S; Mortarino, M; Coliva, A; Seregni, E; Bombardieri, E; Zuccolotto, G; Rosato, A; Colombatti, M; Canevari, S; Figini, M

2013-06-01

Prostate carcinoma is the most common non-cutaneous cancer in developed countries and represents the second leading cause of death. Early stage androgen dependent prostate carcinoma responds well to conventional therapies, but relatively few treatment options exist for patients with hormone-refractory prostate cancer. One of the most suitable targets for antibody-mediated approaches is prostate specific membrane antigen (PSMA) which is a well known tumour associated antigen. PSMA is a type II integral cell-surface membrane protein that is not secreted, and its expression density and enzymatic activity are increased progressively in prostate cancer compared to normal prostate epithelium, thereby making PSMA an ideal target for monoclonal antibody imaging and therapy. To obtain a small protein that can better penetrate tissue, we have engineered a single-chain variable fragment (scFv) starting from the variable heavy and light domains of the murine anti-PSMA monoclonal antibody D2B. scFvD2B was analysed in vitro for activity, stability, internalisation ability and in vivo for targeting specificity. Maintenance of function and immunoreactivity as well as extremely high radiolabelling efficiency and radiochemical purity were demonstrated by in vitro assays and under different experimental conditions. Despite its monovalent binding, scFvD2B retained a good strength of binding and was able to internalise around 40% of bound antigen. In vivo we showed its ability to specifically target only PSMA expressing prostate cancer xenografts. Due to these advantageous properties, scFvD2B has the potential to become a good theranostic reagent for early detection and therapy of prostate cancers. Published by Elsevier Ltd.

Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

PubMed

Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

2017-03-14

Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

Beyond PSA: are new prostate cancer biomarkers of potential value to New Zealand doctors?

PubMed

Ng, Lance; Karunasinghe, Nishi; Benjamin, Challaraj S; Ferguson, Lynnette R

2012-04-20

The widespread introduction of prostate-specific antigen (PSA) screening has enhanced the early detection of prostate cancer within New Zealand. However, uncertainties associated with the test make it difficult to confidently differentiate low-risk patients from those that require a definitive diagnostic biopsy. In consequence, the decisions surrounding prostate cancer treatment become extremely difficult. A number of new tests have become available which might have the potential to complement the current PSA screens. We review a number of the best validated of these which provide data that, although currently not available in clinical practice, some of these might have considerable potential to aid diagnosis, prognosis and therapeutic decisions for men with prostate cancer in New Zealand.

The impact of the United States Preventive Services Task Force (USPTSTF) recommendations against prostate-specific antigen (PSA) testing on PSA testing in Australia.

PubMed

Zargar, Homayoun; van den Bergh, Roderick; Moon, Daniel; Lawrentschuk, Nathan; Costello, Anthony; Murphy, Declan

2017-01-01

To assess the impact of the United States Preventive Services Task Force (USPTSTF) recommendations on prostate-specific antigen (PSA) testing, prostate biopsy, and prostatectomy in Australian men based on the available Medicare data. Events were identified using Medicare item numbers for PSA testing (66655, 66659), prostate biopsy (37219), prostatectomy (37210), and prostatectomy with lymph node dissection (37211). The occurrences of each procedure was queried per 100 000 capita for consecutive financial years over the period 2000-2015. For each item number, reports were also generated for all Australian States. For PSA testing the data was stratified into three age groups of 45-54, 55-64, and 65-74 years. For assessing the rate of prostatectomy the capita rate values for two item numbers of prostatectomy (37210) and prostatectomy with lymph node dissection (37211) were combined. Steady declines in per capita incidences of all five item numbers assessed were seen for the three consecutive financial years (2013-2015) since the publication of the USPTSTF recommendation statement. These declines were seen across all Australian States. When examining the rate of PSA testing for the three age brackets 45-54, 55-64, and 65-74 years, similar trends were identified. Since the introduction of the USPTSTF recommendation statement there has been a steady nationwide decline in per capita incidences of PSA testing, prostate biopsy, and prostatectomy based on the Australian Medicare data. Whether these declines are in the right direction toward reduction in over-diagnosis and overtreatment of clinically insignificant prostate cancer or stage migration toward more locally advanced disease due to lost opportunity in diagnosing and treating early clinically significant prostate cancer will remain to be seen. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Relapsed prostate cancer with neuroendocrine differentiation and high serum levels of carcinoembryonic antigen without elevation of prostrate-specific antigen: a case report.

PubMed

Kinebuchi, Yoshiaki; Noguchi, Wataru; Irie, Kyoko; Nakayama, Tsuyoshi; Kato, Haruaki; Nishizawa, Osamu

2007-02-01

A 62-year-old man had been treated with combined androgen blockade due to cT2bN1M0 prostate cancer, and his serum prostate-specific antigen (PSA) levels decreased and remained under the level of 0.5 ng/mL during therapy. Approximately 40 months after the initial therapy, difficulty on urination and constipation developed gradually, and serum carcinoembryonic antigen (CEA) and pro-gastrin-releasing peptide (ProGRP) levels were high at this point. He underwent transrectal and transurethral biopsy of the prostate, which revealed adenocarcinoma positive for CEA and chromogranin A. He received palliative pelvic irradiation, and oral estramustine phosphate and etoposide combined therapy. Tumor markers decreased and clinical symptoms improved for several months. The patient died of encephalopathy of unknown etiology approximately 11 months after the relapse.

Predicting the risk of patients with biopsy Gleason score 6 to harbor a higher grade cancer.

PubMed

Gofrit, Ofer N; Zorn, Kevin C; Taxy, Jerome B; Lin, Shang; Zagaja, Gregory P; Steinberg, Gary D; Shalhav, Arieh L

2007-11-01

Prostate cancer Gleason score 3 + 3 = 6 is currently the most common score assigned on prostatic biopsies. We analyzed the clinical variables that predict the likelihood of a patient with biopsy Gleason score 6 to harbor a higher grade tumor. The study population consisted of 448 patients with a mean age of 59.1 years who underwent radical prostatectomy between February 2003 to October 2006 for Gleason score 6 adenocarcinoma. The effect of preoperative variables on the probability of a Gleason score upgrade on final pathological evaluation was evaluated using logistic regression, and classification and regression tree analysis. Gleason score upgrade was found in 91 of 448 patients (20.3%). Logistic regression showed that only serum prostate specific antigen and the greatest percent of cancer in a core were significantly associated with a score upgrade (p = 0.0014 and 0.023, respectively). Classification and regression tree analysis showed that the risk of a Gleason score upgrade was 62% when serum prostate specific antigen was higher than 12 ng/ml and 18% when serum prostate specific antigen was 12 ng/ml or less. In patients with serum prostate specific antigen lower than 12 ng/ml the risk of a score upgrade could be dichotomized at a greatest percent of cancer in a core of 5%. The risk was 22.6% and 10.5% when the greatest percent of cancer in a core was higher than 5% and 5% or lower, respectively. The probability of patients with a prostate biopsy Gleason score of 6 to conceal a Gleason score of 7 or higher can be predicted using serum prostate specific antigen and the greatest percent of cancer in a core. With these parameters it is possible to predict upgrade rates as high as 62% and as low as 10.5%.

[Animal models of autoimmune prostatitis and their evaluation criteria].

PubMed

Shen, Jia-ming; Lu, Jin-chun; Yao, Bing

2016-03-01

Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.

68Ga-PSMA Expression in Pseudoangiomatous Stromal Hyperplasia of the Breast.

PubMed

Malik, Dharmender; Basher, Rajender K; Mittal, Bhagwant Rai; Jain, Tarun Kumar; Bal, Amanjit; Singh, Shrawan Kumar

2017-01-01

Ga-labeled prostate-specific membrane antigen ligand PET-CT has emerged as a promising technique to evaluate the extent of disease in patients with prostate carcinoma. We are reporting a 63-year-old man with prostatic carcinoma subjected to Ga-prostate-specific membrane antigen ligand PET-CT for initial staging. In addition to the radiotracer uptake in known primary site (prostate), focal increased radiotracer uptake was also noticed in the left breast. Subsequent biopsy of the breast lesion revealed PASH (pseudoangiomatous stromal hyperplasia), which is a benign mesenchymal proliferative lesion that may present clinically as palpable mass requiring further evaluation to rule out malignancy.

Radical Prostatectomy Findings in Men on Active Surveillance: Variable Findings Dependent on Reason for Surgery and Entry Criteria.

PubMed

Matoso, Andres; Hassan, Oudai; Petrozzino, Florencia; Rao, B Vishal; Carter, H Ballentine; Epstein, Jonathan I

2015-09-01

We studied adverse radical prostatectomy findings in men on an active surveillance program with different entry and exit criteria. The study included 80 men with biopsy progression, 33 who opted out for personal reasons and 24 who initially did not meet entry criteria mainly due to increased prostate specific antigen density. Of men who opted out 78.8% had a higher Gleason score of 6 than men who progressed on biopsy (46.2%, p = 0.002) and men with high prostate specific antigen density (45.8%, p = 0.02). Men with high prostate specific antigen density had less organ confined disease than the group that opted out (p <0.006) and a trend compared to the biopsy progression group (p = 0.07). Mean dominant tumor volume was lower in men who opted out than in those with biopsy progression (0.56 vs 1.1 cc, p = 0.03). The incidence of insignificant cancer was higher in men who opted out (48.4%) than in those with biopsy progression (28.4%, p = 0.05) and those with high prostate specific antigen density (20.8%, p = 0.035). There was a higher incidence of anterior tumor in men with high prostate specific antigen density (55.0%) than with biopsy progression (21.3%, p = 0.009) and a trend compared to those who opted out (27.3%, p = 0.06). The majority of men with biopsy progression still had tumors with features of curable disease. Men who opted out without biopsy progression had even less adverse findings, which supports counseling men to stay on active surveillance while they meet followup criteria. Men with elevated prostate specific antigen density had more anterior tumors and less organ confined cancer, substantiating that the ideal patients for active surveillance are those who meet all entry criteria. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Investigating the Functional Role of Prostate-Specific Membrane Antigen and its Enzymatic Activity in Prostate Cancer Metastasis

DTIC Science & Technology

2007-02-01

saponin (Calbiochem, San Diego, CA) in PBS. Results, Significance, Obstacles and Alternative Approaches: We have generated several different fluorescent...1 integrin antibody P4C10 (Life technologies ). We will conjugate the fluorescent probes to these functional blocking antibodies for live cell...characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. Int. J. Cancer. 62:552-558. 1995. 9. Wright GL Jr

MRI-Derived Cellularity Index as a Potential Noninvasive Imaging Biomarker of Prostate Cancer

DTIC Science & Technology

2014-10-01

previously diagnosed with prostate cancer via standard transrectal ultrasound guided prostate biopsy after prostate specific antigen (PSA) elevation or...around 70% and specificity of 55% (72). Functional MR techniques enhance detection, grading, and staging of prostate cancer through the use of dynamic...and specificity in the diagnosis of prostate cancer by increasing tumor conspicuity on DWI or quantitative ADC maps. How- ever, hemorrhage, inflammatory

National Trends in Prostate Biopsy and Radical Prostatectomy Volumes Following the US Preventive Services Task Force Guidelines Against Prostate-Specific Antigen Screening.

PubMed

Halpern, Joshua A; Shoag, Jonathan E; Artis, Amanda S; Ballman, Karla V; Sedrakyan, Art; Hershman, Dawn L; Wright, Jason D; Shih, Ya Chen Tina; Hu, Jim C

2017-02-01

Studies demonstrate that use of prostate-specific antigen screening decreased significantly following the US Preventive Services Task Force (USPSTF) recommendation against prostate-specific antigen screening in 2012. To determine downstream effects on practice patterns in prostate cancer diagnosis and treatment following the 2012 USPSTF recommendation. Procedural volumes of certifying and recertifying urologists from 2009 through 2016 were evaluated for variation in prostate biopsy and radical prostatectomy (RP) volume. Trends were confirmed using the New York Statewide Planning and Research Cooperative System and Nationwide Inpatient Sample. The study included a representative sample of urologists across practice settings and nationally representative sample of all RP discharges. We obtained operative case logs from the American Board of Urology and identified urologists performing at least 1 prostate biopsy (n = 5173) or RP (n = 3748), respectively. The 2012 USPSTF recommendation against routine population-wide prostate-specific antigen screening. Change in median biopsy and RP volume per urologist and national procedural volume. Following the USPSTF recommendation, median biopsy volume per urologist decreased from 29 to 21 (interquartile range [IQR}, 12-34; P < .001). After adjusting for physician and practice characteristics, biopsy volume decreased by 28.7% following 2012 (parameter estimate, -0.25; SE, 0.03; P < .001). Similarly, following the USPSTF recommendation, median RP volume per urologist decreased from 7 (IQR, 3-15) to 6 (IQR, 2-12) (P < .001), and in adjusted analyses, RP volume decreased 16.2% (parameter estimate, -0.15; SE, 0.05; P = .003). Following the 2012 USPSTF recommendation, prostate biopsy and RP volumes decreased significantly. A panoramic vantage point is needed to evaluate the long-term consequences of the 2012 USPSTF recommendation.

Adoptive cell therapy of prostate cancer using female mice-derived T cells that react with prostate antigens

PubMed Central

Yi, Huanfa; Yu, Xiaofei; Guo, Chunqing; Manjili, Masoud H.; Repasky, Elizabeth A.; Wang, Xiang-Yang

2011-01-01

In this study, we report a novel treatment strategy that could potentially be used to improve efficacy of adoptive cell therapy for patients with prostate cancer. We show that female C57BL/6 mice are able to effectively reject two syngeneic prostate tumors (TRAMP-C2 and RM1) in a T cell-dependent manner. The protective antitumor immunity appears to primarily involve T cell responses reactive against general prostate tumor/tissue antigens, rather than simply to male-specific H-Y antigen. For the first time we show that adoptive transfer of lymphocytes from TRAMP-C2-primed or naive female mice effectively control prostate tumor growth in male mice, when combined with host pre-conditioning (i.e., non-myeloablative lymphodepletion) and IL-2 administration. No pathological autoimmune response was observed in the treated tumor-bearing male mice. Our studies provide new insights regarding the immune-mediated recognition of male-specific tissue, such as the prostate, and may offer new immunotherapy treatment strategies for advanced prostate cancer. PMID:21088965

Trichosanthes kirilowii Exerts Androgenic Activity via Regulation of PSA and KLK2 in 22Rv1 Prostate Cancer Cells.

PubMed

Jeong, Soo-Jin; Choi, Ji-Yoon; Dong, Mi-Sook; Seo, Chang-Seob; Shin, Hyeun-Kyoo

2017-01-01

The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system. TK, AS, SO, and XS enhanced the proliferation of 22Rv1 cells without having cytotoxic effects. All tested herbal extracts increased androgen receptor (AR)-induced transcriptional activity in the absence or presence of dihydrotestosterone (DHT). In an AR-binding assay, TK, but not AS, SO, or XS, produced a significant inhibition of AR binding activity, indicating it has androgenic activity. Additionally, TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen (PSA) and kallikrein 2 (KLK2) compared with untreated control. Taken together, TK-enhanced AR-mediated transcriptional activity might be an attractive candidate drug for treating androgen-related diseases. Trichosantheskirilowii (TK), Asarumsieboldii (AS), Sanguisorbaofficinalis (SO), and Xanthium strumarium (XS) enhanced the proliferation of 22Rv1 cells without having cytotoxic effects.TK, AS, SO, and XS increased androgen receptor (AR)-induced transcriptional activity.TK, but not AS, SO, or XS, produced a significant inhibition against AR-binding activity.TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen and kallikrein 2. Abbreviations used: BPH: benign prostatic hyperplasia; AR: androgen receptor; DHT: dihydrotestosterone; PSA: prostate-specific antigen; TK: Trichosanthes kirilowii; AS: Asarum sieboldii; SO: Sanguisorba officinalis; XS: Xanthium strumarium; ATCC: American Type Culture Collection; FBS: fetal bovine serum; PBS: phosphate-buffered saline; SD: standard deviation; ARE: androgenresponsive element; KLK: kallikrein.

Delivery of Cancer Screening

PubMed Central

Fenton, Joshua J.; Cai, Yong; Weiss, Noel S.; Elmore, Joann G.; Pardee, Roy E.; Reid, Robert J.; Baldwin, Laura-Mae

2012-01-01

Background Patients and physicians strongly endorse the importance of preventive or periodic health examinations (PHEs). However, the extent to which PHEs contribute to the delivery of cancer screening is uncertain. Methods In a retrospective cohort study, we determined the association between receipt of a PHE and cancer testing in a population-based sample of enrollees in a Washington State health plan who were aged 52 to 78 years and eligible for colorectal, breast, or prostate cancer screening in 2002–2003 (N = 64 288). Outcomes included completion of any colorectal cancer testing (fecal occult blood testing, sigmoidoscopy, colonoscopy, or barium enema), screening mammography, and prostate-specific antigen testing. Results More than half (52.4%) of the enrollees received a PHE during the study period. After adjusting for demographics, comorbidity, number of outpatient visits, and historical preventive service use before January 1, 2002, receipt of a PHE was significantly associated with completion of colorectal cancer testing (incidence difference, 40.4% [95% confidence interval (CI), 39.4%–41.3%]; relative incidence, 3.47 [95% CI, 3.34–3.59]), screening mammography [incidence difference, 14.2% [95% CI, 12.7%–15.7%]; relative incidence, 1.23 [95% CI, 1.20–1.25]), and prostate-specific antigen testing (incidence difference, 39.4% [95% CI, 38.3%–40.5%]; relative incidence, 3.06 [95% CI, 2.95–3.18]). Conclusions Among managed care enrollees eligible for cancer screening, PHE receipt is associated with completion of colorectal, breast, and prostate cancer testing. In similar populations, the PHE may serve as a clinically important forum for the promotion of evidence-based colorectal cancer and breast cancer screening and of screening with relatively less empirical support, such as prostate cancer screening. PMID:17389289

The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome

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

Vance, Waseet; Tucker, Susan L.; Crevoisier, Renaud de

2007-03-01

Purpose: To determine the value of a 2-year post-radiotherapy (RT) prostate biopsy for predicting eventual biochemical failure in patients who were treated for localized prostate cancer. Methods and Materials: This study comprised 164 patients who underwent a planned 2-year post-RT prostate biopsy. The independent prognostic value of the biopsy results for forecasting eventual biochemical outcome and overall survival was tested with other factors (the Gleason score, 1992 American Joint Committee on Cancer tumor stage, pretreatment prostate-specific antigen level, risk group, and RT dose) in a multivariate analysis. The current nadir + 2 (CN + 2) definition of biochemical failure wasmore » used. Patients with rising prostate-specific antigen (PSA) or suspicious digital rectal examination before the biopsy were excluded. Results: The biopsy results were normal in 78 patients, scant atypical and malignant cells in 30, carcinoma with treatment effect in 43, and carcinoma without treatment effect in 13. Using the CN + 2 definition, we found a significant association between biopsy results and eventual biochemical failure. We also found that the biopsy status provides predictive information independent of the PSA status at the time of biopsy. Conclusion: A 2-year post-RT prostate biopsy may be useful for forecasting CN + 2 biochemical failure. Posttreatment prostate biopsy may be useful for identifying patients for aggressive salvage therapy.« less

Efficacy Against Human Prostate Cancer by Prostate-specific Membrane Antigen-specific, Transforming Growth Factor-β Insensitive Genetically Targeted CD8+ T-cells Derived from Patients with Metastatic Castrate-resistant Disease.

PubMed

Zhang, Qiang; Helfand, Brian T; Carneiro, Benedito A; Qin, Weijun; Yang, Ximing J; Lee, Chung; Zhang, Weipeng; Giles, Francis J; Cristofanilli, Massimo; Kuzel, Timothy M

2018-05-01

Current immunotherapy has limited efficacy on metastatic castrate-resistant prostate cancer (mCRPC). We therefore sought to improve the antitumor ability of mCRPC patient-derived CD8 + T-cells by the endowment of specificity to prostate-specific membrane antigen (PSMA) and insensitivity to immunosuppressant molecule transforming growth factor-β (TGF-ß) under the control of herpes simplex virus-1 thymidine kinase. CD8 + T-cells were collected by leukapheresis and cultured in a Food and Drug Administration-approved Cell Processing Work Station. We developed a chimeric antigen receptor retroviral construct using an anti-PSMA chimeric immunoglobulin-T-cell receptor(ζ) gene (PZ1) and dominant negative TGF-ß type II receptor (TßRIIDN), that could induce CD8 + T-cells to be PSMA reactive and insensitive to TGF-ß. Cr 51 release assay was performed on PC-3 and PC-3-PSMA. The further antitumor functions of PSMA-specific, TGF-ß insensitive CD8 + T-cells was evaluated using an immunodeficient RAG-1 -/- mouse model. We found PSMA-specific, TGF-ß insensitive CD8 + T-cells from mCRPC were expanded with strong expression of PZ1 and thymidine kinase genes, and their growth was not suppressed by TGF-ß. The survival of these cells decreased sharply after treatment with ganciclovir. Treatment of PSMA-specific TGF-ß, insensitive CD8 + T-cells was associated with 61.58% specific lysis on PC-3-PSMA, and significantly suppressed PC3-PSMA tumor compared with the PC3 tumor. A large amount of tumor apoptosis and CD8 + T-cell infiltration were found only in the PC3-PSMA tumor. This study verified that PSMA-specific, TGF-ß insensitive CD8 + T-cells derived from mCRPC patients could be successfully expanded and used to overcome the immunosuppressive effects of the tumor microenvironment to control PSMA-expressing PC in vitro and in vivo. This may provide a promising approach for men with mCRPC who fail androgen deprivation therapy. We investigated the role of a novel chimeric antigen receptor T-immunotherapy based on autologous metastatic castrate-resistant prostate cancer patient-derived prostate-specific membrane antigen (PSMA)-specific, transforming growth factor-ß insensitive CD8 + T-cells on PSMA-positive prostate cancer. We found that this chimeric antigen receptor T-cells could kill PSMA-positive prostate cancer specifically. The results suggest that this novel immunotherapy treatment is a potential new approach for men with metastatic castrate-resistant prostate cancer. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers

PubMed Central

Filella, Xavier; Foj, Laura

2016-01-01

Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis. PMID:27792187

Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers.

PubMed

Filella, Xavier; Foj, Laura

2016-10-26

Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis.

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

PubMed

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

2015-10-01

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

Prostate cancer: a patient's perspective.

PubMed

Howe, R J

1994-11-01

During the last few years a tremendous amount of media attention has been focused on prostate cancer. This increased visibility has been the direct result of the prostate specific antigen test, which has led to a doubling of the number of new cases detected in just 4 years. With this visibility has come controversy about which treatment is the most effective or whether this disease should be treated aggressively at all. The formation and rapid expansion of the prostate cancer support group movement are reviewed, and the positive and negative impacts of media coverage on present and future patients are assessed. My personal case is reviewed briefly to make a specific point about the hazards of watchful waiting. Other issues, such as mass screening, Prostate Cancer Awareness Week and expenditures for prostate cancer research, are examined in some detail.

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

PubMed

Parwani, Anil V; Marlow, Cameron; Demarzo, Angelo M; Mikolajczyk, Stephen D; Rittenhouse, Harry G; Veltri, Robert W; Chan, Theresa Y

2006-10-01

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Detection of prostate-specific antigen with biomolecule-gated AlGaN/GaN high electron mobility transistors

NASA Astrophysics Data System (ADS)

Li, Jia-dong; Cheng, Jun-jie; Miao, Bin; Wei, Xiao-wei; Xie, Jie; Zhang, Jin-cheng; Zhang, Zhi-qiang; Wu, Dong-min

2014-07-01

In order to improve the sensitivity of AlGaN/GaN high electron mobility transistor (HEMT) biosensors, a simple biomolecule-gated AlGaN/GaN HEMT structure was designed and successfully fabricated for prostate specific antigen (PSA) detection. UV/ozone was used to oxidize the GaN surface and then a 3-aminopropyl trimethoxysilane (APTES) self-assembled monolayer was bound to the sensing region. This monolayer serves as a binding layer for attachment of the prostate specific antibody (anti-PSA). The biomolecule-gated AlGaN/GaN HEMT sensor shows a rapid and sensitive response when the target prostate-specific antigen in buffer solution was added to the antibody-immobilized sensing area. The current change showed a logarithm relationship against the PSA concentration from 0.1 pg/ml to 0.993 ng/ml. The sensitivity of 0.215% is determined for 0.1 pg/ml PSA solution. The above experimental result of the biomolecule-gated AlGaN/GaN HEMT biosensor suggested that this biosensor might be a useful tool for prostate cancer screening.

Tumor Markers

MedlinePlus

... on its own to screen for cancer. For example, the prostate-specific antigen (PSA) test , which measures the level of PSA in the ... Targeted Cancer Therapies Understanding Cancer ... Institute.” Please note that blog posts that are written by individuals from outside the ...

Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin.

PubMed

Dostalova, Simona; Polanska, Hana; Svobodova, Marketa; Balvan, Jan; Krystofova, Olga; Haddad, Yazan; Krizkova, Sona; Masarik, Michal; Eckschlager, Tomas; Stiborova, Marie; Heger, Zbynek; Adam, Vojtech

2018-06-11

Herein, we describe the in vivo effects of doxorubicin (DOX) encapsulated in ubiquitous protein apoferritin (APO) and its efficiency and safety in anti-tumor treatment. APODOX is both passively (through Enhanced Permeability and Retention effect) and actively targeted to tumors through prostate-specific membrane antigen (PSMA) via mouse antibodies conjugated to the surface of horse spleen APO. To achieve site-directed conjugation of the antibodies, a HWRGWVC heptapeptide linker was used. The prostate cancer-targeted and non-targeted nanocarriers were tested using subcutaneously implanted LNCaP cells in athymic mice models, and compared to free DOX. Prostate cancer-targeted APODOX retained the high potency of DOX in attenuation of tumors (with 55% decrease in tumor volume after 3 weeks of treatment). DOX and non-targeted APODOX treatment caused damage to liver, kidney and heart tissues. In contrast, no elevation in liver or kidney enzymes and negligible changes were revealed by histological assessment in prostate cancer-targeted APODOX-treated mice. Overall, we show that the APO nanocarrier provides an easy encapsulation protocol, reliable targeting, high therapeutic efficiency and very low off-target toxicity, and is thus a promising delivery system for translation into clinical use.

Advancing the Capabilities of an Authentic Ex Vivo Model of Primary Human Prostate Cancer

DTIC Science & Technology

2014-10-01

maintained the PTEN expression of the native tissues after 5 days in culture. Prostate-specific membrane antigen ( PSMA ) was detected in benign and malignant...room temperature 1 h room temperature 30 min room temperature Abcam, Cambridge, MA, USA p63 SMA CD68 PSMA Mouse monoclonal Mouse monoclonal Mouse...Prostate-specific membrane antigen ( PSMA ) was detected in benign and malignant glands as expected in both native tissue and in TSCs after 5 days.47

Rise in prostate-specific antigen in men with untreated low-grade prostate cancer is slower during spring-summer.

PubMed

Vieth, R; Choo, R; Deboer, L; Danjoux, C; Morton, G C; Klotz, L

2006-01-01

To test the hypothesis that the rate of rise in prostate-specific antigen (PSA) is slower during the spring-summer than during the rest of the year, we used PSA data from a prospective single-arm cohort study of men who had been followed to characterize a watchful observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The rate of PSA increase was calculated as the visit-to-visit slope of log (PSA) against time, from 1 calendar-quarter visit to the next. The nonparametric Friedman test confirmed differences in rate of PSA rise among the calendar quarters (P = 0.041). Post hoc analysis showed the rate of PSA increase during Q2 was significantly slower than in each one of the other calendar quarters (Q1 versus Q2, P = 0.025; Q3 versus Q2, P = 0.002; Q4 versus Q2, P = 0.013), with no differences among quarters Q1, Q3, and Q4. These results are consistent with the vitamin D hypothesis that the higher 25-hydroxyvitamin D levels associated with spring and summer have a desirable effect on prostate biology. The therapeutic implication is that vitamin D supplementation in the range of 2000 IU/d, a dose comparable to the effect of summer, can benefit men monitored for rising PSA.

Incidental Finding of Cryptococcus on Prostate Biopsy for Prostate Adenocarcinoma Following Cardiac Transplant: Case Report and Review of the Literature.

PubMed

Shah, Sujal I; Bui, Hai; Velasco, Nelson; Rungta, Shilpa

2017-11-06

BACKGROUND Cryptococcus is the third most common invasive fungal organism in immunocompromised patients, including transplant patients, and usually involves the central nervous system and lungs, with a median time to infection of 25 months. We report a case of Cryptococcus of the prostate gland, found as an incidental finding on prostate biopsy for prostate adenocarcinoma, four months following cardiac transplantation. CASE REPORT A 62-year-old male African-American who had a cardiac transplant four months previously, underwent a six-core prostate biopsy for a two-year history of increasing prostate-specific antigen (PSA) levels, and a recent history of non-specific urinary tract symptoms. A prostatic adenocarcinoma, Gleason grade 4+4=8, was diagnosed on histopathology, and 'foamy' cells were seen in the biopsies. Histochemical stains, including Grocott methenamine silver (GMS), and periodic acid-Schiff (PAS) showed abundant round and oval 5-7 µm diameter fungal elements; mucicarmine highlighted the fungal polysaccharide capsule, diagnostic for Cryptococcus. Cryptococcal antigen detection was made by the latex agglutination test and cultures. We reviewed the literature and found 70 published cases (from 1946-2008) of Cryptococcus of the prostate gland, with only one previous case presenting five years following cardiac transplantation. CONCLUSIONS Fungal infections of the prostate are rare, and occur mainly in immunocompromised patients. We present a unique case of prostatic Cryptococcus found incidentally at four months following cardiac transplantation. This case report highlights the need to consider atypical fungal infection as a differential diagnosis for prostatitis in immunosuppressed patients, including transplant patients.

Prostate biopsy

MedlinePlus

... shows that you have a higher than normal prostate specific antigen (PSA) level Your provider discovers a lump or abnormality in your prostate during a digital rectal exam Normal Results Normal ...

Vertebral Hemangioma Mimicking Bone Metastasis in 68Ga-PSMA Ligand PET/CT.

PubMed

Artigas, Carlos; Otte, François-Xavier; Lemort, Marc; van Velthoven, Roland; Flamen, Patrick

2017-05-01

Ga-PSMA PET/CT was performed in a 68-year-old man to evaluate recurrent prostate cancer due to elevated serum prostate-specific antigen level. Images showed a focal uptake in the prostatic gland, suggesting local relapse, and an intense uptake in the 12th thoracic vertebra, with no morphological abnormalities in CT slices. In order to confirm extraprostatic disease and before radiotherapy planning, a full-spine MRI was performed, resulting with the morphological pattern of a vertebral hemangioma. Hystological analysis confirmed the local relapse in the prostate. No radiotherapy treatment was given to the vertebra, and after 1 year of follow-up without systemic treatment, prostate-specific antigen is still undetectable.

Fluorescence of prostate-specific antigen as measured with a portable 1D scanner

NASA Astrophysics Data System (ADS)

Kim, Byeong C.; Jeong, Jin H.; Jeong, Dong S.; Kim, Young M.; Oh, Sang W.; Choi, Eui Y.; Kim, Jae H.; Nahm, Kie B.

2005-01-01

Prostate-specific antigen (PSA) is an androgen-dependent glycoprotein protease (M.W. 33 kDa) and a member of kallikrein super-family of serine protease, and has chymotrypsin-like enzymatic activity. It is synthesized by the prostate epithelial cells and found in the prostate gland and seminal plasma as a major protein. It is widely used as a clinical marker for diagnosis, screening, monitoring and prognosis of prostate cancer. In normal male adults, the concentration of PSA in the blood is below 4 ng/ml and this value increases in patients with the prostate cancer or the benign prostatic hyperplasia (BPH) due to its leakage into the circulatory system. As such, systematic monitoring of the PSA level in the blood can provide critical information about the progress of the prostatic disease. We have developed a compact integral system that can quantitatively measure the concentration of total PSA in human blood. This system utilizes the fluorescence emitted from the dye molecules attached to PSA molecules after appropriate immunoassay-based processing. Developed for the purpose of providing an affordable means of fast point-of-care testing of the prostate cancer, this system proved to be able to detect the presence of the PSA at the level of 0.18 ng/ml in less than 12 minutes, with the actual measurement taking less than 2 minutes. The design concept for this system is presented together with the result for a few representative samples.

Phase II Study of Dutasteride for Recurrent Prostate Cancer During Androgen Deprivation Therapy

PubMed Central

Shah, Satyan K.; Trump, Donald L.; Sartor, Oliver; Tan, Wei; Wilding, Gregory E.; Mohler, James L.

2010-01-01

Purpose We determined the response rate to and safety of a dual 5α-reductase inhibitor, dutasteride, in men with castration recurrent prostate cancer. Materials and Methods A total of 28 men with asymptomatic castration recurrent prostate cancer were treated with 3.5 mg dutasteride daily (luteinizing hormone-releasing hormone treatment continued), and evaluated monthly for response and toxicity. Eligibility included appropriate duration antiandrogen withdrawal, baseline prostate specific antigen 2.0 ng/ml or greater and a new lesion on bone scan, increase in measurable disease using Response Evaluation Criteria in Solid Tumors criteria, or 2 or more consecutive prostate specific antigen measurements increased over baseline. Outcomes were progression, stable disease, partial response (prostate specific antigen less than 50% of enrollment for 4 or more weeks) or complete response. Results There were 25 evaluable men with a mean age of 70 years (range 57 to 88), a mean prostate specific antigen of 61.9 ng/ml (range 5.0 to 488.9) and mean Gleason score 8 (range 6 to 10), 15 of whom had bone metastases. Eight men had 10 grade 3 or higher adverse events using National Cancer Institute Common Terminology Criteria, all of which were judged to be unrelated to treatment. Of the 25 men 14 had disease progression by 2 months, 9 had stable (2.5, 3, 3, 4, 4, 5, 5, 8.5, 9 months) disease, 2 had a partial response and none had a complete response. Overall median time to progression was 1.87 months (range 1 to 10, 95% CI 1.15–3.91). Conclusions Dutasteride rarely produces biochemical responses in men with castration recurrent prostate cancer. However, further study is warranted given its favorable safety profile. PMID:19091347

Vaginal Prostate Specific Antigen (PSA) Is a Useful Biomarker of Semen Exposure Among HIV-Infected Ugandan Women.

PubMed

Woolf-King, Sarah E; Muyindike, Winnie; Hobbs, Marcia M; Kusasira, Adrine; Fatch, Robin; Emenyonu, Nneka; Johnson, Mallory O; Hahn, Judith A

2017-07-01

The practical feasibility of using prostate specific antigen (PSA) as a biomarker of semen exposure was examined among HIV-infected Ugandan women. Vaginal fluids were obtained with self-collected swabs and a qualitative rapid test (ABAcard ® p30) was used to detect PSA. Trained laboratory technicians processed samples on-site and positive PSA tests were compared to self-reported unprotected vaginal sex (UVS) in the last 48 h. A total of 77 women submitted 126 samples for PSA testing at up to three study visits. Of these samples, 31 % (n = 39/126) were PSA positive, and 64 % (n = 25/39) of the positive PSA samples were accompanied by self-report of no UVS at the study visit the PSA was collected. There were no reported difficulties with specimen collection, storage, or processing. These findings provide preliminary data on high levels of misreported UVS among HIV-infected Ugandan women using practically feasible methods for PSA collection and processing.

A Diet, Physical Activity, and Meditation Intervention in Men With Rising Prostate-Specific Antigen (PSA)

DTIC Science & Technology

2006-05-01

AD_________________ Award Number: DAMD17-03-1-0139 TITLE: A Diet , Physical Activity, and...A Diet , Physical Activity, and Meditation Intervention in Men With Rising Prostate- 5a. CONTRACT NUMBER Specific Antigen (PSA...favorably affected by an intensive, vegetable-based diet , plus physical activity and mindfulness-based stress reduction. This randomized trial will

Prostate Cancer MR Imaging

NASA Astrophysics Data System (ADS)

Fütterer, Jurgen J.

With a total of 192,280 new cases predicted for 2009, prostate cancer (PC) now accounts for 25% of all new male cancers diagnosed in the United States [1]. Furthermore, in their lifetime, one in six men will be clinically diagnosed with having PC, although many more men are found to have histological evidence of PC at autopsy [2,3,4]. Presently, approximately 1 in 10 men will die of PC [5,6]. The ever-aging population and wider spread use of the blood prostate-specific antigen (PSA) test [7,8], as well as the tendency to apply lower cut-off levels for this test [9], will further increase the diagnosis of this disease [10].

Can Prostate-Specific Antigen Kinetics before Prostate Biopsy Predict the Malignant Potential of Prostate Cancer?

PubMed

Kim, Sang Jin; Jeong, Tae Yoong; Yoo, Dae Seon; Park, Jinsung; Cho, Seok; Kang, Seok Ho; Lee, Sang Hyub; Jeon, Seung Hyun; Lee, Tchun Yong; Park, Sung Yul

2015-11-01

To predict the malignant potential of prostate cancer (PCa) according to prostate-specific antigen velocity (PSAV), PSA density (PSAD), free/total PSA ratio (%fPSA), and digital rectal examination (DRE). From January 2009 to December 2012, 548 adult male patients were diagnosed with PCa by prostate biopsy at four hospitals in Korea. We retrospectively analyzed 155 adult male patients with an initial PSA level≤10 ng/mL and whose PSA levels had been checked more than two times at least 6 months before they had been diagnosed with PCa, with test intervals of more than 3 months. Patients with a urinary tract infection, and patients who had previously undergone cystoscopy or surgery of the prostate were excluded. We separated patients into two groups according to Gleason sum [Gleason sum≤7 (n=134) or Gleason sum≥8 (n=21)] and the presence of extracapsular invasion [organ confined (n=129) or extracapsular invasion (n=26)]. Differences between the groups were compared. The group with a Gleason sum≥8 or extracapsular invasion of PCa showed high PSAV and significantly lower %fPSA. There were no significant differences in PSAD and the presence of an abnormality on DRE between two groups. In PCa patients treated with other therapies besides prostatectomy, a high PSA velocity and a low %fPSA may predict high grade PCa with a Gleason sum≥8 or the presence of extracapsular invasion.

Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas.

PubMed

Mohanty, Sambit K; Smith, Steven C; Chang, Elena; Luthringer, Daniel J; Gown, Allen M; Aron, Manju; Amin, Mahul B

2014-08-01

New immunohistochemical (IHC) markers of urothelial carcinoma (UCa) and prostatic adenocarcinoma (PCa) have emerged in recent years, yet comparative studies to establish markers remain lacking. We aimed to identify an effective but parsimonious approach for poorly differentiated bladder neck lesions, to establish a best practice panel approach in a setting simulating prospective use. We tested the performance of a panel of IHC markers on whole sections of a consecutive cohort of transurethral resection specimens of poorly differentiated, challenging bladder neck resections (n=36). In the setting of poorly differentiated bladder neck carcinomas, biomarker sensitivities for UCa were as follows: GATA3, 100%; S100P, 88%; p63, 75%; and cytokeratin (CK) 5/6, 56%; specificities of each were 100%. CK7 and CK20 showed sensitivities of 75% and 63%, though these were only 85% and 80% specific. For PCa markers, NKX3.1, p501S, prostate-specific membrane antigen, and androgen receptor (AR) each showed 100% sensitivity, outperforming ERG (35%) and prostate-specific antigen (PSA; 25%). All the prostate histogenesis markers were 100% specific, except for AR, which was positive in 13% of the UCa cases. Novel IHC markers show improved diagnostic performance that enables positive and negative support for identifying histogenesis with the use of as few as two markers for this critical therapeutic distinction. PSA underperforms newer markers. Copyright© by the American Society for Clinical Pathology.

Progress Against Prostate Cancer | NIH MedlinePlus the Magazine

MedlinePlus

... those diagnosed being 45 or older. What Is PSA? Prostate specific antigen, or PSA, is a substance produced by the prostate and released into the blood. PSA levels are often high in men with prostate ...

Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study

PubMed Central

Young, Grace J; Harrison, Sean; Turner, Emma L; Walsh, Eleanor I; Oliver, Steven E; Ben-Shlomo, Yoav; Evans, Simon; Lane, J Athene; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Martin, Richard M; Metcalfe, Chris

2017-01-01

Objectives Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). Setting, participants and outcome measures Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man’s age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. Results The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45–49 years to 53.0% for men aged 65–69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively). Conclusion A high proportion of men aged 45–69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. Trial registration number ISRCTN20141297, NCT02044172. PMID:29084797

225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer.

PubMed

Kratochwil, Clemens; Bruchertseifer, Frank; Giesel, Frederik L; Weis, Mirjam; Verburg, Frederik A; Mottaghy, Felix; Kopka, Klaus; Apostolidis, Christos; Haberkorn, Uwe; Morgenstern, Alfred

2016-12-01

Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to 225 Ac-PSMA-617 therapy. 68 Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of 225 Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with 68 Ga-PSMA-11 PET/CT. Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect. Targeted α-therapy with 225 Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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

PubMed

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

2014-12-01

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

Avoidance of anticipated regret: the ordering of prostate-specific antigen tests.

PubMed

Sorum, Paul C; Mullet, Etienne; Shim, Junseop; Bonnin-Scaon, Sylvie; Chasseigne, Gérard; Cogneau, Joël

2004-01-01

When making decisions, people are known to try to minimize the regret that would be provoked by unwanted consequences of these decisions. The authors explored the strength and determinants of such anticipated regret in a study of physicians' decisions to order prostate-specific antigen (PSA) tests. 32 US and 33 French primary care physicians indicated the likelihood they would order a PSA for 32 hypothetical men presenting for routine physical exams. They then indicated how much regret they would feel if they found advanced prostate cancer in 12 other patients for whom they had chosen not to order PSAs several years before. The latter patients differed according to age (55, 65, or 75 years), a prior request or not for PSA testing, and no or some irregularity of the prostate on the earlier rectal exam. ANOVA found that regret was higher when the patient had requested a PSA, the prostate was irregular, and the patient was younger. Shape had less effect when the patient had requested a PSA. US physicians had more regret than the French, patient request had a greater impact on the Americans, and increasing patient age reduced regret more among the French. In a 1-way correlation, the regret score was associated with the likelihood of ordering PSAs for both the French (r = 0.64, P < 0.005) and the Americans (r = 0.42, P< 0.02). In a regression analysis too, the regret score was the most important predictor of the likelihood of ordering a PSA (beta = 0.37, P < 0.0001). Regret over failing to diagnose aggressive prostate cancer is associated with a policy of ordering PSAs. This regret appears to be culturally sensitive.

Prostate-Specific Membrane Antigen Expression in Distal Radius Fracture.

PubMed

Hoberück, Sebastian; Michler, Enrico; Kaiser, Daniel; Röhnert, Anne; Zöphel, Klaus; Kotzerke, Jörg

2018-06-12

A 79-year old man with prostate cancer under active surveillance for 5 years was referred for a PSMA-PET/MRI for re-evaluation because of a rising prostate-specific antigen value. PET/MRI revealed a ribbonlike tracer accumulation in a healing fracture of the distal radius. This case illustrates that PSMA expression may occur in healing bone fractures in the distal radius. It can be assumed that benign causes of tracer accumulations in the upper extremities are missed in PET/CT due to elevated position of the arms during image acquisition.

Androgen Ablation Augments Prostate Cancer Vaccine Immunogenicity Only When Applied After Immunization

PubMed Central

Koh, Yi T.; Gray, Andrew; Higgins, Sean A.; Hubby, Bolyn; Kast, W. Martin

2009-01-01

Background Androgen ablation (AA) causes apoptosis of normal and neoplastic prostate cells. It is a standard treatment for advanced prostate cancer. Androgen ablation-mediated immunological effects include bone marrow hyperplasia, thymic regeneration, T and B cell lymphopoeisis and restoration of age-related peripheral T cell dysfunction. Androgens also regulate the transcription of several cytokines. Dendritic cells (DC) are the most potent antigen presenting cells that can activate antigen-specific naïve T cells. Despite myriad clinical trials involving DC-based prostate cancer immunotherapies, the effects of AA on DC function remain largely uncharacterized. Therefore, we investigated the effects of AA on DC and whether it could improve the efficacy of prostate cancer immunotherapy. Methods Cytokine expression changes due to AA were quantified by multiplex ELISA. Flow cytometry was used to assess AA-mediated effects on DC maturation and expression of costimulatory markers. Mixed leukocyte reactions and cell-mediated lysis assays elucidated the role of androgens in DC function. The effect of AA on the efficacy of vaccination against a prostate tumor-associated antigen was tested using Elispot assays. Results Androgen ablation increased dendritic cell maturation and costimulatory marker expression, but had no effect on DC costimulatory function. However, DC isolated from castrated mice increased the expression of key cytokines by antigen-experienced T cells while decreasing their expression in naïve cells. Finally, androgen ablation improved immune responses to vaccination only when applied after immunization. Conclusion Androgen ablation causes differential effects of DC on primary and secondary T cell responses, thus augmenting vaccine immunogenicity only when applied after immunization. PMID:19143030

A Quantitative Model for the Dynamics of Serum Prostate-Specific Antigen as a Marker for Cancerous Growth

PubMed Central

Swanson, Kristin R.; True, Lawrence D.; Lin, Daniel W.; Buhler, Kent R.; Vessella, Robert; Murray, James D.

2001-01-01

Prostate-specific antigen (PSA) is an enzyme produced by both normal and cancerous prostate epithelial cells. Although PSA is the most widely used serum marker to detect and follow patients with prostatic adenocarcinoma, there are certain anomalies in the values of serum levels of PSA that are not understood. We developed a mathematical model for the dynamics of serum levels of PSA as a function of the tumor volume. Our model results show good agreement with experimental observations and provide an explanation for the existence of significant prostatic tumor mass despite a low-serum PSA. This result can be very useful in enhancing the use of serum PSA levels as a marker for cancer growth. PMID:11395397

Imaging Prostate Cancer With Prostate-Specific Membrane Antigen PET/CT and PET/MRI: Current and Future Applications.

PubMed

Hope, Thomas A; Afshar-Oromieh, Ali; Eiber, Matthias; Emmett, Louise; Fendler, Wolfgang P; Lawhn-Heath, Courtney; Rowe, Steven P

2018-06-27

The purpose of this article is to describe the large number of radiotracers being evaluated for prostate-specific membrane antigen (PSMA) PET, which is becoming a central tool in the staging of prostate cancer. PSMA PET is a highly promising modality for the staging of prostate cancer because of its higher detection rate compared with that of conventional imaging. Both PET/CT and PET/MRI offer benefits with PSMA radiotracers, and PSMA PET findings frequently lead to changes in management. It is imperative that subsequent treatment changes be evaluated to show improved outcomes. PSMA PET also has potential applications, including patient selection for PSMA-based radioligand therapy and evaluation of treatment response.

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

PubMed

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

2014-03-01

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

Prostate-specific antigen density values among patients with symptomatic prostatic enlargement in Nigeria.

PubMed

Udeh, Emeka I; Nnabugwu, Ikenna I; Ozoemena, Francis O; Ugwumba, Fred O; Aderibigbe, Adesina S O; Ohayi, Samuel R; Echetabu, Kevin N

2016-06-29

This study aims to estimate the prostate-specific antigen density (PSAD) cutoff level for detecting prostate cancer (CAP) in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. We addressed this research question: Is the international PSAD cutoff of 0.15 ideal for detecting CAP in our symptomatic patients with "grey zone PSA?" To estimate the prostate-specific antigen density (PSAD) cutoff level for detecting CAP in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. Prospective. A tertiary medical center in Enugu, Nigeria. Two hundred and fifty-four men with either benign prostatic hyperplasia (BPH) or CAP were recruited. Patients with PSA above 4 ng/ml or abnormal digital rectal examination or hypoechoic lesion in the prostate were biopsied. PSAD and histology report of BPH or CAP. Ninety-seven patients had CAP while 157 had benign prostatic hyperplasia (BPH). Seventy-two patients had their serum PSA value within the range of 4.0 and 10 ng/ml. PSAD cutoff level to detect CAP was 0.04 (sensitivity 95.88 %; specificity 28.7 %). The PSAD cutoff level generated for Nigerian men in this study is 0.04 which is relatively different from international consensus. This PSAD cutoff level has a positive correlation with histology and could detect patients with CAP who have "grey zone PSA."

Anti-Tumor Effect of the Alphavirus-based Virus-like Particle Vector Expressing Prostate-Specific Antigen in a HLA-DR Transgenic Mouse Model of Prostate Cancer

PubMed Central

Riabov, V.; Tretyakova, I.; Alexander, R. B.; Pushko, P.; Klyushnenkova, E. N.

2015-01-01

The goal of this study was to determine if an alphavirus-based vaccine encoding human Prostate-Specific Antigen (PSA) could generate an effective anti-tumor immune response in a stringent mouse model of prostate cancer. DR2bxPSA F1 male mice expressing human PSA and HLA-DRB1*1501 transgenes were vaccinated with virus-like particle vector encoding PSA (VLPV-PSA) followed by the challenge with Transgenic Adenocarcinoma of Mouse Prostate cells engineered to express PSA (TRAMP-PSA). PSA-specific cellular and humoral immune responses were measured before and after tumor challenge. PSA and CD8 reactivity in the tumors was detected by immunohistochemistry. Tumor growth was compared in vaccinated and control groups. We found that VLPV-PSA could infect mouse dendritic cells in vitro and induce a robust PSA-specific immune response in vivo. A substantial proportion of splenic CD8+ T cells (19.6±7.4%) produced IFNγ in response to the immunodominant peptide PSA65–73. In the blood of vaccinated mice, 18.4±4.1% of CD8+ T cells were PSA-specific as determined by the staining with H-2Db/PSA65–73 dextramers. VLPV-PSA vaccination also strongly stimulated production of IgG2a/b anti-PSA antibodies. Tumors in vaccinated mice showed low levels of PSA expression and significant CD8 T cell infiltration. Tumor growth in VLPV-PSA vaccinated mice was significantly delayed at early time points (p=0.002, Gehan-Breslow test). Our data suggest that TC-83-based VLPV-PSA vaccine can efficiently overcome immune tolerance to PSA, mediate rapid clearance of PSA-expressing tumor cells and delay tumor growth. The VLPV-PSA vaccine will undergo further testing for the immunotherapy of prostate cancer. PMID:26319744

Immune Impact Induced by PROSTVAC (PSA-TRICOM), a Therapeutic Vaccine for Prostate Cancer

PubMed Central

Gulley, James L.; Madan, Ravi A.; Tsang, Kwong Y.; Jochems, Caroline; Marté, Jennifer L.; Farsaci, Benedetto; Tucker, Jo A.; Hodge, James W.; Liewehr, David J.; Steinberg, Seth M.; Heery, Christopher R.; Schlom, Jeffrey

2013-01-01

PSA-TRICOM (PROSTVAC) is a novel vector-based vaccine designed to generate a robust immune response against prostate-specific antigen (PSA)–expressing tumor cells. The purpose of this report is to present an overview of both published studies and new data in the evaluation of immune responses to the PSA-TRICOM vaccine platform, currently in phase III testing. Of 104 patients tested for T-cell responses, 57% (59/104) demonstrated a ≥ 2-fold increase in PSA-specific T cells 4 weeks after vaccine (median 5-fold increase) compared with pre-vaccine, and 68% (19/28) of patients tested mounted post-vaccine immune responses to tumor-associated antigens not present in the vaccine (antigen-spreading). The PSA-specific immune responses observed 28 days after vaccine (i.e., likely memory cells) are quantitatively similar to the levels of circulating T cells specific for influenza seen in the same patients. Measurements of systemic immune response to PSA may underestimate the true therapeutic immune response (as this does not account for cells that have trafficked to the tumor) and does not include antigen-spreading. Furthermore, while the entire PSA gene is the vaccine, only one epitope of PSA is evaluated in the T-cell responses. Since this therapeutic vaccine is directed at generating a cellular/Th1 immune response (T-cell costimulatory molecules and use of a viral vector), it is not surprising that < 0.6% of patients (2/349) tested have evidence of PSA antibody-induction following vaccine. This suggests that post-vaccine PSA kinetics were not affected by PSA antibodies. An ongoing phase III study will evaluate the systemic immune responses and correlation with clinical outcomes. PMID:24778277

Lifestyle and Clinical Health Behaviors and PSA Tests

ERIC Educational Resources Information Center

Norris, Cynthia; McFall, Stephanie

2006-01-01

This study assessed the association of lifestyle and clinical health behaviors with prostate specific antigen (PSA) tests. The study used cross-sectional data from the 2002 Behavioral Risk Factor Surveillance System (BRFSS). We used Stata 8.0 to take into account the complex sample design in analyses. Both lifestyle and clinical health behaviors…

Dendritic Cells Program Non-Immunogenic Prostate-Specific T Cell Responses Beginning at Early Stages of Prostate Tumorigenesis

PubMed Central

Mihalyo, Marianne A.; Hagymasi, Adam T.; Slaiby, Aaron M.; Nevius, Erin E.; Adler, Adam J.

