Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China.

PubMed

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-02

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China

PubMed Central

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-01

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients. PMID:29416625

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.

Increasing Early Detection of Prostate Cancer in African American Men Through a Culturally Targeted Print Intervention

DTIC Science & Technology

2006-03-01

of a protein called prostate-specific antigen (PSA). Normally, PSA is found in the blood at very low levels. Elevated PSA readings can be a sign of...cancer. ♦ Prostate Specific Antigen test (also called PSA test) - This simple blood test measures the level of a protein called prostate- specific...meat ♦ Lycopene, a compound in cooked tomato products and watermelon . 9 A number of Black men say they have problems with their

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

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

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.

Re-examining Prostate-specific Antigen (PSA) Density: Defining the Optimal PSA Range and Patients for Using PSA Density to Predict Prostate Cancer Using Extended Template Biopsy.

PubMed

Jue, Joshua S; Barboza, Marcelo Panizzutti; Prakash, Nachiketh S; Venkatramani, Vivek; Sinha, Varsha R; Pavan, Nicola; Nahar, Bruno; Kanabur, Pratik; Ahdoot, Michael; Dong, Yan; Satyanarayana, Ramgopal; Parekh, Dipen J; Punnen, Sanoj

2017-07-01

To compare the predictive accuracy of prostate-specific antigen (PSA) density vs PSA across different PSA ranges and by prior biopsy status in a prospective cohort undergoing prostate biopsy. Men from a prospective trial underwent an extended template biopsy to evaluate for prostate cancer at 26 sites throughout the United States. The area under the receiver operating curve assessed the predictive accuracy of PSA density vs PSA across 3 PSA ranges (<4 ng/mL, 4-10 ng/mL, >10 ng/mL). We also investigated the effect of varying the PSA density cutoffs on the detection of cancer and assessed the performance of PSA density vs PSA in men with or without a prior negative biopsy. Among 1290 patients, 585 (45%) and 284 (22%) men had prostate cancer and significant prostate cancer, respectively. PSA density performed better than PSA in detecting any prostate cancer within a PSA of 4-10 ng/mL (area under the receiver operating characteristic curve [AUC]: 0.70 vs 0.53, P < .0001) and within a PSA >10 mg/mL (AUC: 0.84 vs 0.65, P < .0001). PSA density was significantly more predictive than PSA in detecting any prostate cancer in men without (AUC: 0.73 vs 0.67, P < .0001) and with (AUC: 0.69 vs 0.55, P < .0001) a previous biopsy; however, the incremental difference in AUC was higher among men with a previous negative biopsy. Similar inferences were seen for significant cancer across all analyses. As PSA increases, PSA density becomes a better marker for predicting prostate cancer compared with PSA alone. Additionally, PSA density performed better than PSA in men with a prior negative biopsy. Copyright © 2017 Elsevier Inc. All rights reserved.

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 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) ...

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

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.

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.

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.

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

Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis.

PubMed

Filella, Xavier; Giménez, Nuria

2013-04-01

The usefulness of %[-2] proPSA and Prostate Health Index (phi) in the detection of prostate cancer are currently unknown. It has been suggested that these tests can distinguish prostate cancer from benign prostatic diseases better than PSA or %fPSA. We performed a systematic review and meta-analysis of the available scientific evidence to evaluate the clinical usefulness of %[-2] proPSA and phi. Relevant published papers were identified by searching computerized bibliographic systems. Data on sensitivity and specificity were extracted from 12 studies: 10 studies about %[-2] proPSA (3928 patients in total, including 1762 with confirmed prostate cancer) and eight studies about phi (2919 patients in total, including 1515 with confirmed prostate cancer). The sensitivity for the detection of prostate cancer was 90% for %[-2] proPSA and phi, while the pooled specificity was 32.5% (95% CI 30.6-34.5) and 31.6% (95% CI 29.2-34.0) for %[-2] proPSA and phi, respectively. The measurement of %[-2] proPSA improves the accuracy of prostate cancer detection in comparison with PSA or %fPSA, particularly in the group of patients with PSA between 2 μg/L and 10 μg/L. Similar results were obtained measuring phi. Using these tests, it is possible to reduce the number of unnecessary biopsies, maintaining a high cancer detection rate. Published results also showed that %[-2] proPSA and phi are related to the aggressiveness of the tumor.

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

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 .