2010-01-01

BACKGROUND Prostate cancer promotes the development of T cell tolerance towards prostatic antigens, potentially limiting the efficacy of prostate cancer vaccines targeting these antigens. Here, we sought to determine the stage of disease progression when T cell tolerance develops, as well as the role of steady state dendritic cells (DC) and CD4+CD25+ T regulatory cells (Tregs) in programming tolerance. METHODS The response of naïve HA-specific CD4+ T cells were analyzed following adoptive transfer into Pro-HA × TRAMP transgenic mice harboring variably-staged HA-expressing prostate tumors on two genetic backgrounds that display different patterns and kinetics of tumorigenesis. The role of DC and Tregs in programming HA-specific CD4 cell responses were assessed via depletion. RESULTS HA-specific CD4 cells underwent non-immunogenic responses at all stages of tumorigenesis in both genetic backgrounds. These responses were completely dependent on DC, but not appreciably influenced by Tregs. CONCLUSIONS These results suggest that tolerogenicity is an early and general property of prostate tumors. PMID:17221844

Using Serological Proteome Analysis to Identify Serum Anti-Nucleophosmin 1 Autoantibody as a Potential Biomarker in European-American and African-American Patients With Prostate Cancer.

PubMed

Dai, Liping; Li, Jitian; Xing, Mengtao; Sanchez, Tino W; Casiano, Carlos A; Zhang, Jian-Ying

2016-11-01

The prostate-specific antigen (PSA) testing has been widely implemented for the early detection and management of prostate cancer (PCa). However, the lack of specificity has led to overdiagnosis, resulting in many possibly unnecessary biopsies and overtreatment. Therefore, novel serological biomarkers with high sensitivity and specificity are of vital importance needed to complement PSA testing in the early diagnosis and effective management of PCa. This is particularly critical in the context of PCa health disparities, where early detection and management could help reduce the disproportionately high PCa mortality observed in African-American men. Previous studies have demonstrated that sera from patients with PCa contain autoantibodies that react with tumor-associated antigens (TAAs). The serological proteome analysis (SERPA) approach was used to identify tumor-associated antigens (TAAs) of PCa. In evaluation study, the level of anti-NPM1 antibody was examined in sera from test cohort, validation cohort, as well as European-American (EA) and African-American (AA) men with PCa by using immunoassay. Nucleophosmin 1 (NPM1) as a 33 kDa TAA in PCa was identified and characterized by SERPA approach. Anti-NPM1 antibody level in PCa was higher than in benign prostatic hyperplasia (BPH) patients and healthy individuals. Receiver operating characteristic (ROC) curve analysis showed similar high diagnostic value for PCa in the test cohort (area under the curve (AUC):0.860) and validation cohort (AUC: 0.822) to differentiate from normal individuals and BPH. Interestingly, AUC values were significantly higher for AA PCa patients. When considering concurrent serum measurements of anti-NPM1 antibody and PSA, 97.1% PCa patients at early stage were identified correctly, while 69.2% BPH patients who had elevated PSA levels were found to be anti-NPM1 negative. Additionally, anti-NPM1 antibody levels in PCa patients at early stage significantly increased after surgery treatment. This intriguing data suggested that NPM1 can elicit autoantibody response in PCa and might be a potential biomarker for the immunodiagnosis and prognosis of PCa, and for supplementing PSA testing in distinguishing PCa from BPH. Prostate 76:1375-1386, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An Analytical Study of Prostate-Specific Antigen Dynamics.

PubMed

Esteban, Ernesto P; Deliz, Giovanni; Rivera-Rodriguez, Jaileen; Laureano, Stephanie M

2016-01-01

The purpose of this research is to carry out a quantitative study of prostate-specific antigen dynamics for patients with prostatic diseases, such as benign prostatic hyperplasia (BPH) and localized prostate cancer (LPC). The proposed PSA mathematical model was implemented using clinical data of 218 Japanese patients with histological proven BPH and 147 Japanese patients with LPC (stages T2a and T2b). For prostatic diseases (BPH and LPC) a nonlinear equation was obtained and solved in a close form to predict PSA progression with patients' age. The general solution describes PSA dynamics for patients with both diseases LPC and BPH. Particular solutions allow studying PSA dynamics for patients with BPH or LPC. Analytical solutions have been obtained and solved in a close form to develop nomograms for a better understanding of PSA dynamics in patients with BPH and LPC. This study may be useful to improve the diagnostic and prognosis of prostatic diseases.

Potential surrogate endpoints for prostate cancer survival: analysis of a phase III randomized trial.

PubMed

Ray, Michael E; Bae, Kyounghwa; Hussain, Maha H A; Hanks, Gerald E; Shipley, William U; Sandler, Howard M

2009-02-18

The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial. Patients (n = 1554 randomly assigned and 1521 evaluable for this analysis) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent androgen deprivation therapy with external beam radiation therapy and then randomly assigned to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm). Data from landmark analyses at 3 and 5 years for general clinical treatment failure (defined as documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy) and/or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice's four criteria. All statistical tests were two-sided. At 3 years, 1364 patients were alive and contributed data for analysis. Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years. At 5 years, 1178 patients were alive and contributed data for analysis. Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years (P = .08), both endpoints were consistent with Prentice's remaining criteria. Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years. These endpoints, however, must be validated in other datasets.

Opportunistic testing versus organized prostate-specific antigen screening: outcome after 18 years in the Göteborg randomized population-based prostate cancer screening trial.

PubMed

Arnsrud Godtman, Rebecka; Holmberg, Erik; Lilja, Hans; Stranne, Johan; Hugosson, Jonas

2015-09-01

It has been shown that organized screening decreases prostate cancer (PC) mortality, but the effect of opportunistic screening is largely unknown. To compare the ability to reduce PC mortality and the risk of overdiagnosis between organized and opportunistic screening. The Göteborg screening study invited 10 000 randomly selected men for prostate-specific antigen (PSA) testing every 2 yr since 1995, with a prostate biopsy recommended for men with PSA ≥2.5 ng/ml. The control group of 10 000 men not invited has been exposed to a previously reported increased rate of opportunistic PSA testing. Both groups were followed until December 31, 2012. Observed cumulative PC incidence and mortality rates in both groups were calculated using the actuarial method. Using historical data from 1990-1994 (pre-PSA era), we calculated expected PC incidence and mortality rates in the absence of any PSA testing. The number needed to invite (NNI) and the number needed to diagnose (NND) were calculated by comparing the expected versus observed incidence and mortality rates. At 18 yr, 1396 men were diagnosed with PC and 79 men died of PC in the screening group, compared to 962 and 122, respectively, in the control group. In the screening group, the observed cumulative PC incidence/mortality was 16%/0.98% compared to expected values of 6.8%/1.7%. The corresponding values for the control group were 11%/1.5% and 6.9%/1.7%. Organized screening was associated with an absolute PC-specific mortality reduction of 0.72% (95% confidence interval [CI] 0.50-0.94%) and relative risk reduction of 42% (95% CI 28-54%). There was an absolute reduction in PC deaths of 0.20% (95% CI -0.06% to 0.47%) and a relative risk reduction of 12% (95% CI -5 to 26%) associated with opportunistic PSA testing. NNI and NND were 139 (95% CI 107-200) and 13 for organized biennial screening and 493 (95% CI 213- -1563) and 23 for opportunistic screening. The extent of opportunistic screening could not be measured; incidence trends were used as a proxy. Organized screening reduces PC mortality but is associated with overdiagnosis. Opportunistic PSA testing had little if any effect on PC mortality and resulted in more overdiagnosis, with almost twice the number of men needed to be diagnosed to save one man from dying from PC compared to men offered an organized biennial screening program. Prostate-specific antigen (PSA) screening within the framework of an organized program seems more effective than unorganized screening. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

An ecologic study of prostate-specific antigen screening and prostate cancer mortality in nine geographic areas of the United States.

PubMed

Shaw, Pamela A; Etzioni, Ruth; Zeliadt, Steven B; Mariotto, Angela; Karnofski, Kent; Penson, David F; Weiss, Noel S; Feuer, Eric J

2004-12-01

Ecologic studies of cancer screening examine cancer mortality rates in relation to use of population screening. These studies can be confounded by treatment patterns or influenced by choice of outcome and time horizon. Interpretation can be complicated by uncertainty about when mortality differences might be expected. The authors examined these issues in an ecologic analysis of prostate-specific antigen (PSA) screening and prostate cancer mortality across nine cancer registries in the United States. Results suggested a weak trend for areas with greater PSA screening rates to have greater declines in prostate cancer mortality; however, the magnitude of this trend varied considerably with the time horizon and outcome measure. A computer model was used to determine whether divergence of mortality declines would be expected under an assumption of a clinically significant survival benefit due to screening. Given a mean lead time of 5 years, the model projected that differences in mortality between high- and low-use areas should be apparent by 1999 in the absence of other factors affecting mortality. The authors concluded that modest differences in PSA screening rates across areas, together with additional sources of variation, could have produced a negative ecologic result. Ecologic analyses of the effectiveness of PSA testing should be interpreted with caution.

Prostate Cancer Screening In Men Ages 75 And Older Fell By 8 Percentage Points After Task Force Recommendation

PubMed Central

Howard, David H.; Tangka, Florence K.; Guy, Gery P.; Ekwueme, Donatus U.; Lipscomb, Joseph

2016-01-01

In 2008 the US Preventive Services Task Force recommended against screening men ages 75 and older for prostate cancer. Using Medicare Current Beneficiary Survey Access to Care files and linked claims, we compared trends in prostate-specific antigen (PSA) testing rates between men ages 75 and older and men ages 65–74. We estimate that the revised recommendation led to a 7.9-percentage-point decline in annual PSA testing rates over two years among men ages 75 and older. Although 42 percent of men in this age group continue to receive PSA tests, our results highlight the potential of guidelines with negative recommendations to reduce the use of low-value medical care. PMID:23459740

Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice.

PubMed

Lyons, Scott K; Lim, Ed; Clermont, Anne O; Dusich, Joan; Zhu, Lingyun; Campbell, Kenneth D; Coffee, Richard J; Grass, David S; Hunter, John; Purchio, Tony; Jenkins, Darlene

2006-05-01

Several transgenic mouse models of prostate cancer have been developed recently that are able to recapitulate many key biological features of the human condition. It would, therefore, be desirable to employ these models to test the efficacy of new therapeutics before clinical trial; however, the variable onset and non-visible nature of prostate tumor development limit their use for such applications. We now report the generation of a transgenic reporter mouse that should obviate these limitations by enabling noninvasive in vivo bioluminescence imaging of normal and spontaneously transformed prostate tissue in the mouse. We used an 11-kb fragment of the human prostate-specific antigen (PSA) promoter to achieve specific and robust expression of firefly luciferase in the prostate glands of transgenic mice. Ex vivo bioluminescence imaging and in situ hybridization analysis confirmed that luciferase expression was restricted to the epithelium in all four lobes of the prostate. We also show that PSA-Luc mice exhibit decreased but readily detectable levels of in vivo bioluminescence over extended time periods following androgen ablation. These results suggest that this reporter should enable in vivo imaging of both androgen-dependent and androgen-independent prostate tumor models. As proof-of-principle, we show that we could noninvasively image SV40 T antigen-induced prostate tumorigenesis in mice with PSA-Luc. Furthermore, we show that our noninvasive imaging strategy can be successfully used to image tumor response to androgen ablation in transgenic mice and, as a result, that we can rapidly identify individual animals capable of sustaining tumor growth in the absence of androgen.

3D-Printed Supercapacitor-Powered Electrochemiluminescent Protein Immunoarray

PubMed Central

Kadimisetty, Karteek; Mosa, Islam M.; Malla, Spundana; Satterwhite-Warden, Jennifer E.; Kuhns, Tyler; Faria, Ronaldo C.; Lee, Norman H.; Rusling, James F.

2015-01-01

Herein we report a low cost, sensitive, supercapacitor-powered electrochemiluminescent (ECL) protein immunoarray fabricated by an inexpensive 3-dimensional (3D) printer. The immunosensor detects three cancer biomarker proteins in serum within 35 min. The 3D-printed device employs hand screen printed carbon sensors with gravity flow for sample/reagent delivery and washing. Prostate cancer biomarker proteins, prostate specific antigen (PSA), prostate specific membrane antigen (PSMA) and platelet factor-4 (PF-4) in serum were captured on the antibody-coated carbon sensors followed by delivery of detection-antibody-coated Ru(bpy)32+ (RuBPY)-doped silica nanoparticles in a sandwich immunoassay. ECL light was initiated from RuBPY in the silica nanoparticles by electrochemical oxidation with tripropylamine (TPrA) co-reactant using supercapacitor power and ECL was captured with a CCD camera. The supercapacitor was rapidly photo-recharged between assays using an inexpensive solar cell. Detection limits were 300–500 fg mL−1 for the 3 proteins in undiluted calf serum. Assays of 6 prostate cancer patient serum samples gave good correlation with conventional single protein ELISAs. This technology could provide sensitive onsite cancer diagnostic tests in resource-limited settings with the need for only moderate-level training. PMID:26406460

STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors

PubMed Central

Hubert, Rene S.; Vivanco, Igor; Chen, Emily; Rastegar, Shiva; Leong, Kahan; Mitchell, Steve C.; Madraswala, Rashida; Zhou, Yanhong; Kuo, James; Raitano, Arthur B.; Jakobovits, Aya; Saffran, Douglas C.; Afar, Daniel E. H.

1999-01-01

In search of novel genes expressed in metastatic prostate cancer, we subtracted cDNA isolated from benign prostatic hypertrophic tissue from cDNA isolated from a prostate cancer xenograft model that mimics advanced disease. One novel gene that is highly expressed in advanced prostate cancer encodes a 339-amino acid protein with six potential membrane-spanning regions flanked by hydrophilic amino- and carboxyl-terminal domains. This structure suggests a potential function as a channel or transporter protein. This gene, named STEAP for six-transmembrane epithelial antigen of the prostate, is expressed predominantly in human prostate tissue and is up-regulated in multiple cancer cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma. Immunohistochemical analysis of clinical specimens demonstrates significant STEAP expression at the cell–cell junctions of the secretory epithelium of prostate and prostate cancer cells. Little to no staining was detected at the plasma membranes of normal, nonprostate human tissues, except for bladder tissue, which expressed low levels of STEAP at the cell membrane. Protein analysis located STEAP at the cell surface of prostate-cancer cell lines. Our results support STEAP as a cell-surface tumor-antigen target for prostate cancer therapy and diagnostic imaging. PMID:10588738

The dual role of paramagnetic particles for integrated lysis and measurement in a rapid immunoassay for intracellular proteins.

PubMed

Sharif, Elham; Kiely, Janice; Wraith, Patrick; Luxton, Richard

2013-05-01

A novel, integrated lysis and immunoassay methodology and system for intracellular protein measurement are described. The method uses paramagnetic particles both as a lysis agent and assay label resulting in a rapid test requiring minimal operator intervention, the test being homogeneous and completed in less than 10 min. A design study highlights the critical features of the magnetic detection system used to quantify the paramagnetic particles and a novel frequency-locked loop-based magnetometer is presented. A study of paramagnetic particle enhanced lysis demonstrates that the technique is more than twice as efficient at releasing intracellular protein as ultrasonic lysis alone. Results are presented for measurements of intracellular prostate specific antigen in an LNCAP cell line. This model was selected to demonstrate the rapidity and efficiency of intracellular protein quantification. It was shown that, on average, LNCAP cells contained 0.43 fg of prostate specific antigen. This system promises an attractive solution for applications that require a rapid determination of intracellular proteins.

Pittsburgh Tuskegee Prostate Training Program

DTIC Science & Technology

2014-05-01

11 . SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT X Approved for public release; distribution...Prostate Specific Membrane Antigen ( Psma ) and Folate Levels on Gene Expression and Proliferation in Prostatic Cancer Cells Denise O’Keefe Table...

PSA Velocity Does Not Improve Prostate Cancer Detection

Cancer.gov

A rapid increase in prostate-specific antigen (PSA) levels is not grounds for automatically recommending a prostate biopsy, according to a study published online February 24, 2011, in the Journal of the National Cancer Institute.

Plasma cell-free DNA and its DNA integrity as biomarker to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate-specific antigen.

PubMed

Feng, Jiang; Gang, Feng; Li, Xiao; Jin, Tang; Houbao, Huang; Yu, Cao; Guorong, Li

2013-08-01

To investigate whether plasma cell-free DNA (cfDNA) or its integrity could differentiate prostate cancer from benign prostate hyperplasia (BPH) in patients with serum prostate-specific antigen (PSA) ≥ 4 ng/ml. Ninety-six patients with prostate cancer and 112 patients with BPH were enrolled. cfDNA levels in plasma before prostate biopsy were quantified by real-time PCR amplification of ALU gene (product size of 115 bp), and quantitative ratio of ALU (247 bp) to ALU (115 bp) reflected the integrity of cfDNA. In patients with serum PSA ≥ 4 ng/ml, there were significant differences in plasma cfDNA or its integrity between the patients with prostate cancer (19.74 ± 4.43, 0.34 ± 0.05) and patients with BPH (7.36 ± 1.58, 0.19 ± 0.03; P < 0.001, P < 0.001). Prostate cancer could be differentiated with a sensitivity of 73.2 % and a specificity of 72.7 % by cfDNA (AUC = 0.864). The integrity of cfDNA had a sensitivity of 81.7 % and a specificity of 78.8 % for the distinguishing prostate cancer from BPH (AUC = 0.910). cfDNA and its integrity could be applied to differentiate prostate cancer from BPH in patients with serum PSA ≥ 4 ng/ml.

Advances in prostate-specific membrane antigen PET of prostate cancer.

PubMed

Bouchelouche, Kirsten; Choyke, Peter L

2018-05-01

In recent years, a large number of reports have been published on prostate-specific membrane antigen (PSMA)/PET in prostate cancer (PCa). This review highlights advances in PSMA PET in PCa during the past year. PSMA PET/computed tomography (CT) is useful in detection of biochemical recurrence, especially at low prostate-specific antigen (PSA) values. The detection rate of PSMA PET is influenced by PSA level. For primary PCa, PSMA PET/CT shows promise for tumour localization in the prostate, especially in combination with multiparametric MRI (mpMRI). For primary staging, PSMA PET/CT can be used in intermediate and high-risk PCa. Intraoperative PSMA radioligand guidance seems promising for detection of malignant lymph nodes. While the use of PSMA PET/MRI in primary localized disease is limited to high and intermediate-risk patients and localized staging, in the recurrence setting, PET/MRI can be particularly helpful when the lesions are subtle. PSMA PET/CT is superior to choline PET/CT and other conventional imaging modalities. Molecular imaging with PSMA PET continues to pave the way for personalized medicine in PCa.However, large prospective clinical studies are still needed to fully evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa.

Point/Counterpoint: early detection of prostate cancer: do the benefits outweigh the consequences?

PubMed

Carroll, Peter R; Vickers, Andrew J

2014-05-01

Few clinical issues have polarized the oncology community as much as screening for prostate cancer, with advocates of prostate-specific antigen (PSA) testing vocal on one side and skeptics just as vocal on the other. At the NCCN 19th Annual Conference, Dr. Peter R. Carroll and Dr. Andrew J. Vickers tackled the controversy surrounding early detection of prostate cancer, focusing attention on the randomized trial results at the heart of the matter; over-detection (the Achilles' heel of screening); and the rationale behind the new, streamlined 2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection, which emphasize selective early detection and treatment and are tightly aligned with the NCCN Guidelines for Prostate Cancer. Copyright © 2014 by the National Comprehensive Cancer Network.

Trichosanthes kirilowii Exerts Androgenic Activity via Regulation of PSA and KLK2 in 22Rv1 Prostate Cancer Cells

PubMed Central

Jeong, Soo-Jin; Choi, Ji-Yoon; Dong, Mi-Sook; Seo, Chang-Seob; Shin, Hyeun-Kyoo

2017-01-01

Background: The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. Objective: We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. Materials and Methods: Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system. Results: TK, AS, SO, and XS enhanced the proliferation of 22Rv1 cells without having cytotoxic effects. All tested herbal extracts increased androgen receptor (AR)-induced transcriptional activity in the absence or presence of dihydrotestosterone (DHT). In an AR-binding assay, TK, but not AS, SO, or XS, produced a significant inhibition of AR binding activity, indicating it has androgenic activity. Additionally, TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen (PSA) and kallikrein 2 (KLK2) compared with untreated control. Conclusion: Taken together, TK-enhanced AR-mediated transcriptional activity might be an attractive candidate drug for treating androgen-related diseases. SUMMARY Trichosantheskirilowii (TK), Asarumsieboldii (AS), Sanguisorbaofficinalis (SO), and Xanthium strumarium (XS) enhanced the proliferation of 22Rv1 cells without having cytotoxic effects.TK, AS, SO, and XS increased androgen receptor (AR)-induced transcriptional activity.TK, but not AS, SO, or XS, produced a significant inhibition against AR-binding activity.TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen and kallikrein 2. Abbreviations used: BPH: benign prostatic hyperplasia; AR: androgen receptor; DHT: dihydrotestosterone; PSA: prostate-specific antigen; TK: Trichosanthes kirilowii; AS: Asarum sieboldii; SO: Sanguisorba officinalis; XS: Xanthium strumarium; ATCC: American Type Culture Collection; FBS: fetal bovine serum; PBS: phosphate-buffered saline; SD: standard deviation; ARE: androgenresponsive element; KLK: kallikrein PMID:28216900

Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial

PubMed Central

Bergdahl, Anna Grenabo; Wilderäng, Ulrica; Aus, Gunnar; Carlsson, Sigrid; Damber, Jan-Erik; Frånlund, Maria; Geterud, Kjell; Khatami, Ali; Socratous, Andreas; Stranne, Johan; Hellström, Mikael; Hugosson, Jonas

2016-01-01

Background Magnetic resonance imaging (MRI) and targeted biopsies (TB) have shown potential to more accurately detect significant prostate cancer (PC) compared to prostate-specific antigen (PSA) and systematic biopsies (SB). Objective To compare sequential screening (PSA + MRI) with conventional PSA screening. Design, Setting and Participants Of 384 attendees in the 10th screening round of the Göteborg randomised screening trial, 124 men, median age 69.5, had a PSA of ≥1.8 ng/ml and underwent a prebiopsy MRI. Men with suspicious lesions on MRI and/or PSA ≥3.0 ng/ml were referred for biopsy. SB was performed blinded to MRI results and TB was performed in men with tumour-suspicious findings on MRI. Three screening strategies were compared (PSA≥3.0+SB; PSA≥3.0+MRI+TB and PSA≥1.8+MRI+TB). Outcome Measurements and Statistical Analysis Cancer detection rates, sensitivity and specificity were calculated per screening strategy and compared using McNemar´s test. Results and Limitations In total, 28 PC were detected, of which 20 were diagnosed in biopsy-naïve men. Both PSA≥3.0+MRI and PSA≥1.8+MRI significantly increased specificity compared with PSA≥3.0+SB (0.92 and 0.79 vs. 0.52; p<0.002 for both), while sensitivity was significantly higher for PSA≥1.8+MRI compared with PSA>=3.0+MRI (0.73 vs. 0.46, p=0.008). The detection rate of significant cancer was higher with PSA≥1.8+MRI compared to PSA≥3.0+SB (5.9 vs. 4.0%), while the detection rate of insignificant cancer was lowered by PSA≥3.0+MRI (0.3 vs. 1.2%). The primary limitation of this study is the small sample of men. Conclusion A screening strategy with a lowered PSA cut-off followed by TB in MRI-positive men seems to increase the detection of significant cancers while improving specificity. If replicated, these results may contribute to a paradigm shift in future screening. Patient Summary Major concerns in prostate-specific antigen screening are overdiagnosis and underdiagnosis. We evaluated whether prostate magnetic resonance imaging could improve the balance of benefits to harm in prostate cancer screening, and we found promising potential of using magnetic resonance imaging in addition to prostate-specific antigen. PMID:26724840

PSMA-Specific Theranostic Nanoplex for Combination of TRAIL Gene and 5-FC Prodrug Therapy of Prostate Cancer

PubMed Central

Chen, Zhihang; Penet, Marie-France; Krishnamachary, Balaji; Banerjee, Sangeeta R.; Pomper, Martin G.; Bhujwalla, Zaver M.

2015-01-01

Metastatic prostate cancer causes significant morbidity and mortality and there is a critical unmet need for effective treatments. We have developed a theranostic nanoplex platform for combined imaging and therapy of prostate cancer. Our prostate-specific membrane antigen (PSMA) targeted nanoplex is designed to deliver plasmid DNA encoding tumor necrosis factor related apoptosis-inducing ligand (TRAIL), together with bacterial cytosine deaminase (bCD) as a prodrug enzyme. Nanoplex specificity was tested using two variants of human PC3 prostate cancer cells in culture and in tumor xenografts, one with high PSMA expression and the other with negligible expression levels. The expression of EGFP-TRAIL was demonstrated by fluorescence optical imaging and real-time PCR. Noninvasive 19F MR spectroscopy detected the conversion of the nontoxic prodrug 5-fluorocytosine (5-FC) to cytotoxic 5-fluorouracil (5-FU) by bCD. The combination strategy of TRAIL gene and 5-FC/bCD therapy showed significant inhibition of the growth of prostate cancer cells and tumors. These data demonstrate that the PSMA-specific theranostic nanoplex can deliver gene therapy and prodrug enzyme therapy concurrently for precision medicine in metastatic prostate cancer. PMID:26706476

Promoter methylation of MCAM, ERα and ERβ in serum of early stage prostate cancer patients.

PubMed

Brait, Mariana; Banerjee, Mithu; Maldonado, Leonel; Ooki, Akira; Loyo, Myriam; Guida, Elisa; Izumchenko, Evgeny; Mangold, Leslie; Humphreys, Elizabeth; Rosenbaum, Eli; Partin, Alan; Sidransky, David; Hoque, Mohammad Obaidul

2017-02-28

Prostate cancer (PC) is the second most common cancer among men worldwide. Currently, the most common non-invasive approach for screening and risk assessment of PC is measuring the level of serum prostate-specific antigen (PSA). However, the sensitivity of PSA is 42.8 % and specificity is 41.1%. As a result, the serum PSA test leads to numerous unneeded biopsies. Therefore, a rigorous search for biomarkers for early detection of PC is ongoing. In this study, we aim to assess a panel of epigenetic markers in an intend to develop an early detection test for PC. The sensitivity and specificity of hypermethylation of MCAM was 66% and 73% respectively which is an improvement from the sensitivity and specificity of PSA. Considering a combination marker panel of MCAM, ERα and ERβ increased the sensitivity to 75% and the specificity became 70% for the minimally invasive early detection test of PC. Sixteen primary matched tumor and serum were analyzed by quantitative methylation specific PCR (QMSP) to determine analytical and clinical sensitivity of the genes tested (SSBP2, MCAM, ERα, ERβ, APC, CCND2, MGMT, GSTP1, p16 and RARβ2). Additionally, serum samples from eighty four cases of PC, thirty controls and seven cases diagnosed as high grade Prostatic Intraepithelial Neoplasia (HGPIN) were analyzed. Promoter methylation of MCAM, ERα and ERβ have a potential to be utilized as biomarker for the early detection of prostate PC as their sensitivity and specificity seem to be better than serum PSA in our cohort of samples. After robust validation in a larger prospective cohort, our findings may reduce the numbers of unwarranted prostate biopsies.

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

PubMed

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

2017-10-01

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

Exploring the complexities of prostate cancer screening with a view to supporting informed consent.

PubMed

Laws, Tom A

2004-10-01

Men request to be screened for prostate cancer because they believe they are exhibiting responsible health promotion behaviour and there are definite benefits from the early detection of the disease. This belief about the benefits is in contrast to several national guidelines recommending that screening for prostate cancer not be done. Despite the guidelines men continue to request to be screened and doctors continue to supply screening tests to asymptomatic males. The lack of an appropriate screening test has been a key factor in supporting recommendations not to screen. However, recent studies show improved accuracy in the use of serum prostate specific antigens (PSA) as a screening tool. This implies that a revision of the guidelines might soon be appropriate. It is important that nurses and other health professionals are kept abreast of developments in prostate screening to assist men with their screening options to ensure their fully informed consent.

The Role of Positron Emission Tomography With (68)Gallium (Ga)-Labeled Prostate-specific Membrane Antigen (PSMA) in the Management of Patients With Organ-confined and Locally Advanced Prostate Cancer Prior to Radical Treatment and After Radical Prostatectomy.

PubMed

Rai, Bhavan Prasad; Baum, Richard Paul; Patel, Amit; Hughes, Robert; Alonzi, Roberto; Lane, Tim; Adshead, Jim; Vasdev, Nikhil

2016-09-01

The role of positron emission tomography (PET) with (68)Gallium (Ga)-labeled prostate-specific membrane antigen (PSMA) imaging for prostate cancer is gaining prominence. Current imaging strategies, despite having progressed significantly, have limitations, in particular their ability to diagnose metastatic lymph node involvement. Preliminary results of PET with (68)Ga-labeled PSMA have shown encouraging results, particularly in the recurrent prostate cancer setting. Furthermore, the ability of PET with (68)Ga-labeled PSMA of playing a dual diagnostic and therapeutic setting (theranostics) is currently being investigated as well. PET with (68)Ga-labeled PSMA certainly has a role to play in bridging some of the voids in contemporary prostate cancer imaging tools. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-01-01

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

A Glu-urea-Lys Ligand-conjugated Lipid Nanoparticle/siRNA System Inhibits Androgen Receptor Expression In Vivo

PubMed Central

Lee, Justin B; Zhang, Kaixin; Tam, Yuen Yi C; Quick, Joslyn; Tam, Ying K; Lin, Paulo JC; Chen, Sam; Liu, Yan; Nair, Jayaprakash K; Zlatev, Ivan; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Rennie, Paul S; Cullis, Pieter R

2016-01-01

The androgen receptor plays a critical role in the progression of prostate cancer. Here, we describe targeting the prostate-specific membrane antigen using a lipid nanoparticle formulation containing small interfering RNA designed to silence expression of the messenger RNA encoding the androgen receptor. Specifically, a Glu-urea-Lys PSMA-targeting ligand was incorporated into the lipid nanoparticle system formulated with a long alkyl chain polyethylene glycol-lipid to enhance accumulation at tumor sites and facilitate intracellular uptake into tumor cells following systemic administration. Through these features, and by using a structurally refined cationic lipid and an optimized small interfering RNA payload, a lipid nanoparticle system with improved potency and significant therapeutic potential against prostate cancer and potentially other solid tumors was developed. Decreases in serum prostate-specific antigen, tumor cellular proliferation, and androgen receptor levels were observed in a mouse xenograft model following intravenous injection. These results support the potential clinical utility of a prostate-specific membrane antigen–targeted lipid nanoparticle system to silence the androgen receptor in advanced prostate cancer. PMID:28131285

Prostate cancer testing: behaviour, motivation and attitudes among Western Australian men.

PubMed

Slevin, T J; Donnelly, N; Clarkson, J P; English, D R; Ward, J E

1999-08-16

To estimate the proportion of Western Australian men aged 40-80 years who had been tested for prostate cancer, their experiences of screening and perception of its benefit. Cross-sectional survey (random telephone survey) of Western Australian men conducted in February 1998. 400 men aged 40-80 years from 670 eligible households (60% response rate from contactable households with eligible men). Proportion of respondents tested for prostate cancer (by prostate-specific antigen [PSA] test or digital rectal examination); reasons for having been tested; information provided by the doctor before testing; reasons given for and beliefs about the benefits of testing. Of 391 asymptomatic men, 220 (56%) recalled having been tested for prostate cancer and 167 (43%) had had a PSA test. Of those tested, 86% had their first test in the previous five years. The two most common reasons for testing were media publicity and general practitioner recommendation. Thirty-eight per cent of men tested during the previous five years reported that the doctor did not discuss the "pros and cons" of the test; 39% reported a discussion of less than five minutes' duration; 17% were given printed information before undergoing the test for the first time. Half were "very convinced" of the benefits of testing for prostate cancer. Men are being tested for prostate cancer with minimal pretest counselling or written information.

Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer

PubMed Central

Lee, John K.; Bangayan, Nathanael J.; Chai, Timothy; Smith, Bryan A.; Pariva, Tiffany E.; Yun, Sangwon; Vashisht, Ajay; Zhang, Qingfu; Park, Jung Wook; Corey, Eva; Huang, Jiaoti; Wohlschlegel, James; Witte, Owen N.

2018-01-01

Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer. Here, we show that PrAd and NEPC can be broadly discriminated by cell-surface profiles based on the analysis of prostate cancer gene expression datasets. To overcome a dependence on predictions of human cell-surface genes and an assumed correlation between mRNA levels and protein expression, we integrated transcriptomic and cell-surface proteomic data generated from a panel of prostate cancer cell lines to nominate cell-surface markers associated with these cancer subtypes. FXYD3 and CEACAM5 were validated as cell-surface antigens enriched in PrAd and NEPC, respectively. Given the lack of effective treatments for NEPC, CEACAM5 appeared to be a promising target for cell-based immunotherapy. As a proof of concept, engineered chimeric antigen receptor T cells targeting CEACAM5 induced antigen-specific cytotoxicity in NEPC cell lines. Our findings demonstrate that the surfaceomes of PrAd and NEPC reflect unique cancer differentiation states and broadly represent vulnerabilities amenable to therapeutic targeting. PMID:29686080

Psychological impact of serial prostate-specific antigen tests in Japanese men waiting for prostate biopsy.

PubMed

Kobayashi, Minoru; Nukui, Akinori; Kamai, Takao

2017-02-01

It is common to repeat prostate-specific antigen (PSA) measurements for men with intermediate PSA elevation before prostate biopsy. In this scenario, men with persistently elevated PSA values may have considerable psychological distress. We attempted to determine whether elevated PSA values have psychological effects on these men in association with the timing of measurement, PSA kinetics, and biopsy results. In order to investigate the initial and late effects of PSA tests on psychological distress during serial measurements, two groups of men with screen-positive results (PSA ≥3 ng/ml) were studied-205 men whose first questionnaires regarding anxiety and depression were taken at initial screening (group A), and 103 men whose questionnaires were taken at repeated measurement for prior PSA elevation (group B). The level of distress was generally low. There were no significant differences in distress between the two groups, suggesting a constant psychological effect by elevated PSA values over a long period of time. The distress of men in group A increased significantly as PSA levels rose and decreased when they fell to normal range. On the other hand, the distress of men in group B did not change regardless of PSA kinetics, indicating that their psychological condition seemed susceptible to subtle PSA change only in the initial phase of measurements. Unexpectedly, men with benign results showed insignificant but higher distress after prostate biopsy. Although a small fraction of men have psychological distress caused by changes in PSA levels, the benefits, risks (psychological and physical), and limitations of PSA tests must be adequately explained to the patients before entering the screening program.

Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial.

PubMed

Johnston, Thomas J; Shaw, Greg L; Lamb, Alastair D; Parashar, Deepak; Greenberg, David; Xiong, Tengbin; Edwards, Alison L; Gnanapragasam, Vincent; Holding, Peter; Herbert, Phillipa; Davis, Michael; Mizielinsk, Elizabeth; Lane, J Athene; Oxley, Jon; Robinson, Mary; Mason, Malcolm; Staffurth, John; Bollina, Prasad; Catto, James; Doble, Andrew; Doherty, Alan; Gillatt, David; Kockelbergh, Roger; Kynaston, Howard; Prescott, Steve; Paul, Alan; Powell, Philip; Rosario, Derek; Rowe, Edward; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E

2017-03-01

Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17μg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Long-term response to combination therapy with estramustine and somatostatin analogue in a patient with androgen ablation-refractory prostate cancer.

PubMed

Cerulli, Costantino; Sciarra, Alessandro; Salvatori, Gianfilippo; Di Silverio, Franco

2004-12-01

We report on a patient with androgen ablation-refractory prostate adenocarcinoma who had an objective response for longer than 24 months using a combination of estramustine and lanreotide. At baseline from our combination therapy, his prostate-specific antigen level was 21.30 ng/mL and serum chromogranin A level was 816 ng/mL. The patient discontinued complete androgen deprivation therapy and underwent combination therapy with oral estramustine 420 mg/day plus lanreotide acetate 73.9 mg intramuscularly every 4 weeks. After 33 months of follow-up, the patient was alive without clinical disease progression, and his prostate-specific antigen and chromogranin A level was 0.10 and 12 ng/mL, respectively.

Theranostics of prostate cancer: from molecular imaging to precision molecular radiotherapy targeting the prostate specific membrane antigen.

PubMed

Kulkarni, Harshad R; Singh, Aviral; Langbein, Thomas; Schuchardt, Christiane; Mueller, Dirk; Zhang, Jingjing; Lehmann, Coline; Baum, Richard P

2018-06-01

Alterations at the molecular level are a hallmark of cancer. Prostate cancer is associated with the overexpression of prostate-specific membrane antigen (PSMA) in a majority of cases, predominantly in advanced tumors, increasing with the grade or Gleason's score. PSMA can be selectively targeted using radiolabeled PSMA ligands. These small molecules binding the PSMA can be radiolabeled with γ-emitters like 99m Tc and 111 In or positron emitters like 68 Ga and 18 F for diagnosis as well as with their theranostic pairs such as 177 Lu (β-emitter) or 225 Ac (α-emitter) for therapy. This review summarizes the theranostic role of PSMA ligands for molecular imaging and targeted molecular radiotherapy, moving towards precision oncology.

Prostate-specific membrane antigen for prostate cancer theranostics: from imaging to targeted therapy.

PubMed

Arsenault, Frédéric; Beauregard, Jean-Mathieu; Pouliot, Frédéric

2018-06-22

In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i.e. theranostic) PSMA tracers. Development in small PSMA-targeted molecules labeled with gallium-68 and fluorine-18 show promising results for primary staging and detection of disease at biochemical recurrence using PET/computed tomography (PET/CT). Studies show a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and bone scan) or choline PET tracers, especially for restaging after prostate-specific antigen failure following loco-regional therapy. In addition, some PSMA tracers can be labeled with beta-minus and alpha particle emitters, yielding encouraging response rates and low toxicity, and potentially offering a new line of targeted therapy for metastatic castration-resistant PCa. PSMA-targeted tracers have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given their specific biodistribution toward PCa tissue, PSMA RLT now offers new therapeutic possibilities to target metastatic PCa. Prospective multicenter randomized studies investigating the clinical impact management impacts of PSMA-targeted molecules are urgently needed.

The prognostic significance of prostate specific antigen in metastatic hormone-resistant prostate cancer.

PubMed Central

Fosså, S. D.; Waehre, H.; Paus, E.

1992-01-01

Twenty-seven of 152 patients (18%) with progressing hormone resistant prostate cancer had normal serum levels of prostate specific antigen (PSA less than or equal to 10 micrograms l-1), when referred for secondary treatment. PSA was significantly correlated with the extent of skeletal metastases (R: 0.35) and the levels of hemoglobin (R: -0.19) and serum alkaline phosphatase (R: 0.30). In a multivariate Cox regression analysis the survival of the 152 patients was not correlated with the PSA level but with the patients performance status, the level of hemoglobin, and the time between primary hormone treatment and relapse. The lack of serum PSA to predict survival may be explained by a heterogenous composition of hormone resistant prostate cancer as regards differentiated and/or PSA producing vs undifferentiated and/or PSA non-producing cells. PMID:1379059

The Use of Biomarkers in Prostate Cancer Screening and Treatment

PubMed Central

Alford, Ashley V.; Brito, Joseph M.; Yadav, Kamlesh K.; Yadav, Shalini S.; Tewari, Ashutosh K.; Renzulli, Joseph

2017-01-01

Prostate cancer screening and diagnosis has been guided by prostate-specific antigen levels for the past 25 years, but with the most recent US Preventive Services Task Force screening recommendations, as well as concerns regarding overdiagnosis and overtreatment, a new wave of prostate cancer biomarkers has recently emerged. These assays allow the testing of urine, serum, or prostate tissue for molecular signs of prostate cancer, and provide information regarding both diagnosis and prognosis. In this review, we discuss 12 commercially available biomarker assays approved for the diagnosis and treatment of prostate cancer. The results of clinical validation studies and clinical decision-making studies are presented. This information is designed to assist urologists in making clinical decisions with respect to ordering and interpreting these tests for different patients. There are numerous fluid and biopsy-based genomic tests available for prostate cancer patients that provide the physician and patient with different information about risk of future disease and treatment outcomes. It is important that providers be able to recommend the appropriate test for each individual patient; this decision is based on tissue availability and prognostic information desired. Future studies will continue to emphasize the important role of genomic biomarkers in making individualized treatment decisions for prostate cancer patients. PMID:29472826

Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy.

PubMed

Ng, Sweet Ping; Tran, Thu; Moloney, Philip; Sale, Charlotte; Mathlum, Maitham; Ong, Grace; Lynch, Rod

2015-12-01

Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.

Incidental detection of prostate-specific antigen-negative metastatic prostate cancer initially presented with solitary pulmonary nodule on fluorodeoxyglucose positron emission tomography/computed tomography

PubMed Central

Erdogan, Ezgi Basak; Buyukpinarbasili, Nur; Ziyade, Sedat; Akman, Tolga; Turk, Haci Mehmet; Aydin, Mehmet

2015-01-01

A 71-year-old male patient with solitary pulmonary nodule underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showing slightly increased FDG uptake in this nodule. In addition, PET/CT detected hypermetabolic sclerotic bone lesions in the right second rib and 7th thoracic vertebrae, which were interpreted as possible metastases, and mildly increased FDG uptake in the prostate gland highly suspicious of malignancy. The patient's prostate-specific antigen (PSA) level was within normal range (3.8 ng/dL). The histopathological examination of the lung nodule and right second rib lesion proved metastases from prostate cancer, then the prostate biopsy-confirmed prostate adenocarcinoma. The unique feature of this case is to emphasize the importance of performing PET/CT for solitary pulmonary nodule in detecting PSA-negative metastatic prostate cancer. This case indicated that it should be kept in mind that, even if the PSA is negative, a lung metastasis of prostate cancer may be an underlying cause in patients evaluated for solitary pulmonary nodule by FDG PET/CT. PMID:26170575

Being screened for prostate cancer: a simple blood test or a commitment to treatment?

PubMed

Oliffe, John

2006-01-01

The virtues of screening men for prostate cancer continue to be debated in political and public health, as well as clinical forums. Science has been unable to accurately predict screening benefits, yet many men are required to make informed decisions about prostate cancer screening. Clinicians' screening practices have been reported, but little research attention has been given to patients' experiences. The purpose of this study was to describe patients' perspectives of being screened and subsequently diagnosed with prostate cancer. Thirty-five Anglo-Australian men were interviewed, and the data were analyzed using ethnographic content analysis. The findings indicated that most participants experienced screening as a continuum of 3 tests, rather than the simple prostate-specific antigen blood test they had often anticipated. Commitment to a definitive diagnosis when abnormality was detected through screening and uptake of active treatment(s) when prostate cancer was confirmed were strongly represented in this study. The findings offer insight to the complex and often rapid sequence of events that can accompany prostate cancer screening. This has implications for the information that needs to be discussed with men before, rather than after prostate cancer screening has commenced.

A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.

PubMed

Rigau, Marina; Ortega, Israel; Mir, Maria Carmen; Ballesteros, Carlos; Garcia, Marta; Llauradó, Marta; Colás, Eva; Pedrola, Núria; Montes, Melania; Sequeiros, Tamara; Ertekin, Tugce; Majem, Blanca; Planas, Jacques; Ruiz, Anna; Abal, Miguel; Sánchez, Alex; Morote, Juan; Reventós, Jaume; Doll, Andreas

2011-12-01

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. Copyright © 2011 Wiley Periodicals, Inc.

68Ga-Prostate-Specific Membrane Antigen PET/CT in Triple-Negative Breast Cancer.

PubMed

Passah, Averilicia; Arora, Saurabh; Damle, Nishikant Avinash; Tripathi, Madhavi; Bal, Chandrasekhar; Subudhi, T Kishan; Arora, Geetanjali

2018-06-01

The prostate-specific membrane antigen (PSMA) is a transmembrane protein with elevated expression in prostate cancer cells. Breast cancer also shows PSMA expression. We present the case of a 30-year-old woman with triple-negative bilateral breast carcinoma who underwent bilateral mastectomy, chemotherapy, and radiotherapy. She developed a left chest wall and liver recurrence after primary therapy. Her recurrent disease was also triple-negative. In view of the known poor prognosis and very limited therapeutic options, we performed Ga-PSMA PET/CT scan to explore the possibility of PSMA-based therapy as a future option after exhausting standard-of-care treatments.

High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

PubMed

Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

2015-01-01

Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence appears clinically feasible, with longer term evaluation required to assess ultimate efficacy and late toxicity rates. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

The Research Implications of Prostate Specific Antigen Registry Errors: Data from the Veterans Health Administration.

PubMed

Guo, David P; Thomas, I-Chun; Mittakanti, Harsha R; Shelton, Jeremy B; Makarov, Danil V; Skolarus, Ted A; Cooperberg, Mathew R; Sonn, Geoffrey A; Chung, Benjamin I; Brooks, James D; Leppert, John T

2018-04-06

We sought to characterize the effects of prostate specific antigen registry errors on clinical research by comparing cohorts based on cancer registry prostate specific antigen values with those based directly on results in the electronic health record. We defined sample cohorts of men with prostate cancer using data from the VHA (Veterans Health Administration), including those with a prostate specific antigen value less than 4.0, 4.0 to 10.0, 10.0 to 20.0 and 20.0 to 98.0 ng/ml, respectively. We compared the composition of each cohort and overall patient survival when using PSA values from the VACCR (Veteran Affairs Central Cancer Registry) vs the gold standard electronic health record laboratory file results. There was limited agreement among cohorts when defined by cancer registry PSA values vs the laboratory file of the electronic health record. The least agreement of 58% was seen in patients with PSA less than 4.0 ng/ml and greatest agreement of 89% was noted among patients with PSA between 4.0 and 10.0 ng/ml. In each cohort patients assigned to a cohort based only on the cancer registry PSA value had significantly different overall survival when compared with patients assigned based on registry and laboratory file PSA values. Cohorts based exclusively on cancer registry PSA values may have high rates of misclassification that can introduce concerning differences in key characteristics and result in measurable differences in clinical outcomes. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study.

PubMed

Young, Grace J; Harrison, Sean; Turner, Emma L; Walsh, Eleanor I; Oliver, Steven E; Ben-Shlomo, Yoav; Evans, Simon; Lane, J Athene; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Martin, Richard M; Metcalfe, Chris

2017-10-30

Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man's age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45-49 years to 53.0% for men aged 65-69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively). A high proportion of men aged 45-69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. ISRCTN20141297,NCT02044172. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Spacer length impacts the efficacy of targeted docetaxel conjugates in prostate-specific membrane antigen expressing prostate cancer.

PubMed

Peng, Zheng-Hong; Sima, Monika; Salama, Mohamed E; Kopečková, Pavla; Kopeček, Jindřich

2013-12-01

Combination of targeted delivery and controlled release is a powerful technique for cancer treatment. In this paper, we describe the design, synthesis, structure validation and biological properties of targeted and non-targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-docetaxel conjugates. Docetaxel (DTX) was conjugated to HPMA copolymer via a tetrapeptide spacer (-GFLG-). 3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid (DUPA) was used as the targeting moiety to actively deliver DTX for treatment of Prostate-Specific Membrane Antigen (PSMA) expressing prostate cancer. Short and long spacer DUPA monomers were prepared, and four HPMA copolymer--DTX conjugates (non-targeted, two targeted with short spacer of different molecular weight and targeted with long spacer) were prepared via Reversible Addition-Fragmentation Chain Transfer (RAFT) copolymerization. Following confirmation of PSMA expression on C4-2 cell line, the DTX conjugates' in vitro cytotoxicity was tested against C4-2 tumor cells and their anticancer efficacies were assessed in nude mice bearing s.c. human prostate adenocarcinoma C4-2 xenografts. The in vivo results show that the spacer length between targeting moieties and HPMA copolymer backbone can significantly affect the treatment efficacy of DTX conjugates against C4-2 tumor bearing nu/nu mice. Moreover, histological analysis indicated that the DUPA-targeted DTX conjugate with longer spacer had no toxicity in major organs of treated mice.

Spacer length impacts the efficacy of targeted docetaxel conjugates in prostate-specific membrane antigen expressing prostate cancer

PubMed Central

Peng, Zheng-Hong; Sima, Monika; Salama, Mohamed E.; Kopečková, Pavla; Kopeček, Jindřich

2015-01-01

Combination of targeted delivery and controlled release is a powerful technique for cancer treatment. In this paper, we describe the design, synthesis, structure validation and biological properties of targeted and non-targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-docetaxel conjugates. Docetaxel (DTX) was conjugated to HPMA copolymer via a tetrapeptide spacer (–GFLG-). 3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid (DUPA) was used as the targeting moiety to actively deliver DTX for treatment of Prostate-Specific Membrane Antigen (PSMA) expressing prostate cancer. Short and long spacer DUPA monomers were prepared, and four HPMA copolymer – DTX conjugates (non-targeted, two targeted with short spacer of different molecular weight and targeted with long spacer) were prepared via Reversible Addition-Fragmentation Chain Transfer (RAFT) copolymerization. Following confirmation of PSMA expression on C4-2 cell line, the DTX conjugates’ in vitro cytotoxicity was tested against C4-2 tumor cells and their anticancer efficacies were assessed in nude mice bearing s.c. human prostate adenocarcinoma C4-2 xenografts. The in vivo results show that the spacer length between targeting moieties and HPMA copolymer backbone can significantly affect the treatment efficacy of DTX conjugates against C4-2 tumor bearing nu/nu mice. Moreover, histological analysis indicated that the DUPA-targeted DTX conjugate with longer spacer had no toxicity in major organs of treated mice. PMID:24160903

Trajectories of quality of life, life satisfaction, and psychological adjustment after prostate cancer.

PubMed

Chambers, Suzanne K; Ng, Shu Kay; Baade, Peter; Aitken, Joanne F; Hyde, Melissa K; Wittert, Gary; Frydenberg, Mark; Dunn, Jeff

2017-10-01

To describe trajectories of health-related quality of life (QoL), life satisfaction, and psychological adjustment for men with prostate cancer over the medium to long term and identify predictors of poorer outcomes using growth mixture models. One-thousand sixty-four (82.4% response) men diagnosed with prostate cancer were recruited close to diagnosis and assessed over a 72-month (6-year) period with self-report assessment of health-related QoL, life satisfaction, cancer-related distress, and prostate specific antigen anxiety. Urinary, bowel, and sexual function were also assessed using validated questionnaires. Poorer physical QOL was predicted by older age, lower education, lower income, comorbidities, and receiving hormone therapy. Lower life satisfaction was related to younger age, lower income, not being partnered, and comorbidities. Poorer psychological trajectories were predicted by younger age, lower income, comorbidities, and receiving radical prostatectomy or brachytherapy. Better urinary, bowel, and sexual function were related to better global outcomes over time. Anxiety about prostate specific antigen testing was rare. Distinct trajectories exist for medium- to long-term QoL, life satisfaction, and psychological adjustment after prostate cancer; with age and socioeconomic deprivation playing a differential role in men's survivorship profile and the impact of functional status on outcomes increasing over time. These results reinforce the need for an appraisal of men's life course in addition to treatment side effects when planning survivorship care after cancer. © 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

Evaluation of a novel label-free photonic-crystal biosensor imaging system for the detection of prostate cancer cells

NASA Astrophysics Data System (ADS)

DeLuna, Frank; Ding, XiaoFie; Sun, Lu-Zhe; Ye, Jing Yong

2017-02-01

Biomarker screening for prostate-specific antigen (PSA) is the current clinical standard for detection of prostate cancer. However this method has shown many limitations, mainly in its specificity, which can lead to a high false positive rate. Thus, there is a growing need in developing a more specific detection system for prostate cancer. Using a Photonic- Crystal-based biosensor in a Total-Internal-Reflection (PC-TIR) configuration, we demonstrate the use of refractive index (RI) to accomplish label-free detection of prostate cancer cells against non-cancerous prostate epithelial cells. The PC-TIR biosensor possesses an open microcavity, which in contrast to traditional closed microcavities, allows for easier access of analyte molecules or cells to interact with its sensing surface. In this study, an imaging system was designed using the PC-TIR biosensor to quantify cell RI as the contrast parameter for prostate cancer detection. Non-cancerous BPH-1 prostate epithelial cells and prostate cancer PC-3 cells were placed on a single biosensor and measured concurrently. Recorded image data was then analyzed through a home-built MatLab program. Results demonstrate that RI is a suitable variable for differentiation between prostate cancer cells and non-cancerous prostate epithelial cells. Our study shows clinical potential in utilizing RI test for the detection of prostate cancer.

Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

PubMed

Hansel, D E; DeMarzo, A M; Platz, E A; Jadallah, S; Hicks, J; Epstein, J I; Partin, A W; Netto, G J

2007-05-01

Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in group 1 (23 of 39, 59%). Early prostate cancer antigen was negative in 41% of group 4 who were known to harbor prostate carcinoma. The proportion of early prostate cancer antigen positivity was statistically significantly lower in group 2 than in each of the other groups when compared pairwise. A lower proportion of early prostate cancer antigen positivity was encountered in older archival tissue blocks (p<0.0001) pointing to a potential confounding factor. Corrected for block age, group 3 was the only group to remain statistically significantly different in early prostate cancer antigen positivity compared to the reference group 2. Similar findings were obtained when adjustments for patient age were made and when analysis was based on secondary outcome measurements. Our study showed a higher proportion of early prostate cancer antigen expression in initial negative prostate biopsy of patients who were diagnosed with prostate carcinoma on subsequent followup biopsies. We found a relatively high proportion of early prostate cancer antigen positivity (59%) in the group with first time negative biopsies and a potential 41% rate of false-negative early prostate cancer antigen staining in benign biopsies from cases with documented prostate carcinoma on concurrent cores. The lower early prostate cancer antigen positivity in cases with older blocks raises the question of a confounding effect of block age. Additional studies on the antigenic properties of early prostate cancer antigen in archival material are required to further delineate the usefulness of early prostate cancer antigen immunostaining on biopsy material.

Characterization of the behavior of three definitions of prostate-specific antigen-based biochemical failure in relation to detection and follow-up biases: comparison with the American Society for Therapeutic Radiology and Oncology consensus definition.

PubMed

Williams, Scott G

2006-03-01

To examine the impact of detection biases on three prostate cancer biochemical failure (bF) definitions in comparison with the existing American Society for Therapeutic Radiology and Oncology Consensus Definition (ACD). Three alternative bF definitions were tested against the ACD: three rises in prostate-specific antigen (PSA) level without backdating, nadir plus 2 ng/mL, and a threshold PSA level of >3 ng/mL, according to data from 1050 men. The mean time between PSA tests (MTBT), regularity of collection, and calendar year of analysis were examined in each bF definition. The MTBT produced a statistically significant difference in the derived hazard ratio for identification of bF in all definitions. The influence of test regularity was statistically significant beyond the median level of regularity in all definitions. The year of analysis impacted greatly on the ACD, whereas the three alternative definitions exhibited minor follow-up duration variations by comparison. The alternative definitions had reliable follow-up when the crude median time to censoring was at least 1.6 times greater than that of failure. Detection biases will always be a significant issue in defining bF. A number of alternative failure definitions have more predictable interactions with these biases than the existing ACD.

Prostate-Specific Antigen and Prostate-Specific Antigen Velocity as Threshold Indicators in 11C-Acetate PET/CTAC Scanning for Prostate Cancer Recurrence

PubMed Central

Dusing, Reginald W.; Peng, Warner; Lai, Sue-Min; Grado, Gordon L.; Holzbeierlein, Jeffrey M.; Thrasher, J. Brantley; Hill, Jacqueline; Van Veldhuizen, Peter J.

2014-01-01

Purpose The aim of this study was to identify which patient characteristics are associated with the highest likelihood of positive findings on 11C-acetate PET/computed tomography attenuation correction (CTAC) (PET/CTAC) scan when imaging for recurrent prostate cancer. Methods From 2007 to 2011, 250 11C-acetate PET/CTAC scans were performed at a single institution on patients with prostate cancer recurrence after surgery, brachytherapy, or external beam radiation. Of these patients, 120 met our inclusion criteria. Logistic regression analysis was used to examine the relationship between predictability of positive findings and patients’ characteristics, such as prostate-specific antigen (PSA) level at the time of scan, PSA kinetics, Gleason score, staging, and type of treatment before scan. Results In total, 68.3% of the 120 11C-acetate PET/CTAC scans were positive. The percentage of positive scans and PSA at the time of scanning and PSA velocity (PSAV) had positive correlations. The putative sensitivity and specificity were 86.6% and 65.8%, respectively, when a PSA level greater than 1.24 ng/mL was used as the threshold for scanning. The putative sensitivity and specificity were 74% and 75%, respectively, when a PSAV level greater than 1.32 ng/mL/y was used as the threshold. No significant associations were found between scan positivity and age, PSA doubling time, Gleason score, staging, or type of treatment before scanning. Conclusions This retrospective study suggests that threshold models of PSA greater than 1.24 ng/mL or PSAV greater than 1.32 ng/mL per year are independent predictors of positive findings in 11C-acetate PET/CTAC imaging of recurrent prostate cancer. PMID:25036021

Does [-2]Pro-Prostate Specific Antigen Meet the Criteria to Justify Its Inclusion in the Clinical Decision-Making Process?

PubMed

Sanchis-Bonet, Angeles; Barrionuevo-González, Marta; Bajo-Chueca, Ana; Morales-Palacios, Nelson; Sanchez-Chapado, Manuel

2018-01-01

To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets the criteria to justify its inclusion in a predictive model of prostate cancer (PCa) diagnosis and in the clinical decision-making process. A total 172 men with total prostate-specific antigen of 2-10 ng/mL underwent measurement of free PSA and p2PSA before prostate biopsy in an observational and prospective study. From these measurements, the Prostate Health Index (PHI) was calculated. Clinical and analytical predictive models were created incorporating PHI. Of 172 men, 72 (42%) were diagnosed with PCa, 33 (46%) of whom were found to be with high-grade disease. PHI score was the most predictive of biopsy outcomes in terms of discriminative ability (area under the curve = 0.79), with an added gain in predictive accuracy of 17%. All the models that incorporated PHI worked better in terms of calibration close to 45° on the slope. In the decision curve analysis, at a threshold probability of 40% we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors. PHI score is a more discriminant biomarker, has superior calibration and superior net benefit, and provides a higher rate of avoided biopsies; thus, it can be useful for aiding in making a more informed decision for each patient. © 2018 S. Karger AG, Basel.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

PubMed

Thompson, J E; van Leeuwen, P J; Moses, D; Shnier, R; Brenner, P; Delprado, W; Pulbrook, M; Böhm, M; Haynes, A M; Hayen, A; Stricker, P D

2016-05-01

We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Biomarkers in prostate cancer: what’s new?

PubMed Central

Sartori, David A.; Chan, Daniel W.

2014-01-01

Purpose of review This review is intended to provide an overview of the current state of biomarkers for prostate cancer (PCa), with a focus on biomarkers approved by the US Food and Drug Administration (FDA) as well as biomarkers available from Clinical Laboratory Improvement Amendment (CLIA)-certified clinical laboratories within the last 1–2 years. Recent findings During the past 2 years, two biomarkers have been approved by the US FDA. These include proPSA as part of the Prostate Health Index (phi) by Beckman Coulter, Inc and PCA3 as Progensa by Gen Probe, Inc. With the advances in genomic and proteomic technologies, several new CLIA-based laboratory-developed tests have become available. Examples are Oncotype DX from Genomics Health, Inc, and Prolaris from Myriad Genetics, Inc. In most cases, these new tests are based on a combination of multiple genomic or proteomic biomarkers. Summary Several new tests, as discussed in this review, have become available during the last 2 years. Although the intended use of most of these tests is to distinguish PCa from benign prostatic conditions with better sensitivity and specificity than prostate-specific antigen, studies have shown that some of them may also be useful in the differentiation of aggressive from nonaggressive forms of PCa. PMID:24626128

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

PubMed

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

2017-11-01

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

Highly specific expression of luciferase gene in lungs of naive nude mice directed by prostate-specific antigen promoter

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

Li Hongwei; Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA 22908; Li Jinzhong

PSA promoter has been demonstrated the utility for tissue-specific toxic gene therapy in prostate cancer models. Characterization of foreign gene overexpression in normal animals elicited by PSA promoter should help evaluate therapy safety. Here we constructed an adenovirus vector (AdPSA-Luc), containing firefly luciferase gene under the control of the 5837 bp long prostate-specific antigen promoter. A charge coupled device video camera was used to non-invasively image expression of firefly luciferase in nude mice on days 3, 7, 11 after injection of 2 x 10{sup 9} PFU of AdPSA-Luc virus via tail vein. The result showed highly specific expression of themore » luciferase gene in lungs of mice from day 7. The finding indicates the potential limitations of the suicide gene therapy of prostate cancer based on selectivity of PSA promoter. By contrary, it has encouraging implications for further development of vectors via PSA promoter to enable gene therapy for pulmonary diseases.« less

[Pathogens in expressed prostatic secretion and their correlation with serum prostate specific antigen: analysis of 320 cases].

PubMed

Wang, Shu-Xia; Zhang, Jia-Ming; Wu, Kai; Chen, Juan; Shi, Jian-Feng

2014-08-01

To investigate the pathogenic infection and its drug resistance in expressed prostatic secretion (EPS) and its correlation with serum PSA, and provide some evidence for the systematic and normalized diagnosis and treatment of prostatitis. Three EPS swabs were collected from each of the 320 prostatis patients following measurement of the serum PSA level, 1 for bacterial culture and identification, 1 for detection of Mycoplasma and drug sensitivity, and the other for examination of Chlamydia trachomatis antigen by colloidal gold immunoblot. Totally 244 strains were isolated from the 320 EPS samples, including 188 bacterial strains (dominated by Staphylococcus and sensitive to vancomycin or linezolid) and 44 Mycoplasma and Chlamydia strains (mainly Ureaplasma urealyticum and susceptible to josamycin or doxycycline). The serum PSA level was significantly higher in the pathogen-positive than in the pathogen-negative group ([6.98 +/- 0.56] microg/L vs [2.32 +/- 0.12] microg/L, P < 0.05). Prostatitis may lead to the elevation of the serum PSA level and the pathogens involved vary in their resistance to different antibacterial spectrums. Therefore, appropriate and individualized antibiotic therapy should be selected according to etiological diagnosis and the results of drug sensitivity test.

Development of Prostate Specific Membrane Antigen (PSMA) Inhibitors Coupled to 99mTc(CO)3+ with Enhanced Specific Activity for SPECT Imaging

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

Paul; D.; Benny,

2011-12-20

The overall objectives of the project were two fold: 1) the development of new facile reactions for coupling radioactive complexes with biomolecules and 2) the development of a novel molecular imaging targeting vector for Prostate Specific Membrane Antigen (PSMA) for prostate cancer. The didactic approach allowed the synergistic exploration of new technologies for coupling reactions of radioactive complexes that can be applied to a novel targeting moiety. As part of the project, a number of students (undergraduate, graduate and post-doctoral) were trained in radiochemical techniques for preparing and characterizing radiometal complexes. Results from the experiments within the project have generatedmore » several presentations and publications.« less

PSA and beyond: alternative prostate cancer biomarkers

PubMed Central

2016-01-01

Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia

PubMed Central

Pashayan, N; Powles, J; Brown, C; Duffy, S W

2006-01-01

This study aimed to estimate the extent of ‘overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR)=1.45, 95% confidence intervals (CI) 1.02–2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5 to 10 years, 40–64% of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals. PMID:16832417

Characteristics of men responding to an invitation to undergo testing for prostate cancer as part of a randomised trial.

PubMed

Walsh, Eleanor I; Turner, Emma L; Lane, J Athene; Donovan, Jenny L; Neal, David E; Hamdy, Freddie C; Martin, Richard M

2016-10-13

Sociodemographic characteristics are associated with participating in cancer screening and trials. We compared the characteristics of those responding with those not responding to a single invitation for prostate-specific antigen (PSA) testing for prostate cancer as part of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP). Age, rurality and deprivation among 197,763 men from 271 cluster-randomised primary care centres in the UK were compared between those responding (n = 90,300) and those not responding (n = 100,953) to a prostate cancer testing invitation. There was little difference in age between responders and nonresponders. Responders were slightly more likely to come from urban rather than rural areas and were slightly less deprived than those who did not respond. These data indicate similarities in age and only minor differences in deprivation and urban location between responders and nonresponders. These differences were smaller, but in the same direction as those observed in other screening trials. ISRCTN92187251 . Registered on 29 November 2004.

The Relationship Between Education and Prostate-Specific Antigen Testing Among Urban African American Medicare Beneficiaries

PubMed Central

Pollack, Craig Evan; Garza, Mary A.; Yeh, Hsin-Chieh; Markakis, Diane; Phelan-Emrick, Darcy F.; Wenzel, Jennifer; Shapiro, Gary R.; Bone, Lee; Johnson, Lawrence

2017-01-01

Purpose We examined the association between socioeconomic status (SES) and prostate-specific antigen (PSA) cancer screening among older African American men. Methods We analyzed baseline data from a sample of 485 community-dwelling African American men who participated in the Cancer Prevention and Treatment Demonstration Trial. The outcome was receipt of PSA screening within the past year. SES was measured using income and educational attainment. Sequential multivariate logistic regression models were performed to study whether health care access, patient–provider relationship, and cancer fatalism mediated the relationship between SES and PSA screening. Results Higher educational attainment was significantly associated with higher odds of PSA screening in the past year (odds ratio (OR) 2.08 for college graduate compared to less than high school graduate, 95 % confidence interval (CI) 1.03–4.24); income was not. Health care access and patient–provider communication did not alter the relationship between education and screening; however, beliefs regarding cancer fatalism partially mediated the observed relationship. Conclusion Rates of prostate cancer screening among African American men vary by level of educational attainment; beliefs concerning cancer fatalism help explain this gradient. Understanding the determinants of cancer fatalism is a critical next step in building interventions that seek to ensure equitable access to prostate cancer screening. PMID:26863336

The Relationship Between Education and Prostate-Specific Antigen Testing Among Urban African American Medicare Beneficiaries.

PubMed

Hararah, Mohammad Khalid; Pollack, Craig Evan; Garza, Mary A; Yeh, Hsin-Chieh; Markakis, Diane; Phelan-Emrick, Darcy F; Wenzel, Jennifer; Shapiro, Gary R; Bone, Lee; Johnson, Lawrence; Ford, Jean G

2015-06-01

We examined the association between socioeconomic status (SES) and prostate-specific antigen (PSA) cancer screening among older African American men. We analyzed baseline data from a sample of 485 community-dwelling African American men who participated in the Cancer Prevention and Treatment Demonstration Trial. The outcome was receipt of PSA screening within the past year. SES was measured using income and educational attainment. Sequential multivariate logistic regression models were performed to study whether health care access, patient-provider relationship, and cancer fatalism mediated the relationship between SES and PSA screening. Higher educational attainment was significantly associated with higher odds of PSA screening in the past year (odds ratio (OR) 2.08 for college graduate compared to less than high school graduate, 95 % confidence interval (CI) 1.03-4.24); income was not. Health care access and patient-provider communication did not alter the relationship between education and screening; however, beliefs regarding cancer fatalism partially mediated the observed relationship. Rates of prostate cancer screening among African American men vary by level of educational attainment; beliefs concerning cancer fatalism help explain this gradient. Understanding the determinants of cancer fatalism is a critical next step in building interventions that seek to ensure equitable access to prostate cancer screening.

3D-printed supercapacitor-powered electrochemiluminescent protein immunoarray.

PubMed

Kadimisetty, Karteek; Mosa, Islam M; Malla, Spundana; Satterwhite-Warden, Jennifer E; Kuhns, Tyler M; Faria, Ronaldo C; Lee, Norman H; Rusling, James F

2016-03-15

Herein we report a low cost, sensitive, supercapacitor-powered electrochemiluminescent (ECL) protein immunoarray fabricated by an inexpensive 3-dimensional (3D) printer. The immunosensor detects three cancer biomarker proteins in serum within 35 min. The 3D-printed device employs hand screen printed carbon sensors with gravity flow for sample/reagent delivery and washing. Prostate cancer biomarker proteins, prostate specific antigen (PSA), prostate specific membrane antigen (PSMA) and platelet factor-4 (PF-4) in serum were captured on the antibody-coated carbon sensors followed by delivery of detection-antibody-coated Ru(bpy)3(2+) (RuBPY)-doped silica nanoparticles in a sandwich immunoassay. ECL light was initiated from RuBPY in the silica nanoparticles by electrochemical oxidation with tripropylamine (TPrA) co-reactant using supercapacitor power and ECL was captured with a CCD camera. The supercapacitor was rapidly photo-recharged between assays using an inexpensive solar cell. Detection limits were 300-500f gmL(-1) for the 3 proteins in undiluted calf serum. Assays of 6 prostate cancer patient serum samples gave good correlation with conventional single protein ELISAs. This technology could provide sensitive onsite cancer diagnostic tests in resource-limited settings with the need for only moderate-level training. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of a PET Prostate-Specific Membrane Antigen Imaging Agent: Preclinical Translation for Future Clinical Application

DTIC Science & Technology

2017-10-01

94103 REPORT DATE : October 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland...display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE...Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Development of a PET Prostate-Specific Membrane Antigen

The efficiency of 18F labelling of a prostate specific membrane antigen ligand via strain-promoted azide-alkyne reaction: reaction speed versus hydrophilicity.

PubMed

Wang, Mengzhe; McNitt, Christopher D; Wang, Hui; Ma, Xiaofen; Scarry, Sarah M; Wu, Zhanhong; Popik, Vladimir V; Li, Zibo

2018-06-27

Here we report the 18F labeling of a prostate specific membrane antigen (PSMA) ligand via a strain promoted oxa-dibenzocyclooctyne (ODIBO)- or bicyclo[6.1.0]nonyne (BCN)-azide reaction. Although ODIBO reacts with azide 20 fold faster than BCN, in vivo PET imaging suggests that 18F-BCN-azide-PSMA demonstrated much higher tumor uptake and a much higher tumor to background contrast.

Applying strategies from libertarian paternalism to decision making for prostate specific antigen (PSA) screening

PubMed Central

2011-01-01

Background Despite the recent publication of results from two randomized clinical trials, prostate specific antigen (PSA) screening for prostate cancer remains a controversial issue. There is lack of agreement across studies that PSA screening significantly reduces prostate cancer mortality. In spite of these facts, the widespread use of PSA testing in the United States leads to overdetection and overtreatment of clinically indolent prostate cancer, and its associated harms of incontinence and impotence. Discussion Given the inconclusive results from clinical trials and incongruent PSA screening guidelines, the decision to screen for prostate cancer with PSA testing is an uncertain one for patients and health care providers. Screening guidelines from some health organizations recommend an informed decision making (IDM) or shared decision making (SDM) approach for deciding on PSA screening. These approaches aim to empower patients to choose among the available options by making them active participants in the decision making process. By increasing involvement of patients in the clinical decision-making process, IDM/SDM places more of the responsibility for a complex decision on the patient. Research suggests, however, that patients are not well-informed of the harms and benefits associated with prostate cancer screening and are also subject to an assortment of biases, emotion, fears, and irrational thought that interferes with making an informed decision. In response, the IDM/SDM approaches can be augmented with strategies from the philosophy of libertarian paternalism (LP) to improve decision making. LP uses the insights of behavioural economics to help people better make better choices. Some of the main strategies of LP applicable to PSA decision making are a default decision rule, framing of decision aids, and timing of the decision. In this paper, we propose that applying strategies from libertarian paternalism can help with PSA screening decision-making. Summary Our proposal to augment IDM and SDM approaches with libertarian paternalism strategies is intended to guide patients toward a better decision about testing while maintaining personal freedom of choice. While PSA screening remains controversial and evidence conflicting, a libertarian-paternalism influenced approach to decision making can help prevent the overdiagnosis and overtreatment of prostate cancer. PMID:21510865

Applying strategies from libertarian paternalism to decision making for prostate specific antigen (PSA) screening.

PubMed

Wheeler, David C; Szymanski, Konrad M; Black, Amanda; Nelson, David E

2011-04-21

Despite the recent publication of results from two randomized clinical trials, prostate specific antigen (PSA) screening for prostate cancer remains a controversial issue. There is lack of agreement across studies that PSA screening significantly reduces prostate cancer mortality. In spite of these facts, the widespread use of PSA testing in the United States leads to overdetection and overtreatment of clinically indolent prostate cancer, and its associated harms of incontinence and impotence. Given the inconclusive results from clinical trials and incongruent PSA screening guidelines, the decision to screen for prostate cancer with PSA testing is an uncertain one for patients and health care providers. Screening guidelines from some health organizations recommend an informed decision making (IDM) or shared decision making (SDM) approach for deciding on PSA screening. These approaches aim to empower patients to choose among the available options by making them active participants in the decision making process. By increasing involvement of patients in the clinical decision-making process, IDM/SDM places more of the responsibility for a complex decision on the patient. Research suggests, however, that patients are not well-informed of the harms and benefits associated with prostate cancer screening and are also subject to an assortment of biases, emotion, fears, and irrational thought that interferes with making an informed decision. In response, the IDM/SDM approaches can be augmented with strategies from the philosophy of libertarian paternalism (LP) to improve decision making. LP uses the insights of behavioural economics to help people better make better choices. Some of the main strategies of LP applicable to PSA decision making are a default decision rule, framing of decision aids, and timing of the decision. In this paper, we propose that applying strategies from libertarian paternalism can help with PSA screening decision-making. Our proposal to augment IDM and SDM approaches with libertarian paternalism strategies is intended to guide patients toward a better decision about testing while maintaining personal freedom of choice. While PSA screening remains controversial and evidence conflicting, a libertarian-paternalism influenced approach to decision making can help prevent the overdiagnosis and overtreatment of prostate cancer.

The Stockholm-3 (STHLM3) Model can Improve Prostate Cancer Diagnostics in Men Aged 50-69 yr Compared with Current Prostate Cancer Testing.

PubMed

Eklund, Martin; Nordström, Tobias; Aly, Markus; Adolfsson, Jan; Wiklund, Peter; Brandberg, Yvonne; Thompson, James; Wiklund, Fredrik; Lindberg, Johan; Presti, Joseph C; StLezin, Mark; Clements, Mark; Egevad, Lars; Grönberg, Henrik

2016-11-23

Prostate cancer screening is associated with low specificity, unnecessary biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA) ≥3ng/ml as an indication for biopsy. Urologists in today's current prostate cancer testing (CPT) have access to numerous variables in addition to PSA (eg, age, ethnicity, family history, free PSA, PSA velocity, digital rectal examination, and prostate volume) to support biopsy decisions. We estimated the number of prostate cancers diagnosed and prostate biopsies performed if S3M replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men enrolled in the STHLM3 validation cohort 2012-2015. With the same sensitivity as CPT to diagnose Gleason score ≥7 prostate cancer, S3M was estimated to reduce the number of men biopsied by 53% (95% confidence interval [CI]: 41-65%), avoid 76% (95% CI: 67-81%) of negative biopsies, and reduce Gleason score 6 cancers by 23% (95% CI: 6-40%). S3M has the potential to improve prostate cancer diagnostics by better selecting men with high risk of GS ≥7 prostate cancer. We modeled the effect the Stockholm-3 model would have on prostate cancer diagnostics if it replaced current clinical practice. We found that Stockholm-3 model may substantially reduce the number of biopsies, while maintaining the same sensitivity to diagnose clinically significant prostate cancer. Copyright © 2016. Published by Elsevier B.V.

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

PubMed

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

2015-07-01

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

Technological aspects of delivering cryotherapy for prostate cancer.

PubMed

Lau, Benjamin; Shah, Taimur Tariq; Valerio, Massimo; Hamid, Sami; Ahmed, Hashim Uddin; Arya, Manit

2015-03-01

Since the era of prostate specific antigen (PSA) testing, there has been a stage and grade migration seen with prostate cancer along with a reduction in mortality. Subsequently, concerns have been raised about the over treatment of patients following the diagnosis of localized prostate cancers. Cryotherapy, in which extremely low temperatures induce cell death via multiple mechanisms, has seen a drastic improvement in its technology since the 1800s. Such advances have improved oncological outcomes while reducing complication rates. Furthermore, technological advances have allowed the development of focal cryotherapy which aims to reduce morbidity associated with more radical whole-gland therapies. There is growing evidence that focal cryotherapy provides good oncological and morbidity rates when compared with traditional radical/whole-gland therapies.

Role of Hsp90 in Androgen-Refractory Prostate Cancer

DTIC Science & Technology

2010-03-01

designed siRNA sequence using Intergrated DNA Technologies RNAi online software tool (IDT, Coralville, IA). The sequence of siRNA specific for...proliferation and production of prostate-specific antigen in androgen-sensitive pros- tatic cancer cells, LNCaP, by dihydrotestosterone. Endocrinology 136

[Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

PubMed

Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

2016-01-01

To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (P<0.05). The patients with prostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (P<0.001). Multiple linear regression analysis showed that IL-8 and IL-6 levels and white blood cell count in the prostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

Repeat prostate-specific antigen (PSA) test before prostate biopsy: a 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer.

PubMed

De Nunzio, Cosimo; Lombardo, Riccardo; Nacchia, Antonio; Tema, Giorgia; Tubaro, Andrea

2018-07-01

To analyse the impact of repeating a prostate-specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12-core transrectal ultrasonography-guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA 1 ) and 4 weeks later on the day before biopsy (PSA 2 ). Variations in PSA level were defined as: stable PSA 2 within a 10% variation, stable PSA 2 within a 20% variation, PSA 2 decreased by ≥10%, PSA 2 decreased by ≥20%, PSA 2 increased by ≥10%, PSA 2 increased by ≥20%, and PSA 2 <4 ng/mL. Percentages and multinomial logistic regression were used to analyse biopsy outcomes. High-grade cancer was defined as Grade group ≥3. Overall, 331 patients were enrolled. Prostate cancer was diagnosed in 153/331 (46%) patients and of them 80/153 (52%) had high-grade disease. When compared to the rest of the population, patients with a stable PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P < 0.05) and high grade disease (OR 2.56, P < 0.05), patients with a PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P < 0.05) and high grade disease (OR 0.13, P < 0.05), whilst patients with a PSA2 increased by ≥10% had an increased risk of high-grade prostate cancer (OR 1.93, P < 0.05). When PSA returned to normal values (<4 ng/mL) both risks of prostate cancer and high-grade disease were reduced (OR 0.33 and 0.01, respectively, P = 0.001). In a cohort of Italian men undergoing prostate biopsy, a reduction of ≥20% in PSA levels significantly reduced the risk of high-grade prostate cancer. Further multicentre studies should validate our present results. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Measurements of free and total PSA, tissue polypeptide-specific antigen (TPS), and CYFRA 21-1 in prostate cancer patients under intermittent androgen suppression therapy.

PubMed

Theyer, G; Dürer, A; Theyer, U; Haberl, I; Ulsperger, E; Baumgartner, G; Hamilton, G

1999-10-01

The present study evaluated monthly measurements of free and total prostate-specific antigen (PSA), and the tumor proliferation markers tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 21-1 (CYFRA 21-1) in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Thirty-four men received alternating cycles of 8 month androgen suppression and treatment cessation (mean duration, 10.3 months) until PSA increased to >20 microg/l. Measurements of testosterone, percentage of free PSA, TPS, and CYFRA 21-1 were performed using ELISA and RIA assays. Periods of androgen suppression resulted in reversible reductions of testosterone (from 6 +/- 0.8 to <0.58 ng/ml), PSA (from 31.2 +/- 4.5 to <1.7 microg/l), and prostatic volume (mean reduction, 22.2 +/- 4.6%), indicating apoptotic regression of the tumors. Upon treatment cessation, testosterone increased to 6.1 +/- 0.56 ng/ml within 2 months, followed by an increase of PSA to 5.8 +/- 0.8 microg/l. The mean percentage of free PSA (15.1 +/- 2.6%) exhibited no significant change during the whole IAS cycle. TPS showed a decrease of 50% after 3 months, and CYFRA 21-1 a 25% decrease after 7 months of androgen suppression treatment. During treatment cessation, TPS exceeded the normal cutoff value of 90 U/l late in tumor regrowth (9-11 months), whereas CYFRA 21-1 remained below the normal cutoff value of 3.3 ng/ml. PSA is the best and most sensitive marker of prostate cancer regression and regrowth during IAS cycles of the markers tested in this study. Free PSA constitutes approximately 15% of total PSA (range, 5-32%), and its percentage showed no significant change during IAS cycles. The TPS and CYFRA 21-1 proliferation marker changes in IAS seem to be related mainly to effects on normal androgen-dependent tissues. Copyright 1999 Wiley-Liss, Inc.

‘A matter of faith, not science’: analysis of media coverage of prostate cancer screening in Australian news media 2003-2006

PubMed Central

MacKenzie, Ross; Chapman, Simon; Holding, Simon; McGeechan, Kevin

2007-01-01

Objective Despite a near universal absence of evidence-based policies supporting population screening for prostate cancer, the prostate-specific antigen (PSA) test is aggressively promoted in the media as a life-saving form of screening. The objective of this study was to examine media coverage of prostate-cancer screening in Australia. Design Frame analysis of all direct or attributed quotes about prostate cancer. Setting Australian capital city newspapers (February 2003-December 2006) and Sydney television news (January 2003-December 2006). Main outcome measures Quotes regarding prostate cancer screening: n=436 in newspapers and television news. Results Seven rhetorical frames were identified. 86% of all quotes framed prostate screening and its outcomes as desirable, associating PSA testing as being consonant with other early-detection cancer-control messages. Adverse surgical sequelae to screening were often minimized, scientific progress highlighted and gender equity appeals appropriated. Those questioning screening were vilified, with epidemiology being framed as an inferior form of knowledge than clinical experience. Conclusions Australian men are exposed to unbalanced and often non-evidence-based appeals to seek PSA testing. There is a disturbing lack of effort to redress this imbalance. PMID:18048709

The performance characteristics of prostate-specific antigen and prostate-specific antigen density in Chinese men.

PubMed

Teoh, Jeremy Yc; Yuen, Steffi Kk; Tsu, James Hl; Wong, Charles Kw; Ho, Brian Sh; Ng, Ada Tl; Ma, Wai-Kit; Ho, Kwan-Lun; Yiu, Ming-Kwong

2017-01-01

We investigated the performance characteristics of prostate-specific antigen (PSA) and PSA density (PSAD) in Chinese men. All Chinese men who underwent transrectal ultrasound-guided prostate biopsy (TRUS-PB) from year 2000 to 2013 were included. The receiver operating characteristic (ROC) curves for both PSA and PSAD were analyzed. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at different cut-off levels were calculated. A total of 2606 Chinese men were included. For the ROC, the area under curve was 0.770 for PSA (P < 0.001) and 0.823 for PSAD (P < 0.001). PSA of 4.5 ng ml-1 had sensitivity of 94.4%, specificity of 14.1%, PPV of 29.5%, and NPV of 86.9%; PSAD of 0.12 ng ml-1 cc-1 had sensitivity of 94.5%, specificity of 26.6%, PPV of 32.8%, and NPV of 92.7%. On multivariate logistic regression analyses, PSA cut-off at 4.5 ng ml-1 (OR 1.61, 95% CI 1.05-2.45, P= 0.029) and PSAD cut-off at 0.12 ng ml-1 cc-1 (OR 6.22, 95% CI 4.20-9.22, P< 0.001) were significant predictors for prostate cancer detection on TRUS-PB. In conclusion, the performances of PSA and PSAD at different cut-off levels in Chinese men were very different from those in Caucasians. PSA of 4.5 ng ml-1 and PSAD of 0.12 ng ml-1 cc-1 had near 95% sensitivity and were significant predictors of prostate cancer detection in Chinese men.

Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

PubMed

Choo, Richard; Klotz, Laurence; Deboer, Gerrit; Danjoux, Cyril; Morton, Gerard C

2004-08-01

To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: < 2 years, 26 patients; 2-5 years, 65; 5-10 years, 42; 10-20 years, 26; 20-50 years, 16; >50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

[11C]choline-PET-guided helical tomotherapy and estramustine in a patient with pelvic-recurrent prostate cancer: local control and toxicity profile after 24 months.

PubMed

Alongi, Filippo; Schipani, Stefano; Samanes Gajate, Ana Maria; Rosso, Alberto; Cozzarini, Cesare; Fiorino, Claudio; Alongi, Pierpaolo; Picchio, Maria; Gianolli, Luigi; Messa, Cristina; Di Muzio, Nadia

2010-01-01

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.

Deep Learning Role in Early Diagnosis of Prostate Cancer

PubMed Central

Reda, Islam; Khalil, Ashraf; Elmogy, Mohammed; Abou El-Fetouh, Ahmed; Shalaby, Ahmed; Abou El-Ghar, Mohamed; Elmaghraby, Adel; Ghazal, Mohammed; El-Baz, Ayman

2018-01-01

The objective of this work is to develop a computer-aided diagnostic system for early diagnosis of prostate cancer. The presented system integrates both clinical biomarkers (prostate-specific antigen) and extracted features from diffusion-weighted magnetic resonance imaging collected at multiple b values. The presented system performs 3 major processing steps. First, prostate delineation using a hybrid approach that combines a level-set model with nonnegative matrix factorization. Second, estimation and normalization of diffusion parameters, which are the apparent diffusion coefficients of the delineated prostate volumes at different b values followed by refinement of those apparent diffusion coefficients using a generalized Gaussian Markov random field model. Then, construction of the cumulative distribution functions of the processed apparent diffusion coefficients at multiple b values. In parallel, a K-nearest neighbor classifier is employed to transform the prostate-specific antigen results into diagnostic probabilities. Finally, those prostate-specific antigen–based probabilities are integrated with the initial diagnostic probabilities obtained using stacked nonnegativity constraint sparse autoencoders that employ apparent diffusion coefficient–cumulative distribution functions for better diagnostic accuracy. Experiments conducted on 18 diffusion-weighted magnetic resonance imaging data sets achieved 94.4% diagnosis accuracy (sensitivity = 88.9% and specificity = 100%), which indicate the promising results of the presented computer-aided diagnostic system. PMID:29804518

Dominant-Negative TGF-β Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication.

PubMed

Kloss, Christopher C; Lee, Jihyun; Zhang, Aaron; Chen, Fang; Melenhorst, Jan Joseph; Lacey, Simon F; Maus, Marcela V; Fraietta, Joseph A; Zhao, Yangbing; June, Carl H

2018-05-08

Cancer has an impressive ability to evolve multiple processes to evade therapies. While immunotherapies and vaccines have shown great promise, particularly in certain solid tumors such as prostate cancer, they have been met with resistance from tumors that use a multitude of mechanisms of immunosuppression to limit effectiveness. Prostate cancer, in particular, secretes transforming growth factor β (TGF-β) as a means to inhibit immunity while allowing for cancer progression. Blocking TGF-β signaling in T cells increases their ability to infiltrate, proliferate, and mediate antitumor responses in prostate cancer models. We tested whether the potency of chimeric antigen receptor (CAR) T cells directed to prostate-specific membrane antigen (PSMA) could be enhanced by the co-expression of a dominant-negative TGF-βRII (dnTGF-βRII). Upon expression of the dominant-negative TGF-βRII in CAR T cells, we observed increased proliferation of these lymphocytes, enhanced cytokine secretion, resistance to exhaustion, long-term in vivo persistence, and the induction of tumor eradication in aggressive human prostate cancer mouse models. Based on our observations, we initiated a phase I clinical trial to assess these CAR T cells as a novel approach for patients with relapsed and refractory metastatic prostate cancer (ClinicalTrials.gov: NCT03089203). Copyright © 2018. Published by Elsevier Inc.

Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen.

PubMed

Agnihotri, Shalini; Mittal, Rama Devi; Kapoor, Rakesh; Mandhani, Anil

2014-10-01

To test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA). Overall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4 ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography-guided biopsy was done only when PSA level did not decrease less than 4 ng/ml. Mean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6678 pg/ml (SD±1985.7) than in control, i.e., 1543 pg/ml (SD±375.7) (P<0.001). Following anti-inflammatory treatment, there was a significant decrease in the mean level of IL-8 from baseline to 5622 pg/ml (SD±1870.66) (P<0.001). Corresponding to this, a significant decrease was noted in total PSA levels to less than 4 ng/ml in 105 (65.62%) patients. Men with the highest levels of IL-8 had a greater degree of erectile dysfunction. Men with symptomatic benign prostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy. Copyright © 2014 Elsevier Inc. All rights reserved.

Recurrent Medullary Thyroid Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT: Exploring New Theranostic Avenues.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Parida, Girish Kumar; Singhal, Abhinav; Nalli, Harish; Dattagupta, Shreya; Bal, Chandrasekar

2018-05-01

The prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells. Few other malignancies have shown expression of PSMA. We present a case of 35-year-old man with medullary thyroid carcinoma, post total thyroidectomy and bilateral neck dissection, now presenting with rising calcitonin levels (doubling time 9 months) and local neck recurrence with negative I-MIBG scan. We decided to perform Ga-PSMA-HBED-CC PET/CT scan to assess PSMA expression and explore the therapeutic option in view of rising serum calcitonin. It revealed intense PSMA uptake in the soft tissue mass in left thyroid bed and cervical lymph nodes.

Lumbar Osteophyte Avid on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Jochumsen, Mads Ryø; Madsen, Michael Alle; Gammelgaard, Lise; Bouchelouche, Kirsten

2018-06-01

A 75-year-old man with recently diagnosed high-risk prostate cancer was referred for primary staging with Ga-prostate-specific membrane antigen (PSMA) PET/CT. The scan revealed intense Ga-PSMA uptake in a lumbar osteophyte on the right side of level L2/L3, whereas several other spinal osteophytes showed no Ga-PSMA uptake. MRI findings in the L3 vertebra was consistent with a benign Modic type 1 lesion, but MRI showed no signs of malignancy in the osteophyte with high Ga-PMSA uptake. This case presents an osteophyte as an addition to the list of potential benign pitfalls to be aware of when interpreting Ga-PSMA PET/CT.

Quantitative Detection of Prostatic-Specific Antigens by Using Scanning Electron Microscopy for the Analysis of Protein Chips.

PubMed

Lee, Jisu; Jung, Moon Youn; Park, Hyung Ju

2017-04-01

We reported that quantitative detection of prostatic-specific antigen (PSA), which is the biomarker of prostate cancer, could be carried out by calculating the number density and the area ratio of gold nanoparticle probes on the surface of silicon oxide chips. When chips selectively activated with PSA were immersed in the gold nanoparticles conjugated with prostatic specific antigens-poly clonal antibodies (PSA-pAb), it was possible to observe changes in the number density and the area ratio of gold nanoparticles on the surface of the chips according to the concentration of PSA with scanning electron microscopy (SEM) images. As PSA concentration increased, the number density and the area ratio of gold nanoparticle probes on the surfaces of the chips increased accordingly. Conversely, with lower concentration, the number density and the area ratio of gold nanoparticle probes on the surfaces decreased at a certain ratio. We observed the correlations between PSA concentration and number density, area ratio of gold nanoparticle probes through the analysis of SEM images. In addition, it was confirmed that the sizes of the gold nanoparticles affected the detection limit of the number density and the area ratio of gold nanoparticle probes on the surface.

A Community-Driven Intervention for Prostate Cancer Screening in African Americans

ERIC Educational Resources Information Center

Patel, Kushal; Ukoli, Flora; Liu, Jianguo; Beech, Derrick; Beard, Katina; Brown, Byron; Sanderson, Maureen; Kenerson, Donna; Cooper, Leslie; Canto, Marie; Blot, Bill; Hargreaves, Margaret

2013-01-01

The purpose of the study was to assess the impact of an educational intervention on prostate cancer screening behavior and knowledge. Participants were 104 African American men, 45 years and older, who had not been screened for prostate cancer with a prostate-specific antigen and/or digital rectal exam within the past year. All participants…

Prostate-specific antigen (PSA) as a possible biomarker in non-prostatic cancer: A review.

PubMed

Pérez-Ibave, Diana Cristina; Burciaga-Flores, Carlos Horacio; Elizondo-Riojas, Miguel-Ángel

2018-06-01

Prostate-specific antigen (PSA) is a serine protease produced by epithelial prostatic cells and its main function is to liquefy seminal coagulum. Currently, PSA is a biomarker for the diagnosis and screening of prostate cancer and it was the first cancer biomarker approved by the FDA. The quantity and serum isoforms of male PSA, allows distinguishing between carcinoma and benign inflammatory disease of the prostate. Initially, it was thought that PSA was produced only by the prostate, and thus, a protein that was expressed exclusively in men. However, several authors report that PSA is a protein that is expressed by multiple non-prostatic tissues not only in men but also in women. Some authors also report that in women, the expression of this protein is highly related to breast and colon cancer and therefore can act as a possible biomarker for early detection, diagnosis and prognosis of these cancers in women. In this review, we will focus on the characteristics of the PSA at a molecular level, its current clinical implications, the expression of this protein in non-prostatic tissues, and its relationship with cancer, especially in women. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tumour cell lysate-loaded dendritic cell vaccine induces biochemical and memory immune response in castration-resistant prostate cancer patients

PubMed Central

Reyes, D; Salazar, L; Espinoza, E; Pereda, C; Castellón, E; Valdevenito, R; Huidobro, C; Inés Becker, M; Lladser, A; López, M N; Salazar-Onfray, F

2013-01-01

Background: Recently, we produced a tumour antigen-presenting cells (TAPCells) vaccine using a melanoma cell lysate, called TRIMEL, as an antigen source and an activation factor. Tumour antigen-presenting cells induced immunological responses and increased melanoma patient survival. Herein, we investigated the effect of TAPCells loaded with prostate cancer cell lysates (PCCL) as an antigen source, and TRIMEL as a dendritic cell (DC) activation factor; which were co-injected with the Concholepas concholepas haemocyanin (CCH) as an adjuvant on castration-resistant prostate cancer (CRPC) patients. Methods: The lysate mix capacity, for inducing T-cell activation, was analysed by flow cytometry and Elispot. Delayed-type hypersensitivity (DTH) reaction against PCCL, frequency of CD8+ memory T cells (Tm) in blood and prostate-specific antigen (PSA) levels in serum were measured in treated patients. Results: The lysate mix induced functional mature DCs that were capable of activating PCCL-specific T cells. No relevant adverse reactions were observed. Six out of 14 patients showed a significant decrease in levels of PSA. DTH+ patients showed a prolonged PSA doubling-time after treatment. Expansion of functional central and effector CD8+ Tm were detected. Conclusion: Treatment of CRPC patients with lysate-loaded TAPCells and CCH as an adjuvant is safe: generating biochemical and memory immune responses. However, the limited number of cases requires confirmation in a phase II clinical trial. PMID:23989944

Tumour cell lysate-loaded dendritic cell vaccine induces biochemical and memory immune response in castration-resistant prostate cancer patients.

PubMed

Reyes, D; Salazar, L; Espinoza, E; Pereda, C; Castellón, E; Valdevenito, R; Huidobro, C; Inés Becker, M; Lladser, A; López, M N; Salazar-Onfray, F

2013-09-17

Recently, we produced a tumour antigen-presenting cells (TAPCells) vaccine using a melanoma cell lysate, called TRIMEL, as an antigen source and an activation factor. Tumour antigen-presenting cells induced immunological responses and increased melanoma patient survival. Herein, we investigated the effect of TAPCells loaded with prostate cancer cell lysates (PCCL) as an antigen source, and TRIMEL as a dendritic cell (DC) activation factor; which were co-injected with the Concholepas concholepas haemocyanin (CCH) as an adjuvant on castration-resistant prostate cancer (CRPC) patients. The lysate mix capacity, for inducing T-cell activation, was analysed by flow cytometry and Elispot. Delayed-type hypersensitivity (DTH) reaction against PCCL, frequency of CD8(+) memory T cells (Tm) in blood and prostate-specific antigen (PSA) levels in serum were measured in treated patients. The lysate mix induced functional mature DCs that were capable of activating PCCL-specific T cells. No relevant adverse reactions were observed. Six out of 14 patients showed a significant decrease in levels of PSA. DTH(+) patients showed a prolonged PSA doubling-time after treatment. Expansion of functional central and effector CD8(+) Tm were detected. Treatment of CRPC patients with lysate-loaded TAPCells and CCH as an adjuvant is safe: generating biochemical and memory immune responses. However, the limited number of cases requires confirmation in a phase II clinical trial.

CCR study: evidence for benefit of TARP vaccine for men with early stage prostate cancer | Center for Cancer Research

Cancer.gov

Results from a pilot clinical trial found that TARP, or T-cell receptor gamma chain alternate reading frame protein, vaccination slowed prostate-specific antigen (PSA) rise in the majority of patients with early stage prostate cancer.

An inducible model of abacterial prostatitis induces antigen specific inflammatory and proliferative changes in the murine prostate

PubMed Central

Haverkamp, Jessica M.; Charbonneau, Bridget; Meyerholz, David K.; Cohen, Michael B.; Snyder, Paul W.; Svensson, Robert U.; Henry, Michael D.; Wang, Hsing- Hui

2011-01-01

Background Prostatitis is a poorly understood disease and increasing evidence suggests inflammation is involved in other prostatic diseases, including prostate cancer. Methods The ability of pre-activated CD8 T cells to induce prostatitis was examined by adoptive transfer into POET-3 mice or POET-3/Luc/Pten−/+ mice. Characterization of the inflammatory response was determined by examining leukocyte infiltration by histological analysis, flow cytometry and by evaluating cytokine and chemokine levels in prostate tissue. The impact of inflammation on the prostate was evaluated by monitoring epithelial cell proliferation over time. Results Initiation of inflammation by ovalbumin specific CD8+ T cells (OT-I cells) resulted in development of acute prostatitis in the anterior, dorsolateral and anterior prostate of POET-3 and POET-3/Luc/Pten−/+ mice. Acute prostatitis was characterized by recruitment of adoptively transferred OT-I cells and importantly, autologous CD4+ and CD8+ T cells, myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg). In concert with leukocyte infiltration elevated levels of pro-inflammatory cytokines and chemokines were observed. Inflammation also resulted in marked epithelial cell proliferation that was sustained up to 80 days post adoptive-transfer of OT-I cells. Conclusions The POET-3 model represents a novel mouse model to study both acute and chronic prostate inflammation in an antigen-specific system. Further, the POET-3 mouse model can be crossed with other genetic models of disease such as the C57/Luc/Pten−/− model of prostate cancer, allowing the impact of prostatitis on other prostatic diseases to be evaluated. PMID:21656824

Camel heavy chain antibodies against prostate-specific membrane antigen.

PubMed

Evazalipour, Mehdi; Tehrani, Bahram Soltani; Abolhassani, Mohsen; Morovvati, Hamid; Omidfar, Kobra

2012-12-01

Prostate-specific membrane antigen (PSMA), a type II integral membrane glycoprotein, is highly overexpressed in all forms of prostate cancer tissues. It has also been demonstrated in a wide range of neovasculature of non-prostatic solid tumors, including bladder, pancreas, lung, kidney, colorectal, and gastric cancers. Given the unique expression of PSMA, it is considered an alluring target for antibody-based imaging and therapy of cancer. In the present study, the production and characterization of camel heavy chain antibodies (HCAbs) specific for the external domain of the PSMA are reported. Due to the absence of the CH1 domain, HCAbs are smaller than their counterparts in conventional antibodies. In this study, camel antibodies were generated through immunization of Camelus dromedarius with a synthetic 28 amino acid peptide corresponding to the external surface domain of antigen and PSMA-expressing cell lines. Different binding properties to protein A and protein G affinity columns were deployed to separate three subclasses of camel IgG. The affinity purified HCAbs bound selectively to the synthetic peptide in enzyme linked immunosorbent assay (ELISA) and reacted specifically with PSMA-expressing cell line through immunocytochemistry study. Currently, we are attempting to develop recombinant variable domain of these heavy chain antibodies (VHH or nanobody) for tumor imaging and cancer therapy.

68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml: Two case reports and a literature review

PubMed Central

Petersen, Lars J.; Nielsen, Julie B.; Dettmann, Katja; Fisker, Rune V.; Haberkorn, Uwe; Stenholt, Louise; Zacho, Helle D.

2017-01-01

Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on 68Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (<2 ng/ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with 18F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, 68Ga-PSMA PET/CT is promising for the restaging of patients with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics. PMID:28685078

Technology diffusion and diagnostic testing for prostate cancer

PubMed Central

Schroeck, Florian R.; Kaufman, Samuel R.; Jacobs, Bruce L.; Skolarus, Ted A.; Miller, David C.; Weizer, Alon Z.; Montgomery, Jeffrey S.; Wei, John T.; Shahinian, Vahakn B.; Hollenbeck, Brent K.

2013-01-01

Purpose While the dissemination of robotic prostatectomy and intensity-modulated radiotherapy (IMRT) may fuel increased use of prostatectomy and radiotherapy, these new technologies may also have spillover effects related to diagnostic testing for prostate cancer. Therefore, we examined the association of regional technology penetration with receipt of prostate specific antigen (PSA) testing and prostate biopsy. Methods In this retrospective cohort study, we included 117,857 men age 66 and older from the 5% sample of Medicare beneficiaries living in the Surveillance Epidemiology and End Results (SEER) areas from 2003 – 2007. Regional technology penetration was measured as the number of providers performing robotic prostatectomy or IMRT per population in a healthcare market (i.e., hospital referral region). We assessed the association of technology penetration with rates of PSA testing and prostate biopsy with generalized estimating equations. Results High technology penetration was associated with increased rates of PSA testing (442 versus 425 per 1,000 person-years, p<0.01) and similar rates of prostate biopsy (10.1 versus 9.9 per 1,000 person-years, p=0.69). The impact of technology penetration on PSA testing and prostate biopsy was much smaller than the effect of age, race, and comorbidity (e.g., PSA testing rate per 1,000 person-years: 485 versus 373 for men with only one versus 3+ co-morbid conditions, p<0.01). Conclusions Increased technology penetration was associated with slightly higher rates of PSA testing and no change in prostate biopsy rates. Collectively, our findings temper concerns that adoption of new technology accelerates diagnostic testing for prostate cancer. PMID:23669564

A highly sensitive capillary electrophoresis immunoassay strategy based on dual-labeled gold nanoparticles enhancing chemiluminescence for the detection of prostate-specific antigen.