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

[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.

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.

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.

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.

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

Low percentage of free prostate-specific antigen (PSA) is a strong predictor of later detection of prostate cancer among Japanese men with serum levels of total PSA of 4.0 ng/mL or less.

PubMed

Sasaki, Mitsuharu; Ishidoya, Shigeto; Ito, Akihiro; Saito, Hideo; Yamada, Shigeyuki; Mitsuzuka, Koji; Kaiho, Yasuhiro; Shibuya, Daisuke; Yamaguchi, Takuhiro; Arai, Yoichi

2014-11-01

To investigate the effect of the percentage of free prostate-specific antigen (%fPSA) on future prostate cancer risk. We examined serum total PSA (tPSA) and %fPSA annually in a prostate cancer-screening cohort between July 2001 and June 2011. Men with tPSA >4.0 ng/mL or tPSA of 2.0-4.0 ng/mL with %fPSA ≤12% were screened as positive and were recommended to undergo a biopsy. The study population consisted of 6368 men, aged 40-79 years, who had tPSA ≤4.0 ng/mL at initial screening and who subsequently underwent 1 or more screenings. We calculated the cumulative risk and hazard ratio of prostate cancer stratified by the initial %fPSA groups as quartiles of prostate cancer patients. During a median follow-up of 36 months, 119 men were diagnosed with prostate cancer. The lowest quartile of %fPSA (<13.3%) was associated with a 21.2-fold higher risk of having prostate cancer compared with the highest quartile (>22.2%). For the subset with an initial tPSA ≤1.0 ng/mL, all men diagnosed with cancer had an initial %fPSA ≤33.3% (median). For the subset with tPSA >1.0 ng/mL, men with %fPSA ≤23.0% (median) had significantly higher risk for cancer than those with %fPSA >23.0% (P <.0001). Of the 114 men with prostate cancer in whom pathologic findings were available, 79 (69.3%) had a Gleason score ≥3 + 4 = 7. A low %fPSA is a strong predictor of a subsequent diagnosis of prostate cancer among men with tPSA levels ≤4.0 ng/mL. Measurement of %fPSA might enhance the detection of high-grade cancer that warrants aggressive treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Ethnicity Is an Independent Determinant of Age-Specific PSA Level: Findings from a Multiethnic Asian Setting

PubMed Central

Sothilingam, Selvalingam; Malek, Rohan; Sundram, Murali; Hisham Bahadzor, Badrul; Ong, Teng Aik; Ng, Keng Lim; Sivalingam, Sivaprakasam; Razack, Azad Hassan Abdul

2014-01-01

Objectives To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting. Materials and Methods We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis. Results There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05). Conclusion These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population. PMID:25111507

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.

Merging digital rectal exam, family history, age and prostate-specific antigen to create a decision-making tool.

PubMed

Ankerst, Donna Pauler; Thompson, Ian M

2006-12-01

In this paper, we report on risk factors for prostate cancer detection on biopsy as found in the Prostate Cancer Prevention Trial (PCPT), with special emphasis on the independent contribution of prostate-specific antigen (PSA) velocity to prostate cancer risk over that provided by PSA. For this study, we used a subset of PCPT placebo arm participants who had had at least one prostate biopsy and a digital rectal examination (DRE) and PSA measured within 1 year prior to biopsy. In order to evaluate PSA velocity, we also required an additional PSA measurement within 3 years prior to biopsy, yielding 5,519 PCPT placebo arm participants for inclusion in the analysis. The risk of prostate cancer rose from 11.1% for PSA values less than 1 ng/mL to 43.3% for PSA values greater than 6 ng/mL and the risk of high-grade disease rose from 1.0% to 22.0% across these two PSA intervals. It was in fact no longer statistically significant as soon as the single predictor PSA was added to the risk equation, whereas PSA remained statistically significant even when velocity was in the risk equation. Furthermore, in a head-to-head comparison of predictive strength as a single predictor in a model, assessed by maximized log likelihood, PSA was more predictive than PSA velocity. These findings occurred for every definition of velocity that was considered and hence we concluded that velocity did not add independent prognostic information to prostate cancer risk over that provided by PSA. Similarly, age, which is also a predictor of prostate cancer in the absence of other factors, did not add independent prognostic information to PSA, DRE, family history, and prior biopsy.