PubMed

Li, Shuting; Shi, Min; Zhao, Jingjin; Zhang, Liangliang; Huang, Yong; Zhao, Shulin

2017-07-01

An enzyme and antibody dual labeled gold nanoparticles enhancing chemiluminescence strategy was developed for highly sensitive CE immunoassay (IA) of prostate-specific antigen (PSA). In this work, gold nanoparticles were labeled with horseradish peroxidase and antiprostate specific antigen-antibody, and used as the marker (Ab * ). After PSA (antigen, Ag) was added into the system, a noncompetitive immune reaction was happen between Ab * and Ag to form an immune complex (Ag-Ab * ). Subsequently, the obtained Ag-Ab * and unreacted Ab * were separated by CE, and the chemiluminescence intensity of Ag-Ab * was used to estimate PSA concentration. The calibration curve showed a good linearity in the range of 0.25-10 ng/mL. Based on a S/N of 3, the detection limit for PAS was estimated to be 0.092 ng/mL. Proposed CE method was applied for PSA quantification in human serum samples from healthy volunteers and patients with prostate cancer. The obtained results demonstrated that the proposed CE method may serve as an alternative tool for clinical analysis of PSA. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical implications of prostate-specific antigen in men and women.

PubMed

Yu, H

2000-01-01

Prostate-specific antigen (PSA) is a valuable tumor marker for prostate cancer. Although it is indeed produced at an extremely high level by the prostate, PSA is also expressed in many female tissues, especially those regulated by sex steroid hormones. PSA is detected in both normal and abnormal breast tissue, as well as in various breast fluids, including milk, nipple aspirate, and cyst fluid. Clinical studies suggest that the presence of PSA in breast tissue may indicate a favorable prognosis for breast cancer patients. Levels of PSA in nipple aspirate fluid, however, may be indicative of breast cancer risk. Concentrations of PSA in serum are elevated in pregnant women as well as in women who have excess androgens. More studies are necessary to determine the clinical implications of the presence of PSA in amniotic fluid and female serum.

Detection of early stage prostate cancer by using a simple carbon nanotube@paper biosensor.

PubMed

Ji, Sungkyung; Lee, Myeongsoon; Kim, Don

2018-04-15

This study is an investigation for an inexpensive, simple and sensitive biosensor to detect prostate cancer using bioactivated-multi wall carbon nanotubes (MWCNTs, diameter of 20nm, length of 5µm) and a micro-pore filter paper (pore size of 0.45µm). For the immunoassay of prostate specific antigen (PSA), which is a biomarker of prostate cancer, MWCNTs were activated with PSA antibody (monoclonal antibody of the prostate specific antigen) by using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide sodium salt (NHSS). The activated MWCNTs were deposited on the micro-pore filter paper to use as a biosensor. The prepared biosensor can assay from 0 to 500ng/mL of PSA level within 2h with the detection limit of 1.18ng/mL by the measurement of resistance change. The resistance change was caused by site selective interaction between PSA and PSA-antigen with an inexpensive bench top digital multimeter (5 1/2 digits). The detection range and sensitivity of the prepared sensor are good enough to diagnose the early stage of prostate cancer (> 4ng/mL of PSA). This paper-based biosensor is about 20 times cheaper (fabricated biosensor price: 2.4 $) and over 10 times faster than enzyme-linked immunosorbent assay (ELISA), which is a general method for the detection of a specific protein in the modernized hospitals. Furthermore, the maximum detection limit is about 50 times higher than ELISA. Copyright © 2017 Elsevier B.V. All rights reserved.

Specific probe selection from landscape phage display library and its application in enzyme-linked immunosorbent assay of free prostate-specific antigen.

PubMed

Lang, Qiaolin; Wang, Fei; Yin, Long; Liu, Mingjun; Petrenko, Valery A; Liu, Aihua

2014-03-04

Probes against targets can be selected from the landscape phage library f8/8, displaying random octapeptides on the pVIII coat protein of the phage fd-tet and demonstrating many excellent features including multivalency, stability, and high structural homogeneity. Prostate-specific antigen (PSA) is usually determined by immunoassay, by which antibodies are frequently used as the specific probes. Herein we found that more advanced probes against free prostate-specific antigen (f-PSA) can be screened from the landscape phage library. Four phage monoclones were selected and identified by the specificity array. One phage clone displaying the fusion peptide ERNSVSPS showed good specificity and affinity to f-PSA and was used as a PSA capture probe in a sandwich enzyme-linked immunosorbent assay (ELISA) array. An anti-human PSA monoclonal antibody (anti-PSA mAb) was used to recognize the captured antigen, followed by horseradish peroxidase-conjugated antibody (HRP-IgG) and o-phenylenediamine, which were successively added to develop plate color. The ELISA conditions such as effect of blocking agent, coating buffer pH, phage concentration, antigen incubation time, and anti-PSA mAb dilution for phage ELISA were optimized. On the basis of the optimal phage ELISA conditions, the absorbance taken at 492 nm on a microplate reader was linear with f-PSA concentration within 0.825-165 ng/mL with a low limit of detection of 0.16 ng/mL. Thus, the landscape phage is an attractive biomolecular probe in bioanalysis.

Radioligand therapy of metastatic castration-resistant prostate cancer: current approaches.

PubMed

Awang, Zool Hilmi; Essler, Markus; Ahmadzadehfar, Hojjat

2018-05-23

Prostate Cancer is the forth most common type of cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer. Therefore it is an appropriate target for diagnostic and therapy of prostate cancer and its metastases. This article discusses several articles on radionuclide treatments in prostate cancer and the results on PSMA therapy with either beta or alpha emitters as a salvage therapy.

64Cu-Labeled Inhibitors of Prostate-Specific Membrane Antigen for PET Imaging of Prostate Cancer

PubMed Central

2015-01-01

Prostate-specific membrane antigen (PSMA) is a well-recognized target for identification and therapy of a variety of cancers. Here we report five 64Cu-labeled inhibitors of PSMA, [64Cu]3–7, which are based on the lysine–glutamate urea scaffold and utilize a variety of macrocyclic chelators, namely NOTA(3), PCTA(4), Oxo-DO3A(5), CB-TE2A(6), and DOTA(7), in an effort to determine which provides the most suitable pharmacokinetics for in vivo PET imaging. [64Cu]3–7 were prepared in high radiochemical yield (60–90%) and purity (>95%). Positron emission tomography (PET) imaging studies of [64Cu]3–7 revealed specific accumulation in PSMA-expressing xenografts (PSMA+ PC3 PIP) relative to isogenic control tumor (PSMA– PC3 flu) and background tissue. The favorable kinetics and high image contrast provided by CB-TE2A chelated [64Cu]6 suggest it as the most promising among the candidates tested. That could be due to the higher stability of [64Cu]CB-TE2A as compared with [64Cu]NOTA, [64Cu]PCTA, [64Cu]Oxo-DO3A, and [64Cu]DOTA chelates in vivo. PMID:24533799

Efficacy, Predictive Factors, and Prediction Nomograms for 68Ga-labeled Prostate-specific Membrane Antigen-ligand Positron-emission Tomography/Computed Tomography in Early Biochemical Recurrent Prostate Cancer After Radical Prostatectomy.

PubMed

Rauscher, Isabel; Düwel, Charlotte; Haller, Bernhard; Rischpler, Christoph; Heck, Matthias M; Gschwend, Jürgen E; Schwaiger, Markus; Maurer, Tobias; Eiber, Matthias

2018-05-01

Recently, 68 Ga-labeled prostate-specific membrane antigen (PSMA)-ligand positron-emission tomography (PET) imaging has been shown to improve detection rates in recurrent prostate cancer (PC). However, published studies include only small patient numbers at low prostate-specific antigen (PSA) values. For this study, 272 consecutive patients with biochemical recurrence after radical prostatectomy and PSA value between 0.2 and 1ng/ml were included. The 68 Ga-PSMA-ligand PET/computed tomography (CT) was evaluated, and detection rates were determined and correlated to various clinical variables using univariate and multivariable analyses. Subgroups of patients with very low (0.2-0.5ng/ml) and low (>0.5-1.0ng/ml) PSA values were analyzed. In total, lesions indicative of PC recurrence were detected in 55% (74/134) and 74% (102/138) with very low and low PSA values, respectively. Main sites of recurrence were pelvic or retroperitoneal lymph nodes metastases, followed by local recurrence and bone metastases with higher probability in the low versus very low PSA subgroup. Detection rates significantly increased with higher PSA values, primary pT≥3a, primary pN+ disease, grade group ≥4, previous radiation therapy, and concurrent androgen deprivation therapy (ADT) in univariate analysis. In a multivariable logistic regression model, concurrent ADT and PSA values were identified as most relevant predictors of positive 68 Ga-PSMA-ligand PET/CT. Further, prediction nomograms were established, which may help in estimating pretest PSMA-ligand PET positivity in clinical practice. In our study, 68 Ga-labeled prostate-specific membrane antigen (PSMA)-ligand positron-emission tomography (PET)/computed tomography (CT) detected recurrent disease after radical prostatectomy in 55% (74/134) and 74% (102/138) of patients with very low (0.2-0.5ng/ml) and low (>0.5-1.0ng/ml) prostate-specific antigen values, respectively. On the basis of these data, it seems reasonable to perform 68 Ga-PSMA-ligand PET/CT also in patients with early biochemical recurrence, as it can tailor further therapy decisions (eg, local vs systemic treatment). The established prediction nomograms can further assist urologists in discussions on the use of 68 Ga-PSMA-ligand PET/CT with their patients in specific clinical settings. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Patterns of cancer screening in primary care from 2005 to 2010.

PubMed

Martires, Kathryn J; Kurlander, David E; Minwell, Gregory J; Dahms, Eric B; Bordeaux, Jeremy S

2014-01-15

Cancer screening recommendations vary widely, especially for breast, prostate, and skin cancer screening. Guidelines are provided by the American Cancer Society, the US Preventive Services Task Force, and various professional organizations. The recommendations often differ with regard to age and frequency of screening. The objective of this study was to determine actual rates of screening in the primary care setting. Data from the National Ambulatory Medical Care Survey were used. Only adult visits to non-federally employed, office-based physicians for preventive care from 2005 through 2010 were examined. Prevalence rates for breast, pelvic, and rectal examinations were calculated, along with the rates for mammograms, Papanicolaou smears, and prostate-specific antigen tests. Factors associated with screening, including age, race, smoking status, and insurance type, were examined using t tests and chi-square tests. In total, 8521 visits were examined. The rates of most screening examinations and tests were stable over time. Clinical breast examinations took place significantly more than mammography was ordered (54.8% vs 34.6%; P<.001). White patients received more mammography (P=.031), skin examinations (P<.010), digital rectal examinations (P<.010), and prostate-specific antigen tests (P=.003) than patients of other races. Patients who paid with Medicare or private insurance received more screening than patients who had Medicaid or no insurance (P<.010). Current cancer screening practices in primary care vary significantly. Cancer screening may not follow evidence-based practices and may not be targeting patients considered most at risk. Racial and socioeconomic disparities are present in cancer screening in primary care. © 2013 American Cancer Society.

Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer: A post-hoc analysis of the placebo-controlled PREVAIL trial.

PubMed

Kimura, Go; Yonese, Junji; Fukagai, Takashi; Kamba, Tomomi; Nishimura, Kazuo; Nozawa, Masahiro; Mansbach, Hank; Theeuwes, Ad; Beer, Tomasz M; Tombal, Bertrand; Ueda, Takeshi

2016-05-01

To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50% decline) and time to skeletal-related event. Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide- and 6.1% of placebo-treated Japanese patients. Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL. © 2016 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.

Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography for Prostate Cancer: Distribution of Disease and Implications for Radiation Therapy Planning.

PubMed

Gupta, Sandeep K; Watson, Tahne; Denham, Jim; Shakespeare, Thomas P; Rutherford, Natalie; McLeod, Nicholas; Picton, Kevin; Ainsworth, Paul; Bonaventura, Tony; Martin, Jarad M

2017-11-01

To explore the prostate-specific membrane antigen (PSMA)-avid distribution of prostate cancer (PC) on positron emission tomography (PET), both at the time of initial diagnosis and at the time of relapse after definitive local treatment. A total of 179 PSMA PET scans in patients with nil or ≤3 lesions on conventional imaging were retrospectively categorized into 3 subgroups: group A, high-risk PC with no prior definitive therapy (n=34); group B, prior prostatectomy (n=75); and group C, prior radiation therapy (n=70). The numbers and locations of the PSMA-avid lesions were mapped. The PSMA-positive lesions were identified subjectively by a nuclear medicine physician on the basis of clinical experience and taking into account the recent literature and artefacts. A total of 893 PSMA-avid lesions were identified; at least 1 lesion was detected in 80% of all scans. A high detection rate was present even at very low serum PSA levels (eg, at PSA ≤0.20 ng/mL in group B, the detection rate was 46%). Thirty-eight percent of studies revealed extrapelvic disease (41%, 31%, and 46% in groups A, B, and C, respectively). Almost one-third of all studies showed only oligometastases (24%, 36%, and 31% in groups A, B, and C, respectively). A large proportion of these (40%) were a solitary lesion. Prostate-specific membrane antigen PET demonstrated a large number of otherwise unknown metastatic lesions. Therefore we recommend PSMA PET for more accurate assessment of disease burden in initial staging of high-risk PC, as well as for restaging in patients with prostate-specific antigen relapse after primary therapies. Furthermore, a high proportion of oligometastases on PSMA PET provides a prime opportunity to investigate the role of targeted local therapies for oligometastatic PCs. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Antibiotics may not decrease prostate-specific antigen levels or prevent unnecessary prostate biopsy in patients with moderately increased prostate-specific antigen levels: A meta-analysis.

PubMed

Yang, Lu; Zhu, Yuchun; Tang, Zhuang; Chen, Yongji; Gao, Liang; Liu, Liangren; Han, Ping; Li, Xiang; Wei, Qiang

2015-05-01

To evaluate the effect of empiric antibiotics on decreasing prostate-specific antigen (PSA) levels and the possibility of avoiding unnecessary prostate biopsies (PBs). A systematic search of PubMed, Embase, and the Cochrane Library was performed to identify all randomized controlled trials (RCTs) that compared effects of empiric antibiotics with no treatment or placebo on lowering PSA levels and minimizing unnecessary PBs in patients with moderately increased PSA levels. The Cochrane Collaboration Review Manager software (RevMan 5.1.4) was used for statistical analysis. The inclusion criteria for the study were met by 6 RCTs (1 placebo controlled and 5 no treatment controlled) involving 656 patients. The synthesized data from these RCTs indicated that there were no significant differences between the antibiotic and control groups in the PSA levels after treatment (mean difference [MD] = 0.15, 95% CI:-0.50 to 0.81, P = 0.65], number of patients with decreased PSA levels after treatment (relative risk [RR] = 1.22, 95% CI: 0.90-1.65, P = 0.20], prostate-specific antigen density levels after treatment (MD =-0.04, 95% CI:-0.15 to 0.07, P = 0.47), f/t% PSA after treatment (MD =-1.47, 95% CI:-4.65 to 1.71, P = 0.37), number of patients with responsive PSA (RR = 1.02, 95% CI: 0.58-1.81, P = 0.94), and individual Pca-positiverate in these patients (RR = 1.07, 95% CI: 0.53-2.16, P = 0.86), and Pca-positiverates (RR = 0.85, 95% CI: 0.48-1.50, P = 0.57). However, the antibiotic group had a significant change in the net PSA decrease after treatment compared with the control group (MD = 1.44, 95% CI: 0.70-2.17, P = 0.0001). The use of empiric antibiotics may not significantly decrease PSA levels or avoid unnecessary PBs. Copyright © 2015 Elsevier Inc. All rights reserved.

Cumulative Incidence of False-Positive Results in Repeated, Multimodal Cancer Screening

PubMed Central

Croswell, Jennifer Miller; Kramer, Barnett S.; Kreimer, Aimee R.; Prorok, Phil C.; Xu, Jian-Lun; Baker, Stuart G.; Fagerstrom, Richard; Riley, Thomas L.; Clapp, Jonathan D.; Berg, Christine D.; Gohagan, John K.; Andriole, Gerald L.; Chia, David; Church, Timothy R.; Crawford, E. David; Fouad, Mona N.; Gelmann, Edward P.; Lamerato, Lois; Reding, Douglas J.; Schoen, Robert E.

2009-01-01

PURPOSE Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program. METHODS Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and flexible sigmoidoscopies. Men received serial chest radiographs, flexible sigmoidoscopies, digital rectal examinations, and serum prostate-specific antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period. RESULTS After 14 tests, the cumulative risk of having at least 1 false-positive screening test is 60.4% (95% CI, 59.8%–61.0%) for men, and 48.8% (95% CI, 48.1%–49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (CI, 27.8%–29.3%) for men and 22.1% (95% CI, 21.4%–22.7%) for women. CONCLUSIONS For an individual in a multimodal cancer screening trial, the risk of a false-positive finding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening. PMID:19433838

Biorepository for Prostate Cancer Prevention Trial (PCPT) | Division of Cancer Prevention

Cancer.gov

The PCPT biorepository and extended data was used to further explore the initial suggestion that some men taking finasteride were at risk of developing high-grade prostate cancers, and to look at the value of prostate-specific antigen (PSA) for early detection. Researchers showed that: |

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

PubMed

Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

2018-06-01

Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

White blood cell counts mediate the effects of physical activity on prostate-specific antigen levels.

PubMed

Loprinzi, Paul D; Richart, Sarah M

2014-09-01

The purpose of this study was to examine whether white blood cell (WBC) level mediated the relationship between physical activity and prostate-specific antigen (PSA) levels. Data from the 2003-2006 National Health and Nutrition Examination Survey were used; 1,726 U.S. adult men (aged 40 years or older) provided complete data on the study variables. Participants wore an ActiGraph 7164 accelerometer for a 7-day period to measure their physical activity behavior, and PSA and WBC levels were obtained from a blood sample. After adjustments, results showed that moderate-to-vigorous physical activity (MVPA) was inversely associated with WBC count (b = - .03; 95% CI [ - 0.04, - 0.006; p = .01), and WBC count (b = .10; 95% CI [0.009, 0.18; p = .04) was positively associated with PSA. Both the Sobel (coef. = - .004, SE = .002; z = - 2.0; p = .03) and the Aroian (coef. = - .004, SE = .002; z = - 1.9; p = .03) tests demonstrated that WBC mediated the relationship between physical activity and PSA. Additionally, among 107 participants with prostate cancer, survivors engaging in more MVPA had lower levels of WBC (b = - .04; 95% CI [ - 0.09, - 0.0009; p = .04). Conclusion Physical activity may influence PSA levels through WBC modulation; however, future research is needed to determine the direction of causality. Additionally, prostate cancer survivors engaging in higher levels of MVPA had lower levels of WBC, underscoring the importance of promoting physical activity among prostate cancer survivors.

Prostate cancer targeting motifs: expression of αν β3, neurotensin receptor 1, prostate specific membrane antigen, and prostate stem cell antigen in human prostate cancer cell lines and xenografts.

PubMed

Taylor, Robert M; Severns, Virginia; Brown, David C; Bisoffi, Marco; Sillerud, Laurel O

2012-04-01

Membrane receptors are frequent targets of cancer therapeutic and imaging agents. However, promising in vitro results often do not translate to in vivo clinical applications. To better understand this obstacle, we measured the expression differences in receptor signatures among several human prostate cancer cell lines and xenografts as a function of tumorigenicity. Messenger RNA and protein expression levels for integrin α(ν) β(3), neurotensin receptor 1 (NTSR1), prostate specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA) were measured in LNCaP, C4-2, and PC-3 human prostate cancer cell lines and in murine xenografts using quantitative reverse transcriptase polymerase chain reaction, flow cytometry, and immunohistochemistry. Stable expression patterns were observed for integrin α(ν) and PSMA in all cells and corresponding xenografts. Integrin β(3) mRNA expression was greatly reduced in C4-2 xenografts and greatly elevated in PC-3 xenografts compared with the corresponding cultured cells. NTSR1 mRNA expression was greatly elevated in LNCaP and PC-3 xenografts. PSCA mRNA expression was elevated in C4-2 xenografts when compared with C4-2 cells cultured in vitro. Furthermore, at the protein level, PSCA was re-expressed in all xenografts compared with cells in culture. The regulation of mRNA and protein expression of the cell-surface target proteins α(ν) β(3), NTSR1, PSMA, and PSCA, in prostate cancer cells with different tumorigenic potential, was influenced by factors of the microenvironment, differing between cell cultures and murine xenotransplants. Integrin α(ν) β(3), NTRS1 and PSCA mRNA expression increased with tumorigenic potential, but mRNA expression levels for these proteins do not translate directly to equivalent expression levels of membrane bound protein. Copyright © 2011 Wiley Periodicals, Inc.

[Real-time elastography in the diagnosis of prostate cancer: personal experience].

PubMed

Romagnoli, Andrea; Autieri, Gaspare; Centrella, Danilo; Gastaldi, Christian; Pedaci, Giuseppe; Rivolta, Lorenzo; Pozzi, Emilio; Anghileri, Alessio; Cerabino, Maurizio; Bianchi, Carlo Maria; Roggia, Alberto

2010-01-01

Prostate cancer is the most common cancer in men. In the future, a significant further increase in the incidence of prostate cancer is expected. The indication to perform a prostate biopsy is digital rectal examination suspicious for prostate cancer, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity, and an evidence of hypoechoic area at transrectal ultrasound scan. Unfortunately the specificity and sensibility are still poor. The aim of this retrospective study is to evaluate the specificity and sensibility of real time elastography versus ultrasound transrectal B-mode scan. We retrospectively evaluated 108 pts. having undergone TRUS-guided transrectal prostate biopsy (10 samples). The indication for biopsy is: digital rectal examination, total prostate specific antigen (PSA) value, PSA ratio, PSA density and PSA velocity suspicious for prostate cancer, and/or an evidence of hypoechoic area at transrectal ultrasound scan, and/or hard area at real-time elastography. The mean age of patients is 66.8 years, mean PSA 6.5 ng/mL, and mean ratio 16.5%. We compared the histopathological findings of needle prostate biopsies with the results of transrectal ultrasound and transrectal real-time elastography. 32/108 (29.6%) pts. were positive for prostate cancer (mean Gleason score 7.08), mean PSA 14 ng/mL and mean ratio 9.5%. Transrectal ultrasound scan shows a sensibility of 69% and specificity of 68%. Transrectal ultrasound scan shows a VPP of 51.4%. Transrectal ultrasound scan shows a VPN of 80.9%. Real-time elastography shows a sensibility of 56% and specificity of 85.7%. Real-time elastography shows a VPP of 60.1%. Real-time elastography shows a VPN of 83%. Elastography has a significantly higher specificity for the detection of prostate cancer than the conventionally used examinations including DRE and TRUS. It is a useful real-time diagnostic method because it is not invasive, and simultaneous evaluation is possible while performing TRUS.

GPs views and understanding of PSA testing, screening and early detection; survey.

PubMed

Sutton, J; Melia, J; Kirby, M; Graffy, J; Moss, S

2016-05-01

There is currently no national prostate cancer screening programme in the UK. However, patients 50 years and older are entitled to a prostate specific antigen (PSA) test, if informed on the advantages and disadvantages of testing and their risk of cancer. The Prostate Cancer Risk Management Programme (PCRMP) provides this guidance. The aim of this study was to access GPs' views and understanding of PSA testing, prostate cancer screening and early detection. A total of 708 questionnaires were returned by GPs across two English regions in 2013 and the GP questionnaire responses were quantitatively analysed. In the 699 completed questionnaires, the majority of GPs were well informed about PSA testing, screening and early detection. Only 32% used guidelines for referral, 14% knew all age-specific PSA referral levels, 71% that Black men have a higher prostate cancer risk than White men (22% correctly answered threefold increase) and 82% that family history is a risk factor. A further 78% thought electronic prompts during consultation would encourage PCRMP guideline usage and 75% had never been offered a PSA test and prostate cancer educational course, of which 73% would like to attend a course. Only 23% were aware of the latest PSA screening evidence and 94% would like an update. Participating GPs seem to be well informed but need more information and tools to help follow recommended guidance. In particular, increased awareness of PCRMP guidelines especially by automated methods, further educational courses and evidence updates would be beneficial. © 2016 John Wiley & Sons Ltd.

Comparison of 68Ga-PSMA PET/CT and multiparametric MRI for staging of high-risk prostate cancer68Ga-PSMA PET and MRI in prostate cancer.

PubMed

Tulsyan, Shruti; Das, Chandan J; Tripathi, Madhavi; Seth, Amlesh; Kumar, Rajeev; Bal, Chandrasekhar

2017-12-01

We carried out this study to compare Glu-NH-CO-NH-Lys-(Ahx) [Ga(HBED-CC)] [Ga prostate-specific membrane antigen-11 (PSMA-11)] PET with multiparametric MRI (mpMRI) for the staging of high-risk prostate cancer. This was a prospective study in which 36 patients with high-risk prostate cancer were included. The criteria for inclusion were biopsy-proven prostate cancer with a serum prostate specific antigen of at least 20 and/or Gleason's score of at least 8. Each patient then underwent both gallium-68 (Ga)-PSMA PET/computed tomography (CT) and mpMRI including diffusion-weighted whole-body imaging with background body signal suppression within an interval of 1 week and both modalities were compared for staging of primary disease, lymph node, and distant metastasis. The median age of the 36 patients included was 65 years (range: 44-80 years) and the median prostate specific antigen was 94.3 ng/ml (range: 20-19005  ng/ml). Concordance for localization of primary on Ga-PSMA PET/CT and MRI was observed in 19/36 (52.7%) patients. Concurrence for T staging on Ga-PSMA and MRI was observed in 58.3% of patients. Ga-PSMA PET/CT detected higher numbers of patients with regional (29) and nonregional (15) lymph nodes in comparison with MRI (20 and 5, respectively). Concurrence for regional and nonregional lymph node staging was observed in 72.2% of patients. Additional sites of metastatic disease reported on Ga-PSMA PET/CT were to the skeleton in one patient, the lung in two patients, and the liver in one patient. This study suggests that Ga-PSMA PET/CT is useful for lymph node and metastases staging in high-risk prostate cancers, whereas its utility for staging of disease in the prostate is limited.

Prostate-specific antigen increase during dutasteride to indicate the need for prostate biopsy: influence of prostatic inflammation.

PubMed

Sciarra, Alessandro; Maggi, Martina; Fasulo, Andrea; Salciccia, Stefano; Gentile, Vincenzo; Cattarino, Susanna; Gentilucci, Alessandro

2017-08-01

The aim of this study was to analyze the significance of an increase in total prostate-specific antigen (PSA) serum levels despite dutasteride treatment as a predictor of prostate cancer (PC) at biopsy. We focused our attention on the rate of the first PSA increase and on the influence of prostatic inflammation. From 2011 to 2016, 365 men with a previous negative prostate biopsy and persistent elevated PSA levels received dutasteride treatment. The population was followed for a range of 12-48 months. One hundred twelve cases with a confirmed PSA increase >0.5 ng/ml over the nadir value during the follow-up were included in Group A and underwent a new prostate biopsy. In Group A, the PSA increase was associated with PC at the re-biopsy in 66% of cases. The percentage of PSA reduction after 6 months of treatment was not a significant indicator of the risk for PC. The distribution of inflammatory infiltrates significantly (p<00.01) varied from positive to negative prostate biopsies. The relative risk for PC at biopsy significantly increased according to PSA level during dutasteride. Treatment with dutasteride can help to analyze PSA kinetic. A persistent prostatic inflammation is a factor able to reduce the performance of PSA kinetic during dutasteride treatment.

Evidence of prostate cancer "reverse stage migration" toward more advanced disease at diagnosis: Data from the Pennsylvania Cancer Registry.

PubMed

Reese, Adam C; Wessel, Sean R; Fisher, Susan G; Mydlo, Jack H

2016-08-01

The widespread adoption of prostate-specific antigen-based prostate cancer screening caused a stage migration toward earlier stage disease at diagnosis. We investigated whether this stage migration has persisted in a contemporary analysis of a population-based statewide cancer registry. We analyzed the Pennsylvania Cancer Registry, a statewide registry of all newly diagnosed cancers. Data were collected on prostate cancers diagnosed between 1992 and 2012. We determined age-adjusted prostate cancer incidence and mortality rates, as well as the distribution of tumor stage (localized, regional, or metastatic) at diagnosis, and assessed for changes in these variables over time using joinpoint analysis. Between 1992 and 2012, 210,831 new cases of prostate cancer were diagnosed in Pennsylvania, and 33,948 men died of disease. Age-adjusted prostate cancer incidence rates, and specifically the incidence of localized disease, have decreased dramatically since 2007 to 2008. Due to the decreased diagnosis of localized disease, regional and metastatic tumors have made up a greater percentage of all prostate cancer diagnoses in recent years, despite a relatively stable incidence of these advanced stage tumors. Over the past 2 decades, age-adjusted prostate cancer incidence rates in Pennsylvania have decreased, primarily because of the decreased detection of early-stage disease. There has been a corresponding shift toward more advanced disease at diagnosis. These findings may be explained by the decreased use of prostate-specific antigen-based screening, among other factors. The 2012 United States Preventative Services Task Force recommendations against prostate cancer screening may exacerbate this concerning trend, potentially resulting in an increase in prostate cancer-specific mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Implementation of a 5-Minute Magnetic Resonance Imaging Screening Protocol for Prostate Cancer in Men With Elevated Prostate-Specific Antigen Before Biopsy.

PubMed

Weiss, Jakob; Martirosian, Petros; Notohamiprodjo, Mike; Kaufmann, Sascha; Othman, Ahmed E; Grosse, Ulrich; Nikolaou, Konstantin; Gatidis, Sergios

2018-03-01

The aims of this study were to establish a 5-minute magnetic resonance (MR) screening protocol for prostate cancer in men before biopsy and to evaluate effects on Prostate Imaging Reporting and Data System (PI-RADS) V2 scoring in comparison to a conventional, fully diagnostic multiparametric MR imaging (mpMRI) approach. Fifty-two patients with elevated prostate-specific antigen levels and without prior biopsy were prospectively included in this institutional review board-approved study. In all patients, an mpMRI protocol according to the PI-RADS recommendations was acquired on a 3 T MRI system. In addition, an accelerated diffusion-weighted imaging sequence was acquired using simultaneous multislice technique (DW-EPISMS). Two readers independently evaluated the images for the presence/absence of prostate cancer according to the PI-RADS criteria and for additional findings. In a first reading session, only the screening protocol consisting of axial T2-weighted and DW-EPISMS images was made available. In a subsequent reading session, the mpMRI protocol was assessed blinded to the results of the first reading, serving as reference standard. Both readers successfully established a final diagnosis according to the PI-RADS criteria in the screening and mpMRI protocol. Mean lesion size was 1.2 cm in the screening and 1.4 cm in the mpMRI protocol (P = 0.4) with 35% (18/52) of PI-RADS IV/V lesions. Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100% for both readers with no significant differences in comparison to the mpMRI standard (P = 1.0). In 3 patients, suspicious lymph nodes were reported as additional finding, which were equally detectable in the screening and mpMRI protocol. A 5-minute MR screening protocol for prostate cancer in men with elevated prostate-specific antigen levels before biopsy is applicable for clinical routine with similar diagnostic performance as the full diagnostic mpMRI approach.

[The value of PHI/PCA3 in the early diagnosis of prostate cancer].

PubMed

Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P

2016-01-12

To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

Expression of Cancer/Testis Antigens in Prostate Cancer is Associated With Disease Progression

PubMed Central

Suyama, Takahito; Shiraishi, Takumi; Zeng, Yu; Yu, Wayne; Parekh, Nehal; Vessella, Robert L.; Luo, Jun; Getzenberg, Robert H.; Kulkarni, Prakash

2011-01-01

Background The cancer/testis antigens (CTAs) are a unique group of proteins normally expressed in germ cells but aberrantly expressed in several types of cancers including prostate cancer (PCa). However, their role in PCa has not been fully explored. Methods CTA expression profiling in PCa samples and cell lines was done utilizing a custom microarray that contained probes for two-thirds of all CTAs. The data were validated by quantitative PCR (Q-PCR). Functional studies were carried out by silencing gene expression with siRNA. DNA methylation was determined by methylation-specific PCR. Results A majority of CTAs expressed in PCa are located on the X chromosome (CT-X antigens). Several CT-X antigens from the MAGEA/CSAG subfamilies are coordinately upregulated in castrate-resistant prostate cancer (CRPC) but not in primary PCa. In contrast, PAGE4 is highly upregulated in primary PCa but is virtually silent in CRPC. Further, there was good correlation between the extent of promoter DNA methylation and CTA expression. Finally, silencing the expression of MAGEA2 the most highly upregulated member, significantly impaired proliferation of prostate cancer cells while increasing their chemosensitivity. Conclusions Considered together, the remarkable stage-specific expression patterns of the CT-X antigens strongly suggests that these CTAs may serve as unique biomarkers that could potentially be used to distinguish men with aggressive disease who need treatment from men with indolent disease not requiring immediate intervention. The data also suggest that the CT-X antigens may be novel therapeutic targets for CRPC for which there are currently no effective therapeutics. PMID:20583133

Evaluation of molecular species of prostate-specific antigen complexed with immunoglobulin M in prostate cancer and benign prostatic hyperplasia.

PubMed

Goč, Sanja; Janković, Miroslava

2013-01-01

This study was aimed at defining molecular species of prostate-specific antigen (PSA) in immune complexes with immunoglobulin M (IgM). Having in mind the oligoreactivity of IgM and its preference for carbohydrate antigens, there is the possibility that it can selectively recognize known PSA glycoisoforms. PSA-IgM complexes and free PSA fractions were separated from the sera of subjects with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) by gel filtration and subjected to on-chip immunoaffinity and ion-exchange chromatography. PSA-immunoreactive species were detected using surface-enhanced laser desorption/ionization time of flight mass spectrometry. The obtained spectra were analyzed for protein and glycan composition. The general pattern of the molecular species of PCa PSA and BPH PSA found in complexes with IgM was similar. It comprised major peaks at 17 kDa and minor peaks at 28 kDa, corresponding to the entire mature glycosylated PSA. The main difference was the presence of incompletely glycosylated 26.8 kDa species, having putative paucimannosidic structures, observed in PCa PSA-IgM, but not in BPH PSA-IgM. Characteristic PCa PSA-IgM glycoforms pose the question of the possible role of glycosylation as a framework for immune surveillance and may be of interest in light of recent data indicating mannose-containing glycans as cancer biomarker.

New Bacterial Infection in the Prostate after Transrectal Prostate Biopsy.

PubMed

Seo, Yumi; Lee, Gilho

2018-04-23

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

Activation of innate immunity by prostate specific antigen (PSA).

PubMed

Kodak, James A; Mann, Dean L; Klyushnenkova, Elena N; Alexander, Richard B

2006-11-01

Prostate specific antigen (PSA) is a serine protease secreted by the prostatic epithelium. The only known function of the protein is to cleave seminogelin. We wished to determine if PSA activated peripheral blood mononuclear cells (PBMC). PBMC and selected sub-populations were cultured with purified PSA. Secretion of IFNgamma was measured by cytokine capture flow cytometry and enzyme-linked immunosorbent assay. We observed secretion of IFNgamma and a proliferative response in PBMC cultured with PSA. We found that NK cells were the source of the IFNgamma but NK cells were not directly stimulated by PSA. Rather, a soluble factor secreted primarily by CD14 monocytes in response to PSA stimulated NK cells to secrete IFNgamma. PSA induces a pro-inflammatory response that results in the secretion of INFgamma by NK cells. The presence of large amounts of PSA could contribute to the common finding of inflammatory infiltrates in the prostate.

Enhanced detection sensitivity of prostate-specific antigen via PSA-conjugated gold nanoparticles based on localized surface plasmon resonance: GNP-coated anti-PSA/LSPR as a novel approach for the identification of prostate anomalies.

PubMed

Jazayeri, M H; Amani, H; Pourfatollah, A A; Avan, A; Ferns, G A; Pazoki-Toroudi, H

2016-10-01

Prostate-specific antigen (PSA) is used to screen for prostate disease, although it has several limitations in its application as an organ-specific or cancer-specific marker. Furthermore, a highly specific/sensitive and/or label-free identification of PSA still remains a challenge in the diagnosis of prostate anomalies. We aimed to develop a gold nanoparticle (GNP)-conjugated anti-PSA antibody-based localized surface plasmon resonance (LSPR) as a novel approach to detect prostatic disease. A total of 25 nm colloidal gold particles were prepared followed by conjugation with anti-PSA pAb (GNPs-PSA pAb). LSPR was used to monitor the absorption changes of the aggregation of the particles. The size, shape and stability of the GNP-anti-PSA were evaluated by dynamic light scattering transmission electron microscopy (TEM) and zetasizer. The GNPs-conjugated PSA-pAb was successfully synthesized and subsequently characterized using ultraviolet absorption spectroscopy and TEM to determine the size distribution, crystallinity and stability of the particles (for example, stability of GNP: 443 mV). To increase the stability of the particles, we pegylated GNPs using an N-(3-dimethylaminopropyl)-N*-ethylcarbodiimide hydrochloride (EDC)/N-hydroxylsuccinimide (NHS) linker (for example, stability of GNP after pegylation: 272 mV). We found a significant increase in the absorbance and intensity of the particles with extinction peak at 545/2 nm, which was shifted by ~1 nm after conjugation. To illustrate the potential of the GNPs-PSA pAb to bind specifically to PSA, LSPR was used. We found that the extinction peak shifted 3 nm for a solution of 100 nM unlabeled antigen. In summary, we have established a novel approach for improving the efficacy/sensitivity of PSA in the assessment of prostate disease, supporting further investigation on the diagnostic value of GNP-conjugated anti-PSA/LSPR for the detection of prostate cancer.

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

PubMed Central

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

2017-01-01

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

Current Status of Prostate-Specific Membrane Antigen Targeting in Nuclear Medicine: Clinical Translation of Chelator Containing Prostate-Specific Membrane Antigen Ligands Into Diagnostics and Therapy for Prostate Cancer.

PubMed

Kratochwil, Clemens; Afshar-Oromieh, Ali; Kopka, Klaus; Haberkorn, Uwe; Giesel, Frederik L

2016-09-01

The prostate-specific membrane antigen (PSMA) is expressed by approximately 90% of prostate carcinomas. The expression correlates with unfavorable prognostic factors, such as a high Gleason score, infiltrative growth, metastasis, and hormone-independence. The high specificity, especially in the undifferentiated stage, makes it an excellent target for diagnosis and therapy. Therefore, antibodies and small molecule inhibitors have been developed for imaging and therapy. In 2011 PSMA-11, a ligand that consists of the Glu-urea-motif and the chelator HBED-CC, which can be exclusively radiolabeled with (68)Ga for PET imaging, presented the clinical breakthrough for prostate cancer diagnostics. In two large diagnostic studies (n = 319 and n = 248) PET/CT with PSMA-11 successfully localized the recurrent tumor in approximately 90% of patients with biochemical relapse. Integrating PSMA-PET/CT into the planning phase of radiotherapy, the treatment concept is changed in 30%-50% of the patients. The combination of the Glu-urea-motif with DOTA, which can be labeled with several diagnostic and therapeutic radionuclides, opened new avenues for therapeutic usage of the small-molecule PSMA ligands. In the beginning of 2016, there are four confirmative reports (n = 19, n = 24, n = 30, and n = 56) from four different centers reporting a PSA response in approximately 70% of patients treated with (177)Lu-labeled PSMA ligands. In conclusion, the data available up to now indicate a widespread use of PSMA ligands for diagnostic applications with respect to staging, detection of recurrence, or metastases in patients with rising tumor markers and for therapy in case of failure of guideline-compliant treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

68Ga-PSMA-11 PET/CT in Newly Diagnosed Carcinoma of the Prostate: Correlation of Intraprostatic PSMA Uptake with Several Clinical Parameters.

PubMed

Koerber, Stefan A; Utzinger, Maximilian T; Kratochwil, Clemens; Kesch, Claudia; Haefner, Matthias F; Katayama, Sonja; Mier, Walter; Iagaru, Andrei H; Herfarth, Klaus; Haberkorn, Uwe; Debus, Juergen; Giesel, Frederik L

2017-12-01

68 Ga-prostate-specific membrane antigen (PSMA) PET/CT is a promising diagnostic tool for patients with prostate cancer. Our study evaluates SUVs in benign prostate tissue and malignant, intraprostatic tumor lesions and correlates results with several clinical parameters. Methods: One hundred four men with newly diagnosed prostate carcinoma and no previous therapy were included in this study. SUV max was measured and correlated with biopsy findings and MRI. Afterward, data were compared with current prostate-specific antigen (PSA) values, Gleason score (GS), and d'Amico risk classification. Results: In this investigation a mean SUV max of 1.88 ± 0.44 in healthy prostate tissue compared with 10.77 ± 8.45 in malignant prostate lesions ( P < 0.001) was observed. Patients with higher PSA, higher GS, and higher d'Amico risk score had statistically significant higher PSMA uptake on PET/CT ( P < 0.001 each). Conclusion: PSMA PET/CT is well suited for detecting the intraprostatic malignant lesion in patients with newly diagnosed prostate cancer. Our findings indicate a significant correlation of PSMA uptake with PSA, GS, and risk classification according to the d'Amico scale. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

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

PubMed

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

2014-05-01

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

Identification of structural and secretory lectin-binding glycoproteins of normal and cancerous human prostate.

PubMed

Lad, P M; Cooper, J F; Learn, D B; Olson, C V

1984-12-07

We have utilized the technique of lectin-loading of SDS gels with iodinated concanavalin A and wheat germ agglutinin to identify glycoproteins in prostatic and seminal fluids as well as in prostate tissue fractions. The following subunits which bound both lectins were detected: (a) 50, 43 and 38 kDa subunits common to prostatic and seminal fluids, and an additional 55 kDa subunit which predominates only in prostatic fluid; (b) 78, 55, 50 and 43 kDa subunits in prostatic tissue cytosol and (c) 195, 170, 135, 116 and 95 kDa subunits present in the particulate fractions of prostatic tissue. Immunoblotting using specific rabbit antibodies revealed the 50 kDa band to be prostatic acid phosphatase and the 38 kDa band to be prostate-specific antigen. Interestingly, antibodies directed toward prostatic acid phosphatase were found to cross-react with the 43 kDa band. Fractionation on sucrose gradients showed that several of these particulate glycoproteins were associated with a vesicle fraction enriched in adenylate cyclase activity, implying that they are plasma membrane glycoproteins. Comparison of soluble and particulate fractions of normal and cancerous tissue homogenates was made by densitometric scanning of autoradiograms of lectin-loaded gels. Similar relative intensities of lectin-binding were obtained for corresponding proteins in normal and cancerous tissue fractions. Also, immunoblotting showed no differences in prostatic acid phosphatase or prostate-specific antigen between normal and cancerous soluble homogenate fractions. Our results suggest that major lectin-binding proteins are conserved in the transition from normal to cancerous tissue. These results may be useful in developing a multiple-marker profile of metastatic prostate cancer and for the design of imaging agents, such as monoclonal antibodies, to prominent soluble and particulate prostate glycoproteins.

Microfluidic-integrated patterned ITO immunosensor for rapid detection of prostate-specific membrane antigen biomarker in prostate cancer.

PubMed

Seenivasan, Rajesh; Singh, Chandra K; Warrick, Jay W; Ahmad, Nihal; Gunasekaran, Sundaram

2017-09-15

An optically transparent patterned indium tin oxide (ITO) three-electrode sensor integrated with a microfluidic channel was designed for label-free immunosensing of prostate-specific membrane antigen (PSMA), a prostate cancer (PCa) biomarker, expressed on prostate tissue and circulating tumor cells but also found in serum. The sensor relies on cysteamine capped gold nanoparticles (N-AuNPs) covalently linked with anti-PSMA antibody (Ab) for target specificity. A polydimethylsiloxane (PDMS) microfluidic channel is used to efficiently and reproducibly introduce sample containing soluble proteins/cells to the sensor. The PSMA is detected and quantified by measuring the change in differential pulse voltammetry signal of a redox probe ([Fe(CN) 6 ] 3- /[Fe(CN) 6 ] 4- ) that is altered upon binding of PSMA with PSMA-Ab immobilized on N-AuNPs/ITO. Detection of PSMA expressing cells and soluble PSMA was tested. The limit of detection (LOD) of the sensor for PSMA-based PCa cells is 6/40µL (i.e., 150 cells/mL) (n=3) with a linear range of 15-400 cells/40µL (i.e., 375-10,000 cells/mL), and for the soluble PSMA is 0.499ng/40µL (i.e., 12.5ng/mL) (n=3) with the linear range of 0.75-250ng/40µL (i.e., 19-6250ng/mL), both with an incubation time of 10min. The results indicate that the sensor has a suitable sensitivity and dynamic range for routine detection of PCa circulating tumor cells and can be adapted to detect other biomarkers/cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors

PubMed Central

Heiser, Axel; Coleman, Doris; Dannull, Jens; Yancey, Donna; Maurice, Margaret A.; Lallas, Costas D.; Dahm, Philipp; Niedzwiecki, Donna; Gilboa, Eli; Vieweg, Johannes

2002-01-01

Autologous dendritic cells (DCs) transfected with mRNA encoding prostate-specific antigen (PSA) are able to stimulate potent, T cell–mediated antitumor immune responses in vitro. A phase I trial was performed to evaluate this strategy for safety, feasibility, and efficacy to induce T cell responses against the self-protein PSA in patients with metastatic prostate cancer. In 13 study subjects, escalating doses of PSA mRNA–transfected DCs were administered with no evidence of dose-limiting toxicity or adverse effects, including autoimmunity. Induction of PSA-specific T cell responses was consistently detected in all patients, suggesting in vivo bioactivity of the vaccine. Vaccination was further associated with a significant decrease in the log slope PSA in six of seven subjects; three patients that could be analyzed exhibited a transient molecular clearance of circulating tumor cells. The demonstration of vaccine safety, successful in vivo induction of PSA-specific immunity, and impact on surrogate clinical endpoints provides a scientific rationale for further clinical investigation of RNA-transfected DCs in the treatment of human cancer. PMID:11828001

Use of prostate-specific antigen testing as a disease surveillance tool following radical prostatectomy

PubMed Central

Trantham, Laurel Clayton; Nielsen, Matthew E.; Mobley, Lee R.; Wheeler, Stephanie B.; Carpenter, William R.; Biddle, Andrea K.

2013-01-01

Background Prostate-specific antigen (PSA) testing is recommended every 6 to 12 months for the first 5 years following radical prostatectomy as a means to detect potential disease recurrence. Despite substantial research on factors affecting treatment decisions, recurrence, and mortality, little is known about whether men receive guideline-concordant surveillance testing or whether receipt varies by year of diagnosis, time since treatment, or other individual characteristics. Methods Surveillance testing following radical prostatectomy among elderly men was examined using Surveillance, Epidemiology, and End Results cancer registry data linked to Medicare claims. Multivariate logistic regression was used to examine the effect of demographic, tumor, and county-level characteristics on the odds of receiving surveillance testing within a given one-year period following treatment. Results Overall, receipt of surveillance testing was high, with 96% of men receiving at least one test the first year after treatment and approximately 80% receiving at least one test in the fifth year after treatment. Odds of not receiving a test declined with time since treatment. Non-married men, men with less advanced disease, and non-Hispanic Blacks and Hispanics had higher odds of not receiving a surveillance test. Year of diagnosis did not affect the receipt of surveillance tests. Conclusion Most men receive guideline-concordant surveillance PSA testing after prostatectomy, although evidence of a racial disparity between non-Hispanic Whites and some minority groups exists. The decline in surveillance over time suggests the need for well-designed long-term surveillance plans following radical prostatectomy. PMID:23893821

Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Treatment of Prostate Cancer

DTIC Science & Technology

2009-07-01

prostate lysate (0.1 to 10 ug/ml) hemocyanin (0.1 to 1 ug/ml) MDCK (1 ug/ml) or canine vaccine (Parvo, rabies, and distemper at a 1:500 dilution of...We determined that a prostate cell lysate prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition to the...known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the dog made IgG

The role of prostate-specific antigen in light of new scientific evidence.

PubMed

Hernández, C; Morote, J; Miñana, B; Cózar, J M

2013-06-01

Review the scientific evidence acquired in recent years on Prostate-Specific Antigen (PSA). Analysis of the available evidence on the current role of PSA, according to a panel of experts who recorded their experience on the subject. Currently, PSA cannot be considered solely an indicator of the presence or absence of prostate cancer. Rather, the determination of PSA assists the urologist in indicating the most appropriate treatment for a patient with benign prostatic hypertrophic (BPH), as well as in suspecting a prostatic tumour when the PSA reading increases >0,3 ng/ml, in patients treated with 5-alpha-reductase inhibitor, over the reading achieved at six months of having initiated this treatment. Moreover, PSA is a key factor in the follow-up of patients with prostate adenocarcinoma who undergo surgery, radiation therapy or minimally invasive techniques. PSA helps to define biochemical recurrence, suggest the existence of a local or distal recurrence and propose or rule out adjuvant therapies. New data on the current role of PSA in the management of patients treated for BPH and/or prostate cancer should be taken into account. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

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

PubMed

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

2016-11-30

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

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

PubMed Central

2016-01-01

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

Investigating the prostate specific antigen, body mass index and age relationship: is an age-BMI-adjusted PSA model clinically useful?

PubMed

Harrison, Sean; Tilling, Kate; Turner, Emma L; Lane, J Athene; Simpkin, Andrew; Davis, Michael; Donovan, Jenny; Hamdy, Freddie C; Neal, David E; Martin, Richard M

2016-12-01

Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age-BMI-adjusted PSA model would be clinically useful for detecting prostate cancer. Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50-69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m 2 . Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status. In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7-2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m 2 (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m 2 increase in BMI (95% CI 3.4-6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0-15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age-BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer. Age and BMI were associated with small changes in PSA. An age-BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer.

PubMed

Salazar-Onfray, Flavio; Pereda, Cristián; Reyes, Diego; López, Mercedes N

2013-01-01

Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.

Are blood group isoantigens lost from malignant prostatic epithelium? Immunohistochemical support for the preservation of the H isoantigen.

PubMed Central

Vowden, P.; Lowe, A. D.; Lennox, E. S.; Bleehen, N. M.

1986-01-01

Previous studies while demonstrating the presence of blood group isoantigens on normal prostatic epithelium have failed to identify such antigens on malignant prostatic tissue. Using a series of blood group specific monoclonal antibodies directed towards the A, B, H and Y antigens we have reinvestigated blood group isoantigen expression in both benign prostatic hypertrophy and prostatic adenocarcinoma. Results obtained from areas of benign prostatic hypertrophy are in broad agreement with those published however though we were unable to detect either A or B blood group isoantigens Type 2H and Y isoantigens were identified in 10 of the 12 tumours. These findings, while differing from previously reported results, lend support to the suggested connection between ontogenesis, oncogenesis and blood group isoantigen expression and also support the proposed link between Type 2 structures and malignant transformation. Images Figure 1 Figure 2 PMID:2421753

A new model consists of intravesical prostatic protrusion, prostate volume and serum prostatic-specific antigen in the evaluation of prostate cancer.

PubMed

Xu, Ding; Yu, Yongjiang; Zhu, Yunkai; Huang, Tao; Chen, Yaqing; Qi, Jun

2014-04-01

The Prostate-specific antigen (PSA) level is largely used to diagnose prostate cancer (PCa) in last decades. However, its specificity is low in patients with a PSA level ranging from 4.0 to 10.0 ng/ml. This study aims to define the correlation between intravesical prostatic protrusion (IPP) and PSA and to establish a new model to predict PCa. A total of 339 patients order than 45 years examined between October 2010 and June 2012 were enrolled. Eligible patients were recommended for transrectal ultrasonography (TRUS)-guided prostate biopsies after measuring total prostate volume (TPV), tranzisional zone volume (TZV) and IPP. The levels of total PSA (tPSA), free PSA (fPSA) were analyzed by using Hybritech calibrated Access tPSA and fPSA assays. A new mathematical model, named IPP removed PCa predicting score (IRPPS), consists of tPSA, TZV and IPP was established. The predictive accuracy of IRPPS, PSA density (PSAD), %PSA and tPSA were compared using receiver-operator characteristic (ROC) analysis. Eighty-six patients had PSA levels of 4.0-10.0 ng/ml. Twenty of them were diagnosed as PCa. Using ROC curves, the areas under the curve for IRPPS, PSAD and %PSA and tPSA were 0.786, 0.768 and 0.664 and 0.585, respectively. We suggested IPP grade had a significant relationship with serum tPSA levels. The predictive accuracy of IRPPS was higher than the other 3 indictors.

Older Korean American men's prostate cancer screening behavior: the prime role of culture.

PubMed

Lee, Hee Yun; Jung, Yunkyung

2013-12-01

East and South Asian male immigrants show markedly low odds of prostate cancer screening as compared to U.S.-born men. However, knowledge about these immigrants' culture-based screening behavior and barriers to screening is extremely limited. This study investigates factors influencing receipt of prostate cancer screening among Korean American immigrant men, particularly investigating culture's impact on screening behaviors. Data were collected through a convenience and purposive sampling technique from 134 Korean American males aged 50 and older recruited in New York City. A structured questionnaire was used and cultural variables were measured by adopting items from Tang and colleagues' work. Approximately 60 % of the sample had received a prostate-specific antigen (PSA) test in their lifetime, and of these, about 66 % reported having done so in the previous 12 months. Logistic regression analysis revealed that a crisis-oriented intervention approach was associated with a substantially reduced likelihood of screening. A positive correlation was noted between the use of Eastern medicine and PSA test receipt. Further analysis revealed a significant interaction effect between use of Eastern medicine and age in predicting PSA test uptake. Culture-specific intervention strategies for increasing prostate cancer screening in this group are discussed, with particular attention to increasing pertinent health literacy. Health professionals should consider the cultural domain when working with Korean immigrant men in order to provide culturally competent care.

Laboratory evaluations of erectile dysfunction: an evidence based approach.

PubMed

Bodie, Joshua; Lewis, Jean; Schow, Doug; Monga, Manoj

2003-06-01

We evaluate the prevalence of laboratory abnormalities in men presenting for initial evaluation and therapy of erectile dysfunction. The computerized charts of men receiving treatment for erectile dysfunction from 1987 to 2002 were retrospectively reviewed. We pooled laboratory data for 3,547 men with erectile dysfunction to assess the prevalence of laboratory abnormalities. Values of the common laboratory screening tests for erectile dysfunction were recorded for testosterone, prolactin, luteinizing hormone, thyroid-stimulating hormone, hemoglobin A(Ic), prostate specific antigen, hemoglobin, cholesterol and creatinine. Of those patients evaluated 18.7% had low testosterone, 4.6% had increased prolactin, 14.6% had abnormal luteinizing hormone, 4.0% had increased thyroid-stimulating hormone, 8.3% had increased prostate specific antigen, 26.5% had anemia and 11.9% tested had renal insufficiency. A high percentage of patients presenting with a primary complaint of erectile dysfunction had increased hemoglobin A(Ic) and total serum cholesterol levels (52.9% and 48.4%, respectively). An evidence based approach to standardization of laboratory evaluations for men presenting with erectile dysfunction is recommended. Laboratory screening should be directed to identify those risk factors that may benefit from lifestyle modification and pharmacological intervention.

Testing and referral patterns in the years surrounding the US Preventive Services Task Force recommendation against prostate-specific antigen screening.

PubMed

Hutchinson, Ryan; Akhtar, Abdulhadi; Haridas, Justin; Bhat, Deepa; Roehrborn, Claus; Lotan, Yair

2016-12-15

Since the US Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA) screening, there have been conflicting reports regarding the impact on the behavior of providers. This study analyzed real-world data on PSA ordering and referral practices in the years surrounding the recommendation. A whole-institution sample of entered PSA orders and urology referrals was obtained from the electronic medical record. The study was performed at a tertiary referral center with a catchment in the southern United States. PSA examinations were defined as screening when they were ordered by providers with appointments in internal medicine, family medicine, or general internal medicine. Linear and quadratic regression analyses were performed, and joinpoint regression was used to assess for trend inflection points. Between January 2010 and July 2015, there were 275,784 unique ambulatory visits for men. There were 63,722 raw PSA orders, and 54,684 were evaluable. Primary care providers ordered 17,315 PSA tests and 858 urology referrals. The number of PSA tests per ambulatory visit, the number of referrals per ambulatory visit, the age at the time of the urology referral, and the proportion of PSA tests performed outside the recommended age range did not significantly change. The PSA value at the time of referral increased significantly (P = .022). Joinpoint analysis revealed no joinpoints in the analysis of total PSA orders, screening PSA tests, or examinations per 100 visits. In the years surrounding the USPSTF recommendation, PSA behavior did not change significantly. Patients were referred at progressively higher average PSA levels. The implications for prostate cancer outcomes from these trends warrant further research into provider variables associated with actual PSA utilization. Cancer 2016;122:3785-3793. © 2016 American Cancer Society. © 2016 American Cancer Society.

Ethnic and racial differences in prostate cancer incidence and mortality.

PubMed

Farkas, A; Marcella, S; Rhoads, G G

2000-01-01

Prostate cancer (CaP) incidence and mortality vary strikingly among ethnic, racial, and national groups. There is evidence that genetic, environmental, and social factors jointly-and often in combination-contribute to the observed differences in various populations. Noteworthy is the high rate of both CaP incidence and mortality among African Americans. Changes in the epidemiology of CaP since the advent of prostate specific antigen testing suggest that improved access to screening and treatment may serve to reduce somewhat the differences between the white and African-American populations. However, because the causes of these differences are likely to be multifactorial, a variety of strategies addressing the range of causes will be necessary to reduce the excess African-American mortality from this disease.

Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies against Prostate Cancer

DTIC Science & Technology

2000-07-01

Copenhagen, Copenhagen, Denmark To develop adjuvant therapy for glioma patients vaccination by autologous Neovascularization of blood vessels is...on the physiology of solid Vaccines : Novel Antigens and Vectors I tumors and their response to treatment. #5056 DNA VACCINATION OF BRAIN TUMOR...involvement of Mtsl(S1 0OA4) Cal’-binding protein in DNA vaccination with irradiation of tumor. The induced immunological processes tumour progression and

Prostate-specific Membrane Antigen PET: Clinical Utility in Prostate Cancer, Normal Patterns, Pearls, and Pitfalls.

PubMed

Hofman, Michael S; Hicks, Rodney J; Maurer, Tobias; Eiber, Matthias

2018-01-01

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast. Currently, gallium 68 ( 68 Ga)-PSMA-11 (or HBED-PSMA) is the most widely used radiotracer for PSMA positron emission tomography (PET)/computed tomography (CT) or PSMA PET/magnetic resonance (MR) imaging. Evolving evidence demonstrates superior sensitivity and specificity of PSMA PET compared to conventional imaging, with frequent identification of subcentimeter prostate cancer lesions. PSMA PET is effective for imaging disease in the prostate, lymph nodes, soft tissue, and bone in a "one-stop-shop" examination. There is emerging evidence for its clinical value in staging of high-risk primary prostate cancer and localization of disease in biochemical recurrence. The high sensitivity provided by PSMA PET, with frequent identification of small-volume disease, is redefining patterns of disease spread compared with those seen at conventional imaging. In metastatic castration-resistant prostate cancer, PSMA PET is frequently used for theranostic selection (eg, lutetium 177-PSMA radionuclide therapy), but its potential use for therapy monitoring is still under debate. However, evidence on its proper use to improve patient-related outcomes, particularly in the setting of early biochemical recurrence and targeted treatment of oligometastatic disease, is still missing. Despite the term prostate specific, PSMA functions as a folate hydrolase and is expressed in a range of normal tissues and in other benign and malignant processes. Knowledge of its physiologic distribution and other causes of uptake is essential to minimize false-positive imaging findings. © RSNA, 2018.

A Multi-Institutional Prospective Trial Confirms Noninvasive Blood Test Maintains Predictive Value in African American Men.

PubMed

Punnen, Sanoj; Freedland, Stephen J; Polascik, Thomas J; Loeb, Stacy; Risk, Michael C; Savage, Stephen; Mathur, Sharad C; Uchio, Edward; Dong, Yan; Silberstein, Jonathan L

2018-06-01

The 4Kscore® test accurately detects aggressive prostate cancer and reduces unnecessary biopsies. However, its performance in African American men has been unknown. We assessed test performance in a cohort of men with a large African American representation. Men referred for prostate biopsy at 8 Veterans Affairs medical centers were prospectively enrolled in the study. All men underwent phlebotomy for 4Kscore test assessment prior to prostate biopsy. The primary outcome was the detection of Grade Group 2 or higher cancer on biopsy. We assessed the discrimination, calibration and clinical usefulness of 4Kscore to predict Grade Group 2 or higher prostate cancer and compared it to a base model consisting of age, digital rectal examination and prostate specific antigen. Additionally, we compared test performance in African American and nonAfrican American men. Of the 366 enrolled men 205 (56%) were African American and 131 (36%) had Grade Group 2 or higher prostate cancer. The 4Kscore test showed better discrimination (AUC 0.81 vs 0.74, p <0.01) and higher clinical usefulness on decision curve analysis than the base model. Test prediction closely approximated the observed risk of Grade Group 2 or higher prostate cancer. There was no difference in test performance in African American and nonAfrican American men (0.80 vs 0.84, p = 0.32), The test outperformed the base model in each group. The 4Kscore test accurately predicts aggressive prostate cancer for biopsy decision making in African American and nonAfrican American men. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Genetic variant as a marker for bladder cancer therapy

Cancer.gov

Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

Tailored community cancer education programs: Pawsox and prostates.

PubMed

Glicksman, Arvin S; Meyer, Andrea; Dipiero, Maureen

2010-06-01

To assess the prostate cancer screening practices in Rhode Island, we designed a questionnaire which was sent to 150 primary care physicians. A population-based survey was distributed to 194 men over 40 asking about screening history and risk factors. Eighty-five percent of primary care physicians reported performing annual prostate-specific antigen tests (PSAs) and digital rectal exams, 63% recognized family history as a risk factor, and 14% identified African Americans as a high-risk population. The survey found that 48% of men recognized family history as a risk factor and 6% understood that African Americans were at high risk. Each year, 200 men, primarily SED, are invited to a PawSox baseball game where physicians provide information on prostate cancer risk, treatment options, and outcomes. Free PSAs are provided. The questionnaire and survey demonstrate a need for more public education regarding prostate cancer in high-risk populations. Tailored community-based interventions, such as the Pawsox & Prostate program, can be effective professional and public education strategies to increase screening in high-risk populations.

A Perspective on the Evolving story of PSMA Biology and PSMA Based Imaging and Endoradiotherapeutic Strategies.

PubMed

O'Keefe, Denise S; Bacich, Dean J; Huang, Steve S; Heston, Warren D

2018-04-19

We will review the evolution of knowledge of the biology of Prostate-Specific Membrane Antigen (PSMA) and how the translation to therapy has also developed. The usual key to discovery is a realistic model for experimentation and hypothesis testing. This is especially true for the prostate where the human prostate differs significantly from that of other often used species for research models. We will emphasize the genetic characterization of PSMA, The nature of the PSMA protein and its role as a carboxypeptidase, with differing important substrates and products in different tissues. We will give special prominence to its importance as a target for imaging and therapy in prostate cancer and its under-developed role for imaging and targeting the neovasculature of tumors other than prostate cancer. Lastly we will bring attention to its importance in other non-prostatic tissues. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Advanced generation anti-prostate specific membrane antigen designer T cells for prostate cancer immunotherapy.

PubMed

Ma, Qiangzhong; Gomes, Erica M; Lo, Agnes Shuk-Yee; Junghans, Richard P

2014-02-01

Adoptive immunotherapy by infusion of designer T cells (dTc) engineered with chimeric antigen receptors (CARs) for tumoricidal activity represents a potentially highly specific modality for the treatment of cancer. In this study, 2nd generation (gen) anti-prostate specific membrane antigen (PSMA) dTc were developed for improving the efficacy of previously developed 1st gen dTc for prostate cancer immunotherapy. The 1st gen dTc are modified with chimeric immunoglobulin-T cell receptor (IgTCR) while the 2nd gen dTc are engineered with an immunoglobulin-CD28-T cell receptor (IgCD28TCR), which incorporates a CD28 costimulatory signal for optimal T cell activation. A 2nd gen anti-PSMA IgCD28TCR CAR was constructed by inserting the CD28 signal domain into the 1st gen CAR. 1st and 2nd gen anti-PSMA dTc were created by transducing human T cells with anti-PSMA CARs and their antitumor efficacy was compared for specific activation on PSMA-expressing tumor contact, cytotoxicity against PSMA-expressing tumor cells in vitro, and suppression of tumor growth in an animal model. The 2nd gen dTc can be optimally activated to secrete larger amounts of cytokines such as IL2 and IFNγ than 1st gen and to proliferate more vigorously on PSMA-expressing tumor contact. More importantly, the 2nd gen dTc preserve the PSMA-specific cytotoxicity in vitro and suppress tumor growth in animal models with significant higher potency. Our results demonstrate that 2nd gen anti-PSMA designer T cells exhibit superior antitumor functions versus 1st gen, providing a rationale for advancing this improved agent toward clinical application in prostate cancer immunotherapy. © 2013 Wiley Periodicals, Inc.

Label-free in vitro prostate cancer cell detection via photonic-crystal biosensor

NASA Astrophysics Data System (ADS)

DeLuna, Frank; Ding, XiaoFei; Sagredo, Ismael; Bustamante, Gilbert; Sun, Lu-Zhe; Ye, Jing Yong

2018-02-01

Prostate-specific antigen (PSA) biomarker assays are the current clinical method for mass screening of prostate cancer. However, high false-positive rates are often reported due to PSA's low specificity, leading to an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we demonstrated the feasibility of using cellular refractive indices (RI) as a unique contrast parameter to accomplish label-free detection of prostate cancer cells via variance testing, but were unable to determine if a specific cell was cancerous or noncancerous. In this paper, we report the use of our Photonic-Crystal biosensor in a Total-Internal-Reflection (PC-TIR) configuration to construct a label-free imaging system, which allows for the detection of individual prostate cancer cells utilizing cellular RI as the only contrast parameter. Noncancerous prostate (BPH-1) cells and prostate cancer (PC-3) cells were mixed at varied ratios and measured concurrently. Additionally, we isolated and induced PC-3 cells to undergo epithelial-mesenchymal transition (EMT) by exposing these cells to soluble factors such as TGF-β1. The biophysical characteristics of the cellular RI were quantified extensively in comparison to non-induced PC-3 cells as well as BPH-1 cells. EMT is a crucial mechanism for the invasion and metastasis of epithelial tumors characterized by the loss of cell-cell adhesion and increased cell mobility. Our study shows promising clinical potential in utilizing the PC-TIR biosensor imaging system to not only detect prostate cancer cells, but also evaluate prostate cancer progression.

Multiple biomarkers biosensor with just-in-time functionalization: Application to prostate cancer detection.

PubMed

Parra-Cabrera, C; Samitier, J; Homs-Corbera, A

2016-03-15

We present a novel lab-on-a-chip (LOC) device for the simultaneous detection of multiple biomarkers using simple voltage measurements. The biosensor functionalization is performed in-situ, immediately before its use, facilitating reagents storage and massive devices fabrication. Sensitivity, limit of detection (LOD) and limit of quantification (LOQ) are tunable depending on the in-chip flown sample volumes. As a proof-of-concept, the system has been tested and adjusted to quantify two proteins found in blood that are susceptible to be used combined, as a screening tool, to diagnose prostate cancer (PCa): prostate-specific antigen (PSA) and spondin-2 (SPON2). This combination of biomarkers has been reported to be more specific for PCa diagnostics than the currently accepted but rather controversial PSA indicator. The range of detection for PSA and SPON2 could be adjusted to the clinically relevant range of 1 to 10 ng/ml. The system was tested for specificity to the evaluated biomarkers. This multiplex system can be modified and adapted to detect a larger quantity of biomarkers, or different ones, of relevance to other specific diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

High-sensitivity detection of PSA by time-resolved fluorometry with Europium chelate

NASA Astrophysics Data System (ADS)

Nahm, Kie B.; Jeong, Jin H.; Kim, Byoung C.; Kim, Jae H.; Kim, Young M.; Jeong, Dong S.; Oh, Sang W.; Choi, Eui Y.; Ko, Dong S.

2006-01-01

Prostate-specific antigen (PSA) is an androgen-dependent glycoprotein protease (M.W. 33 kDa) and a member of kallikrein super-family of serine protease, and has chymotrypsin-like enzymatic activity. It is synthesized by the prostate epithelial cells and found in the prostate gland and seminal plasma as a major protein. It is widely used as a clinical marker for diagnosis, screening, monitoring and prognosis of prostate cancer. In normal male adults, the concentration of PSA in the blood is below 4 ng/ml and this value increases in patients with the prostate cancer or the benign prostatic hyperplasia (BPH) due to its leakage into the circulatory system. As such, systematic monitoring of the PSA level in the blood can provide critical information about the progress of the prostatic disease. We have fabricated a bread-board time resolved fluorescence system that could detect a concentration of Prostate Specific Antigen t-PSA) at clinically meaningful level in plasma as well as in whole blood sample. We chose Europium chelates as the fluorescence markers to attach to the PSA for its long decay lifetime and relative photostability. We have simplified the electronic circuits considerably by employing a MCS. With this setup, we have successfully proved that PSA concentration of 4pg/mL can be detected with acceptable reliability.

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone

PubMed Central

O'Sullivan, J M; McCready, V R; Flux, G; Norman, A R; Buffa, F M; Chittenden, S; Guy, M; Pomeroy, K; Cook, G; Gadd, J; Treleaven, J; Al-Deen, A; Horwich, A; Huddart, R A; Dearnaley, D P

2002-01-01

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates. British Journal of Cancer (2002) 86, 1715–1720. doi:10.1038/sj.bjc.6600348 www.bjcancer.com © 2002 Cancer Research UK PMID:12087455

Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia.

PubMed

Marks, L S; Partin, A W; Epstein, J I; Tyler, V E; Simon, I; Macairan, M L; Chan, T L; Dorey, F J; Garris, J B; Veltri, R W; Santos, P B; Stonebrook, K A; deKernion, J B

2000-05-01

We tested the effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled trial. We randomized 44 men 45 to 80 years old with symptomatic BPH into a trial of a saw palmetto herbal blend versus placebo. End points included routine clinical measures (symptom score, uroflowmetry and post-void residual urine volume), blood chemistry studies (prostate specific antigen, sex hormones and multiphasic analysis), prostate volumetrics by magnetic resonance imaging, and prostate biopsy for zonal tissue morphometry and semiquantitative histology studies. Saw palmetto herbal blend and placebo groups had improved clinical parameters with a slight advantage in the saw palmetto group (not statistically significant). Neither prostate specific antigen nor prostate volume changed from baseline. Prostate epithelial contraction was noted, especially in the transition zone, where percent epithelium decreased from 17.8% at baseline to 10.7% after 6 months of saw palmetto herbal blend (p <0.01). Histological studies showed that the percent of atrophic glands increased from 25. 2% to 40.9% after treatment with saw palmetto herbal blend (p <0.01). The mechanism of action appeared to be nonhormonal but it was not identified by tissue studies of apoptosis, cellular proliferation, angiogenesis, growth factors or androgen receptor expression. We noted no adverse effects of saw palmetto herbal blend. When the study was no longer blinded, 41 men elected to continue therapy in an open label extension. Saw palmetto herbal blend appears to be a safe, highly desirable option for men with moderately symptomatic BPH. The secondary outcome measures of clinical effect in our study were only slightly better for saw palmetto herbal blend than placebo (not statistically significant). However, saw palmetto herbal blend therapy was associated with epithelial contraction, especially in the transition zone (p <0.01), indicating a possible mechanism of action underlying the clinical significance detected in other studies.

Development of glycan specific lectin based immunoassay for detection of prostate specific antigen.

PubMed

Bhanushali, Paresh B; Badgujar, Shamkant B; Tripathi, Mukesh M; Gupta, Sanjeev; Murthy, Vedang; Krishnasastry, Musti V; Puri, Chander P

2016-05-01

We describe an analytical approach for the detection and verification of glycosylation patterns of prostate specific antigen (PSA), a key biomarker currently used for understanding the onset and prognosis of prostate cancer. PSA has been purified from the human seminal plasma and total PSA from prostate cancer sera. PSA is a monomeric glycoprotein with an apparent molecular mass 28040.467 Da, which exhibits a characteristic protease activity against casein and gelatin. Its optimal protease activity is centered on neutral pH. Peptide mass fingerprint analysis of the purified PSA has yielded peptides that partially match with known database sequences (Uniprot ID P07288). Tryptic digestion profile of isolated PSA, infer the exclusive nature of PSA and may be additive molecule in the dictionary of seminal proteins. Surface plasmon resonance and lectin immunoassay revealed direct interaction between a newly developed anti-PSA monoclonal antibody (C4E6) and PSA. A lectin based immunoassay is reported here which was achieved with the C4E6 anti-PSA antibody and biotinylated plant lectins. This investigation provides an alternative method to isolate and quantify PSA with altered glycosylation which might be seen in the prostate cancer and developing a lectin based immunoassay to detect PSA in serum of prostate cancer patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Targeting prostate cancer: Prostate-specific membrane antigen based diagnosis and therapy.

PubMed

Wüstemann, Till; Haberkorn, Uwe; Babich, John; Mier, Walter

2018-05-17

The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules. This review elaborates the diversity of PSMA targeting agents while focusing on the radioactively labeled tracers for diagnosis and endoradiotherapy. A variety of radionuclides have been shown to either enable precise diagnosis or efficiently treat the tumor with minimal effects to nontargeted organs. Most small molecules with affinity for PSMA are based on either a phosphonate or a urea-based binding motif. Based on these pharmacophores, major effort has been made to identify modifications to achieve ideal pharmacokinetics while retaining the specific targeting of the PSMA binding pocket. Several tracers have now shown excellent clinical usability in particular for molecular imaging and therapy as proven by the efficiency of theranostic approaches in current studies. The archetypal expression profile of PSMA may be exploited for the treatment with alpha emitters to break radioresistance and thus to bring the power of systemic therapy to higher levels. © 2018 Wiley Periodicals, Inc.

Serum total prostate-specific antigen values in men with symptomatic prostate enlargement in Nigeria: role in clinical decision-making.

PubMed

Nnabugwu, Ikenna I; Ugwumba, Fred O; Enivwenae, Oghenekaro A; Udeh, Emeka I; Otene, Chris O; Nnabugwu, Chinwe A

2015-01-01

Prostatic enlargement is a common cause of bladder outlet obstruction in men in Nigeria. Malignant enlargements must be differentiated from benign enlargements for adequate treatment of each patient. High serum total prostate-specific antigen (tPSA) levels suggest malignancy, but some of the biopsies done due to a serum tPSA value >4 ng/mL would be negative for malignancy because of the low specificity of tPSA for prostate cancer. This study aims to compare the histologic findings of all prostate specimens obtained from core needle biopsy, open simple prostatectomy, and transurethral resection of the prostate with the respective serum tPSA values in an attempt to decipher the role of serum tPSA in the management of these patients. The case notes of patients attended to from April 2009 to March 2012 were analyzed. Essentially, the age of the patient, findings on digital rectal examination, abdominopelvic ultrasonography report on the prostate, serum tPSA, and histology reports from biopsy or prostatectomy specimens as indicated were extracted for analysis. The relationship between age, findings on digital rectal examination, serum tPSA, abdominopelvic ultrasonography report, and histology are compared. A statistically significant relationship existed between a malignant histology and age 65 years and older, suspicious findings on digital rectal examination, suspicious ultrasonography findings, and serum tPSA >10 ng/mL, but not tPSA >4 ng/mL. In Nigerian patients with symptomatic prostate enlargement, serum tPSA should be seen as a continuum with increasing risk of prostate malignancy.

Should modest elevations in prostate-specific antigen, International Prostate Symptom Score, or their rates of increase over time be used as surrogate measures of incident benign prostatic hyperplasia?

PubMed

Schenk, Jeannette M; Hunter-Merrill, Rachel; Zheng, Yingye; Etzioni, Ruth; Gulati, Roman; Tangen, Catherine; Thompson, Ian M; Kristal, Alan R

2013-09-01

Although surrogate measures of benign prostatic hyperplasia (BPH) are often used in epidemiologic studies, their performance characteristics are unknown. Using data from the Prostate Cancer Prevention Trial (n = 5,986), we evaluated prostate-specific antigen (PSA), International Prostate Symptom Score (IPSS), and their rates of change as predictors of incident BPH. BPH (n = 842 cases) was defined as medical or surgical treatment or at least 2 IPSS of 15 or higher. Proportional hazards models were used to measure the associations of baseline PSA, IPSS, and their velocities over 2 years with BPH risk, and time-dependent receiver-operating characteristic curves were used to measure their discriminatory performance. Unit increases in PSA, IPSS, and IPSS velocity were associated with 34%, 35%, and 29% (all P < 0.001) increases in BPH risk, respectively. The areas under the receiver-operating characteristic curves were significantly greater than 0.5 for PSA (0.58, 95% confidence interval (CI): 0.56, 0.60), IPSS (0.77, 95% CI: 0.75, 0.78), and IPSS velocity (0.63, 95% CI: 0.61, 0.65); however there were no cut points at which sensitivity and specificity were both above 75%. We concluded that moderate elevations in PSA, IPSS, or their rates of change should not be used as surrogate measures of incident BPH.

Real-time individual predictions of prostate cancer recurrence using joint models

PubMed Central

Taylor, Jeremy M. G.; Park, Yongseok; Ankerst, Donna P.; Proust-Lima, Cecile; Williams, Scott; Kestin, Larry; Bae, Kyoungwha; Pickles, Tom; Sandler, Howard

2012-01-01

Summary Patients who were previously treated for prostate cancer with radiation therapy are monitored at regular intervals using a laboratory test called Prostate Specific Antigen (PSA). If the value of the PSA test starts to rise, this is an indication that the prostate cancer is more likely to recur, and the patient may wish to initiate new treatments. Such patients could be helped in making medical decisions by an accurate estimate of the probability of recurrence of the cancer in the next few years. In this paper, we describe the methodology for giving the probability of recurrence for a new patient, as implemented on a web-based calculator. The methods use a joint longitudinal survival model. The model is developed on a training dataset of 2,386 patients and tested on a dataset of 846 patients. Bayesian estimation methods are used with one Markov chain Monte Carlo (MCMC) algorithm developed for estimation of the parameters from the training dataset and a second quick MCMC developed for prediction of the risk of recurrence that uses the longitudinal PSA measures from a new patient. PMID:23379600

Prostate cancer screening by prostate-specific antigen (PSA); a relevant approach for the small population of the Cayman Islands.

PubMed

Jyoti, Shravana Kumar; Blacke, Camille; Patil, Pallavi; Amblihalli, Vibha P; Nicholson, Amanda

2018-01-01

The common tool for diagnosing prostate cancer is prostate-specific antigen (PSA), but the high sensitivity and low specificity of PSA testing are the problems in clinical practice. There are no proper guidelines to investigate the suspected prostate cancer in the Cayman Islands. We correlated PSA levels with the incidence of prostate cancers by tissue diagnosis and proposed logical protocol for prostate screening by using PSA test in this small population. A total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. The patients were divided into subgroups by baseline PSA levels as follows: <4, 4.1-10, 10.1-20, 20.1-50, 50.1-100, and >100 ng/mL and were correlated to the age and presence of cancer. Benign lesions had lower PSA levels compared to cancer which generally had higher values. Only three cases that had less than 4 ng/mg were turned out to be malignant. When PSA value was more than 100 ng/mL, all the cases were malignant. Between PSA values of 4-100 ng/mL, the probability of cancer diagnosis was 56.71% (76 cancers out of 134 in this range). Limitation of PSA testing has the risk of over diagnosis and the resultant negative biopsies owing to poor specificity. Whereas the cutoff limit for cancer diagnosis still remains 4 ng/mL from our study, most of the patients can be assured of benign lesion below this level and thus morbidity associated with the biopsy can be prevented. When the PSA value is greater than 100 ng, biopsy procedure was mandatory as there were 100% cancers above this level. On the background of vast literature linking PSA to prostate cancer and its difficulty in implementing in clinical practice, we studied literature of this conflicting and complex topic and tried to bring relevant protocols to the small population of Cayman Islands for the screening of prostate cancer. In this study, a total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. As a result of this research work, it can be concluded that a benign diagnosis can be given with a fair certainty when the PSA was below 4 ng/mL and a level of 100 ng/mL can be very unfavorable for the patients. This study helped to solidify the cancer screening protocols in Cayman Islands. The PSA level can reassure and educate the patients towards the diagnosis of cancer of prostate in Cayman Islands. Benign diagnosis can be given with a fair certainty when the PSA was below 4 ng/mL and a level of 100 ng/mL can be very unfavorable for the patients. This study helped to solidify the cancer screening protocols in Cayman.

Validation of the prognostic grouping of the seventh edition of the tumor-nodes-metastasis classification using a large-scale prospective cohort study database of prostate cancer treated with primary androgen deprivation therapy.

PubMed

Kimura, Tomokazu; Onozawa, Mizuki; Miyazaki, Jun; Kawai, Koji; Nishiyama, Hiroyuki; Hinotsu, Shiro; Akaza, Hideyuki

2013-09-01

In the TNM seventh edition, a prognostic grouping for prostate cancer incorporating prostate-specific antigen and Gleason score was advocated. The present study was carried out to evaluate and validate prognostic grouping in prostate cancer patients. The 15 259 study patients treated with primary androgen deprivation therapy were enrolled in the Japan Study Group of Prostate Cancer. Overall survival was stratified by tumor-nodes-metastasis, Gleason score and prostate-specific antigen, and extensively analyzed. The accuracy of grouping systems was evaluated by the concordance index. The 5-year overall survival in prognostic grouping-I, IIA, IIB, III and IV was 90.0%, 88.3%, 84.8%, 80.6% and 57.1%, respectively. When considering subgroup stratification, the 5-year overall survival of subgroups prognostic grouping-IIA, IIB, III and IV was 80.9∼90.5%, 75.4∼91.8%, 75.7∼89.0% and 46.9∼86.2%, respectively. When prognostic grouping-IIB was subclassified into IIB1 (except IIB2) and IIB2 (T1-2b, prostate-specific antigen >20, Gleason score ≥8, and T2c, Gleason score ≥8), the 5-year overall survival of IIB2 was significantly lower than that of IIB1 (79.4% and 87.3%, P < 0.0001). Also, when prognostic grouping-IV was subclassified into IV1 (except IV2) and IV2 (M1, prostate-specific antigen >100 or Gleason score ≥8), the 5-year overall survival of prognostic grouping-IV1 was superior to that of IV2 (72.9% and 49.5%, P < 0.0001). Prognostic groupings were reclassified into modified prognostic groupings, divided into modified prognostic grouping-A (prognostic grouping-I, IIA, and IIB1), modified prognostic grouping-B (prognostic grouping-IIB2 and III), modified prognostic grouping-C (prognostic grouping-IV1) and modified prognostic grouping-D (prognostic grouping-IV2). The concordance index of prognostic grouping and modified prognostic grouping for overall survival was 0.670 and 0.685, respectively. Prognostic grouping could stratify the prognosis of prostate cancer patients. However, there is considerable variation among the prognostic grouping subgroups. Thus, the use of a modified prognostic grouping for patients treated with primary androgen deprivation therapy is advisable. © 2013 The Japanese Urological Association.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

PubMed

Turner, E L; Metcalfe, C; Donovan, J L; Noble, S; Sterne, J A C; Lane, J A; Avery, K N; Down, L; Walsh, E; Davis, M; Ben-Shlomo, Y; Oliver, S E; Evans, S; Brindle, P; Williams, N J; Hughes, L J; Hill, E M; Davies, C; Ng, S Y; Neal, D E; Hamdy, F C; Martin, R M

2014-06-10

Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Prostate Cancer: Serum and Tissue Markers

PubMed Central

Miller, Gary J; Brawer, Michael K; Sakr, Wael A; Thrasher, J Brantley; Townsend, Ronald

2001-01-01

The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the “gold standard,” has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and the clinical emergence of prostate cancer; the possible correlation of serum insulin-like growth factor levels with the risk for developing prostate cancer; and the latest advances in radiologic staging. PMID:16985995

Nomograms to predict the pathological stage of clinically localized prostate cancer in Korean men: comparison with western predictive tools using decision curve analysis.

PubMed

Jeong, Chang Wook; Jeong, Seong Jin; Hong, Sung Kyu; Lee, Seung Bae; Ku, Ja Hyeon; Byun, Seok-Soo; Jeong, Hyeon; Kwak, Cheol; Kim, Hyeon Hoe; Lee, Eunsik; Lee, Sang Eun

2012-09-01

To develop and evaluate nomograms to predict the pathological stage of clinically localized prostate cancer after radical prostatectomy in Korean men. We reviewed the medical records of 2041 patients who had clinical stages T1c-T3a prostate cancer and were treated solely with radical prostatectomy at two hospitals. Logistic regressions were carried out to predict organ-confined disease, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis using preoperative variables and resulting nomograms. Internal validations were assessed using the area under the receiver operating characteristic curve and calibration plot, and then external validations were carried out on 129 patients from another hospital. Head-to-head comparisons with 2007 Partin tables and Cancer of the Prostate Risk Assessment score were carried out using the area under the curve and decision curve analysis. The significant predictors for organ-confined disease and extraprostatic extension were clinical stage, prostate-specific antigen, Gleason score and a percent positive core of biopsy. Significant predictors for seminal vesicle invasion were prostate-specific antigen, Gleason score and percent positive core, and those for lymph node metastasis were prostate-specific antigen and percent positive core. The area under the curve of established nomograms for organ-confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were 0.809, 0.804, 0.889 and 0.838, respectively. The nomograms were well calibrated and externally validated. These nomograms showed significantly higher accuracies and net benefits than two Western tools in Korean men. This is the first study to have developed and fully validated nomograms to predict the pathological stage of prostate cancer in an Asian population. These nomograms might be more accurate and useful for Korean men than other predictive models developed using Western populations. © 2012 The Japanese Urological Association.

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

Pommier, Pascal, E-mail: Pascal.pommier@lyon.unicancer.fr; Chabaud, Sylvie; Lagrange, Jean-Leon

Purpose: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Patients and Methods: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: “low risk” (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus “high risk” (T3 or Gleason score >6 ormore » prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. Results: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Conclusion: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.« less

Profile of NF-κBp(65/NFκBp50) among prostate specific antigen sera levels in prostatic pathologies.

PubMed

Bouraoui, Y; Ben Jemaa, A; Rodriguez, G; Ben Rais, N; Fraile, B; Paniagua, R; Sellemi, S; Royuela, M; Oueslati, R

2012-10-01

The aim of this work was to characterise the immunoexpression of NF-κB (p50/p65) in human prostatic pathologies and to study its profiles of activation among sera prostate specific antigen antigen (PSA) according the three groups: 0-4ng/mL, 4-20ng/mL and >20ng/mL. Twenty-four men with benign prostate hyperplasia (BPH); 19 men with prostate cancer (PC) and five men with normal prostates (NP). Immunohistochemical and western blot analysis was performed. Serum levels of PSA were assayed by immulite autoanalyser. In BPH and PC samples, immunoexpressions were observed for NF-κBp65 and NF-κBp50; while in NP samples, only were detected NF-κBp50. PC samples showed immunoreactions to NF-κBp65 and NF-κBp50 more intense (respectively 24.18±0.67 and 28.23±2.01) than that observed in BPH samples (respectively18.46±2.04 and 18.66±1.59) with special localisation in the nucleus. Different profiles of NF-κBp65 immunoexpressions were observed and BPH patients with sera PSA levels between 0-4ng/mL presented a significant weak percentage compared to BPH patients with sera PSA levels between 4-20ng/mL and >20ng/mL. No immunoreactions to NF-κBp65 were observed in PC patients with sera PSA levels between 4-20ng/mL. The sensibility of both NF-κB and PSA to inflammation allowed confirming the relationship between these two molecules and its involvement in prostatic diseases progression (inflammatory and neoplasic). Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Finasteride Treatment Alters Tissue Specific Androgen Receptor Expression in Prostate Tissues

PubMed Central

Bauman, Tyler M.; Sehgal, Priyanka D.; Johnson, Karen A.; Pier, Thomas; Bruskewitz, Reginald C.; Ricke, William A.; Huang, Wei

2014-01-01

BACKGROUND Normal and pathologic growth of the prostate is dependent on the synthesis of dihydrotestosterone (DHT) from testosterone by 5α-reductase. Finasteride is a selective inhibitor of 5α-reductase 2, one isozyme of 5α-reductase found in abundance in the human prostate. The objective of this study was to investigate the effects of finasteride on androgen receptor expression and tissue morphology in human benign prostatic hyperplasia specimens. METHODS Patients undergoing transurethral resection of the prostate and either treated or not treated with finasteride between 2004 and 2010 at the University of Wisconsin-Hospital were retrospectively identified using an institutional database. Prostate specimens from each patient were triple-stained for androgen receptor, prostate-specific antigen, and basal marker cytokeratin 5. Morphometric analysis was performed using the multispectral imaging, and results were compared between groups of finasteride treated and non-treated patients. RESULTS Epithelial androgen receptor but not stromal androgen receptor expression was significantly lower in patients treated with finasteride than in non-treated patients. Androgen receptor-regulated prostate-specific antigen was not significantly decreased in finasteride-treated patients. Significant luminal epithelial atrophy and basal cell hyperplasia were prevalent in finasteride treated patients. Epithelial androgen receptor expression was highly correlated to the level of luminal epithelial atrophy. CONCLUSIONS In this study, finasteride decreased the expression of epithelial androgen receptor in a tissue specific manner. The correlation between epithelial androgen receptor and the extent of luminal epithelial atrophy suggests that epithelial androgen receptor may be directly regulating the atrophic effects observed with finasteride treatment. PMID:24789081

Audit of prostate cancer: lessons learnt for current clinical practice, surrogates for quality of care and standardisation and quality assurance.

PubMed

Silcocks, P; Needham, P; Hemsley, F

1999-07-01

Two-hundred and fifty-one prostate cancer patients first registered during 1994 were sampled from a Regional Cancer Registry. In the six months after diagnosis, 39% received drug treatment alone, while 37% had no active treatment. Eighty-one percent of cases were histologically proven. Seventy-six percent had a prostate specific antigen (PSA) test and in 3% the PSA test was the basis for diagnosis. Of histologically proven cases 29% had a Gleason grade. None were staged by clinicians. Key lessons were: The result was a snapshot of current clinical practice which suggested other possible surrogates for quality of care, such as basis of stage and timing of investigations; There is a need for standardisation and quality assurance of the content of pathology reports; Standard treatment protocols would aid recording and comparison of treatments.

Recent Patterns in Shared Decision Making for Prostate-Specific Antigen Testing in the United States.

PubMed

Fedewa, Stacey A; Gansler, Ted; Smith, Robert; Sauer, Ann Goding; Wender, Richard; Brawley, Otis W; Jemal, Ahmedin

2018-03-01

Previous studies report infrequent use of shared decision making for prostate-specific antigen (PSA) testing. It is unknown whether this pattern has changed recently considering increased emphasis on shared decision making in prostate cancer screening recommendations. Thus, the objective of this study is to examine recent changes in shared decision making. We conducted a retrospective cross-sectional study among men aged 50 years and older in the United States using 2010 and 2015 National Health Interview Survey (NHIS) data (n = 9,598). Changes in receipt of shared decision making were expressed as adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). Analyses were stratified on PSA testing (recent [in the past year] or no testing). Elements of shared decision making assessed included the patient being informed about the advantages only, advantages and disadvantages, and full shared decision making (advantages, disadvantages, and uncertainties). Among men with recent PSA testing, 58.5% and 62.6% reported having received ≥1 element of shared decision making in 2010 and 2015, respectively ( P = .054, aPR = 1.04; 95% CI, 0.98-1.11). Between 2010 and 2015, being told only about the advantages of PSA testing significantly declined (aPR = 0.82; 95% CI, 0.71-0.96) and full shared decision making prevalence significantly increased (aPR = 1.51; 95% CI, 1.28-1.79) in recently tested men. Among men without prior PSA testing, 10% reported ≥1 element of shared decision making, which did not change with time. Between 2010 and 2015, there was no increase in shared decision making among men with recent PSA testing though there was a shift away from only being told about the advantages of PSA testing towards full shared decision making. Many men receiving PSA testing did not receive shared decision making. © 2018 Annals of Family Medicine, Inc.

New serum biomarkers for prostate cancer diagnosis

PubMed Central

Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

2014-01-01

Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

Prostate Cancer in Deceased Liver Donors.

PubMed

Skalski, M; Gierej, B; Ziarkiewicz-Wróblewska, B; Hołówko, W; Krawczyk, M

2016-06-01

Prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. The aim of this study was to assess the prevalence of prostate cancer in a group of deceased liver donors. A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n = 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the prostate performed before making the decision regarding liver graft utilization. In the group of 30 donors who underwent prostate examination, 3 (10%) were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine section. liver transplantation was not performed in these cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy specimens. The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to prostate-specific antigen serum concentration (P = .578) or age (P = .730) was not statistically significant. Increased prostate-specific antigen serum concentrations without a diagnosis of prostate cancer in histopathologic examinations should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the frozen biopsy sample, the procured organ should not be used for transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

The influence of physician recommendation on prostate-specific antigen screening.

PubMed

Pucheril, Daniel; Dalela, Deepansh; Sammon, Jesse; Sood, Akshay; Sun, Maxine; Trinh, Quoc-Dien; Menon, Mani; Abdollah, Firas

2015-10-01

Prostate-specific antigen (PSA) screening is controversial, and little is known regarding a physician's effect on a patient's decision to undergo screening. This study's objective was to evaluate the effect of a patient's understanding of the risks and benefits of screening compared to the final recommendation of the provider on the patient's decision to undergo PSA screening. Using the 2012 Behavioral Risk Factor Surveillance System, men older than 55 years who did not have a history of prostate cancer/prostate "problem" and who reported a PSA test within the preceding year were considered to have undergone screening. The percentages of men informed and not informed of the risks and benefits of screening and the percentage men receiving recommendations for PSA screening from their provider were reported. Multivariable complex-sample logistic regression calculated the odds of undergoing screening. In all, 75% of men were informed of screening benefits; however, 32% were informed of screening risks. After being informed of both, 56% of men opted for PSA screening if the provider recommended it, compared with only 21% when not recommended. Men receiving a recommendation to undergo PSA testing had higher odds of undergoing screening (odds ratio [OR] = 4.98, 95% CI: 4.53-5.48) compared with those who were only informed about screening benefits (OR = 2.40, 95% CI: 2.18-2.65) or risks (OR = 0.92, 95% CI: 0.86-0.98). Significant limitations include recall and nonresponse bias. Patients' decision to undergo or forgo PSA screening is heavily influenced by the recommendation of their physician; it is imperative that physicians are cognizant of their biases and facilitate a shared decision-making process. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2006-12-01

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

Prostate-specific antigen density is predictive of outcome in suboptimal prostate seed brachytherapy.

PubMed

Benzaquen, David; Delouya, Guila; Ménard, Cynthia; Barkati, Maroie; Taussky, Daniel

In prostate seed brachytherapy, a D 90 of <130 Gy is an accepted predictive factor for biochemical failure (BF). We studied whether there is a subpopulation that does not need additional treatment after a suboptimal permanent seed brachytherapy implantation. A total of 486 patients who had either BF or a minimum followup of 48 months without BF were identified. BF was defined according to the Phoenix definition (nadir prostate-specific antigen + 2). Univariate and multivariate analyses were performed, adjusting for known prognostic factors such as D 90 and prostate-specific antigen density (PSAD) of ≥0.15 ng/mL/cm 3 , to evaluate their ability to predict BF. Median followup for patients without BF was 72 months (interquartile range 56-96). BF-free recurrence rate at 5 years was 95% and at 8 years 88%. In univariate analysis, PSAD and cancer of the prostate risk assessment score were predictive of BF. On multivariate analysis, none of the factors remained significant. The best prognosis had patients with a low PSAD (<0.15 ng/mL/cm 3 ) and an optimal implant at 30 days after implantation (as defined by D 90  ≥ 130 Gy) compared to patients with both factors unfavorable (p = 0.006). A favorable PSAD was associate with a good prognosis, independently of the D 90 (<130 Gy vs. ≥130 Gy, p = 0.7). Patients with a PSAD of <0.15 ng/mL/cm 3 have little risk of BF, even in the case of a suboptimal implant. These results need to be validated in other patients' cohorts. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Radiation-Induce Immune Modulation in Prostate Cancer

DTIC Science & Technology

2005-01-01

Prostate-specific antigen Prostate carcinoma Mammoglobin-A Breast carcinoma Overexpressed Alpha - fetoprotein Hepatocellular carcinoma and yolk-sac tumors...Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic/Langerhans cells from cord blood CD34+ hematopoietic progenitor...additional subsets, e.g. Langerhans cells of the epidermis, and dermal or interstitial DC. PDC are the major interferon- alpha (IFNca) producing cells

[Testosterone replacement therapy for late-onset hypogonadism after radical prostatectomy: a case report].

PubMed

Nakano, Kosuke; Kiuchi, Hiroshi; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio

2014-08-01

A 53-year-old man presented to our hospital with a few-month history of fatigue and anorexia. His aging male's symptoms (AMS) score was 57, and the free testosterone value was low (6.5 pg/ml). He was diagnosed with severe late-onset hypogonadism indicative of androgen replacement therapy (ART). His serum prostate specific antigen was 8.7 ng/ml, and pelvic magnetic resonance imaging showed a low intensity area in the peripheral zone of the prostate. A systematic 10-core prostate biopsy revealed one core of adenocarcinoma with a Gleason score of 3 + 3=6. Imaging examination revealed organ-confined prostate cancer that was cT2aN0M0. Given his desire for ART for the treatment of hypogonadism, the patient underwent open radical prostatectomy. Pathologic examination demonstrated prostate adenocarcinoma that was pT2aN0, and Gleason score of 3 + 3=6. After confirming that the prostate specific antigen value was under 0.01 ng/ml for three years after prostatectomy, the patient received 125 mg methyltestosterone monthly. His hypogonadism-related symptoms diminished and AMS score dropped to 48. During a three-year follow-up of ART, no biochemical recurrence was found.

Prostate-specific membrane antigen as a target for cancer imaging and therapy

PubMed Central

KIESS, A. P.; BANERJEE, S. R.; MEASE, R. C.; ROWE, S. P.; RAO, A.; FOSS, C. A.; CHEN, Y.; YANG, X.; CHO, S. Y.; NIMMAGADDA, S.; POMPER, M. G.

2016-01-01

The prostate-specific membrane antigen (PSMA) is a molecular target whose use has resulted in some of the most productive work toward imaging and treating prostate cancer over the past two decades. A wide variety of imaging agents extending from intact antibodies to low-molecular-weight compounds permeate the literature. In parallel there is a rapidly expanding pool of antibody-drug conjugates, radiopharmaceutical therapeutics, small-molecule drug conjugates, theranostics and nanomedicines targeting PSMA. Such productivity is motivated by the abundant expression of PSMA on the surface of prostate cancer cells and within the neovasculature of other solid tumors, with limited expression in most normal tissues. Animating the field is a variety of small-molecule scaffolds upon which the radionuclides, drugs, MR-detectable species and nanoparticles can be placed with relative ease. Among those, the urea-based agents have been most extensively leveraged, with expanding clinical use for detection and more recently for radiopharmaceutical therapy of prostate cancer, with surprisingly little toxicity. PSMA imaging of other cancers is also appearing in the clinical literature, and may overtake FDG for certain indications. Targeting PSMA may provide a viable alternative or first-line approach to managing prostate and other cancers. PMID:26213140

Irreversible Electroporation for Prostate Cancer as Salvage Treatment Following Prior Radiation and Cryotherapy.

PubMed

Murray, Katie S; Akin, Oguz; Coleman, Jonathan A

2017-01-01

Salvage treatment options after localized primary treatment failure of prostate cancer are limited and associated with risk for serious complications. We report on the management details of a 57-year-old African American man treated with partial-gland ablation using irreversible electroporation following local recurrence after brachytherapy and prior salvage cryoablation. Therapeutic and functional outcomes were assessed by conventional means, including serum prostate-specific antigen values and prostate biopsy results.

Prostate Expression Databases: Gene Expression Resources for Comparative Studies of Prostate Carcinogenesis

DTIC Science & Technology

2008-01-01

lesions of low -grade prostatic intraepithelial neoplasia (PIN). Over time, osteopontin expressing dysplastic cells seemed to increase in number in high...neoplasia (PIN) lesions, not seen at 2.5 months, were mostly low grade at 12 months and then turning to an abundant combination of low -grade PIN...Prostate specific antigen (PSA) allows the diagnosis of low grade, localized PCa, that allows the physician to offer the patient several efficacious

Interactions between Dietary Factors and Inflammation in Prostate Carcinogenesis

DTIC Science & Technology

2006-12-01

prostatic inflammation/cell damage as measured by serum prostate specific antigen concentration. J Urol. 2006 May;175(5):1937-42. Sutcliffe S...diets rich in red meat and animal fat, and low in vegetables and fruits, are consumed in Western cultures. Although not unequivocal, there is...epidemiologic evidence of a link between prostate cancer incidence and mortality and consumption of red meat and animal fats (6–9). The biological mechanism by

Prostate-Specific Antigen (PSA)–Based Population Screening for Prostate Cancer: An Economic Analysis

PubMed Central

Tawfik, A

2015-01-01

Background The prostate-specific antigen (PSA) blood test has become widely used in Canada to test for prostate cancer (PC), the most common cancer among Canadian men. Data suggest that population-based PSA screening may not improve overall survival. Objectives This analysis aimed to review existing economic evaluations of population-based PSA screening, determine current spending on opportunistic PSA screening in Ontario, and estimate the cost of introducing a population-based PSA screening program in the province. Methods A systematic literature search was performed to identify economic evaluations of population-based PSA screening strategies published from 1998 to 2013. Studies were assessed for their methodological quality and applicability to the Ontario setting. An original cost analysis was also performed, using data from Ontario administrative sources and from the published literature. One-year costs were estimated for 4 strategies: no screening, current (opportunistic) screening of men aged 40 years and older, current (opportunistic) screening of men aged 50 to 74 years, and population-based screening of men aged 50 to 74 years. The analysis was conducted from the payer perspective. Results The literature review demonstrated that, overall, population-based PSA screening is costly and cost-ineffective but may be cost-effective in specific populations. Only 1 Canadian study, published 15 years ago, was identified. Approximately $119.2 million is being spent annually on PSA screening of men aged 40 years and older in Ontario, including close to $22 million to screen men younger than 50 and older than 74 years of age (i.e., outside the target age range for a population-based program). A population-based screening program in Ontario would cost approximately $149.4 million in the first year. Limitations Estimates were based on the synthesis of data from a variety of sources, requiring several assumptions and causing uncertainty in the results. For example, where Ontario-specific data were unavailable, data from the United States were used. Conclusions PSA screening is associated with significant costs to the health care system when the cost of the PSA test itself is considered in addition to the costs of diagnosis, staging, and treatment of screen-detected PCs. PMID:26366237

The Utility of PET/CT in the Planning of External Radiation Therapy for Prostate Cancer.