Configuration and validation of a novel prostate disease nomogram predicting prostate biopsy outcome: A prospective study correlating clinical indicators among Filipino adult males with elevated PSA level.

PubMed

Chua, Michael E; Tanseco, Patrick P; Mendoza, Jonathan S; Castillo, Josefino C; Morales, Marcelino L; Luna, Saturnino L

2015-04-01

To configure and validate a novel prostate disease nomogram providing prostate biopsy outcome probabilities from a prospective study correlating clinical indicators and diagnostic parameters among Filipino adult male with elevated serum total prostate specific antigen (PSA) level. All men with an elevated serum total PSA underwent initial prostate biopsy at our institution from January 2011 to August 2014 were included. Clinical indicators, diagnostic parameters, which include PSA level and PSA-derivatives, were collected as predictive factors for biopsy outcome. Multiple logistic-regression analysis involving a backward elimination selection procedure was used to select independent predictors. A nomogram was developed to calculate the probability of the biopsy outcomes. External validation of the nomogram was performed using separate data set from another center for determination of sensitivity and specificity. A receiver-operating characteristic (ROC) curve was used to assess the accuracy in predicting differential biopsy outcome. Total of 552 patients was included. One hundred and ninety-one (34.6%) patients had benign prostatic hyperplasia, and 165 (29.9%) had chronic prostatitis. The remaining 196 (35.5%) patients had prostate adenocarcinoma. The significant independent variables used to predict biopsy outcome were age, family history of prostate cancer, prior antibiotic intake, PSA level, PSA-density, PSA-velocity, echogenic findings on ultrasound, and DRE status. The areas under the receiver-operating characteristic curve for prostate cancer using PSA alone and the nomogram were 0.688 and 0.804, respectively. The nomogram configured based on routinely available clinical parameters, provides high predictive accuracy with good performance characteristics in predicting the prostate biopsy outcome such as presence of prostate cancer, high Gleason prostate cancer, benign prostatic hyperplasia, and chronic prostatitis.

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.

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.

[PSA interest and prostatitis: literature review].

PubMed

Bruyère, F; Amine Lakmichi, M

2013-12-01

Prostatitis is easily diagnosed but sometimes associated with PSA measurement. An increased PSA in an asymptomatic patient may be associated with antibiotic use to eliminate the inflammatory part and to confirm prostate biopsy. It seems interesting to confirm or infirm these attitudes with a systematic review of the literature We performed a literature review using the words [prostatitis], [acute prostatitis], [prostate specific antigen], [PSA], in the MEDLINE, Pubmed and AMBASE database searching for articles in French or English published in the past 20 years. PSA is not always increased during an acute prostatitis episode. An increased PSA in an asymptomatic man does not seem to be systematically correlated to prostate inflammation. Analyzing the studies, it seems inaccurate to measure PSA value during a febrile urinary infection episode in men. Systematic use of antibiotic to decrease PSA and not performing prostate biopsy is not relevant and may induce resistance to antibiotic and doesn't induce a reduction risk of having prostate biopsy. PSA is unnecessary in case of febrile urinary tract infection in men. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Cancer Today

MedlinePlus

... your doctor if you are considering having a prostate-specific antigen (PSA) test or digital rectal examination (DRE). Skin ... regular colonoscopy for cancer of the colon, serum prostatic-specific antigen (PSA) for prostate cancer, mammography for breast cancer, ...

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.

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.

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.

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.

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.

Prostate specific antigen enhances the innate defence of prostatic epithelium against Escherichia coli infection.

PubMed

Townes, Claire L; Ali, Ased; Gross, Naomi; Pal, Deepali; Williamson, Stuart; Heer, Rakesh; Robson, Craig N; Pickard, Robert S; Hall, Judith