PubMed

Calais, Jeremie; Cao, Minsong; Nickols, Nicholas G

2018-04-01

Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising level of prostate-specific antigen after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, the irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and the salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of PET into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. 18 F-FDG PET/CT is now routinely used in radiation planning for several cancer types. However, 18 F-FDG PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include 18 F-sodium fluoride, 11 C-acetate, 11 C- or 18 F-choline, 18 F-fluciclovine, and 68 Ga- or 18 F-labeled ligands that bind prostate-specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific but have not yet received Food and Drug Administration New Drug Application approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT-aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of 18 F-fluciclovine PET/CT for planning of salvage radiotherapy with clinical endpoints are under way. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Positive surgical margins after robotic assisted radical prostatectomy: a multi-institutional study.

PubMed

Patel, Vipul R; Coelho, Rafael F; Rocco, Bernardo; Orvieto, Marcelo; Sivaraman, Ananthakrishnan; Palmer, Kenneth J; Kameh, Darien; Santoro, Luigi; Coughlin, Geoff D; Liss, Michael; Jeong, Wooju; Malcolm, John; Stern, Joshua M; Sharma, Saurabh; Zorn, Kevin C; Shikanov, Sergey; Shalhav, Arieh L; Zagaja, Gregory P; Ahlering, Thomas E; Rha, Koon H; Albala, David M; Fabrizio, Michael D; Lee, David I; Chauhan, Sanket

2011-08-01

Positive surgical margins are an independent predictive factor for biochemical recurrence after radical prostatectomy. We analyzed the incidence of and associative factors for positive surgical margins in a multi-institutional series of 8,418 robotic assisted radical prostatectomies. We analyzed the records of 8,418 patients who underwent robotic assisted radical prostatectomy at 7 institutions. Of the patients 323 had missing data on margin status. Positive surgical margins were categorized into 4 groups, including apex, bladder neck, posterolateral and multifocal. The records of 6,169 patients were available for multivariate analysis. The variables entered into the logistic regression models were age, body mass index, preoperative prostate specific antigen, biopsy Gleason score, prostate weight and pathological stage. A second model was built to identify predictive factors for positive surgical margins in the subset of patients with organ confined disease (pT2). The overall positive surgical margin rate was 15.7% (1,272 of 8,095 patients). The positive surgical margin rate for pT2 and pT3 disease was 9.45% and 37.2%, respectively. On multivariate analysis pathological stage (pT2 vs pT3 OR 4.588, p<0.001) and preoperative prostate specific antigen (4 or less vs greater than 10 ng/ml OR 2.918, p<0.001) were the most important independent predictive factors for positive surgical margins after robotic assisted radical prostatectomy. Increasing prostate weight was associated with a lower risk of positive surgical margins after robotic assisted radical prostatectomy (OR 0.984, p<0.001) and a higher body mass index was associated with a higher risk of positive surgical margins (OR 1.032, p<0.001). For organ confined disease preoperative prostate specific antigen was the most important factor that independently correlated with positive surgical margins (4 or less vs greater than 10 ng/ml OR 3.8, p<0.001). The prostatic apex followed by a posterolateral site was the most common location of positive surgical margins after robotic assisted radical prostatectomy. Factors that correlated with cancer aggressiveness, such as pathological stage and preoperative prostate specific antigen, were the most important factors independently associated with an increased risk of positive surgical margins after robotic assisted radical prostatectomy. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer.

PubMed

Rhodes, Daniel R; Sanda, Martin G; Otte, Arie P; Chinnaiyan, Arul M; Rubin, Mark A

2003-05-07

Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence. Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided. Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003). EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence after radical prostatectomy and may be useful in defining a cohort of high-risk patients.

Prostate cancer involving bilateral seminal vesicles along with bone and testicular metastases: a case report.

PubMed

Gao, Qingqiang; Chen, Jianhuai; Dai, Yutian

2018-03-09

In the past 20 years, the incidence of prostate cancer has risen rapidly. It has been ranked as the third most common malignant tumor of the male genitourinary system. Testicular metastasis is uncommon in prostate cancer. Most cases are incidentally found in the treatment of prostate cancer with orchiectomy. Therefore, we believed it was necessary to report the case of our patient with this disease. We present a case of a 69-year-old Han Chinese man with a high total prostate-specific antigen level. A transrectal ultrasound-guided prostate biopsy was performed. A pathology report showed prostate cancer tissue with a Gleason score of 4 + 4 = 8/10. Imaging findings suggested that the prostate cancer tissue involved bilateral seminal vesicles and multiple bones. Next, radioactive seed implantation was carried out, and endocrine therapy was continued after the operation. Then enlargement of the left scrotum was found along with a total prostate-specific antigen level of 19.21 ng/ml. Computed tomography of the middle abdomen and pelvic cavity revealed 2.0 × 1.3-cm lesions of the left testis. The patient underwent a left testicular high resection and right orchiectomy. The postoperative pathology report showed metastatic prostate cancer cells in the left testis. Testicular metastasis of prostate cancer is rare. Therefore, a testicular physical examination is necessary for patients without relapse to avoid a missed diagnosis. Testicular metastasis should be treated according to the principle of treatment for advanced prostate adenocarcinoma if testicular metastasis of prostate adenocarcinoma is detected.

Risk stratification and staging in prostate cancer with prostatic specific membrane antigen PET/CTObjective: A one-stop-shop.

PubMed

Gupta, Manoj; Choudhury, Partha Sarathi; Rawal, Sudhir; Goel, Harish Chandra; Singh, Amitabh; Talwar, Vineet; Sahoo, Saroj Kumar

2017-01-01

Current imaging modalities for prostate cancer (PC) had limitations for risk stratification and staging. Magnetic resonance imaging (MRI) frequently underestimated lymphatic metastasis while bone scintigraphy often had diagnostic dilemmas. Prostatic specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has been remarkable in diagnosing PC recurrence and staging. We hypothesized it can become one-stop-shop for initial risk stratification and staging. Ninety seven PSMA PET-CT studies were re analysed for tumor node metastases (TNM) staging and risk stratification of lymphatic and distant metastases proportion. The histopathology of 23/97 patients was available as gold standard. Chi-square test was used for proportion comparison. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), over-estimation, under-estimation and correct-estimation of T and N stages were calculated. Cohen's kappa coefficient (k) was derived for inter-rater agreement. Lymphic or distant metastases detection on PSMA PET/CT increased significantly with increase in risk category. PSMA PET/CT sensitivity, specificity, PPV and NPV for extra prostatic extension (EPE), seminal vesicle invasion (SVI) and lymphatic metastases were 63.16%, 100%, 100%, 36.36% & 55%, 100%, 100%, 25% and 65.62%, 99.31%, 87.50%, 97.53%, respectively. Cohen's kappa coefficient showed substantial agreement between PSMA PET/CT and histopathological lymphic metastases (κ 0.734) however, it was just in fair agreement (κ 0.277) with T stage. PSMA PET/CT over-estimated, under-estimated and correct-estimated T and N stages in 8.71%, 39.13%, 52.17% and 8.71%, 4.35%, 86.96% cases, respectively. We found that PSMA PET/CT has potential for initial risk stratifications with reasonable correct estimation for N stage. However, it can underestimate T stage. Hence, we suggest that PSMA PET/CT should be used for staging and initial risk stratification of PC as one-stop-shop with regional MRI in surgically resectable cases.

Pathological, Oncologic and Functional Outcomes of a Prospective Registry of Salvage High Intensity Focused Ultrasound Ablation for Radiorecurrent Prostate Cancer.

PubMed

Siddiqui, Khurram M; Billia, Michele; Arifin, Andrew; Li, Fan; Violette, Philippe; Chin, Joseph L

2017-01-01

In this prospective registry we prospectively assessed the oncologic, functional and safety outcomes of salvage high intensity focused ultrasound for radiorecurrent prostate cancer. A total of 81 men were prospectively recruited and evaluated at regular scheduled study visits to 6 months after high intensity focused ultrasound and thereafter as per standard of care. Transrectal ultrasound guided biopsy was performed at 6 months. The primary end point was absence or histological persistence of disease at 6-month biopsy. Secondary end points included quality of life, biochemical recurrence-free survival, overall survival, cancer specific survival and progression to androgen deprivation therapy. Survival analysis was performed according to the Kaplan-Meier method and multivariate analysis was performed using the log rank (Mantel-Cox) test. Mean ± SD prostate specific antigen before high intensity focused ultrasound was 4.06 ± 2.88 ng/ml. At 6 months 63 men underwent biopsy, of whom 22 (35%) had residual disease. At a mean followup of 53.5 ± 31.6 months median biochemical recurrence-free survival was 63 months. The 5-year overall and cancer specific survival rates were 88% and 94.4%, respectively. Nadir prostate specific antigen less than 0.5 ng/ml was a significant predictor of biochemical recurrence-free survival (p=0.014, 95% CI 1.22-5.87). I-PSS significantly increased (p <0.001) while IIEF-5 scores decreased and the SF-36 score did not change significantly. The rate of rectal fistulization and severe incontinence was 3.7% each. A total of 223 complications were recorded in the 180 days after high intensity focused ultrasound (Clavien-Dindo grade 1-195, grade II-20, grade III-7, grade IVa-1). Salvage high intensity focused ultrasound appears to be a viable treatment option for radiorecurrent prostate cancer, with acceptable morbidity. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes.

PubMed

Yan, Lisa; Da Silva, Diane M; Verma, Bhavna; Gray, Andrew; Brand, Heike E; Skeate, Joseph G; Porras, Tania B; Kanodia, Shreya; Kast, W Martin

2015-02-15

LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown to activate immune cells and result in tumor regression in a virally-induced tumor model, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration toward an anti-tumoral milieu, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Real Time PCR was used to evaluate expression of forced LIGHT and other immunoregulatory genes in prostate tumors samples. For in vivo studies, adenovirus encoding murine LIGHT was injected intratumorally into TRAMP-C2 prostate cancer cell tumor bearing mice. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor-specific lymphocytes were quantified via ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. LIGHT expression peaked within 48 hr of infection, recruited effector T cells that recognized mouse prostate stem cell antigen (PSCA) into the tumor microenvironment, and inhibited infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated immunosuppression. Prostate 75:280-291, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

High voltage-derived enhancement of electric conduction in nanogap devices for detection of prostate-specific antigen

NASA Astrophysics Data System (ADS)

Park, Hyung Ju; Chi, Young Shik; Choi, Insung S.; Yun, Wan Soo

2010-07-01

We report a simple method of enhancing electric conductance in nanogap devices without any additional treatments, such as silver-enhancing process. The low electric conductance after selective immobilization of biofunctionalized gold nanoparticles in the gap region was greatly enhanced by repeated I-V scans at relatively high voltage ranges of -5 to 5 V, which was attributed to the formation of a new conduction pathway across the gap. The higher conduction state of the nanogap device showed a very stable I-V curve, which was used as an excellent measure of the existence of prostate-specific antigen.

The PSA testing dilemma: GPs' reports of consultations with asymptomatic men: a qualitative study.

PubMed

Clements, Alison; Watson, Eila; Rai, Tanvi; Bukach, Colleen; Shine, Brian; Austoker, Joan

2007-06-25

The National Health Service Prostate Cancer Risk Management Programme (PCRMP) has recommended that screening for prostate cancer is available for asymptomatic men, on the understanding that they have been provided with full and balanced information about the advantages and limitations of the prostate-specific antigen (PSA) test. Guidance has been distributed to all GPs in England and Wales to assist in the provision of information to men. This study aimed to elicit GPs' accounts of their discussions with asymptomatic men who consult with concerns about prostate cancer in order to identify the degree to which the PCRMP guidance was reflected in these consultations. Qualitative interview study. Semi-structured telephone interviews with 21 GPs from 18 GP practices in Oxfordshire. All GPs reported undertaking some discussion with asymptomatic men about the PSA test. They described focussing most of the discussion on the false-positive and false-negative rates of the test, and the risks associated with a prostate biopsy. They reported less discussion of the potential for diagnosing indolent cancers, the dilemmas regarding treatment options for localised prostate cancer and the potential benefits of testing. Considerable variation existed between GPs in their accounts of the degree of detail given, and GP's presentation of information appeared to be affected by their personal views of the PSA test. The GPs in this study appear to recognise the importance of discussions regarding PSA testing; however, a full and balanced picture of the associated advantages and limitations does not seem to be consistently conveyed. Factors specific to PSA testing which appeared to have an impact on the GPs' discussions were the GP's personal opinions of the PSA test, and the need to counter men's primarily positive views of the benefits of PSA testing. Awareness of the impact of their views on the consultations may help GPs give men a more balanced presentation of the benefits and limitations of the PSA test.

Post-void residual urinary volume is an independent predictor of biopsy results in men at risk for prostate cancer.

PubMed

Cormio, Luigi; Lucarelli, Giuseppe; Netti, Giuseppe Stefano; Stallone, Giovanni; Selvaggio, Oscar; Troiano, Francesco; Di Fino, Giuseppe; Sanguedolce, Francesca; Bufo, Pantaleo; Grandaliano, Giuseppe; Carrieri, Giuseppe

2015-04-01

to determine whether peak flow rate (PFR) and post-void residual urinary volume (PVRUV) predict prostate biopsy outcome. The study population consisted of 1780 patients undergoing first prostate biopsy. Patients with prostate cancer (PCa) had significantly greater prostate-specific antigen (PSA) and PFR but lower prostate volume (PVol) and PVRUV than those without PCa. Receiver operator characteristic curve analysis showed that PVol and PVRUV were the most accurate predictors of biopsy outcome. The addition of PVRUV to the multivariate logistic regression model based on standard clinical parameters (age, PSA, digital rectal examination, PVol) significantly increased the predictive accuracy of the model in both the population overall (79% vs. 77%; p=0.001) and patients with PSA levels up to 10 ng/ml (74.3% vs. 71.7%; p=0.005). PVRUV seems to be an accurate non-invasive test to predict biopsy outcome that can be used alone or in combination with PVol in the decision-making process for men potentially facing a prostate biopsy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Quantitative Time-Resolved Fluorescence Imaging of Androgen Receptor and Prostate-Specific Antigen in Prostate Tissue Sections.

PubMed

Krzyzanowska, Agnieszka; Lippolis, Giuseppe; Helczynski, Leszek; Anand, Aseem; Peltola, Mari; Pettersson, Kim; Lilja, Hans; Bjartell, Anders

2016-05-01

Androgen receptor (AR) and prostate-specific antigen (PSA) are expressed in the prostate and are involved in prostate cancer (PCa). The aim of this study was to develop reliable protocols for reproducible quantification of AR and PSA in benign and malignant prostate tissue using time-resolved fluorescence (TRF) imaging techniques. AR and PSA were detected with TRF in tissue microarrays from 91 PCa patients. p63/ alpha-methylacyl-CoA racemase (AMACR) staining on consecutive sections was used to categorize tissue areas as benign or cancerous. Automated image analysis was used to quantify staining intensity. AR intensity was significantly higher in AMACR+ and lower in AMACR- cancer areas as compared with benign epithelium. The PSA intensity was significantly lower in cancer areas, particularly in AMACR- glands. The AR/PSA ratio varied significantly in the AMACR+ tumor cells as compared with benign glands. There was a trend of more rapid disease progression in patients with higher AR/PSA ratios in the AMACR- areas. This study demonstrates the feasibility of developing reproducible protocols for TRF imaging and automated image analysis to study the expression of AR and PSA in benign and malignant prostate. It also highlighted the differences in AR and PSA protein expression within AMACR- and AMACR+ cancer regions. © 2016 The Histochemical Society.

68Ga-PSMA PET/CT in Patients with Rising Prostatic-Specific Antigen After Definitive Treatment of Prostate Cancer: Detection Efficacy and Diagnostic accuracy.

PubMed

Hamed, Maged Abdel Galil; Basha, Mohammad Abd Alkhalik; Ahmed, Hussien; Obaya, Ahmed Ali; Afifi, Amira Hamed Mohamed; Abdelbary, Eman H

2018-06-20

68 Ga-prostate-specific membrane antigen-11 ( 68 Ga-PSMA-11) is a recently developed positron emission tomography (PET) tracer that can detect prostate cancer (PC) relapses and metastases with high contrast resolution. The aim of this study was to assess the detection efficacy and diagnostic accuracy of 68 Ga-PSMA PET/CT image in patients with rising prostatic-specific antigen (PSA) after treatment of PC. The present prospective study included 188 patients who exhibited rising of PSA level on a routine follow-up examination after definitive treatment of PC. All patients underwent a 68 Ga-PSMA PET/CT examination. For each patient, we determined the disease stage, the Gleason score, and the maximum standardized uptake value of the local recurrence and extraprostatic metastases. The detection efficacy and diagnostic accuracy of 68 Ga-PSMA PET/CT were established by histopathology and clinical and imaging follow-up as the reference standards. 68 Ga-PSMA PET/CT detected tumour relapse in 165 patients (35 patients had local recurrence, 106 patients had extraprostatic metastases, and 24 patients had combined lesions). The sensitivity, specificity, and accuracy values of 68 Ga-PSMA PET/CT examination in the detection of PC recurrence were 98.8%, 100%, and 98.8%, respectively. 68 Ga-PSMA PET/CT revealed an overall detection rate of 87.8% (165/188) in patients with rising PSA (median of 2.2 ng/mL, and range of 0.01-70 ng/mL). 68 Ga-PSMA PET/CT is a valuable tool for the detection of PC local recurrence or extraprostatic metastases following rising PSA levels after primary definitive therapy and should be incorporated during routine work-up. Copyright © 2018. Published by Elsevier Inc.

The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA

PubMed Central

Fleshner, Katherine; Carlsson, Sigrid V.; Roobol, Monique J.

2017-01-01

Guidelines conflict regarding recommendations for prostate-specific antigen (PSA) screening for early detection of prostate cancer. The United States Preventive Services Task Force (USPSTF) assigned a grade of D (recommending against screening) for men 75 and older in 2008 and for men of all ages in 2012. We reviewed temporal trends in rates of screening before and after the 2012 recommendation based on a literature search for studies published between 2011/01/01–2016/10/03 on PSA utilization patterns, changes in prostate cancer incidence and biopsy patterns, and how the recommendation has shaped physician and patient attitudes about PSA screening and subsequent ordering of other screening tests. Rates of PSA screening decreased by 3–10 percentage points among all age groups and within most U.S. geographic regions. Rates of prostate biopsy and prostate cancer incidence have declined in unison, with a notable shift towards higher grade, stage and risk upon detection. Despite the recommendation, some physicians reported ongoing willingness to screen appropriately selected men, and men largely reported intending to continue to ask for the PSA test. In the coming years, we expect to have a better picture of whether these decreased rates of screening will impact prostate cancer metastasis and mortality. PMID:27995937

Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study.

PubMed

Abrate, Alberto; Lazzeri, Massimo; Lughezzani, Giovanni; Buffi, Nicolòmaria; Bini, Vittorio; Haese, Alexander; de la Taille, Alexandre; McNicholas, Thomas; Redorta, Joan Palou; Gadda, Giulio M; Lista, Giuliana; Kinzikeeva, Ella; Fossati, Nicola; Larcher, Alessandro; Dell'Oglio, Paolo; Mistretta, Francesco; Freschi, Massimo; Guazzoni, Giorgio

2015-04-01

To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer. © 2014 The Authors. BJU International © 2014 BJU International.

Use of prostate-specific antigen testing as a disease surveillance tool following radical prostatectomy.

PubMed

Trantham, Laurel Clayton; Nielsen, Matthew E; Mobley, Lee R; Wheeler, Stephanie B; Carpenter, William R; Biddle, Andrea K

2013-10-01

Prostate-specific antigen (PSA) testing is recommended every 6 to 12 months for the first 5 years following radical prostatectomy as a means to detect potential disease recurrence. Despite substantial research on factors affecting treatment decisions, recurrence, and mortality, little is known about whether men receive guideline-concordant surveillance testing or whether receipt varies by year of diagnosis, time since treatment, or other individual characteristics. Surveillance testing following radical prostatectomy among elderly men was examined using Surveillance, Epidemiology, and End Results cancer registry data linked to Medicare claims. Multivariate logistic regression was used to examine the effect of demographic, tumor, and county-level characteristics on the odds of receiving surveillance testing within a given 1-year period following treatment. Overall, receipt of surveillance testing was high, with 96% of men receiving at least one test the first year after treatment and approximately 80% receiving at least one test in the fifth year after treatment. Odds of not receiving a test declined with time since treatment. Nonmarried men, men with less-advanced disease, and non-Hispanic blacks and Hispanics had higher odds of not receiving a surveillance test. Year of diagnosis did not affect the receipt of surveillance tests. Most men receive guideline-concordant surveillance PSA testing after prostatectomy, although evidence of a racial disparity between non-Hispanic whites and some minority groups exists. The decline in surveillance over time suggests the need for well-designed long-term surveillance plans following radical prostatectomy. Cancer 2013;119:3523-3530.. © 2013 American Cancer Society. Copyright © 2013 American Cancer Society.

Engineered T cells for pancreatic cancer treatment

PubMed Central

Katari, Usha L; Keirnan, Jacqueline M; Worth, Anna C; Hodges, Sally E; Leen, Ann M; Fisher, William E; Vera, Juan F

2011-01-01

Objective Conventional chemotherapy and radiotherapy produce marginal survival benefits in pancreatic cancer, underscoring the need for novel therapies. The aim of this study is to develop an adoptive T cell transfer approach to target tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen that is frequently expressed by pancreatic cancer cells. Methods Expression of PSCA on cell lines and primary tumour samples was confirmed by immunohistochemistry. Healthy donor- and patient-derived T cells were isolated, activated in vitro using CD3/CD28, and transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these cells to kill tumour cells was analysed by chromium-51 (Cr51) release. Results Prostate stem cell antigen was expressed on >70% of the primary tumour samples screened. Activated, CAR-modified T cells could be readily generated in clinically relevant numbers and were specifically able to kill PSCA-expressing pancreatic cancer cell lines with no non-specific killing of PSCA-negative target cells, thus indicating the potential efficacy and safety of this approach. Conclusions Prostate stem cell antigen is frequently expressed on pancreatic cancer cells and can be targeted for immune-mediated destruction using CAR-modified, adoptively transferred T cells. The safety and efficacy of this approach indicate that it deserves further study and may represent a promising novel treatment for patients with pancreatic cancer. PMID:21843265

Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

PubMed

Lokant, M T; Naz, R K

2015-04-01

Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P < 0.01) compared with PC and prostatitis. All others were nonsignificant (P < 0.05). Men (33%) with BPH had PSA antibodies by ELISA and Western blot. These discoveries may find clinical application in differential diagnosis among prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis. © 2014 Blackwell Verlag GmbH.

A Phase I Trial of Samarium-153-Lexidronam Complex for Treatment of Clinically Nonmetastatic High-Risk Prostate Cancer: First Report of a Completed Study

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

Valicenti, Richard K., E-mail: richard.valicenti@ucdmc.ucdavis.ed; Trabulsi, Edouard; Intenzo, Charles

Purpose: We completed a Phase I trial to determine the maximum tolerated dose of samarium-153 EDTMP ({sup 153}Sm) with hormonal therapy (HT) and radiation therapy (RT) in high-risk clinically nonmetastatic prostate cancer. Methods and Materials: High-risk M0 prostate cancer patients (prostate-specific antigen >20 ng/mL, Gleason score >7, or >T3) were eligible for this prospective trial of dose-escalated radioactive {sup 153}Sm-EDTMP (.25-2.0 mCi/kg) as primary or postoperative therapy. After 1 month of HT, we administered {sup 153}Sm-EDTMP followed by 4 more months of HT, 46.8 Gy to the pelvic region and 23.4 Gy to the prostate target (TD = 70.2 Gy).more » The primary endpoint was Grade III toxicity or higher by the National Cancer Institute Common Toxicity Criteria. Results: Twenty-nine patients enrolled (median prostate-specific antigen = 8.2 ng/mL, 27/29 (93%) T stage {>=}T2b, 24/29 (83%) had Gleason >7) and received {sup 153}Sm-EDTMP (.25 mCi/kg, 4 patients; 0.5 mCi/kg, 4 patients; 0.75 mCi/kg, 6 patients; 1.0 mCi/kg, 6 patients; 1.5 mCi/kg, 5 patients; 2.0mCi/kg, 4 patients). Twenty-eight patients underwent all planned therapy without delays (1 patient required surgery before the start of RT). With a median follow-up time of 23 months, there were 2 patients (7 %) experiencing Grade III hematologic toxicity. There were no other Grade III or IV side effects. Conclusions: Our trial demonstrates that 2 mCi/kg {sup 153}Sm -EDTMP with HT and RT was safe and feasible in men with high-risk M0 prostate cancer. A Phase II study to test this treatment is currently underway by the Radiation Therapy Oncology Group.« less

Percent free prostate-specific antigen for prostate cancer diagnosis in Chinese men with a PSA of 4.0-10.0 ng/mL: Results from the Chinese Prostate Cancer Consortium.

PubMed

Chen, Rui; Xie, Liping; Cai, Xiaobing; Huang, Yiran; Zhou, Liqun; Ma, Lulin; Gao, Xu; Xu, Chuanliang; Ren, Shancheng; Shao, Pengfei; Xu, Danfeng; Xu, Kexin; Ye, Zhangqun; Liu, Chunxiao; Ye, Dingwei; Lu, Li; Fu, Qiang; Hou, Jianquan; Yuan, Jianlin; He, Dalin; Zhou, Tie; Wang, Fubo; He, Biming; Sun, Yinghao

2015-04-01

To test the diagnostic performance of percent free prostate-specific antigen (%fPSA) in predicting any prostate cancer (PCa) and high-grade prostate cancer (HGPCa) in a retrospective multi-center biopsy cohort with a PSA level of 4.0-10.0 ng/mL in China. Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st, 2010 to December 31st, 2013. Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization (WHO) standard. The diagnostic accuracy of PSA, %fPSA, and %fPSA in combination with PSA (%fPSA + PSA) was determined using the area under the receiver operating characteristic (ROC) curve (AUC). A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included, and the detection rate of PCa was 25.1%. The AUC of %fPSA and %fPSA + PSA in predicting any PCa was superior to PSA alone in men aged ≥60 years (0.623 vs. 0.534, p  < 0.0001) but not in men aged 40-59 years (0.517 vs. 0.518, p  = 0.939). Similar result was yield in predicting HGPCa. In a clinical setting of Chinese men with 4.0-10.0 ng/mL PSA undergoing initial prostate biopsy, adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients ≥60 but not in patients aged 40-59 years.

p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) repress prostate specific antigen levels in human prostate cancer cell lines.

PubMed

Wong, Lilian I L; Labrecque, Mark P; Ibuki, Naokazu; Cox, Michael E; Elliott, John E; Beischlag, Timothy V

2015-03-25

Despite stringent restrictions on their use by many countries since the 1970s, the endocrine disrupting chemicals, DDT and DDE are still ubiquitous in the environment. However, little attention has been directed to p,p'-DDT and the anti-androgen, p,p'-DDE on androgen receptor (AR) target gene transcription in human cells. Inhibitors of androgenic activity may have a deleterious clinical outcome in prostate cancer screens and progression, therefore we determined whether environmentally relevant concentrations of p,p'-DDT and p,p'-DDE negatively impact AR-regulated expression of prostate-specific antigen (PSA), and other AR target genes in human LNCaP and VCaP prostate cancer cells. Quantitative real-time PCR and immuno-blotting techniques were used to measure intracellular PSA, PSMA and AR mRNA and protein levels. We have shown for the first time that p,p'-DDT and p,p'-DDE repressed R1881-inducible PSA mRNA and protein levels in a dose-dependent manner. Additionally, we used the fully automated COBAS PSA detection system to determine that extracellular PSA levels were also significantly repressed. These chemicals achieve this by blocking the recruitment of AR to the PSA promoter region at 10 μM, as demonstrated by the chromatin immunoprecipitation (ChIP) in LNCaP cells. Both p,p'-DDT and p,p'-DDE repressed R1881-inducible AR protein accumulation at 10 μM. Thus, we conclude that men who have been exposed to either DDT or DDE may produce a false-negative PSA test when screening for prostate cancer, resulting in an inaccurate clinical diagnosis. More importantly, prolonged exposure to these anti-androgens may mimic androgen ablation therapy in individuals with prostate cancer, thus exacerbating the condition by inadvertently forcing adaptation to this stress early in the disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

68Ga-PSMA-11 PET Represents the Tumoricidal Effect of 223Ra in a Patient With Castrate-Resistant Metastatic Prostate Cancer.

PubMed

Ahmadzadehfar, Hojjat; Schlenkhoff, Carl Diedrich; Rogenhofer, Sebastian; Yordanova, Anna; Essler, Markus

2016-09-01

A 64-year-old man with prostate cancer and an increasing prostate-specific antigen (PSA) level under therapy with abiraterone acetate underwent a therapy with Ra. Before the first therapy and 4 weeks after the last cycle, the patient underwent Ga-PSMA PET, which showed a clear response of bone metastases.

Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml−1

PubMed Central

Chen, Rui; Zhou, Li-Qun; Cai, Xiao-Bing; Xie, Li-Ping; Huang, Yi-Ran; He, Da-Lin; Gao, Xu; Xu, Chuan-Liang; Ding, Qiang; Wei, Qiang; Yin, Chang-Jun; Ren, Shan-Cheng; Wang, Fu-Bo; Tian, Ye; Sun, Zhong-Quan; Fu, Qiang; Ma, Lu-Lin; Zheng, Jun-Hua; Ye, Zhang-Qun; Ye, Ding-Wei; Xu, Dan-Feng; Hou, Jian-Quan; Xu, Ke-Xin; Yuan, Jian-Lin; Gao, Xin; Liu, Chun-Xiao; Pan, Tie-Jun; Sun, Ying-Hao

2015-01-01

Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0–10.0 ng ml−1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1–20.0 ng ml−1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml−1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0–10.0 ng ml−1 and 10.1–20.0 ng ml−1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0–10.0 ng ml−1 and 10.1–20.0 ng ml−1. PMID:25926603

Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml(-1).

PubMed

Chen, Rui; Zhou, Li-Qun; Cai, Xiao-Bing; Xie, Li-Ping; Huang, Yi-Ran; He, Da-Lin; Gao, Xu; Xu, Chuan-Liang; Ding, Qiang; Wei, Qiang; Yin, Chang-Jun; Ren, Shan-Cheng; Wang, Fu-Bo; Tian, Ye; Sun, Zhong-Quan; Fu, Qiang; Ma, Lu-Lin; Zheng, Jun-Hua; Ye, Zhang-Qun; Ye, Ding-Wei; Xu, Dan-Feng; Hou, Jian-Quan; Xu, Ke-Xin; Yuan, Jian-Lin; Gao, Xin; Liu, Chun-Xiao; Pan, Tie-Jun; Sun, Ying-Hao

2015-01-01

Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml-1 , however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 , respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 .

Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

PubMed

Doluoglu, Omer Gokhan; Ceylan, Cavit; Kilinc, Fatih; Gazel, Eymen; Resorlu, Berkan; Odabas, Oner

2016-01-01

We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer. The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5-20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6-20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32). Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa.

Temporarily deferred therapy (watchful waiting) for men younger than 70 years and with low-risk localized prostate cancer in the prostate-specific antigen era.

PubMed

Carter, Corey A; Donahue, Timothy; Sun, Leon; Wu, Hongyu; McLeod, David G; Amling, Christopher; Lance, Raymond; Foley, John; Sexton, Wade; Kusuda, Leo; Chung, Andrew; Soderdahl, Douglas; Jackmaan, Stephen; Moul, Judd W

2003-11-01

Watchful waiting (WW) is an acceptable strategy for managing prostate cancer (PC) in older men. Prostate-specific antigen (PSA) testing has resulted in a stage migration, with diagnoses made in younger men. An analysis of the Department of Defense Center for Prostate Disease Research Database was undertaken to document younger men with low- or intermediate-grade PC who initially chose WW. We identified men choosing WW who were diagnosed between January 1991 and January 2002, were 70 years or younger, had a Gleason score < or = 6 with no Gleason pattern 4, had no more than three positive cores on biopsy, and whose clinical stage was < or = T2 and PSA level was < or = 20. We analyzed their likelihood of remaining on WW, the factors associated with secondary treatment, and the influence of comorbidities. Three hundred thirteen men were identified. Median follow-up time was 3.8 years. Median age was 65.4 years (range, 41 to 70 years). Ninety-eight patients remained on WW; 215 proceeded to treatment. A total of 57.3% and 73.2% chose treatment within the first 2 and 4 years, respectively. Median PSA doubling time (DT) was 2.5 years for those who underwent therapy; those remaining on WW had a median DT of 25.8 years. The type of secondary treatment was associated with the number of patient's comorbidities (P =.012). Younger patients who choose WW seemed more likely to receive secondary treatment than older patients. PSA DTs often predict the use of secondary treatment. The number of comorbidities a patient has influences the type of secondary therapy chosen. The WW strategy may better be termed temporarily deferred therapy.

Prostate specific antigen bounce is related to overall survival in prostate brachytherapy.

PubMed

Hinnen, Karel A; Monninkhof, Evelyn M; Battermann, Jan J; van Roermund, Joep G H; Frank, Steven J; van Vulpen, Marco

2012-02-01

To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy. We analyzed 975 patients treated with (125)I implantation monotherapy between 1992 and 2006. All patients had tumor Stage ≤ 2c, Gleason score ≤ 7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors. Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20-0.48). A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival. Copyright © 2012 Elsevier Inc. All rights reserved.

Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes

PubMed Central

Yan, Lisa; Da Silva, Diane M.; Verma, Bhavna; Gray, Andrew; Brand, Heike E.; Skeate, Joseph G.; Porras, Tania B.; Kanodia, Shreya; Kast, W. Martin

2014-01-01

Background LIGHT, a ligand for lymphotoxin-β receptor (LTβR) and herpes virus entry mediator, is predominantly expressed on activated immune cells and LTβR signaling leads to the recruitment of lymphocytes. The interaction between LIGHT and LTβR has been previously shown in a virus induced tumor model to activate immune cells and result in tumor regression, but the role of LIGHT in tumor immunosuppression or in a prostate cancer setting, where self antigens exist, has not been explored. We hypothesized that forced expression of LIGHT in prostate tumors would shift the pattern of immune cell infiltration, would inhibit T regulatory cells (Tregs) and would induce prostate cancer tumor associated antigen (TAA) specific T cells that would eradicate tumors. Methods Real Time PCR was used to evaluate expression of forced LIGHT and various other genes in prostate tumors samples. Adenovirus encoding murine LIGHT was injected intratumorally into TRAMP C2 prostate cancer cell tumor bearing mice for in vivo studies. Chemokine and cytokine concentrations were determined by multiplex ELISA. Flow cytometry was used to phenotype tumor infiltrating lymphocytes and expression of LIGHT on the tumor cell surface. Tumor specific lymphocytes were quantified via an ELISpot assay. Treg induction and Treg suppression assays determined Treg functionality after LIGHT treatment. Results LIGHT expression peaked within 48 hours of infection, recruited effector T cells into the tumor microenvironment that recognized mouse prostate stem cell antigen (PSCA) and inhibited the infiltration of Tregs. Tregs isolated from tumor draining lymph nodes had impaired suppressive capability after LIGHT treatment. LIGHT in combination with a therapeutic vaccine, PSCA TriVax, reduced tumor burden. Conclusion Forced LIGHT treatment combined with PSCA TriVax therapeutic vaccination delays prostate cancer progression in mice by recruiting effector T lymphocytes to the tumor and inhibiting Treg mediated immunosuppression. PMID:25399517

Relationship of age, prostate-specific antigen, and prostate volume in Indonesian men with benign prostatic hyperplasia.

PubMed

Putra, Ida Bagus O W; Hamid, Agus R A H; Mochtar, Chaidir A; Umbas, Rainy

2016-06-01

To investigate the relationship between age, prostate specific antigen (PSA), and prostate volume (PV) in Indonesian men with histologically proven benign prostatic hyperplasia. Data were generated from our BPH database from June 1994 until December 2013. Subjects were men with a minimum age of 40 years with chief complaint of LUTS or urinary retention, diagnosed with BPH. All patients underwent TRUS-guided prostate biopsy. Patients with PSA level >10 ng/mL were excluded from the study to exclude the possibility of occult prostate cancer. PV was measured with TRUS. Appropriate statistical tests were employed for data analysis. In all, 1638 patients were enrolled in our study. There was a statistically significant difference in PSA (P = 0.03) and PV (P < 0.0001) between age groups. Overall correlation between age, PSA, and PV were: i). Age and PV (r = 0.12, P < 0.0001); ii). Age and PSA (r = 0.07, P = 0.008); iii). PSA and PV (r = 0.26, P < 0.0001). Subgroup analysis in terms of indwelling catheter use versus without: i). Age 66.09 ± 8 years versus 65.38 ± 7.66 years (P = 0.158); ii). PSA 4.93 ± 2.62 ng/mL versus 4.68 ± 2.82 ng/mL (P = 0.038); iii). PV 47.58 ± 21.33 mL versus 41.43 ± 20.55 mL (P < 0.0001). Correlation between age, PSA, and PV in patients were similar in patients with and without indwelling catheter. In Indonesian men with biopsy-proven BPH, both PV and PSA increased with ageing. Prostate volume was significantly correlated with PSA. Even though the results were weaker, these results are consistent with results in other sets of population. The results vary between different countries and thus, ethnicities. Indonesia is a populous a sociocultural and ethnically diverse country. Therefore, aside from PSA, age, and PV, when investigating men with BPH, ethnicity may also need to be taken into account.

Compact CdZnTe-based gamma camera for prostate cancer imaging

NASA Astrophysics Data System (ADS)

Cui, Yonggang; Lall, Terry; Tsui, Benjamin; Yu, Jianhua; Mahler, George; Bolotnikov, Aleksey; Vaska, Paul; De Geronimo, Gianluigi; O'Connor, Paul; Meinken, George; Joyal, John; Barrett, John; Camarda, Giuseppe; Hossain, Anwar; Kim, Ki Hyun; Yang, Ge; Pomper, Marty; Cho, Steve; Weisman, Ken; Seo, Youngho; Babich, John; LaFrance, Norman; James, Ralph B.

2011-06-01

In this paper, we discuss the design of a compact gamma camera for high-resolution prostate cancer imaging using Cadmium Zinc Telluride (CdZnTe or CZT) radiation detectors. Prostate cancer is a common disease in men. Nowadays, a blood test measuring the level of prostate specific antigen (PSA) is widely used for screening for the disease in males over 50, followed by (ultrasound) imaging-guided biopsy. However, PSA tests have a high falsepositive rate and ultrasound-guided biopsy has a high likelihood of missing small cancerous tissues. Commercial methods of nuclear medical imaging, e.g. PET and SPECT, can functionally image the organs, and potentially find cancer tissues at early stages, but their applications in diagnosing prostate cancer has been limited by the smallness of the prostate gland and the long working distance between the organ and the detectors comprising these imaging systems. CZT is a semiconductor material with wide band-gap and relatively high electron mobility, and thus can operate at room temperature without additional cooling. CZT detectors are photon-electron direct-conversion devices, thus offering high energy-resolution in detecting gamma rays, enabling energy-resolved imaging, and reducing the background of Compton-scattering events. In addition, CZT material has high stopping power for gamma rays; for medical imaging, a few-mm-thick CZT material provides adequate detection efficiency for many SPECT radiotracers. Because of these advantages, CZT detectors are becoming popular for several SPECT medical-imaging applications. Most recently, we designed a compact gamma camera using CZT detectors coupled to an application-specific-integratedcircuit (ASIC). This camera functions as a trans-rectal probe to image the prostate gland from a distance of only 1-5 cm, thus offering higher detection efficiency and higher spatial resolution. Hence, it potentially can detect prostate cancers at their early stages. The performance tests of this camera have been completed. The results show better than 6-mm resolution at a distance of 1 cm. Details of the test results are discussed in this paper.

Prostate-specific membrane antigen-based imaging in prostate cancer: impact on clinical decision making process.

PubMed

Demirkol, Mehmet Onur; Acar, Ömer; Uçar, Burcu; Ramazanoğlu, Sultan Rana; Sağlıcan, Yeşim; Esen, Tarık

2015-05-01

There is an ongoing need for an accurate imaging modality which can be used for staging purposes, metastatic evaluation, predicting biologic aggresiveness and investigating recurrent disease in prostate cancer. Prostate specific membrane antigen, given its favorable molecular characteristics, holds a promise as an ideal target for prostate cancer-specific nuclear imaging. In this study, we evaluated our initial results of PSMA based PET/CT imaging in prostate cancer. A total of 22 patients with a median age and serum PSA level of 68 years and 4.15 ng/ml, respectively underwent Ga-68 PSMA PET/CT in our hospital between Februrary and August 2014. Their charts were retrospectively reviewed in order to document the clinical characteristics, the indications for and the results of PSMA based imaging and the impact of Ga-68 PSMA PET/CT findings on disease management. The most common indications were rising PSA after local ± adjuvant treatment followed by staging and metastatic evaluation before definitive or salvage treatment. All except 2 patients had prostatic ± extraprostatic PSMA positive lesions. For those who had a positive result; treatment strategies were tailored accordingly. Above the PSA level of 2 ng/ml, none of the PSMA based nuclear imaging studies revealed negative results. PSMA based nuclear imaging has significantly impacted our way of handling patients with prostate cancer. Its preliminary performance in different clinical scenarios and ability to detect lesions even in low PSA values seems fairly promising and deserves to be supplemented with further clinical studies. © 2015 Wiley Periodicals, Inc.

Treatment- and Disease-Related Complications of Prostate Cancer

PubMed Central

Simoneau, Anne R

2006-01-01

One of the highlights of the 16th International Prostate Cancer Update was a session on treatment- and disease-related complications of prostate disease. It began with presentation of a challenging case of rising prostate-specific antigen levels after radical prostatectomy, followed by an overview of the use of zoledronic acid in prostate cancer, a review of side effects of complementary medicines, an overview of complications of cryotherapy, an assessment of complications of brachytherapy and external beam radiation therapy, and a comparison of laparoscopy versus open prostatectomy. PMID:17021643

The role of blood neutrophil count and the neutrophil-to-lymphocyte ratio as a predictive factor for prostate biopsy results.

PubMed

Kamali, Koosha; Ashrafi, Mojtaba; Shadpour, Pejman; Ameli, Mojtaba; Khayyamfar, Amirmahdi; Abolhasani, Maryam; Azizpoor, Amin

2018-04-01

It is apparent that prostate cancer has harmful effects on the erythrocytes, leucocytes, and platelets. In addition, it has been suggested that the toxic granules in neutrophils lead to inflammation in the cancerous tissues besides the activation of monocytes, so in this study we aimed to evaluate the blood neutrophil count besides the neutrophil-to-lymphocyte ratio as a predictive factor for prostate biopsy results and their relationship with prostate cancer grade in patients undergoing biopsy of the prostate. For all men with irritative lower urinary tract symptoms visiting Hasheminezhad Hospital from January to July 2015, in case of having a suspicious digital rectal examination or aged above 40 years, prostate-specific antigen was requested and in case of abnormal results, they underwent prostate biopsy. In order to examine the study hypothesis, the blood neutrophil count and the neutrophil-to-lymphocyte ratio were measured and compared with the abnormal prostate-specific antigen results and suspicious digital rectal examination. Among the 500 referred samples for biopsy, 352 (70.4%) had a negative biopsy result, while it was positive in the other 148 (29.6). The mean neutrophil count showed no statistical difference regarding the biopsy results (p = 0.381). When measuring the neutrophil-to-lymphocyte ratio again with biopsy results, no statistically significant difference was obtained based on the biopsy results (p = 0.112). Neutrophil count and neutrophil-to-lymphocyte ratio cannot be predictive factors for positive prostate cancer biopsy.

Organic electrochemical transistor based immunosensor for prostate specific antigen (PSA) detection using gold nanoparticles for signal amplification.

PubMed

Kim, Duck-Jin; Lee, Nae-Eung; Park, Joon-Shik; Park, In-Jun; Kim, Jung-Gu; Cho, Hyoung J

2010-07-15

We demonstrated a highly sensitive organic electrochemical transistor (OECT) based immunosensor with a low detection limit for prostate specific antigen/alpha1-antichymotrypsin (PSA-ACT) complex. The poly(styrenesulfonate) doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS) based OECT with secondary antibody conjugated gold nanoparticles (AuNPs) provided a detection limit of the PSA-ACT complex as low as 1pg/ml, as well as improved sensitivity and a dynamic range, due to the role of AuNPs in the signal amplification. The sensor performances were particularly improved in the lower concentration range where the detection is clinically important for the preoperative diagnosis and screening of prostate cancer. This result shows that the OECT-based immunosensor can be used as a transducer platform acceptable to the point-of-care (POC) diagnostic systems and demonstrates adaptability of organic electronics to clinical applications. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Screening for prostate cancer

NASA Technical Reports Server (NTRS)

Weirich, Stephen A.

1993-01-01

Despite recent advances in both the survival and cure rates for many forms of cancer, unfortunately the same has not been true for prostate cancer. In fact, the age-adjusted death rate from prostate cancer has not significantly improved since 1949, and prostate cancer remains the most common cancer in American men, causing the second highest cancer mortality rate. Topics discussed include the following: serum testosterone levels; diagnosis; mortality statistics; prostate-sppecific antigen (PSA) tests; and the Occupational Medicine Services policy at LeRC.

Using T2-Exchange from Ln3+DOTA-Based Chelates for Contrast-Enhanced Molecular Imaging of Prostate Cancer with MRI

DTIC Science & Technology

2015-04-01

antigen ( PSMA ) of prostate cancer cells would then be synthesized and tested with both in vitro and in vivo experiments. Major Findings: We found that the...simplified chemistry. 15. SUBJECT TERMS MRI Contrast Agent, T2 contrast, Prostate Cancer, PSMA Targeted Agent, Early Detection and Diagnosis, Dysprosium... PSMA ), which is significantly over-expressed by prostate cancer cells, has proven to be an excellent target for imaging prostate cancer in mouse

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

PubMed

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

2016-10-01

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

Biomarker validation of self-reported sex among middle-aged female sex workers in China.

PubMed

Guida, Jennifer; Fukunaga, Ami; Liu, Hongjie

2017-03-01

The objective of this study was to examine information bias arising from self-reported sexual activity and its association with syphilitic infections among female sex workers (FSWs) aged 35 years and older in China. A questionnaire was administered to 1245 middle-aged FSWs. Respondents self-reported sexual intercourse in the past 48 hours. The prostate-specific antigen test was used to verify self-reported sexual activity. FSWs were considered discordant if they indicated no sexual intercourse in the past 48 hours on the questionnaire and had a positive prostate-specific antigen test. Logistic regression was used to assess the associations between discordance and syphilis. Three hundred twenty FSWs self-reported no engagement in sexual intercourse in the past 48 hours. One-fourth of respondents (25%) were discordant. Twenty-two percent and 35.8% of discordant FSWs tested positive for active and prevalent syphilis, respectively. After adjusting for confounders, discordant FSWs had 3.8 times the odds of active syphilis (95% confidence interval: 1.52-9.30) and 2.6 times the odds of prevalent syphilis (95% confidence interval: 1.37-5.02), compared with concordant FSWs. FSWs who had active or prevalent syphilis were more likely to be discordant. Data collected via self-reported questionnaire may not be a valid tool to assess sexual behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer

DTIC Science & Technology

2001-07-01

Rogers, H. Ragde, G. M. Kenny, et al. 1999. Follow-up evaluation of a phase II prostate cancer vaccine trial. Prostate 40: 125-129. 69. Troyer, J. K., M...Slusher, D. Price, and J. T. Coyle. 1993. Abnormal acidic amino acids and N-acetylaspartylglutamate in hereditary canine motoneuron disease. Brain Res...levels were at least 10-fold higher, re- promoter, that of the herpesvirus thymidine kinase flecting the greater basal activity of these promoters in gene

Bayesian semiparametric estimation of covariate-dependent ROC curves

PubMed Central

Rodríguez, Abel; Martínez, Julissa C.

2014-01-01

Receiver operating characteristic (ROC) curves are widely used to measure the discriminating power of medical tests and other classification procedures. In many practical applications, the performance of these procedures can depend on covariates such as age, naturally leading to a collection of curves associated with different covariate levels. This paper develops a Bayesian heteroscedastic semiparametric regression model and applies it to the estimation of covariate-dependent ROC curves. More specifically, our approach uses Gaussian process priors to model the conditional mean and conditional variance of the biomarker of interest for each of the populations under study. The model is illustrated through an application to the evaluation of prostate-specific antigen for the diagnosis of prostate cancer, which contrasts the performance of our model against alternative models. PMID:24174579

Localized Surface Plasmon Resonance (LSPR)-Coupled Fiber-Optic Nanoprobe for the Detection of Protein Biomarkers.

PubMed

Wei, Jianjun; Zeng, Zheng; Lin, Yongbin

2017-01-01

Here is presented a miniaturized, fiber-optic (FO) nanoprobe biosensor based on the localized surface plasmon resonance (LSPR) at the reusable dielectric-metallic hybrid interface with a robust, gold nano-disk array at the fiber end facet. The nanodisk array is directly fabricated using electron beam lithography (EBL) and metal lift-off process. The free prostate-specific antigen (f-PSA) has been detected with a mouse anti-human prostate-specific antigen (PSA) monoclonal antibody (mAb) as a specific receptor linked with a self-assembled monolayer (SAM) at the LSPR-FO facet surfaces. Experimental investigation and data analysis found near field refractive index (RI) sensitivity at ~226 nm/RIU with the LSPR-FO nanoprobe, and demonstrated the lowest limit of detection (LOD) at 100 fg/mL (~3 fM) of f-PSA in PBS solutions. The SAM shows insignificant nonspecific binding to the target biomarkers in the solution. The control experimentation using 5 mg/mL bovine serum albumin in PBS and nonspecific surface test shows the excellent specificity and selectivity in the detection of f-PSA in PBS. These results indicate important progress toward a miniaturized, multifunctional fiber-optic technology that integrates informational communication and sensing function for developing a high-performance, label-free, point-of-care (POC) device.

Residual Prostate Cancer in Patients Treated With Endocrine Therapy With or Without Radical Radiotherapy: A Side Study of the SPCG-7 Randomized Trial

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

Solberg, Arne, E-mail: arne.solberg@stolav.n; Haugen, Olav A.; Department of Pathology and Medical Genetics, St. Olav's Hospital, Trondheim University Hospital, Trondheim

2011-05-01

Purpose: The Scandinavian Prostate Cancer Group-7 randomized trial demonstrated a survival benefit of combined endocrine therapy and external-beam radiotherapy over endocrine therapy alone in patients with high-risk prostate cancer. In a subset of the study population, the incidence and clinical implications of residual prostate cancer in posttreatment prostate biopsy specimens was evaluated. Methods and Materials: Biopsy specimens were obtained from 120 of 875 men in the Scandinavian Prostate Cancer Group-7 study. Results: Biopsies were performed at median of 45 months follow-up. In 63 patients receiving endocrine treatment only and 57 patients receiving combined treatment, residual cancer was found in 66%more » (n = 41) and 22% (n = 12), respectively (p < 0.0001). The vast majority of residual tumors were poorly differentiated (Gleason score {>=}8). Endocrine therapy alone was predictive of residual prostate cancer: odds ratio 7.49 (3.18-17.7), p < 0.0001. In patients with positive vs. negative biopsy the incidences of clinical events were as follows: biochemical recurrence 74% vs. 27% (p < 0.0001), local progression 26% vs. 4.7% (p = 0.002), distant recurrence 17% vs. 9.4% (p = 0.27), clinical recurrence 36% vs. 13% (p = 0.006), cancer-specific death 19% vs. 9.7% (p = 0.025). In multivariable analysis, biochemical recurrence was significantly associated with residual cancer: hazard ratio 2.69 (1.45-4.99), p = 0.002, and endocrine therapy alone hazard ratio 3.45 (1.80-6.62), p < 0.0001. Conclusions: Radiotherapy combined with hormones improved local tumor control in comparison with endocrine therapy alone. Residual prostate cancer was significantly associated with serum prostate-specific antigen recurrence, local tumor progression, clinical recurrence, and cancer-specific death in univariable analysis. Residual cancer was predictive of prostate-specific antigen recurrence in multivariable analysis.« less

Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.

PubMed

Sutcliffe, Siobhan; Nevin, Remington L; Pakpahan, Ratna; Elliott, Debra J; Langston, Marvin E; De Marzo, Angelo M; Gaydos, Charlotte A; Isaacs, William B; Nelson, William G; Sokoll, Lori J; Walsh, Patrick C; Zenilman, Jonathan M; Cersovsky, Steven B; Platz, Elizabeth A

2016-05-01

Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men. © 2015 UICC.

Getting Black Men to Undergo Prostate Cancer Screening: The Role of Social Capital.

PubMed

Dean, Lorraine T; Subramanian, S V; Williams, David R; Armstrong, Katrina; Zubrinsky Charles, Camille; Kawachi, Ichiro

2015-09-01

Despite higher rates of prostate cancer-related mortality and later stage of prostate cancer diagnosis, Black/African American men are significantly less likely than non-Hispanic White men to use early detection screening tools, like prostate-specific antigen (PSA) testing for prostate cancer. Lower screening rates may be due, in part, to controversy over the value of prostate cancer screenings as part of routine preventive care for men, but Black men represent a high-risk group for prostate cancer that may still benefit from PSA testing. Exploring the role of social factors that might be associated with PSA testing can increase knowledge of what might promote screening behaviors for prostate cancer and other health conditions for which Black men are at high risk. Using multilevel logistic regression, this study analyzed self-report lifetime use of PSA test for 829 Black men older than 45 years across 381 Philadelphia census tracts. This study included individual demographic and aggregated social capital data from the Public Health Management Corporation's 2004, 2006, and 2008 waves of the Community Health Database, and sociodemographic characteristics from the 2000 U.S. Census. Each unit increase in community participation was associated with a 3 to 3.5 times greater likelihood of having had a PSA test (odds ratio = 3.35). Findings suggest that structural forms of social capital may play a role in screening behaviors for Black men in Philadelphia. A better understanding of the mechanism underlying the link between social capital and screening behaviors can inform how researchers and interventionists develop tools to promote screening for those who need it. © The Author(s) 2014.

Frequency of Unnecessarily Biopsies among Patients with Suspicion of Prostate Cancer in Syrian Men.

PubMed

Bachour, Dala-Maria; Chahin, Emil; Al-Fahoum, Sahar

2015-01-01

The prevalence of prostate cancer is considered high in many countries, and screening tests are very important in order to detect prostate cancer in its early stages; however false positivity with these screening tests means that a lot of patients undergo unnecessary biopsy, which is an invasive procedure, for the confirmatory test. The purpose of this study was to estimate the frequency of unnecessary biopsy cases in patients referred for prostate biopsy in one of the most important and overload cancer centers in Syria. Retrospective data for a period of four years between January 2009 and December 2012 were collected in Al- Bayrouni University Medical hospital in Damascus, Syria. The patients from whom data were collected were referred to our histopathological department because of elevated prostate specific antigen (PSA) serum or an abnormal digital rectal examination (DRE). All patients underwent prostatic TRUS-guided biopsies. Diagnosis of prostate cancer (PCa) or benign prostatic hyperplasia (BPH) was based on histopathological examination and prostate cancers cases were graded and scored according to the Gleason score system. For the 406 patients referred to biopsy, the mean±SD age was 58.4 ±23.3 years. The mean ± SD PSA level was 49.2±21.5 ng/ ml. Of the total we found 237 patients diagnosed with PCa (58. 4%), 166 patients with BPH (40.9%) and 3 cases were unable to be diagnosed (0.7%) because of biopsy collection errors. Our study shows that a high percentage of patients are undergoing unnecessary biopsy, which suggests that the performed screening tests had a high level of false positive and may need re-evaluation.

Health perceptions in patients who undergo screening and workup for prostate cancer.

PubMed

Katz, David A; Jarrard, David F; McHorney, Colleen A; Hillis, Stephen L; Wiebe, Donald A; Fryback, Dennis G

2007-02-01

False-positive screening tests may induce persistent psychological distress. This study was designed to determine whether a positive screening test with negative biopsy findings for prostate cancer is associated with worsened mental health during short-term follow-up. We conducted a cross-sectional telephone survey of two groups of men approximately 2 months after testing: group 1, 109 men with an abnormal prostate-specific antigen level or digital rectal examination findings but with negative biopsy findings for prostate cancer; and group 2, 101 age-matched primary care patients with PSA screening levels in the reference range (less than 4 ng/mL). Primary outcomes included state anxiety and prostate cancer-related worry. Secondary outcomes included Medical Outcomes Study Short Form 36-item Health Survey subscales and sexual function items. Multivariate regression techniques were used to adjust for differences in baseline covariates. Group 1 patients were more worried than group 2 patients about getting prostate cancer (mean worry 3.9 versus 4.5, P = 0.0001, using a 5-point scale, with 1 indicating extreme worry and 5 no worry). Group 1 patients also perceived their risk of prostate cancer to be significantly greater than that of controls (P = 0.001). No significant differences were found across state anxiety or Medical Outcomes Study Short Form 36-item Health Survey subscales. Sexual bother was greater for group 1 patients, with 19% reporting that sexual function was a moderate to big problem compared with 10% of group 2 patients (P = 0.0001). Men with abnormal prostate cancer screening tests report increased cancer-related worry and more problems with sexual function, despite having a negative biopsy result. Effective counseling interventions are needed before prostate cancer screening and during follow-up.

Small cell carcinoma of the prostate presenting with Cushing Syndrome. A narrative review of an uncommon condition.

PubMed

Rueda-Camino, José Antonio; Losada-Vila, Beatriz; De Ancos-Aracil, Cristina Lucía; Rodríguez-Lajusticia, Laura; Tardío, Juan Carlos; Zapatero-Gaviria, Antonio

2016-01-01

Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting with CS. The origin of these neoplasms is still unclear. It may be suspected when laboratory features appear in patients diagnosed with prostatic adenocarcinoma which becomes resistant to specific therapy. SCC usually occurs after the 6th decade. Patients suffering SCC of the prostate presenting with CS usually present symptoms such as hypertension, hyperglycemia, alkalosis or hypokalemia; cushingoid phenotype is less frequent. Cortisol and ACTH levels are often high. Prostatic-specific antigen levels are usually normal. CT scan is the preferred imaging test to localize the lesion, but its performance may be improved by adding other tests, such as FDG-PET scan. All patients have metastatic disease at the time of diagnosis. Lymph nodes, liver and bone are the most frequent metastases sites. Surgery and Ketokonazole are the preferred treatments for CS. The prognosis is very poor: 2- and 5-year survival rates are 27.5 and 14.3%, respectively. Key messages When a patient presents with ectopic Cushing Syndrome but lungs are normal, an atypical localization should be suspected. We should suspect a prostatic origin if Cushing Syndrome is accompanied by obstructive inferior urinary tract symptoms or in the setting of a prostatic adenocarcinoma with rapid clinical and radiological progression with relatively low PSA levels. Although no imaging test is preferred to localize these tumors, FDG-PET-TC can be very useful. Hormone marker scintigraphy (e.g. somatostatin) could be used too. As Cushing Syndrome is a paraneoplastic phenomenon, treatment of the underlying disease may help control hypercortisolism manifestations. These tumors are usually metastatic by the time of diagnosis. They have very poor prognosis.

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

PubMed Central

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

2017-01-01

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

Development and potential applications of microarrays based on fluorescent nanocrystal-encoded beads for multiplexed cancer diagnostics

NASA Astrophysics Data System (ADS)

Brazhnik, Kristina; Grinevich, Regina; Efimov, Anton E.; Nabiev, Igor; Sukhanova, Alyona

2014-05-01

Advanced multiplexed assays have recently become an indispensable tool for clinical diagnostics. These techniques provide simultaneous quantitative determination of multiple biomolecules in a single sample quickly and accurately. The development of multiplex suspension arrays is currently of particular interest for clinical applications. Optical encoding of microparticles is the most available and easy-to-use technique. This technology uses fluorophores incorporated into microbeads to obtain individual optical codes. Fluorophore-encoded beads can be rapidly analyzed using classical flow cytometry or microfluidic techniques. We have developed a new generation of highly sensitive and specific diagnostic systems for detection of cancer antigens in human serum samples based on microbeads encoded with fluorescent quantum dots (QDs). The designed suspension microarray system was validated for quantitative detection of (1) free and total prostate specific antigen (PSA) in the serum of patients with prostate cancer and (2) carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) in the serum of patients with breast cancer. The serum samples from healthy donors were used as a control. The antigen detection is based on the formation of an immune complex of a specific capture antibody (Ab), a target antigen (Ag), and a detector Ab on the surface of the encoded particles. The capture Ab is bound to the polymer shell of microbeads via an adapter molecule, for example, protein A. Protein A binds a monoclonal Ab in a highly oriented manner due to specific interaction with the Fc-region of the Ab molecule. Each antigen can be recognized and detected due to a specific microbead population carrying the unique fluorescent code. 100 and 231 serum samples from patients with different stages of prostate cancer and breast cancer, respectively, and those from healthy donors were examined using the designed suspension system. The data were validated by comparing with the results of the "gold standard" enzyme-linked immunosorbent assay (ELISA). They have shown that our approach is a good alternative to the diagnostics of cancer markers using conventional assays, especially in early diagnostic applications.

Characterization of SPINK1 in Prostate Cancer

DTIC Science & Technology

2011-05-01

4). About 40%–80% of prostate-specific antigen (PSA)-screened prostate cancers harbor ETS gene fusion, whereas the remaining cases are driven by...html can be found in the online version of this article at: Supplementary Material http://stm.sciencemag.org/content/scitransmed/3/72/72ps7... article permission to reproduce this of this article or about obtaining reprintsInformation about obtaining is a registered trademark of AAAS

Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers

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

Koontz, Bridget F., E-mail: bridget.koontz@duke.edu; Tsivian, Matvey; Mouraviev, Vladimir

Purpose: To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. Methods: One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Results: Nine hundred seventy-nine patientsmore » had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Conclusions: Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.« less

Impact of primary Gleason grade on risk stratification for Gleason score 7 prostate cancers.

PubMed

Koontz, Bridget F; Tsivian, Matvey; Mouraviev, Vladimir; Sun, Leon; Vujaskovic, Zeljko; Moul, Judd; Lee, W Robert

2012-01-01

To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Nine hundred seventy-nine patients had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities. Copyright © 2012 Elsevier Inc. All rights reserved.

PCA3 Silencing Sensitizes Prostate Cancer Cells to Enzalutamide-mediated Androgen Receptor Blockade.

PubMed

Özgür, Emre; Celik, Ayca Iribas; Darendeliler, Emin; Gezer, Ugur

2017-07-01

Prostate cancer (PCa) is an androgen-dependent disease. Novel anti-androgens (i.e. enzalutamide) have recently been developed for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Evidence is accumulating that prostate cancer antigen 3 (PCA3) is involved in androgen receptor (AR) signaling. Here, in combination with enzalutamide-mediated AR blockade, we investigated the effect of PCA3 targeting on the viability of PCa cells. In hormone-sensitive LNCaP cells, AR-overexpressing LNCaP-AR + cells and VCaP cells (representing CRPC), PCA3 was silenced using siRNA oligonucleotides. Gene expression and cell viability was assessed in PCA3-silenced and/or AR-blocked cells. PCA3 targeting reduced the expression of AR-related genes (i.e. prostate-specific antigen (PSA) and prostate-specific transcript 1 (non-protein coding) (PCGEM1)) and potentiated the effect of enzalutamide. Proliferation of PCa cells was suppressed upon PCA3 silencing with a greater effect in LNCaP-AR + cells. Furthermore, PCA3 silencing sensitized PCa cells to enzalutamide-induced loss of cell growth. PCA3, as a therapeutic target in PCa, might be used to potentiate AR antagonists. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein].

PubMed

Ahmadzadehfar, H; Albers, P; Bockisch, A; Boegemann, M; Böhme, C; Burchert, W; Dietlein, M; Drzezga, A; Fabry, U; Feldmann, G; Heidenreich, A; Heinzel, A; Herrmann, K; Heyll, A; Höhling, C; Kreuzer, C; Laufer, D; Mengel, R; Mottaghy, F M; Müller, H-W; Müller, S C; Ost, E; Rahbar, K; Reifenhäuser, W; Schäfers, M; Schlenkhoff, C; Schmidt, M; Schmidt-Wolf, I; Wildenhain, C; Zimmer, B; Essler, M

2018-06-01

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

Immunotherapy for Prostate Cancer: Where Do We Go From Here?-PART 2: Checkpoint Inhibitors, Immunotherapy Combinations, Tumor Microenvironment Modulation, and Cellular Therapies.

PubMed

Patel, Amar; Fong, Lawrence

2018-06-15

Therapeutic approaches that harness the power of the immune system to eliminate cancer cells have produced a paradigm shift in the management of a variety of malignancies. Prostate cancer has been a particularly active area of investigation in cancer immunotherapy, with significant laboratory and clinical evidence suggesting that this disease can be a viable target for cytotoxic immune cells. In the first article of this series, we discussed the diverse vaccination approaches that have been employed to prime native antigen-specific responses against prostate cancer, highlighting successes such as sipuleucel-T, as well as the significant challenges that remain. Here we focus on alternative methods of harnessing both adaptive and innate antitumor immunity to target prostate cancer cells. Approaches that enhance the activation of T cells, modulation of the tumor microenvironment to abrogate its inherent immunosuppressive mechanisms, and engineering of antigen-specific antibody and cellular products to target tumor cells will be discussed. We will then look ahead to provide a perspective on how this growing collection of immunotherapeutic approaches may ultimately be combined to target prostate cancer from a variety of angles.

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

PubMed Central

Vos, Larissa J; Janoski, Michele; Wachowicz, Keith; Yahya, Atiyah; Boychak, Oleksandr; Amanie, John; Pervez, Nadeem; Parliament, Matthew B; Pituskin, Edith; Fallone, B Gino; Usmani, Nawaid

2016-01-01

AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods. PMID:27158428

The impact of hypoxemia on serum total and free prostate-specific antigen levels in patients with chronic obstructive pulmonary disease.

PubMed

Ozge, Cengiz; Bozlu, Murat; Ozgur, Eylem Sercan; Tek, Mesut; Tunckiran, Ahmet; Muslu, Necati; Ilvan, Ahmet

2015-05-01

Prostate-specific antigen (PSA) is the most important biochemical marker in the diagnosis and follow-up of patients with prostate cancer. In recent years, a relationship between PSA levels and hypoxic conditions has been described. However, no study has investigated the PSA levels in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the impact of hypoxemia on serum total (tPSA) and free PSA (fPSA) levels in patients with COPD. Between January 2010 and January 2014, 95 male patients who hospitalized for acute exacerbations of COPD and 80 control subjects were enrolled in the study. Serum tPSA and fPSA levels and f/tPSA ratios were determined in all patients on the first day of hospitalization (exacerbation) and 7 days after the treatment (stable state). Statistical analysis included paired t test and Mann-Whitney U test. No statistically significant differences were found between COPD and control groups with regard to the baseline characteristics, except for smoking status. The levels of serum tPSA and fPSA during exacerbation of COPD were significantly higher than the levels of the stable period (p < 0.01), whereas f/tPSA ratio did not change (p > 0.05). Hypoxemia during acute exacerbation of COPD can cause a rise in serum tPSA and fPSA levels, but f/tPSA ratio is not affected. Acute exacerbation of COPD may be added to list of the events in which PSA measurements must be interpreted with caution.

Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old.

PubMed

Loeb, Stacy; Roehl, Kimberly A; Antenor, Jo Ann V; Catalona, William J; Suarez, Brian K; Nadler, Robert B

2006-02-01

Limited data are available concerning the extent to which the initial prostate-specific antigen (PSA) measurement in men younger than age 60 predicts for the risk of prostate cancer (CaP) and how this compares to other known risk factors. From 1991 to 2001, 13,943 men younger than 60 years old participated in a CaP screening study. Men aged 40 to 49 years were eligible for the study if they had a positive family history or African-American heritage, and men older than 50 years were screened without respect to risk factors. The CaP detection rate, PSA velocity, pathologic features, and treatment outcomes were evaluated as a function of the baseline PSA level. The median PSA level was 0.7 ng/mL for men aged 40 to 49 years and 0.9 ng/mL for men aged 50 to 59. A baseline PSA level between the median and 2.5 ng/mL was associated with a 14.6-fold and 7.6-fold increased risk of CaP in men aged 40 to 49 and 50 to 59 years, respectively. A greater baseline PSA value was also associated with a significantly greater PSA velocity, more aggressive tumor features, a greater biochemical progression rate, and a trend toward a greater cancer-specific mortality rate. In men younger than 60, a baseline PSA value between the age-specific median and 2.5 ng/mL was a significant predictor of later CaP and was associated with a significantly greater PSA velocity. A young man's baseline PSA value was a stronger predictor of CaP than family history, race, or suspicious digital rectal examination findings. A greater baseline PSA level was associated with significantly more adverse pathologic features and biochemical progression.

Assessment of nucleosides as putative tumor biomarkers in prostate cancer screening by CE-UV.

PubMed

Buzatto, Adriana Zardini; de Oliveira Silva, Mariana; Poppi, Ronei Jesus; Simionato, Ana Valéria Colnaghi

2017-05-01

Cancer is responsible for millions of deaths worldwide, but most base diseases may be cured if detected early. Screening tests may be used to identify early-stage malignant neoplasms. However, the major screening tool for prostate cancer, the prostate-specific antigen test, has unsuitable sensitivity. Since cancer cells may affect the pattern of consumption and excretion of nucleosides, such biomolecules are putative biomarkers that can be used for diagnosis and treatment evaluation. Using a previously validated method for the analysis of nucleosides in blood serum by capillary electrophoresis with UV-vis spectroscopy detection, we investigated 60 samples from healthy individuals and 42 samples from prostate cancer patients. The concentrations of nucleosides in both groups were compared and a multivariate partial least squares-discriminant analysis classification model was optimized for prediction of prostate cancer. The validation of the model with an independent sample set resulted in the correct classification of 82.4% of the samples, with sensitivity of 90.5% and specificity of 76.7%. A significant downregulation of 5-methyluridine and inosine was observed, which can be indicative of the carcinogenic process. Therefore, such analytes are potential candidates for prostate cancer screening. Graphical Abstract Separation of the studied nucleosides and the internal standard 8-Bromoguanosine by CE-UV (a); classification of the external validation samples (30 from healthy volunteers and 21 from prostate cancer patients) by the developed Partial Least Square - Discriminant Analysis (PLS-DA) model with accuracy of 82.4% (b); Receiver Operating Characteristics (ROC) curve (c); and Variable Importance in the Projection (VIP) values for the studied nucleosides (d). A significant down-regulation of 5- methyluridine (5mU) and inosine (I) was observed, which can be indicative of the presence of prostate tumors.

177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy.

PubMed

Baum, Richard P; Kulkarni, Harshad R; Schuchardt, Christiane; Singh, Aviral; Wirtz, Martina; Wiessalla, Stefan; Schottelius, Margret; Mueller, Dirk; Klette, Ingo; Wester, Hans-Jürgen

2016-07-01

The objective of this study was to analyze the safety and efficacy of the (177)Lu-labeled DOTAGA-based prostate-specific membrane antigen (PSMA) ligand (177)Lu-DOTAGA-(I-y)fk(Sub-KuE) ((177)Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC). Fifty-six mCRPC patients underwent PSMA radioligand therapy (RLT) with (177)Lu-PSMA. (68)Ga-PSMA-(N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid) ((68)Ga-PSMA) PET/CT was used for patient selection and follow-up after PSMA RLT. Hematologic status, renal function, and serum prostate-specific antigen levels were documented before and after therapy. Dosimetry was performed in 30 patients. (177)Lu-PSMA demonstrated high absorbed tumor doses (median, 3.3 mGy/MBq) compared with the levels in normal organs. Parotid glands received higher doses (1.3 mGy/MBq) than kidneys (0.8 mGy/MBq). All patients tolerated the therapy without any acute adverse effects. Except for mild reversible xerostomia in 2 patients, no long-term side effects were observed. There was a small but statistically significant reduction in erythrocyte and leukocyte counts; only the reduction in erythrocyte counts decreased slightly below the reference range. No thrombocytopenia occurred. The severity of pain was significantly reduced in 2 of 6 patients (33.3%). A decrease in prostate-specific antigen levels was noted in 45 of 56 patients (80.4%). Of 25 patients monitored for at least 6 mo after 2 or more PSMA RLT cycles, a molecular response evaluation ((68)Ga-PSMA PET/CT) revealed partial remission in 14, stable disease in 2, and progressive disease in 9 patients. Contrast-enhanced CT revealed partial remission in 5, stable disease in 13, and progressive disease in 7 patients. The median progression-free survival was 13.7 mo, and the median overall survival was not reached during follow-up for 28 mo. PSMA RLT with (177)Lu-PSMA is feasible, safe, and effective in end-stage progressive mCRPC with appropriate selection and follow-up of patients by (68)Ga-PSMA PET/CT through application of the concept of theranostics. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Prostate-specific antigen screening in a high-risk population: lessons from the community and how they relate to large-scale population-based studies.

PubMed

Shelton, Jeremy B; Barocas, Daniel A; Conway, Frances; Hart, Kathleen; Nelson, Kinloch; Richstone, Lee; Gonzalez, Ricardo R; Raman, Jay D; Scherr, Douglas S

2005-05-01

To estimate the incidence of prostate cancer among African-American men and Caribbean immigrants to the United States, to assess the applicability of large-scale prostate screening trials to a community screening program, and to recruit unscreened men. African-American and Caribbean-American men were targeted with a community-based prostate cancer screening program in Jamaica, New York. Serum prostate-specific antigen determination and digital rectal examination were used to determine abnormal findings. The incidence of an abnormal screening examination was used to project the incidence of prostate cancer, which was compared with that in other reported trials. The projected incidence of prostate cancer among African-Americans and Caribbean-Americans older than 50 years was 8% and 7%, respectively, similar to that reported in other trials of African-American men. The projected incidence of prostate cancer in Caribbean-American men aged 40 to 49 years was 1%, the same as the high rate reported among Caribbean men. As in other trials, a family history of prostate cancer and age were strong predictors of abnormal findings. Of the recruited men older than 50 years, 58% had never been screened compared with 42% nationally. Large population-based screening trials have identified ethnic groups at high risk of prostate cancer. This trial detected high rates of abnormal screening findings by targeting ethnicity. The incidence of an abnormal examination was high in Caribbean-American men younger than 50 years old. Finally, this trial successfully recruited underscreened men.

Commentary on "Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen." Agnihotri S, Mittal RD, Kapoor R, Mandhani A, Department of Urology & Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.: Urol Oncol 2014; [Epub ahead of print]. doi: 10.1016/j.urolonc.2014.03.004.

PubMed

Pu, Chunxiao; Wang, Jia; Wei, Qiang; Han, Ping

2015-02-01

To test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA). Overall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography-guided biopsy was done only when PSA level did not decrease less than 4ng/ml. Mean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6,678pg/ml (SD±1,985.7) than in control, i.e., 1,543pg/ml (SD±375.7) (P<0.001). Following anti-inflammatory treatment, there was a significant decrease in the mean level of IL-8 from baseline to 5,622pg/ml (SD±1,870.66) (P<0.001). Corresponding to this, a significant decrease was noted in total PSA levels to less than 4ng/ml in 105 (65.62%) patients. Men with the highest levels of IL-8 had a greater degree of erectile dysfunction. Men with symptomatic benign prostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy. Copyright © 2014 Elsevier Inc. All rights reserved.

Contribution of Caudal Müllerian Duct Mesenchyme to Prostate Development

PubMed Central

Brechka, Hannah; McAuley, Erin M.; Lamperis, Sophia M.; Paner, Gladell P.

2016-01-01

A fundamental understanding of prostate development and tissue homeostasis has the high potential to reveal mechanisms for prostate disease initiation and identify novel therapeutic approaches for disease prevention and treatment. Our current understanding of prostate lineage specification stems from the use of developmental model systems that rely upon the embryonic preprostatic urogenital sinus mesenchyme to induce the formation of mature prostate epithelial cells. It is unclear, however, how the urogenital sinus epithelium can derive both adult urethral glands and prostate epithelia. Furthermore, the vast disparity in disease initiation between these two glands highlights key developmental factors that predispose prostate epithelia to hyperplasia and cancer. In this study we demonstrate that the caudal Müllerian duct mesenchyme (CMDM) drives prostate epithelial differentiation and is a key determinant in cell lineage specification between urethral glands and prostate epithelia. Utilizing both human embryonic stem cells and mouse embryonic tissues, we document that the CMDM is capable of inducing the specification of androgen receptor, prostate-specific antigen, NKX3.1, and Hoxb13-positive prostate epithelial cells. These results help to explain key developmental differences between prostate and urethral gland differentiation, and implicate factors secreted by the caudal Müllerian duct as novel targets for prostate disease prevention and treatment. PMID:27595922

Cancer Specific Mortality in Men Diagnosed with Prostate Cancer before Age 50 Years: A Nationwide Population Based Study.

PubMed

Thorstenson, Andreas; Garmo, Hans; Adolfsson, Jan; Bratt, Ola

2017-01-01

We compared clinical characteristics and cancer specific mortality in men diagnosed with prostate cancer before vs after age 50 years. A total of 919 men 35 to 49 years old and 45,098 men 50 to 66 years old who were diagnosed with prostate cancer between 1998 and 2012 were identified in PCBaSe (Prostate Cancer data Base Sweden). Cancer specific mortality was compared among age groups (35 to 49, 50 to 59, 60 to 63 and 64 to 66 years) with and without adjusting for cancer characteristics, comorbidity and education in a multivariable Cox proportional hazards model. Clinical cancer characteristics indicated that most nonmetastatic cancer in men younger than 50 years was detected after prostate specific antigen testing. The proportion of nonmetastatic vs metastatic disease at diagnosis was similar in all age groups. A strong association between younger age and poor prognosis was apparent in men in whom metastatic disease was diagnosed before age 50 to 55 years. The crude and adjusted HRs of cancer specific mortality were 1.41 (95% CI 1.12-1.79) and 1.28 (95% CI 1.01-1.62) in men diagnosed before age 50 and at age 50 to 59 years, respectively. In men with nonmetastatic disease crude cancer specific mortality increased with older age but adjusted cancer specific mortality was similar in all age groups. Our findings suggest that an aggressive form of metastatic prostate cancer is particularly common in men younger than 50 to 55 years. Genetic studies and trials of intensified systemic treatment are warranted in this patient group. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Novel rolling circle amplification and DNA origami-based DNA belt-involved signal amplification assay for highly sensitive detection of prostate-specific antigen (PSA).

PubMed

Yan, Juan; Hu, Chongya; Wang, Ping; Liu, Rui; Zuo, Xiaolei; Liu, Xunwei; Song, Shiping; Fan, Chunhai; He, Dannong; Sun, Gang

2014-11-26

Prostate-specific antigen (PSA) is one of the most important biomarkers for the early diagnosis and prognosis of prostate cancer. Although many efforts have been made to achieve significant progress for the detection of PSA, challenges including relative low sensitivity, complicated operation, sophisticated instruments, and high cost remain unsolved. Here, we have developed a strategy combining rolling circle amplification (RCA)-based DNA belts and magnetic bead-based enzyme-linked immunosorbent assay (ELISA) for the highly sensitive and specific detection of PSA. At first, a 96-base circular DNA template was designed and prepared for the following RCA. Single stranded DNA (ssDNA) products from RCA were used as scaffold strand for DNA origami, which was hybridized with three staple strands of DNA. The resulting DNA belts were conjugated with multiple enzymes for signal amplification and then employed to magnetic bead based ELISA for PSA detection. Through our strategy, as low as 50 aM of PSA can be detected with excellent specificity.

20-Aminosteroids as a novel class of selective and complete androgen receptor antagonists and inhibitors of prostate cancer cell growth.

PubMed

Fousteris, Manolis A; Schubert, Undine; Roell, Daniela; Roediger, Julia; Bailis, Nikolaos; Nikolaropoulos, Sotiris S; Baniahmad, Aria; Giannis, Athanassios

2010-10-01

Here, the synthesis and the evaluation of novel 20-aminosteroids on androgen receptor (AR) activity is reported. Compounds 11 and 18 of the series inhibit both the wild type and the T877A mutant AR-mediated transactivation indicating AR antagonistic function. Interestingly, minor structural changes such as stereoisomers of the amino lactame moiety exhibit preferences for antagonism among wild type and mutant AR. Other tested nuclear receptors are only weakly or not affected. In line with this, the prostate cancer cell growth of androgen-dependent but not of cancer cells lacking expression of the AR is inhibited. Further, the expression of the prostate specific antigen used as a diagnostic marker is also repressed. Finally steroid 18 enhances cellular senescence that might explain in part the growth inhibition mediated by this derivative. Steroids 11 and 18 are the first steroids that act as complete AR antagonists and exhibit AR specificity. Copyright © 2010 Elsevier Ltd. All rights reserved.

Photoacoustic imaging with an acoustic lens detects prostate cancer cells labeled with PSMA-targeting near-infrared dye-conjugates

NASA Astrophysics Data System (ADS)

Dogra, Vikram; Chinni, Bhargava; Singh, Shalini; Schmitthenner, Hans; Rao, Navalgund; Krolewski, John J.; Nastiuk, Kent L.

2016-06-01

There is an urgent need for sensitive and specific tools to accurately image early stage, organ-confined human prostate cancers to facilitate active surveillance and reduce unnecessary treatment. Recently, we developed an acoustic lens that enhances the sensitivity of photoacoustic imaging. Here, we report the use of this device in conjunction with two molecular imaging agents that specifically target the prostate-specific membrane antigen (PSMA) expressed on the tumor cell surface of most prostate cancers. We demonstrate successful imaging of phantoms containing cancer cells labeled with either of two different PSMA-targeting agents, the ribonucleic acid aptamer A10-3.2 and a urea-based peptidomimetic inhibitor, each linked to the near-infrared dye IRDye800CW. By specifically targeting cells with these agents linked to a dye chosen for optimal signal, we are able to discriminate prostate cancer cells that express PSMA.

Assessment of long-term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy.

PubMed

Merdan, Selin; Tomlins, Scott A; Barnett, Christine L; Morgan, Todd M; Montie, James E; Wei, John T; Denton, Brian T

2015-11-15

In men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy. The authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score-dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided. Incorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust with respect to the model parameters. The use of PCA3 or T2:ERG testing for repeat biopsy decisions can substantially reduce the number of biopsies without significantly affecting 10-year survival. © 2015 American Cancer Society.

Androgen Regulation of p27 in the Normal and Neoplastic Prostate

DTIC Science & Technology

1999-09-01

IL-6 (50) or the flavanoid antioxidant silibinin (5 1) results in increased p27KIP’ expression associated with G1 arrest and neuroendocrine...Commun 257:609-614. 51. Zi X, Agarwal R 1999 Silibinin decreases prostate-specific antigen with cell growth inhibition via GI arrest, leading to

Prostate-specific antigen levels in the United States: implications of various definitions for abnormal.

PubMed

Welch, H Gilbert; Schwartz, Lisa M; Woloshin, Steven

2005-08-03

The finding that some men with a normal prostate-specific antigen (PSA) level (i.e., less than 4 ng/mL) nonetheless have microscopic evidence of prostate cancer has led to some suggestions that the threshold defining abnormal should be lowered to 2.5 ng/mL. We examined the effect of this lower threshold on the number of American men who would be labeled abnormal by a single PSA test. We obtained PSA data on a nationally representative sample of American men 40 years of age and older with no history of prostate cancer and no current inflammation or infection of the prostate gland (n = 1308) from the 2001-2002 National Health and Nutrition Examination Survey. We obtained data on the 10-year risk of prostate cancer death in the pre-PSA era from DevCan, the National Cancer Institute's software to calculate the probability of dying of cancer. Based on NHANES data, approximately 1.5 million American men aged 40 to 69 years have a PSA level over 4.0 ng/mL. Lowering the threshold to 2.5 ng/mL would label an additional 1.8 million men as abnormal, if all men were screened. For men aged 70 years or older, the corresponding numbers are 1.5 and 1.2 million. The proportion of the population affected by different thresholds would vary with age. Among men in their 60s, for example, 17% have a PSA level over 2.5 ng/mL, 5.7% have a PSA level over 4.0 ng/mL, and 1.7% have a PSA level over 10.0 ng/mL. For context, only 0.9% of men in their 60s are expected to die from prostate cancer in the next 10 years. Lowering the PSA threshold to 2.5 ng/mL would double the number of men defined as abnormal, to up to 6 million. Until there is evidence that screening is effective, increasing the number of men recommended for prostate biopsy--and the number potentially diagnosed and treated unnecessarily--would be a mistake.

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

PubMed

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

2014-11-01

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

[Prostate specific antigen and NF-kB in prostatic disease: relation with malignancy].

PubMed

Cansino, J R; Vera, R; Rodríguez de Bethencourt, F; Bouraoui, Y; Rodríguez, G; Prieto, A; de la Peña, J; Paniagua, R; Royuela, M

2011-01-01

NF-kB (p50/p65) is a transcription factor involved in TNF-α-induced cell death resistance by promoting several antiapoptotic genes. We intend to relate the expression of NF-kB (p50 and p65) with serum levels of prostate-specific antigen (PSA), both in normal males and in those with pathologic conditions of the prostate. this study was carried out in 5 normal, 24 benign prostatic hyperplastic (BPH) and 19 patients with prostate cancer (PC). Immunohistochemical and Western blot analyses were performed on tissue and serum PSA was assayed by PSA DPC Immulite assays (Diagnostics Products Corporation, Los Angeles, CA). in controls, p65 NF-kB was not found and p50 was scantly detected in 60% normal samples in the cytoplasm of epithelial cells. Both p50 and p65 were expressed in 62.5% of the samples with BPH and in 63.2% of those with PC. Both increased its frequency of expression with higher PSA serum levels. Activation of NF-kB revealed by its nuclear translocation in prostate cancer could be related to cancer progression and elevated seric PSA levels. A better understanding of the biologic mechanism by which circulating PSA levels increase and its relation with NF-kB expression is needed. Possibly, NF-kB blockage could be used as a therapeutic target to counteract proliferation in prostate cancer. Copyright © 2010 AEU. Published by Elsevier Espana. All rights reserved.

Association between systemic inflammatory markers and serum prostate-specific antigen in men without prostatic disease - the 2001-2008 National Health and Nutrition Examination Survey.

PubMed

McDonald, Alicia C; Vira, Manish A; Vidal, Adriana C; Gan, Wenqi; Freedland, Stephen J; Taioli, Emanuela

2014-05-01

Serum prostate specific antigen (PSA) may be elevated in otherwise healthy men; systemic inflammation has been associated with cancer. The study of systemic inflammatory markers in men without clinical prostate disease, but with elevated PSA may characterize the subgroup of men at higher risk for subsequent prostate cancer. We investigated the associations between systemic inflammatory markers and serum PSA in 3,164 healthy men without prostatic disease, aged >40 years, from the 2001 to 2008 U.S. National Health and Nutrition Examination Survey (NHANES). Serum total PSA levels and concentrations of serum C-reactive protein (CRP) and plasma fibrinogen, neutrophil count, lymphocyte count, and platelet count were recorded. Neutrophil-lymphocyte ratio (NLR) ratio and platelet-lymphocyte (PLR) ratio were calculated. PSA elevation was defined as levels equal or greater than 4 ng/ml. Elevated serum PSA (194 men, 6.1% of the total), was significantly associated with plasma fibrinogen (ORmultiv  = 1.88; 95% CI, 1.09-3.25), and NLR (ORmultiv  = 1.14; 95% CI, 1.03-1.26), after adjustment for age, smoking, body mass index, education, race, co-morbidities, and use of medications. Markers of systemic inflammation were associated with elevated PSA in men without known prostatic disease. Future studies are needed to examine these markers' relationship with prostate cancer occurrence and progression. © 2014 Wiley Periodicals, Inc.

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer.

PubMed

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-26

Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen-glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c -index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.

The clinical effectiveness and cost-effectiveness of the PROGENSA® prostate cancer antigen 3 assay and the Prostate Health Index in the diagnosis of prostate cancer: a systematic review and economic evaluation.

PubMed

Nicholson, Amanda; Mahon, James; Boland, Angela; Beale, Sophie; Dwan, Kerry; Fleeman, Nigel; Hockenhull, Juliet; Dundar, Yenal

2015-10-01

There is no single definitive test to identify prostate cancer in men. Biopsies are commonly used to obtain samples of prostate tissue for histopathological examination. However, this approach frequently misses cases of cancer, meaning that repeat biopsies may be necessary to obtain a diagnosis. The PROGENSA(®) prostate cancer antigen 3 (PCA3) assay (Hologic Gen-Probe, Marlborough, MA, USA) and the Prostate Health Index (phi; Beckman Coulter Inc., Brea, CA, USA) are two new tests (a urine test and a blood test, respectively) that are designed to be used to help clinicians decide whether or not to recommend a repeat biopsy. To evaluate the clinical effectiveness and cost-effectiveness of the PCA3 assay and the phi in the diagnosis of prostate cancer. Multiple publication databases and trial registers were searched in May 2014 (from 2000 to May 2014), including MEDLINE, EMBASE, The Cochrane Library, ISI Web of Science, Medion, Aggressive Research Intelligence Facility database, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number Register and World Health Organization International Clinical Trials Registry Platform. The assessment of clinical effectiveness involved three separate systematic reviews, namely reviews of the analytical validity, the clinical validity of these tests and the clinical utility of these tests. The assessment of cost-effectiveness comprised a systematic review of full economic evaluations and the development of a de novo economic model. The perspective of the evaluation was the NHS in England and Wales. Men suspected of having prostate cancer for whom the results of an initial prostate biopsy were negative or equivocal. The use of the PCA3 score or phi in combination with existing tests (including histopathology results, prostate-specific antigen level and digital rectal examination), multiparametric magnetic resonance imaging and clinical judgement. In addition to documents published by the manufacturers, six studies were identified for inclusion in the analytical validity review. The review identified issues concerning the precision of the PCA3 assay measurements. It also highlighted issues relating to the storage requirements and stability of samples intended for analysis using the phi assay. Fifteen studies met the inclusion criteria for the clinical validity review. These studies reported results for 10 different clinical comparisons. There was insufficient evidence to enable the identification of appropriate test threshold values for use in a clinical setting. In addition, the implications of adding either the PCA3 assay or the phi to clinical assessment were not clear. Furthermore, the addition of the PCA3 assay or the phi to clinical assessment plus magnetic resonance imaging was not found to improve discrimination. No published papers met the inclusion criteria for either the clinical utility review or the cost-effectiveness review. The results from the cost-effectiveness analyses indicated that using either the PCA3 assay or the phi in the NHS was not cost-effective. The main limitations of the systematic review of clinical validity are that the review conclusions are over-reliant on findings from one study, the descriptions of clinical assessment vary widely within reviewed studies and many of the reported results for the clinical validity outcomes do not include either standard errors or confidence intervals. The clinical benefit of using the PCA3 assay or the phi in combination with existing tests, scans and clinical judgement has not yet been confirmed. The results from the cost-effectiveness analyses indicate that the use of these tests in the NHS would not be cost-effective. This study is registered as PROSPERO CRD42014009595. The National Institute for Health Research Health Technology Assessment programme.

Auto-antibodies in prostate cancer: humoral immune response to antigenic determinants coded by the differentially expressed transcripts FLJ23438 and VAMP3.

PubMed

Pontes, E R; Matos, L C; da Silva, E A; Xavier, L S; Diaz, B L; Small, I A; Reis, E M; Verjovski-Almeida, S; Barcinski, M A; Gimba, E R P

2006-10-01

Here we evaluate auto-antibody response against two potential antigenic determinants of genes highly expressed in low Gleason Score prostate cancer (PC) tumor samples, namely FLJ23438 and VAMP3. RT-PCR assays were used to analyze mRNA expression profiles of FLJ23438 and VAMP3 transcripts. The auto-antibody response against FLJ23438 and VAMP3 recombinant proteins was tested by immunoblot assays using PC, benign prostate hyperplasia (BPH), healthy donors (HD), and other human cancers plasma samples. Our data showed that 37% (10/27) and 7.4% (2/27) of PC plasma samples presented auto-antibodies against FLJ23438 and VAMP3, respectively. Only 8.3% (1/12) of BPH plasma samples were reactive for both auto-antibodies, while none (0/12) of HD plasma samples tested were reactive. The prevalence of 37% of positive PC plasma samples for anti-FLJ23438 antibodies suggests that humoral immune response against this antigenic determinant could be a potential serum marker for this cancer. (c) 2006 Wiley-Liss, Inc.

Development of a Ga-68 labeled PET tracer with short linker for prostate-specific membrane antigen (PSMA) targeting.

PubMed

Moon, Sung-Hyun; Hong, Mee Kyung; Kim, Young Ju; Lee, Yun-Sang; Lee, Dong Soo; Chung, June-Key; Jeong, Jae Min

2018-05-15

Glu-Urea-Lys (GUL) derivatives have been reported as prostate-specific membrane antigen (PSMA) agent. We developed derivatives of GUL conjugated with NOTA or DOTA via a thiourea linker and tested their feasibility as PSMA imaging agents after labeling with 68 Ga. NOTA-GUL and DOTA-GUL were synthesized and labeled with 68 Ga using generator-eluted 68 GaCl 3 in 0.1 M HCl in the presence of 1 M NaOAc at pH 5.5. The stabilities of 68 Ga-labeled compounds in human serum were tested at 37.5 °C. A competitive binding assay was performed using the PSMA-positive prostate cancer cell line 22Rv1 and [ 125 I]MIP-1072 (PSMA-specific binding agent) as a tracer. Biodistribution and micro-PET studies were performed using 22Rv1-xenograft BALB/c nude mice. The radiolabeling efficiency of NOTA-GUL (>99%) was higher than that of DOTA-GUL (92%). The IC 50 of Ga-NOTA-GUL was 18.3 nM. In the biodistribution study, tumor uptake of 68 Ga-NOTA-GUL (5.40% ID/g) was higher than that of 68 Ga-DOTA-GUL (4.66% ID/g) at 1 h. Tumor/muscle and tumor/blood uptake ratios of 68 Ga-NOTA-GUL (31.8 and 135, respectively) were significantly higher than those of 68 Ga-DOTA-GUL (16.1 and 31.1, respectively). The tumor/kidney uptake ratio of 68 Ga-NOTA-GUL was 3.4-fold higher than that of 68 Ga-DOTA-GUL. 68 Ga-NOTA-GUL showed specific uptake to PSMA positive tumor xenograft and was blocked by co-injection of the cold ligand. In conclusion, we successfully synthesized 68 Ga-NOTA-GUL and 68 Ga-DOTA-GUL for prostate cancer imaging. 68 Ga-NOTA-GUL showed better radiochemical and biodistribution results. 68 Ga-NOTA-GUL may be a promising PSMA targeting radiopharmaceutical. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer.

PubMed

Park, Sonya Youngju; Zacharias, Claudia; Harrison, Caitlyn; Fan, Richard E; Kunder, Christian; Hatami, Negin; Giesel, Frederik; Ghanouni, Pejman; Daniel, Bruce; Loening, Andreas M; Sonn, Geoffrey A; Iagaru, Andrei

2018-05-16

Purpose To report the results of dual-time-point gallium 68 ( 68 Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of 68 Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUV max ]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68 Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68 Ga-PSMA-11 increased at later acquisition times, with higher mean SUV max (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68 Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68 Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection. © RSNA, 2018 Online supplemental material is available for this article.

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia

PubMed Central

Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-01-01

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa. PMID:29100363

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia.

PubMed

Jia, Gaozhen; Dong, Zhenyang; Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-09-29

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

Emerging Roles of Human Prostatic Acid Phosphatase

PubMed Central

Kong, Hoon Young; Byun, Jonghoe

2013-01-01

Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed. PMID:24009853

Osteopontin is a tumor autoantigen in prostate cancer patients

PubMed Central

TILLI, TATIANA M.; SILVA, ELOÍSIO A.; MATOS, LÍVIA C.; FAGET, DOUGLAS V.; DIAS, BIANCA F.P.; VASCONCELOS, JULIANA S.P.; YOKOSAKI, YASUYUKI; GIMBA, ETEL R.P.

2011-01-01

Anti-tumor antibodies act as biomarkers for the early diagnosis of prostate cancer (PCa). Osteopontin (OPN) is overexpressed in PCa cells and contributes to the progression of the disease. This study aimed to evaluate whether OPN evokes a humoral immune response in PCa patients and whether the reactivity levels of anti-OPN antibodies may be used to better differentiate PCa from benign and healthy donor plasma samples. Plasma samples from biopsy-proven PCa patients (29), benign prostate hyperplasia (BPH) (18) and control healthy donors (HD) (30) were tested by immunoblots using the recombinant human OPN. The frequency of anti-OPN antibodies was significantly higher in PCa (66%) plasma samples as compared to BPH (33%) and HD controls (10%). Anti-OPN antibodies were detected in a high proportion of plasma samples from patients with a Gleason score of less than 6 (57%), prostate-specific antigen levels lower than 10 ng/ml (67%) and pT2 organ-confined disease (70%), suggesting that anti-OPN antibodies may be used as an early serum marker for PCa. To the best of our knowledge, this is the first description of OPN as a tumor autoantigen and one of the most reactive individual autoantigens described thus far. These data support the inclusion of OPN in a multiplex of tumor antigens in order to perform antibody profiling in PCa as well as in other malignancies overexpressing OPN. PMID:22870138

Association of Reported Prostate Cancer Risk Alleles With PSA Levels Among Men Without a Diagnosis of Prostate Cancer

PubMed Central

Wiklund, Fredrik; Zheng, S. Lilly; Sun, Jielin; Adami, Hans-Olov; Lilja, Hans; Hsu, Fang-Chi; Stattin, Pär; Adolfsson, Jan; Cramer, Scott D.; Duggan, David; Carpten, John D.; Chang, Bao-Li; Isaacs, William B.; Grönberg, Henrik; Xu, Jianfeng

2012-01-01

BACKGROUND Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P≤0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend=3.4×10−14. In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. CONCLUSIONS Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening. PMID:19116992

Disparate Vitamin D Activity in the Prostate of Men with African Ancestry

DTIC Science & Technology

2016-10-01

more consistently shown inverse associa- tions (17–19). Interventional studies with vitamin D supplements have reported lower prostate-specific antigen...of vitamin D (22). This pivotal study showed that oral supplementation with vitamin D can alter levels in the prostate tissue, but it also lacked...optimize the assay ( Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/jci.insight.91054DS1). Simi- lar to

A retrospective study: correlation of histologic inflammation in biopsy specimens of Chinese men undergoing surgery for benign prostatic hyperplasia with serum prostate-specific antigen.

PubMed

Song, Lingmin; Zhu, Yuchun; Han, Ping; Chen, Ni; Lin, Dao; Lai, Jianyu; Wei, Qiang

2011-03-01

To reveal the correlation between benign prostatic hyperplasia (BPH) histologic inflammation and serum prostate-specific antigen (sPSA) concentrations, and the possible mechanism. Patients underwent surgery at the Urology Department of West China Hospital of Sichuan University were retrospectively studied. Preoperative sPSA and transrectal ultrasonography were measured. According to the histopathological classification system for chronic prostatic inflammation proposed by the Chronic Prostatitis Collaborative Research Network (CPCRN) and the International Prostatitis Collaborative Network (IPCN), we classified the histologic sections of prostatic biopsy into glandular, periglandular, and stromal inflammation by the anatomical location of inflammatory infiltration. The glandular inflammation was graded according to the inflammatory aggressiveness. The periglandular and stromal inflammation were graded according to the inflammatory density. The correlation between histologic inflammation and sPSA was studied by a multiple regression model in conjunction with age and total prostatic volume. A total of 454 patients with exclusively BPH were analyzed. The periglandular inflammatory infiltration was the most common pattern (95.6%). Single regression analysis revealed that total prostatic volume, the aggressiveness of glandular inflammation, and the intensity of periglandular and stromal inflammation were correlated with sPSA. However, the multiple regression analysis revealed that only the total prostatic volume and the aggressiveness of glandular inflammation were correlated significantly with sPSA (R = .389, 0.289; P = .000). The aggressiveness of glandular inflammatory infiltration in BPH is a significant contributor to elevated sPSA levels. The theory of leakage may be the most reasonable mechanism to reveal the correlation morphologically. We should take inflammation into consideration when interpreting the abnormal elevating of sPSA levels. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-04-01

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

Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy.

PubMed

Janbaziroudsari, Hamid; Mirzaei, Arezoo; Maleki, Nasrollah

2016-09-01

To investigate the relationship of serum prostate-specific antigen (PSA) levels with outcomes of prostate needle biopsy in men 50 or more years old. We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level (≥4ng/mL) or abnormal digital rectal examination, a transrectal ultrasound-guided prostate biopsy was performed. The mean serum total PSA level was 13.73±11.44ng/mL, and the mean serum free PSA level was 4.99±0.97ng/mL. Of the 260 men who had serum total PSA levels of≥4ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4%) had prostate cancer. Benign prostatic hyperplasia with or without prostatitis was diagnosed in 94 patients (67.6%). There was no significant correlation between age and histologic results of prostate needle biopsy (P-value=0.469). The serum free PSA showed no significant correlation with histologic results of prostate needle biopsy, whereas the serum total PSA level had a significant correlation in patients with adenocarcinoma compared with other diagnosis. The overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

The Relationship of Baseline Prostate Specific Antigen and Risk of Future Prostate Cancer and Its Variance by Race.

PubMed

Verges, Daniel P; Dani, Hasan; Sterling, William A; Weedon, Jeremy; Atallah, William; Mehta, Komal; Schreiber, David; Weiss, Jeffrey P; Karanikolas, Nicholas T

2017-01-01

Several studies suggest that a baseline prostate specific antigen (PSA) measured in young men predicts future risk of prostate cancer. Considering recent recommendations against PSA screening, high-risk populations (e.g. black men, men with a high baseline PSA) may be particularly vulnerable in the coming years. Thus, we investigated the relationship between baseline PSA and future prostate cancer in a black majority-minority urban population. A retrospective analysis was performed of the prostate biopsy database (n = 994) at the Brooklyn Veterans Affairs Hospital. These men were referred to urology clinic for elevated PSA and biopsied between 2007 and 2014. Multivariate logistic regression was used to predict positive prostate biopsy from log-transformed baseline PSA, race (black, white, or other), and several other variables. The majority of men identified as black (50.2%). Median age at time of baseline PSA and biopsy was 58.6 and 64.8, respectively. Median baseline PSA was similar among black men and white men (2.70 vs 2.91 for black men vs white men, p = 0.232). Even so, black men were more likely than white men to be diagnosed with prostate cancer (OR 1.62, p < 0.0001). Black men less than age 70 were at particularly greater risk than their white counterparts. Baseline PSA was not a statistically significant predictor of future prostate cancer (p = 0.101). Black men were more likely to be diagnosed with prostate cancer than were white men, despite comparable baseline PSA. In our pre-screened population at the urology clinic, a retrospective examination of baseline PSA did not predict future prostate cancer. Copyright © 2016 National Medical Association. Published by Elsevier Inc. All rights reserved.