2013-10-01

This study investigated whether the increase in serum prostate specific antigen (PSA) typically seen during male urinary tract infection (UTI) is incidental or reflects an innate defence mechanism of the prostate. The protective roles of the whey-acid-motif-4-disulphide core (WFDC) proteins, secretory leukoproteinase inhibitor (SLPI) and WFDC2, in the prostate were also examined. UTI recurrence was assessed retrospectively in men following initial UTI by patient interview. PSA, SLPI, and WFDC2 gene expression were assessed using biopsy samples. LNCaP and DU145 in vitro prostate cell models were utilized to assess the effects of an Escherichia coli challenge on PSA and WFDC gene expression, and bacterial invasion of the prostate epithelium. The effects of PSA on WFDC antimicrobial properties were studied using recombinant peptides and time-kill assays. Men presenting with PSA >4 ng/ml at initial UTI were less likely to have recurrent (r) UTI than those with PSA <4 ng/ml [2/15 (13%) vs. 7/10 (70%), P < 0.01]. Genes encoding PSA, SLPI and WFDC2, were expressed in prostatic epithelium, and the PSA and SLPI proteins co-localized in vivo. Challenging LNCaP (PSA-positive) cells with E. coli increased PSA, SLPI, and WFDC2 gene expression (P < 0.05), and PSA synthesis (P < 0.05), and reduced bacterial invasion. Pre-incubation of DU145 (PSA-negative) cells with PSA also decreased bacterial invasion. In vitro incubation of recombinant SLPI and WFDC2 with PSA resulted in peptide proteolysis and increased E. coli killing. Increased PSA during UTI appears protective against rUTI and in vitro is linked to proteolysis of WFDC proteins supporting enhanced prostate innate defences. Copyright © 2013 Wiley Periodicals, Inc.

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 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.

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.

Risk assessment models to evaluate the necessity of prostate biopsies in North Chinese patients with 4-50 ng/mL PSA.

PubMed

Zhao, Jing; Liu, Shuai; Gao, Dexuan; Ding, Sentai; Niu, Zhihong; Zhang, Hui; Huang, Zhilong; Qiu, Juhui; Li, Qing; Li, Ning; Xie, Fang; Cui, Jilei; Lu, Jiaju

2017-02-07

Prostate-specific antigen (PSA) is widely used for prostate cancer screening, but low specificity results in high false positive rates of prostate biopsies. To develop new risk assessment models to overcome the diagnostic limitation of PSA and reduce unnecessary prostate biopsies in North Chinese patients with 4-50 ng/mL PSA. A total of 702 patients in seven hospitals with 4-10 and 10-50 ng/mL PSA, respectively, who had undergone transrectal ultrasound-guided prostate biopsies, were assessed. Analysis-modeling stage for several clinical indexes related to prostate cancer and renal function was carried out. Multiple logistic regression analyses were used to develop new risk assessment models of prostate cancer for both PSA level ranges 4-10 and 10-50 ng/mL. External validation stage of the new models was performed to assess the necessity of biopsy. The new models for both PSA ranges performed significantly better than PSA for detecting prostate cancers. Both models showed higher areas under the curves (0.937 and 0.873, respectively) compared with PSA alone (0.624 and 0.595), at pre-determined cut-off values of 0.1067 and 0.6183, respectively. Patients above the cut-off values were recommended for immediate biopsy, while the others were actively observed. External validation of the models showed significantly increased detection rates for prostate cancer (4-10 ng/mL group, 39.29% vs 17.79%, p=0.006; 10-50 ng/mL group, 71.83% vs 50.0%, p=0.015). We developed risk assessment models for North Chinese patients with 4-50 ng/mL PSA to reduce unnecessary prostate biopsies and increase the detection rate of prostate cancer.

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.

[Use of [-2] pro PSA and phi index for early detection of prostate cancer: a prospective of 452 patients].

PubMed

Houlgatte, A; Vincendeau, S; Desfemmes, F; Ramirez, J; Benoist, N; Bensalah, K; Durand, X

2012-05-01

Early detection of prostate cancer (Pca) is a real challenge to reduce morbidity and mortality while avoiding over-diagnosis and over-treatment. The prostate specific antigen (PSA) is characterized by its imperfections justifying the evaluation of new serum or urinary specific markers allowing a better selection of patients at risk of developing aggressive Pca. To compare the value of -2pro PSA and phi index to total and free PSA. Serum sampled from 452 patients from two university centers were used to determine levels of PSA before performing biopsies. The patients were included in this study based on the PSA serum concentration between 1.6 ng/mL and 8 ng/mL according to the WHO international standard. All biopsies were performed according to a standardized protocol consisting of 12 cores or more. Sera were analyzed centrally in one of the two institutions with on a single analyzer. Sera from 243 prostate cancer and 208 negative biopsies patients have been taken into account. Sera were analyzed blinded for total PSA, free PSA and [-2] proPSA using Access(®) immunoassay method from Beckman Coulter. The Prostate Health Index (phi) was calculated using the formula phi=([-2] proPSA/fPSA)×sqrt (PSA). The median value of the phi index is significantly (P>0.0001) higher for patients with cancer (phi=65.8) compared to patients with negative biopsies (phi=40.6). At a given sensitivity, the phi index significantly increases the specificity of detection of prostate cancer compared to other markers. The phi index currently appears as the best predictor of prostate cancer for patients with a total PSA between 1.6 and 8 ng/mL according to the WHO standard. The improvement in specificity of the phi index over tPSA could reduce significantly the numbers of unnecessary biopsies. Whether this new biomarker could be an indicator of aggressive prostate cancer remains to be confirmed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