Effects of pumpkin seed oil and saw palmetto oil in Korean men with symptomatic benign prostatic hyperplasia.

PubMed

Hong, Heeok; Kim, Chun-Soo; Maeng, Sungho

2009-01-01

This study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia. For this purpose, a randomized, double-blind, placebo-controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8. Subjects received either sweet potato starch (group A, placebo, 320 mg/day), pumpkin seed oil (group B, 320 mg/day), saw palmetto oil (group C, 320 mg/day) or pumpkin seed oil plus saw palmetto oil (group D, each 320 mg/day). International prostate symptom score, quality of life, serum prostate specific antigen, prostate volume and maximal urinary flow rate were measured. In groups B, C and D, the international prostate symptom score were reduced by 3 months. Quality of life score was improved after 6 months in group D, while those of groups B and C were improved after 3 months, compared to the baseline value. Serum prostate specific antigen was reduced only in group D after 3 months, but no difference was observed in prostate volume in all treatment groups. Maximal urinary flow rate were gradually improved in groups B and C, with statistical significance after 6 months in group B and after 12 months in group C. None of the parameters were significantly improved by combined treatment with pumpkin seed oil and saw palmetto oil. From these results, it is suggested that administrations of pumpkin seed oil and saw palmetto oil are clinically safe and may be effective as complementary and alternative medicine treatments for benign prostatic hyperplasia.

Effects of pumpkin seed oil and saw palmetto oil in Korean men with symptomatic benign prostatic hyperplasia

PubMed Central

Hong, Heeok; Kim, Chun-Soo

2009-01-01

This study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia. For this purpose, a randomized, double-blind, placebo-controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8. Subjects received either sweet potato starch (group A, placebo, 320 mg/day), pumpkin seed oil (group B, 320 mg/day), saw palmetto oil (group C, 320 mg/day) or pumpkin seed oil plus saw palmetto oil (group D, each 320 mg/day). International prostate symptom score, quality of life, serum prostate specific antigen, prostate volume and maximal urinary flow rate were measured. In groups B, C and D, the international prostate symptom score were reduced by 3 months. Quality of life score was improved after 6 months in group D, while those of groups B and C were improved after 3 months, compared to the baseline value. Serum prostate specific antigen was reduced only in group D after 3 months, but no difference was observed in prostate volume in all treatment groups. Maximal urinary flow rate were gradually improved in groups B and C, with statistical significance after 6 months in group B and after 12 months in group C. None of the parameters were significantly improved by combined treatment with pumpkin seed oil and saw palmetto oil. From these results, it is suggested that administrations of pumpkin seed oil and saw palmetto oil are clinically safe and may be effective as complementary and alternative medicine treatments for benign prostatic hyperplasia. PMID:20098586

Folate hydrolase (prostate-specific membrane [corrected] antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature.

PubMed

Samplaski, Mary K; Heston, Warren; Elson, Paul; Magi-Galluzzi, Cristina; Hansel, Donna E

2011-11-01

Folate hydrolase (prostate-specific antigen) 1 (FH(PSA)1), also known as prostate-specific membrane antigen (PSMA), is a transmembrane receptor expressed on prostate cancer cells that correlates with a more aggressive phenotype. Recent studies have demonstrated FH(PSA)1 expression in numerous benign and malignant tissue types, as well as the malignant neovasculature. As FH(PSA)1 represents a diagnostic immunomarker for prostate cancer, we explored its expression pattern in various subtypes of bladder cancer. Immunohistochemical analysis (IHC) of FH(PSA)1 was performed using tissue microarrays constructed from 167 bladder cancers, including 96 urothelial carcinomas (UCCs), 37 squamous cell carcinomas, 17 adenocarcinomas and 17 small cell carcinomas. We used a FH(PSA)1 monoclonal antibody obtained from Dako (clone 3E6, dilution 1:100), which recognizes the epitope present in the 57-134 amino acid region of the extracellular portion of the PSMA molecule. Intensity of IHC staining was scored as 0 (no expression) to 3+ (strong expression), with 2-3+ IHC considered a positive result. FH(PSA)1 demonstrated expression in a subset of bladder cancers and was most common in small cell carcinoma (3/17; 18%), with concurrent expression in non-small cell components in a subset of cases (2/6). FH(PSA)1 expression was less frequent in UCC (3/96; 3%) and adenocarcinoma (2/17; 12%). None of the squamous cell carcinomas demonstrated tumor cell expression of FH(PSA)1. However, all bladder cancers examined expressed FH(PSA)1 in the tumor vasculature, suggesting a potential role for this molecule in mediating new vessel ingrowth. FH(PSA)1 may occasionally be expressed in various subtypes of bladder cancer. These findings suggest cautious use of FH(PSA)1 as a diagnostic marker for prostatic tissue invading the bladder. The finding of FH(PSA)1 in the bladder cancer neovasculature suggests that this molecule may promote tumor growth and may represent a potential new vascular target in this disease.

Use of cancer screening services in Greece and associated social factors: results from the nation-wide Hellas Health I survey.

PubMed

Dimitrakaki, Christine; Boulamatsis, Dimitris; Mariolis, Anargiros; Kontodimopoulos, Nick; Niakas, Dimitris; Tountas, Yannis

2009-06-01

This study estimated the rates of age-appropriate screening practices for breast, cervical, colon and prostate cancer within the general population in Greece and explored the influences of social factors on their use. Data were based on the cross-sectional Hellas Health I survey (2006) conducted on a representative sample of 1005 adults, aged 18-69 years. The percentage of women aged 21-69 years having received the papanicolaou smear test within the past 3 years was 59.4%, and the percentage of women aged 50-69 years having received mammography and the faecal occult blood test (FOBT) within the past 3 years was 53.8 and 8.3%, respectively. There were significant effects of age, education and marital status on carrying out the papanicolaou smear test, age on carrying out mammography, and existence of a family doctor on carrying out the FOBT. In men aged 50-69 years, 40.6% had received the prostate-specific antigen test and 10.9% of men had received the FOBT during the past 3 years. The percentage of men aged 50-69 years who had undergone digital rectal examination within the past 5 years was 20.3%. Multivariate analyses showed significant effects of age, social class, smoking status and type of insurance on carrying out the prostate-specific antigen test and of age on carrying out the digital rectal examination. No effects were revealed for the FOBT in men. The percentage of the population in Greece receiving screening services recommended by the European Council is low and seriously affected by social factors. Public health policies should direct their efforts towards introducing good-quality universal cancer screening and find culturally sensitive ways of addressing the barriers that prevent Greek people from adopting poor-quality cancer screening practices.

Urinary prostate-specific antigen: predictor of benign prostatic hyperplasia progression?

PubMed

Pejcic, Tomislav P; Tulic, Cane Dz; Lalic, Natasa V; Glisic, Biljana D; Ignjatovic, Svetlana D; Markovic, Biljana B; Hadzi-Djokic, Jovan B

2013-04-01

Urinary prostate-specific antigen (uPSA) can be used as additional parameter of benign prostatic hyperplasia (BPH) progression. From January 2001 to December 2011, uPSA was determined in 265 patients with benign prostate. Based on total prostate volume (TPV), the patients with benign prostate were divided in two groups: TPV < 31 mL and TPV ≥ 31 mL. Additional three groups were formed upon MTOPS study criteria: non- progressive BPH group (TPV < 31 mL, PSA < 1.6 ng/mL, age < 62 yrs), intermediate group (one, or two parameters {TPV, PSA, age} increased) and progressive BPH group (TPV ≥ 31 ml, PSA ≥ 1.6 ng/mL, age ≥ 62 yrs). Average uPSA values in the groups TPV < 31 mL and TPV ≥ 31 mL were 119.3 ± 124.5 and 255.5 ± 204.9 ng/mL, respectively and they were significantly different (p < 0.0001). Average uPSA values in the non- progressive BPH group, intermediate group and progressive BPH group were 86.8 ± 82.4 ng/mL, 166.6 ± 164.9 ng/mL and 274.9 ± 208.3 ng/mL, respectively and they were significantly different (p < 0.0001). The level of uPSA correlated significantly with TPV (r = 0.32, p < 0.0001). The cut off uPSA level of 150 ng/mL discriminates the patients with non-progressive BPH and progressive BPH with specificity of 0.83 and sensitivity of 0.67. The level of uPSA reflects prostatic hormonal activity and correlates with TPV, PSA and age. UPSA level ≥ 150 ng/mL can be used as additional predictive parameter of BPH progression.

Questions and answers on prostate multiparameter magnetic resonance imaging: Everything a urologist should know.

PubMed

Catalá, V; Salas, D; Esquena, S; Mateu, S; Algaba, F; Palou, J; de la Torre, P

2016-01-01

For many years, the detection of prostate cancer (PC) and the management of its therapy have been based primarily on prostate-specific antigen, rectal examination and prostate biopsy. However, these parameters have known limitations. Multiparametric magnetic resonance imaging (mpMRI) for prostate cancer has undergone extensive development in recent years, providing morphological and functional information. The aim of this study is to present an updated review of the scope and limitations of prostatic mpMRI for PC, in the framework of a multidisciplinary vision. We conducted a literature review (in PubMed) of articles referencing "mpMRI/staging/ PC/detection/active surveillance/therapy planning/post-therapy". We included 4 systematic reviews and other articles published in high impact-factor journals within the field of radiology and urology. MpMRI provides morphological and functional information concerning PC. This information is integrated into the Prostate Imaging Report and Date System, classifying the probability of clinically significant carcinoma on a scale from 1 to 5. The usefulness of mpMRI is currently being established for patients with high prostate-specific antigen levels and prior negative prostate biopsy; tumour staging in selected cases; assessment of patients who are candidates for active surveillance; the planning of focal treatments; and the assessment of tumour persistence and recurrence. MpMRI currently fills a relevant role in the diagnosis and therapeutic decision-making of PC. More widespread use of the technique requires a cost/benefit analysis. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Prostate-specific membrane antigen PET/MRI validation of MR textural analysis for detection of transition zone prostate cancer.

PubMed

Bates, Anthony; Miles, Kenneth

2017-12-01

To validate MR textural analysis (MRTA) for detection of transition zone (TZ) prostate cancer through comparison with co-registered prostate-specific membrane antigen (PSMA) PET-MR. Retrospective analysis was performed for 30 men who underwent simultaneous PSMA PET-MR imaging for staging of prostate cancer. Thirty texture features were derived from each manually contoured T2-weighted, transaxial, prostatic TZ using texture analysis software that applies a spatial band-pass filter and quantifies texture through histogram analysis. Texture features of the TZ were compared to PSMA expression on the corresponding PET images. The Benjamini-Hochberg correction controlled the false discovery rate at <5%. Eighty-eight T2-weighted images in 18 patients demonstrated abnormal PSMA expression within the TZ on PET-MR. 123 images were PSMA negative. Based on the corrected p-value of 0.005, significant differences between PSMA positive and negative slices were found for 16 texture parameters: Standard deviation and mean of positive pixels for all spatial filters (p = <0.0001 for both at all spatial scaling factor (SSF) values) and mean intensity following filtration for SSF 3-6 mm (p = 0.0002-0.0018). Abnormal expression of PSMA within the TZ is associated with altered texture on T2-weighted MR, providing validation of MRTA for the detection of TZ prostate cancer. • Prostate transition zone (TZ) MR texture analysis may assist in prostate cancer detection. • Abnormal transition zone PSMA expression correlates with altered texture on T2-weighted MR. • TZ with abnormal PSMA expression demonstrates significantly reduced MI, SD and MPP.

Selection of tumor antigens as targets for immune attack using immunohistochemistry: protein antigens.

PubMed

Zhang, S; Zhang, H S; Cordon-Cardo, C; Ragupathi, G; Livingston, P O

1998-11-01

The relative expression of mucin antigens MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC7 and glycoprotein antigens KSA, carcinoembryonic antigen, prostate-specific membrane antigen (PSMA), HER-2/neu, and human chorionic gonadotropin-beta on different cancers and normal tissues is difficult to determine from available reports. We have compared the distribution of these antigens by immunohistology on a broad range of malignant and normal tissues. MUC1 expression was most intense in cancers of breast, lung, ovarian, and endometrial origin; MUC2 was most intense in cancers of colon and prostate origin; and MUC5AC was most intense in cancers of breast and gastric origin. MUC4 was intensely expressed in 50% of cancers of colon and pancreas origin, and MUC3, MUC5B, and MUC7 were expressed in a variety of epithelial cancers, but not so intensely. KSA was intensely and uniformly expressed on all epithelial cancers; carcinoembryonic antigen was expressed in most cancers of breast, lung, colon, pancreas, and gastric origin; and PSMA was expressed only in cancers of prostate origin. Human chorionic gonadotropin-beta was expressed on the majority of sarcomas and cancers of breast, lung, and pancreas origin, although intense staining was not seen. Staining on normal tissues was restricted to one or many normal epithelial tissues ranging from MUC3, MUC4, and PSMA, which were expressed only on epithelia of pancreas, stomach, and prostate origin, respectively, to MUC1 and KSA, which were expressed on most normal epithelia. Expression was restricted to the secretory borders of these epithelia while stroma and other normal tissues were completely negative. These results plus the results of the two previous papers (S. Zhang et al, Int. J. Cancer, 73: 42-49, 1997; S. Zhang et al., Int. J. Cancer, 73: 50-56, 1997) in this series provide the basis for selection of multiple cell surface antigens as targets for antibody-mediated attack against these cancers.

Age related prostate-specific antigen reference range among men in south-East Caspian Sea.

PubMed

Mansourian, A R; Ghaemi, E O; Ahmadi, A R; Marjani, A; Moradi, A; Saifi, A

2007-05-01

The purpose of this study was to describe the distribution of serum prostate specific antigen (PSA) and to determine age-specific reference range in a population of Persian men. Venous blood samples were taken from 287 men, from Gorgan located in the North of Iran, South-East of Caspian Sea, aged 15 > or = 80 year. The serum PSA levels was measured using Enzyme-linked Immunosorbant-Assay (ELISA) technique and age-specific range for PSA level was determined. The serum prostate-specific antigen level for six age group of 15-40 years, 41-50 years, 51-60 years, 61-70 years, 71-80 years and >80 years were mainly in the range of 0-2.5 ng mL(-1), for 76.6%, 2.6-4 ng mL(-1) for 9.1% and as whole 85.7% of all men in this study had < or = 4 ng mL(-1), 8.7 and 5.6% all men of six age group had PSA level of 4.1-10 ng mL(-1) and >10 ng mL(-1), respectively. The findings of present study indicated that a large proportion (76.6%) men in this region have a lower PSA level of 0-2.5 ng mL(-1) and only 9.1% of men have PSA level of 2.6-4 ng mL(-1). It is therefore concluded that acceptable reference range of 0-4 ng mL(-1) for PSA level require further reassessment.

Men's preferences and trade-offs for prostate cancer screening: a discrete choice experiment.

PubMed

Howard, Kirsten; Salkeld, Glenn P; Patel, Manish I; Mann, Graham J; Pignone, Michael P

2015-12-01

Prostate cancer screening using prostate-specific antigen (PSA) remains controversial. In deciding about screening, men must weigh the benefits and harms: little is known about benefit: harm trade-offs men are willing to accept. The objective of this study was to assess men's preferences for PSA screening, and the trade-offs between benefits and harms men are willing to accept when deciding about screening. Preferences of 662 men aged 40-69 were assessed using a discrete choice experiment. PSA screening was described by six attributes: prostate cancer deaths, prostate cancer diagnoses, unnecessary biopsies from false-positive PSA tests, impotence, urinary incontinence/bowel problems and cost. A mixed logit model was used to examine the influence of attributes on men's preferences for PSA testing; benefit: harm trade-offs were also calculated. Men's preferences were significantly influenced by test characteristics, particularly potential mortality benefit, unnecessary biopsies and likelihood of urinary incontinence or bowel problems; preferences were also influenced by age, prior PSA testing experience and perceived risk of prostate cancer. Men were willing to accept between 65 and 233 of 10 000 extra men with unnecessary biopsies, and between 31 and 72 of 10 000 extra men with incontinence/bowel problems to avoid one prostate cancer death. Differences in valuations of attributes and trade-offs acceptable to men of different ages suggest a one size fits all approach to PSA testing, regardless of age, may not reflect men's preferences. Our results can be used by policymakers to ensure screening programmes are in line with men's preferences and by clinicians and patients to facilitate informed discussions of the most relevant benefits and downsides of PSA screening for an individual man. © 2014 John Wiley & Sons Ltd.

Prostate Cancer Patients-Negative Biopsy Controls Discrimination by Untargeted Metabolomics Analysis of Urine by LC-QTOF: Upstream Information on Other Omics

NASA Astrophysics Data System (ADS)

Fernández-Peralbo, M. A.; Gómez-Gómez, E.; Calderón-Santiago, M.; Carrasco-Valiente, J.; Ruiz-García, J.; Requena-Tapia, M. J.; Luque de Castro, M. D.; Priego-Capote, F.

2016-12-01

The existing clinical biomarkers for prostate cancer (PCa) diagnosis are far from ideal (e.g., the prostate specific antigen (PSA) serum level suffers from lack of specificity, providing frequent false positives leading to over-diagnosis). A key step in the search for minimum invasive tests to complement or replace PSA should be supported on the changes experienced by the biochemical pathways in PCa patients as compared to negative biopsy control individuals. In this research a comprehensive global analysis by LC-QTOF was applied to urine from 62 patients with a clinically significant PCa and 42 healthy individuals, both groups confirmed by biopsy. An unpaired t-test (p-value < 0.05) provided 28 significant metabolites tentatively identified in urine, used to develop a partial least squares discriminant analysis (PLS-DA) model characterized by 88.4 and 92.9% of sensitivity and specificity, respectively. Among the 28 significant metabolites 27 were present at lower concentrations in PCa patients than in control individuals, while only one reported higher concentrations in PCa patients. The connection among the biochemical pathways in which they are involved (DNA methylation, epigenetic marks on histones and RNA cap methylation) could explain the concentration changes with PCa and supports, once again, the role of metabolomics in upstream processes.

Incidental Detection of Head and Neck Squamous Cell Carcinoma on 68Ga-PSMA-11 PET/CT.

PubMed

Lawhn-Heath, Courtney; Flavell, Robert R; Glastonbury, Christine; Hope, Thomas A; Behr, Spencer C

2017-04-01

We present a case of an incidentally detected squamous cell carcinoma of the oropharynx on Ga-PSMA-11 PET. A 71-year-old man's condition was diagnosed as prostate carcinoma after a year of rising serum prostate-specific antigen. The staging Ga-PSMA PET/CT demonstrated focal radiotracer uptake in the prostate corresponding to his known primary prostate cancer. However, a PSMA-avid 3.4-cm mass was incidentally found in the right tongue base that was biopsied, confirming squamous cell carcinoma.

Common questions about the diagnosis and management of benign prostatic hyperplasia.

PubMed

Pearson, Ryan; Williams, Pamela M

2014-12-01

Benign prostatic hyperplasia (BPH) is a common condition that increases in prevalence with age. A history should include onset, duration, and severity of lower urinary tract symptoms and medication use to rule out other causes of symptoms. Physical examination includes a digital rectal examination and assessment for bladder distention or neurologic impairment. Recommended tests include serum prostate-specific antigen measurement and urinalysis to help identify infection, genitourinary cancer, or calculi as an alternative cause of lower urinary tract symptoms. BPH severity is assessed using validated, self-administered symptom questionnaires such as the American Urological Association Symptom Index or International Prostate Symptom Score. Mild or nonbothersome symptoms do not require treatment. Bothersome symptoms are managed with lifestyle modifications, medications, and surgery. Alpha blockers are first-line medications for BPH. Surgical referral is indicated if BPH-related complications develop, medical therapy fails, or the patient chooses it. Dietary supplements, such as saw palmetto, pygeum, cernilton, and beta sitosterols, and acupuncture are not recommended for the management of BPH.

Age-Specific Prostate Specific Antigen Cutoffs for Guiding Biopsy Decision in Chinese Population

PubMed Central

Xu, Jianfeng; Jiang, Haowen; Ding, Qiang

2013-01-01

Background Age-specific prostate specific antigen (PSA) cutoffs for prostate biopsy have been widely used in the USA and European countries. However, the application of age-specific PSA remains poorly understood in China. Methods Between 2003 and 2012, 1,848 men over the age of 40, underwent prostate biopsy for prostate cancer (PCa) at Huashan Hospital, Shanghai, China. Clinical information and blood samples were collected prior to biopsy for each patient. Men were divided into three age groups (≤60, 61 to 80, and >80) for analyses. Digital rectal examination (DRE), transrectal ultrasound (prostate volume and nodule), total PSA (tPSA), and free PSA (fPSA) were also included in the analyses. Logistic regression was used to build the multi-variate model. Results Serum tPSA levels were age-dependent (P = 0.008), while %fPSA (P = 0.051) and PSAD (P = 0.284) were age-independent. At a specificity of 80%, the sensitivities for predicting PCa were 83%, 71% and 68% with tPSA cutoff values of 19.0 ng/mL (age≤60),21.0 ng/mL (age 61–80), and 23.0 ng/mL (age≥81). Also, sensitivities at the same tPSA levels were able to reach relatively high levels (70%–88%) for predicting high-grade PCa. Area (AUC) under the receive operating curves (ROCs) of tPSA, %fPSA, PSAD and multi-variate model were different in age groups. When predicting PCa, the AUC of tPSA, %fPSA, PSAD and multi-variate model were 0.90, 0.57, 0.93 and 0.87 respectively in men ≤60 yr; 0.82, 0.70, 0.88 and 0.86 respectively in men 61–80 yr; 0.79, 0.78, 0.87 and 0.88 respectively in men>80 yr. When predicting Gleason Score ≥7 or 8 PCa, there were no significant differences between AUCs of each variable. Conclusion Age-specific PSA cutoff values for prostate biopsy should be considered in the Chinese population. Indications for prostate biopsies (tPSA, %fPSA and PSAD) should be considered based on age in the Chinese population. PMID:23825670

Trends in stage-specific incidence of prostate cancer in Norway, 1980-2010: a population-based study.

PubMed

Møller, Mette H; Kristiansen, Ivar S; Beisland, Christian; Rørvik, Jarle; Støvring, Henrik

2016-10-01

To estimate changes in the stage distribution of prostate cancer during the time period where opportunistic prostate-specific antigen (PSA) testing was introduced. Cancer stage, age, and year of diagnosis were obtained for all men aged >50 years diagnosed with prostate cancer in Norway during the period 1980-2010. Three calendar-time periods (1980-1989, 1990-2000, and 2001-2010) and three age groups (50-65, 66-74, and ≥75 years) were defined. Birth cohorts were categorised into four intervals: ≤1915, 1916-1925, 1926-1940 and ≥1941. We used Poisson regressions to conduct both a time period and cohort-based analysis of trends in the incidence of localised, regional, and distant cancer for each combination of age groups and calendar-time periods or birth cohorts, respectively. Additionally, we explored the effect of cohorts on the stage-specific incidence graphically with a Poisson regression using 5-year age groups, and by estimating cumulative incidence rates for each birth cohort. The annual incidence of localised cancers among men aged 50-65 and 66-74 years rose from 41.4 and 255.2 per 100 000, respectively, before the introduction of PSA testing to 137.9 and 418.7 in 2001-2010 afterwards, corresponding to 3.3 [95% confidence interval (CI) 3.1-3.5] and 1.6 (95% CI 1.6-1.7) fold increases. The incidence of regional cancers increased by a factor seven among men aged <75 years. The incidence of distant cancers in men aged ≥75 years decreased by 29% (95% CI 25-33%). These findings were confirmed in the cohort-based approach. Opportunistic PSA testing substantially increased the incidence of localised and regional prostate cancers among men aged 50-74 years, which was not fully compensated by the 30% decrease in incidence of distant prostate cancers in older men. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Effect of Antigen Retrieval Methods on Nonspecific Binding of Antibody-Metal Nanoparticle Conjugates on Formalin-Fixed Paraffin-Embedded Tissue.

PubMed

Zhang, Yuying; Wang, Xin-Ping; Perner, Sven; Bankfalvi, Agnes; Schlücker, Sebastian

2018-01-02

Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tissues provides important diagnostic and prognostic information in pathology. Metal nanoparticles (NPs) and, in particular, surface-enhanced Raman scattering (SERS) nanotags as a new class of labeling reagents are promising to be used for multiplexed protein profiling on tissue sections. However, nonspecific binding of NPs onto the tissue specimens greatly hampers their clinical applications. In this study, we found that the antigen retrieval method strongly influences the extent of nonspecific binding of the antibody-SERS NP conjugates to the tissue. Our SERS labels comprised ca. 70 nm Au nanostars coated with ethylene glycol-modified Raman reporter molecules for hydrophilic stabilization and subsequent covalent bioconjugation to antibodies. We systematically investigated the influence of heat- and protease-induced epitope retrieval (HIER and PIER, respectively) on the immunostaining quality of prostate-specific antigen (PSA) on human prostate tissue sections. The best staining results were obtained with PIER. Pretreatment of the tissue sections by HIER led to selective but nonspecific adsorption of the antibody-Au nanostar conjugates onto epithelial cells, while enzymatic treatment within PIER did not. In addition to gold nanostars, also other types of metal NPs with different shapes and sizes (including ca. 20 nm quasi-spherical Au NPs and ca. 60 nm quasi-spherical Au/Ag nanoshells) as well as tissue sections from different organs (including prostate and breast) were tested; in each case the same tendency was observed, i.e., PIER yielded better results than HIER. Therefore, we recommend PIER for future NP-based tissue immunostaining such as immuno-SERS microscopy. Alternatively, for antigens that can only be unmasked by heating, PEGylation of the NPs is recommended to avoid nonspecific binding.

Nanoporous gold as a solid support for protein immobilization and development of an electrochemical immunoassay for prostate specific antigen and carcinoembryonic antigen

PubMed Central

Pandey, Binod; Demchenko, Alexei V.; Stine, Keith J.

2013-01-01

Nanoporous gold (NPG) was utilized as a support for immobilizing alkaline phosphatase (ALP) conjugated to monoclonal antibodies against either prostate specific antigen (PSA) or carcinoembryonic antigen (CEA). The antibody-ALP conjugates were coupled to self-assembled monolayers of lipoic acid and used in direct kinetic assays. Using the enzyme substrate p-aminophenylphosphate, the product p-aminophenol was detected by its oxidation near 0.1 V (vs. Ag|AgCl) using square wave voltammetry. The difference in peak current arising from oxidation of p-aminophenol before and after incubation with biomarker increased with biomarker concentration. The response to these two biomarkers was linear up to 10 ng mL-1 for CEA and up to 30 ng mL-1 for PSA. The effect of interference on the PSA assay was studied using bovine serum albumin (BSA) as a model albumin protein. The effect of interference from a serum matrix was examined for the PSA assay using newborn calf serum. A competitive version of the immunoassay using antigen immobilized onto the NPG surface was highly sensitive at lower antigen concentration. Estimates of the surface coverage of the antibody-ALP conjugates on the NPG surface are presented. PMID:23935216

Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer.

PubMed

Chen, Yen-Ching; Giovannucci, Edward; Lazarus, Ross; Kraft, Peter; Ketkar, Shamika; Hunter, David J

2005-12-15

Chronic inflammation has been hypothesized to be a risk factor for prostate cancer. The Toll-like receptor 4 (TLR4) presents the bacterial lipopolysaccharide (LPS), which interacts with ligand-binding protein and CD14 (LPS receptor) and activates expression of inflammatory genes through nuclear factor-kappaB and mitogen-activated protein kinase signaling. A previous case-control study found a modest association of a polymorphism in the TLR4 gene [11381G/C, GG versus GC/CC: odds ratio (OR), 1.26] with risk of prostate cancer. We assessed if sequence variants of TLR4 were associated with the risk of prostate cancer. In a nested case-control design within the Health Professionals Follow-up Study, we identified 700 participants with prostate cancer diagnosed after they had provided a blood specimen in 1993 and before January 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped 16 common (>5%) single nucleotide polymorphisms (SNP) discovered in a resequencing study spanning TLR4 to test for association between sequence variation in TLR4 and prostate cancer. Homozygosity for the variant alleles of eight SNPs was associated with a statistically significantly lower risk of prostate cancer (TLR4_1893, TLR4_2032, TLR4_2437, TLR4_7764, TLR4_11912, TLR4_16649, TLR4_17050, and TLR4_17923), but the TLR4_15844 polymorphism corresponding to 11381G/C was not associated with prostate cancer (GG versus CG/CC: OR, 1.01; 95% confidence interval, 0.79-1.29). Six common haplotypes (cumulative frequency, 81%) were observed; the global test for association between haplotypes and prostate cancer was statistically significant (chi(2) = 14.8 on 6 degrees of freedom; P = 0.02). Two common haplotypes were statistically significantly associated with altered risk of prostate cancer. Inherited polymorphisms of the innate immune gene TLR4 are associated with risk of prostate cancer.

Oligometastatic prostate cancer: shaping the definition with molecular imaging and an improved understanding of tumor biology.

PubMed

Joice, Gregory A; Rowe, Steven P; Pienta, Kenneth J; Gorin, Michael A

2017-11-01

The aim of this review is to discuss how novel imaging modalities and molecular markers are shaping the definition of oligometastatic prostate cancer. To effectively classify a patient as having oligometastatic prostate cancer, diagnostic tests must be sensitive enough to detect subtle sites of metastatic disease. Conventional imaging modalities can readily detect widespread polymetastatic disease but do not have the sensitivity necessary to reliably classify patients as oligometastatic. Molecular imaging using both metabolic- and molecularly-targeted radiotracers has demonstrated great promise in aiding in our ability to define the oligometastatic state. Perhaps the most promising data to date have been generated with radiotracers targeting prostate-specific membrane antigen. In addition, early studies are beginning to define biologic markers in the oligometastatic state that may be indicative of disease with minimal metastatic potential. Recent developments in molecular imaging have allowed for improved detection of metastatic prostate cancer allowing for more accurate staging of patients with oligometastatic disease. Future development of biologic markers may assist in defining the oligometastatic state and determining prognosis.

Prostate-specific antigen kallikrein and acute myocardial infarction: where we are. Where are we going?

PubMed

Patanè, Salvatore; Marte, Filippo

2011-01-07

Prostate-specific antigen (PSA) is an established marker for the detection of prostate cancer. Both elevated and diminished PSA have been reported during acute myocardial infarction. It seems that when elevation of PSA occurs during acute myocardial infarction (AMI), coronary lesions are frequent and often more severe than when a diminution of PSA occurs. PSA has been identified as a member of the human kallikrein family of serine proteases. In recent years, numerous observations have suggested that the activity of the kallikrein-kinin system is related to inflammation and to cardiovascular diseases. PSA kallikrein, however, does not seem to have kinin-generating activity. The inactive precursor form of PSA, proPSA, is converted rapidly to active PSA by Human kallikrein 2 (hK2), suggesting an important in vivo regulatory function byhK2 on PSA activity. However, it has been reported that hK2 might not alone be able to activate proPSA in vivo, but there are also other protease/proteases involved in this event. Moreover, it seems that when elevation of prostate-specific antigen occurs during AMI, it seems to relate to a higher occurrence of major adverse cardiac events in the first 8 days after AMI than when a diminution of PSA occurs. It confirms a possible new intriguing scenario of the role of the PSA in AMI. Although these preliminary observations are suggestive, large studies need to be done to confirm these preliminary results. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

Prostate-specific antigen (PSA) bounce and other fluctuations: which biochemical relapse definition is least prone to PSA false calls? An analysis of 2030 men treated for prostate cancer with external beam or brachytherapy with or without adjuvant androgen deprivation therapy.

PubMed

Pickles, Tom

2006-04-01

To determine the false call (FC) rate for prostate-specific antigen (PSA) relapse according to nine different PSA relapse definitions after a PSA fluctuation (bounce) has occurred after external beam radiation therapy (EBRT) or brachytherapy, with or without adjuvant androgen deprivation therapy. An analysis of a prospective database of 2030 patients was conducted. Prostate-specific antigen relapse was scored according to the American Society for Therapeutic Radiology and Oncology (ASTRO), Vancouver, threshold + n, and nadir + n definitions for the complete data set and then compared against a truncated data set, with data subsequent to the height of the bounce deleted. The FC rate was calculated for each definition. The bounce rate, with this very liberal definition of bounce, was 58% with EBRT and 84% with brachytherapy. The FC rate was lowest with nadir + 2 and + 3 definitions (2.2% and 1.6%, respectively) and greatest with low-threshold and ASTRO definitions (32% and 18%, respectively). The ASTRO definition was particularly susceptible to FC when androgen deprivation therapy was used with radiation (24%). New definitions of biochemical non-evidence of disease that are more robust than the ASTRO definition have been identified. Those with the least FC rates are the nadir + 2 and nadir + 3 definitions, both of which are being considered to replace the ASTRO definition by the 2005 meeting of the Radiation Therapy Oncology Group-ASTRO consensus panel.

The added value of percentage of free to total prostate-specific antigen, PCA3, and a kallikrein panel to the ERSPC risk calculator for prostate cancer in prescreened men.

PubMed

Vedder, Moniek M; de Bekker-Grob, Esther W; Lilja, Hans G; Vickers, Andrew J; van Leenders, Geert J L H; Steyerberg, Ewout W; Roobol, Monique J

2014-12-01

Prostate-specific antigen (PSA) testing has limited accuracy for the early detection of prostate cancer (PCa). To assess the value added by percentage of free to total PSA (%fPSA), prostate cancer antigen 3 (PCA3), and a kallikrein panel (4k-panel) to the European Randomised Study of Screening for Prostate Cancer (ERSPC) multivariable prediction models: risk calculator (RC) 4, including transrectal ultrasound, and RC 4 plus digital rectal examination (4+DRE) for prescreened men. Participants were invited for rescreening between October 2007 and February 2009 within the Dutch part of the ERSPC study. Biopsies were taken in men with a PSA level ≥3.0 ng/ml or a PCA3 score ≥10. Additional analyses of the 4k-panel were done on serum samples. Outcome was defined as PCa detectable by sextant biopsy. Receiver operating characteristic curve and decision curve analyses were performed to compare the predictive capabilities of %fPSA, PCA3, 4k-panel, the ERSPC RCs, and their combinations in logistic regression models. PCa was detected in 119 of 708 men. The %fPSA did not perform better univariately or added to the RCs compared with the RCs alone. In 202 men with an elevated PSA, the 4k-panel discriminated better than PCA3 when modelled univariately (area under the curve [AUC]: 0.78 vs. 0.62; p=0.01). The multivariable models with PCA3 or the 4k-panel were equivalent (AUC: 0.80 for RC 4+DRE). In the total population, PCA3 discriminated better than the 4k-panel (univariate AUC: 0.63 vs. 0.56; p=0.05). There was no statistically significant difference between the multivariable model with PCA3 (AUC: 0.73) versus the model with the 4k-panel (AUC: 0.71; p=0.18). The multivariable model with PCA3 performed better than the reference model (0.73 vs. 0.70; p=0.02). Decision curves confirmed these patterns, although numbers were small. Both PCA3 and, to a lesser extent, a 4k-panel have added value to the DRE-based ERSPC RC in detecting PCa in prescreened men. We studied the added value of novel biomarkers to previously developed risk prediction models for prostate cancer. We found that inclusion of these biomarkers resulted in an increase in predictive ability. Copyright © 2014. Published by Elsevier B.V.

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

PubMed Central

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

2017-01-01

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

Development of Novel Drugs That Target Coactivation Sites of the Androgen Receptor for Treatment of Antiandrogen-Resistant Prostate Cancer

DTIC Science & Technology

2015-12-01

quantifying their effect on the production of the prostate specific antigen (PSA) in prostate cancer cell lines (11). PSA is AR-regulated serine protease and... products . The hydroxylation products were observed in lesser amounts. The IV and IP serum profiles of VPC-13566 suggest that it could be administered IP...Glucocorticoid, mineralocorticoid, progesterone , and androgen receptors. Pharmacological Reviews. 2006;58:782-97. 2. Denmeade SR, Isaacs JT. A

An overview of prostate diseases and their characteristics specific to Asian men.

PubMed

Xia, Shu-Jie; Cui, Di; Jiang, Qi

2012-05-01

In this paper, we reviewed the features of common prostate diseases, such as benign prostatic hyperplasia (BPH), prostate cancer (PCa) and chronic prostatitis (CP) that are specific to Asian men. Compared to the Westerners, Asians exhibit particular characteristics of prostate diseases. Through summarizing the epidemiology, symptomatology, diagnostics and therapeutics of these diseases, we find that Asians have a lower incidence of PCa than whites, but the incidences of BPH and CP are similar. Asian men with CP often suffer from fewer disease sites, but have a higher frequency of pain during urination rather than after sexual climax. Prostate-specific antigen (PSA) is a widely used marker for the diagnosis of PCa in both Asian and Western countries. Although the PSA level may be lower in Asians, the threshold used is based on whites. After reviewing the treatments available for these diseases, we did not find a fundamental difference between Asians and whites. Furthermore, the selection for the most appropriate treatment based on the individual needs of patients remains a challenge to urologists in Asia. After considering the traits of prostate diseases that are specific to Asian men, we hope to pave the way for the development of specific diagnostic and therapeutic strategies targeted specifically to Asian men.

DNA Ploidy Measured on Archived Pretreatment Biopsy Material May Correlate With Prostate-Specific Antigen Recurrence After Prostate Brachytherapy

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

Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca; MacAulay, Calum; Hayes, Malcolm

Purpose: To explore whether DNA ploidy of prostate cancer cells determined from archived transrectal ultrasound-guided biopsy specimens correlates with disease-free survival. Methods and Materials: Forty-seven failures and 47 controls were selected from 1006 consecutive low- and intermediate-risk patients treated with prostate {sup 125}I brachytherapy (July 1998-October 2003). Median follow-up was 7.5 years. Ten-year actuarial disease-free survival was 94.1%. Controls were matched using age, initial prostate-specific antigen level, clinical stage, Gleason score, use of hormone therapy, and follow-up (all P nonsignificant). Seventy-eight specimens were successfully processed; 27 control and 20 failure specimens contained more than 100 tumor cells were used formore » the final analysis. The Feulgen-Thionin stained cytology samples from archived paraffin blocks were used to determine the DNA ploidy of each tumor by measuring integrated optical densities. Results: The samples were divided into diploid and aneuploid tumors. Aneuploid tumors were found in 16 of 20 of the failures (80%) and 8 of 27 controls (30%). Diploid DNA patients had a significantly lower rate of disease recurrence (P=.0086) (hazard ratio [HR] 0.256). On multivariable analysis, patients with aneuploid tumors had a higher prostate-specific antigen failure rate (HR 5.13). Additionally, those with “excellent” dosimetry (V100 >90%; D90 >144 Gy) had a significantly lower recurrence rate (HR 0.25). All patients with aneuploid tumors and dosimetry classified as “nonexcellent” (V100 <90%; D90 <144 Gy) (5 of 5) had disease recurrence, compared with 40% of patients with aneuploid tumors and “excellent” dosimetry (8 of 15). In contrast, dosimetry did not affect the outcome for diploid patients. Conclusions: Using core biopsy material from archived paraffin blocks, DNA ploidy correctly classified the majority of failures and nonfailures in this study. The results suggest that DNA ploidy can be used as a useful marker for aggressiveness of localized prostate cancer. A larger study will be necessary to further confirm our hypothesis.« less

Impact of Prostatic-specific Antigen Threshold and Screening Interval in Prostate Cancer Screening Outcomes: Comparing the Swedish and Finnish European Randomised Study of Screening for Prostate Cancer Centres.

PubMed

Saarimäki, Lasse; Hugosson, Jonas; Tammela, Teuvo L; Carlsson, Sigrid; Talala, Kirsi; Auvinen, Anssi

2017-08-10

The European Randomised Study of Screening for Prostate Cancer trial has shown a 21% reduction in prostate cancer (PC) mortality with prostate-specific antigen (PSA)-based screening. Sweden used a 2-yr screening interval and showed a larger mortality reduction than Finland with a 4-yr interval and higher PSA cut-off. To evaluate the impact of screening interval and PSA cut-off on PC detection and mortality. We analysed the core age groups (55-69 yr at entry) of the Finnish (N=31 866) and Swedish (N=5901) screening arms at 13 yr and 16 yr of follow-up. Sweden used a screening interval of 2 yr and a PSA cut-off of 3.0ng/ml, while in Finland the screening interval was 4 yr and the PSA cut-off 4.0ng/ml (or PSA 3.0-3.9ng/ml with free PSA<16%). We compared PC detection rate and PC mortality between the Finnish and Swedish centres and estimated the impact of different screening protocols. If the Swedish screening protocol had been followed in Finland, 122 additional PC cases would have been diagnosed at screening, 84% of which would have been low-risk cancers, and four leading to PC death. In contrast, if a lower PSA threshold had been applied in Finland, at least 127 additional PC would have been found, with 19 PC deaths. The small number of deaths among cases that would have been potentially detectable in Finland with the Swedish protocol (or those that would have been missed in Sweden with the Finnish approach) is unlikely to explain the differences in mortality in this long of a follow-up. A prostate-specific antigen threshold of 3ng/ml versus 4ng/ml or a screening interval of 2 yr instead of 4 yr is unlikely to explain the larger mortality reduction achieved in Sweden compared with Finland. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Individual and mutual predictors of marital satisfaction among prostate cancer patients and their spouses.

PubMed

Chien, Ching-Hui; Chuang, Cheng-Keng; Liu, Kuan-Lin; Huang, Xuan-Yi; Pang, See-Tong; Wu, Chun-Te; Chang, Ying-Hsu; Liu, Hsueh-Erh

2017-12-01

To determine the individual and mutual predictors of the marital satisfaction of couples in which the husband experienced prostate cancer. Marital satisfaction of patients with prostate cancer has been insufficiently studied in Asian countries as compared with Western countries. This study used a prospective and repeated-measures design. Seventy Taiwanese couples in which the husband had prostate cancer completed measures at 6 and 12 months post-treatment. Assessments of physical symptoms, marital satisfaction, coping behaviour and psychological distress were made. Multiple linear regression was used to analyse the data. The marital satisfaction of patients with prostate cancer and that of their spouses were significantly correlated. At 6 months, spouses' marital satisfaction, patients' appraisal of prostate cancer as a threat and patients' serum prostate-specific antigen levels were found to be the predictors of patients' marital satisfaction. Furthermore, patients' marital satisfaction and their spouses' psychological distress were predictors of spouses' marital satisfaction. At 12 months, spouses' marital satisfaction and patients' appraisal of prostate cancer as harm were predictors of patients' marital satisfaction. Finally, spouses' marital satisfaction (at 6 months) and appraisal of prostate cancer as a threat were predictors of spouses' marital satisfaction. At 6 months post-treatment, patients' and spouses' marital satisfaction will influence each other. However, at 12 months, patients' marital satisfaction exerts an insignificant effect on spouses' marital satisfaction. Moreover, patients' serum prostate-specific antigen level or the negative appraisal of prostate cancer affects their marital satisfaction. Spouses' marital satisfaction is affected by psychological distress and their negative appraisal of prostate cancer. The results can be used to develop interventions for prostate cancer couples. Such an intervention can be used to modify couples' appraisal of prostate cancer by changing incorrect thinking or to ease the psychological distress to improve marital satisfaction. © 2017 John Wiley & Sons Ltd.

Multiplexed BioCD for prostate specific antigen detection

NASA Astrophysics Data System (ADS)

Wang, Xuefeng; Zhao, Ming; Nolte, David D.

2008-02-01

Specific protein concentrations in human body fluid can serve as diagnostic markers for some diseases, and a quantitative and high-throughput technique for multiplexed protein detection would speed up diagnosis and facilitate medical research. For this purpose, our group developed the BioCD, a spinning-disc interferometric biosensor on which antibody is immobilized. The detection system adopts a common-path scheme making it ultra stable. The scaling mass sensitivity is below 10 pg/mm for protein surface density. A 25000-spot antibody BioCD was fabricated to measure the concentration of prostate specific antigen (PSA), a protein indicating prostate cancer if its level is high. Statistical analysis of our immunoassay results projects that the detection limit of PSA would reach 20 pg/ml in a 2 mg/ml background solution. For future prospects, a multiplexed BioCD can be produced for simultaneous diagnosis of diverse diseases. For instance, 100 markers above 200 pg/ml could be measured on a single disc given that the detection limit is inversely proportional to square root of the number of spots.

Prostate-specific antigen bounce after intensity-modulated radiotherapy for prostate cancer.

PubMed

Sheinbein, Courtney; Teh, Bin S; Mai, Wei Y; Grant, Walter; Paulino, Arnold; Butler, E Brian

2010-09-01

To report prostate-specific antigen (PSA) bounce in patients treated with intensity-modulated radiotherapy (IMRT) alone. Previous studies have reported PSA bounce in prostate cancer patients treated with conventional radiotherapy, 3D conformal radiotherapy, and permanent seed brachytherapy. From January 1997 to July 2002, 102 patients with clinically localized prostate cancer were treated with IMRT alone. No patients received androgen ablation. PSA bounce was defined as a PSA increase of at least 0.4 ng/mL, followed by any PSA decrease. Biochemical failure was defined by both the American Society for Therapeutic Radiology and Oncology 1996 and 2006 consensus definitions. The median follow-up was 76 months. The median length of time until the first PSA bounce was 13.6 months. Thirty-three patients (32.4%) had at least 1 PSA bounce, with 25 (24.5%) having 1 bounce; 6 (5.9%), 2 bounces; and 2 (2.0%), 4 bounces. PSA bounce was not significantly associated with biochemical no evidence of disease survival, clinical stage, pretreatment PSA, Gleason combined score, prostate planning target volume, PSA nadir, or mean dose to the prostate. The rate of PSA bounce in patients aged ≤ 70 and > 70 years was 44.4% and 22.8%, respectively (P = .032). Our patient series is the first report on PSA bounce in patients treated with IMRT. Our study confirms that the majority of patients with a bouncing PSA remain biochemically and clinically free of disease with extended follow-up. Copyright © 2010 Elsevier Inc. All rights reserved.

Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and Prostate Cancer Screening.

PubMed

Etzioni, Ruth; Gulati, Roman; Cooperberg, Matt R; Penson, David M; Weiss, Noel S; Thompson, Ian M

2013-04-01

The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. : To examine limitations of basing screening policy on evidence from screening trials. We reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results. Screening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial. Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening-and more favorable harm-benefit tradeoffs-than has been suggested by empirical trial evidence.

Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.

PubMed

Milbrandt, Melissa; Winter, Anke C; Nevin, Remington L; Pakpahan, Ratna; Bradwin, Gary; De Marzo, Angelo M; Elliott, Debra J; Gaydos, Charlotte A; Isaacs, William B; Nelson, William G; Rifai, Nader; Sokoll, Lori J; Zenilman, Jonathan M; Platz, Elizabeth A; Sutcliffe, Siobhan

2017-05-01

To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk. © 2017 Wiley Periodicals, Inc.

Immunotherapy for Prostate Cancer: Lessons from Responses to Tumor-Associated Antigens

PubMed Central

Westdorp, Harm; Sköld, Annette E.; Snijer, Berit A.; Franik, Sebastian; Mulder, Sasja F.; Major, Pierre P.; Foley, Ronan; Gerritsen, Winald R.; de Vries, I. Jolanda M.

2014-01-01

Prostate cancer (PCa) is the most common cancer in men and the second most common cause of cancer-related death in men. In recent years, novel therapeutic options for PCa have been developed and studied extensively in clinical trials. Sipuleucel-T is the first cell-based immunotherapeutic vaccine for treatment of cancer. This vaccine consists of autologous mononuclear cells stimulated and loaded with an immunostimulatory fusion protein containing the prostate tumor antigen prostate acid posphatase. The choice of antigen might be key for the efficiency of cell-based immunotherapy. Depending on the treatment strategy, target antigens should be immunogenic, abundantly expressed by tumor cells, and preferably functionally important for the tumor to prevent loss of antigen expression. Autoimmune responses have been reported against several antigens expressed in the prostate, indicating that PCa is a suitable target for immunotherapy. In this review, we will discuss PCa antigens that exhibit immunogenic features and/or have been targeted in immunotherapeutic settings with promising results, and we highlight the hurdles and opportunities for cancer immunotherapy. PMID:24834066

Detection of tumor markers in prostate cancer and comparison of sensitivity between real time and nested PCR.

PubMed

Matsuoka, Takayuki; Shigemura, Katsumi; Yamamichi, Fukashi; Fujisawa, Masato; Kawabata, Masato; Shirakawa, Toshiro

2012-06-27

The objective of this study is to investigate and compare the sensitivity in conventional PCR, quantitative real time PCR, nested PCR and western blots for detection of prostate cancer tumor markers using prostate cancer (PCa) cells. We performed conventional PCR, quantitative real time PCR, nested PCR, and western blots using 5 kinds of PCa cells. Prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), and androgen receptor (AR) were compared for their detection sensitivity by real time PCR and nested PCR. In real time PCR, there was a significant correlation between cell number and the RNA concentration obtained (R(2)=0.9944) for PSA, PSMA, and AR. We found it possible to detect these markers from a single LNCaP cell in both real time and nested PCR. By comparison, nested PCR reached a linear curve in fewer PCR cycles than real time PCR, suggesting that nested PCR may offer PCR results more quickly than real time PCR. In conclusion, nested PCR may offer tumor maker detection in PCa cells more quickly (with fewer PCR cycles) with the same high sensitivity as real time PCR. Further study is necessary to establish and evaluate the best tool for PCa tumor marker detection.

Prostate specific membrane antigen (PSMA) expression in non-small cell lung cancer

PubMed Central

Heitkötter, Birthe; Schulze, Arik B.; Schliemann, Christoph; Steinestel, Konrad; Trautmann, Marcel; Marra, Alessandro; Hillejan, Ludger; Mohr, Michael; Evers, Georg; Wardelmann, Eva; Rahbar, Kambiz; Görlich, Dennis; Lenz, Georg; Berdel, Wolfgang E.; Hartmann, Wolfgang; Wiewrodt, Rainer; Huss, Sebastian

2017-01-01

Objectives PSMA (prostate-specific membrane antigen) is overexpressed in prostate cancer cells and is reported to be a promising target for antibody-based radioligand therapy in patients with metastasized prostate cancer. Since PSMA expression is not restricted to prostate cancer, the underlying study investigates PSMA expression in non-small cell lung cancer (NSCLC). Material and methods Immunohistochemistry was used to identify PSMA expression in n = 275 samples of NSCLC tissue specimens. By means of CD34 co-expression, the level of PSMA expression in tumor associated neovasculature was investigated. The impact of PSMA expression on clinicopathologic parameters and prognosis was evaluated. Results PSMA tumor cell expression in NSCLC is as low as 6% and was predominantly found in squamous cell carcinoma (p = 0.002). Neovascular PSMA expression was found in 49% of NSCLC. High neovascular PSMA expression was associated with higher tumor grading (G3/G4) (p < 0.001). Neither for PSMA tumor cell expression, nor for PSMA neovascular cell expression prognostic effects were found for the investigated NSCLC cases. Conclusion Here, we report on the expression of PSMA in NSCLC tissue samples. Against the background of a potential treatment with radiolabeled PSMA ligands, our data might serve for the future identification of patients who could benefit from this therapeutic option. PMID:29077706