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.

Early diagnostic role of PSA combined miR-155 detection in prostate cancer.

PubMed

Guo, T; Wang, X-X; Fu, H; Tang, Y-C; Meng, B-Q; Chen, C-H

2018-03-01

As a kind of malignant tumor in the male genitourinary system, prostate cancer exhibits significantly increased occurrence. Prostate-specific antigen (PSA) expression can be seen in the prostate cancer, prostatitis, and other diseases, therefore, lack of diagnostic specificity. The miR-155 expression is abnormally increased in the tumors. Therefore, this study aims to explore the clinical significance of PSA combined miR-155 detection in the early diagnosis of prostate cancer. A total of 86 patients diagnosed with prostate cancer were enrolled in this study. PSA and miR-155 gene expression in tumor tissue were detected by using Real-time PCR. The serum levels of PSA were measured by using enzyme-linked immunosorbent assay (ELISA). The correlation of PSA and miR-155 expression with age, body mass index (BMI), tumor volume, tumor-node-metastasis (TNM) stage, lymph node metastasis (LNM), and other clinicopathological features were analyzed, respectively. Serum PSA expression and PSA gene in tumor tissue were significantly higher compared to that in adjacent tissues (p<0.05). PSA gene and protein increased significantly with the clinical stage of TNM and decreased following the increase of grade (p<0.05). The miR-155 level was significantly elevated in the tumor tissue compared with para-carcinoma tissue (p<0.05). PSA and miR-155 expressions were positively correlated with TNM stage, tumor volume, and LNM, and negatively correlated with grade (p<0.05). PSA and miR-155 were closely related to the clinicopathological features of prostate cancer. Combined detection is helpful for the early diagnosis of prostate cancer.

Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma.

PubMed

Chuang, Ai-Ying; DeMarzo, Angelo M; Veltri, Robert W; Sharma, Rajni B; Bieberich, Charles J; Epstein, Jonathan I

2007-08-01

The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial markers were relatively specific with only a few prostate cancers showing scattered (

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.

Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer.

PubMed

Nordström, Tobias; Akre, Olof; Aly, Markus; Grönberg, Henrik; Eklund, Martin

2018-04-01

Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines. We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7. The median PSA-density was 0.10 ng/ml 2 (IQR 0.075-0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05-1.07 and OR 1.07, 95% CI 1.06-1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml 2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml 2 and 0.15 ng/ml 2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors. PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

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

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.

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.

The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years.

PubMed

Boegemann, Martin; Stephan, Carsten; Cammann, Henning; Vincendeau, Sébastien; Houlgatte, Alain; Jung, Klaus; Blanchet, Jean-Sebastien; Semjonow, Axel

2016-01-01

To prospectively test the diagnostic accuracy of the percentage of prostate specific antigen (PSA) isoform [-2]proPSA (%p2PSA) and the Prostate Health Index (PHI), and to determine their role for discrimination between significant and insignificant prostate cancer at initial and repeat prostate biopsy in men aged ≤65 years. The diagnostic performance of %p2PSA and PHI were evaluated in a multicentre study. In all, 769 men aged ≤65 years scheduled for initial or repeat prostate biopsy were recruited in four sites based on a total PSA (t-PSA) level of 1.6-8.0 ng/mL World Health Organization (WHO) calibrated (2-10 ng/mL Hybritech-calibrated). Serum samples were measured for the concentration of t-PSA, free PSA (f-PSA) and p2PSA with Beckman Coulter immunoassays on Access-2 or DxI800 instruments. PHI was calculated as (p2PSA/f-PSA × √t-PSA). Uni- and multivariable logistic regression models and an artificial neural network (ANN) were complemented by decision curve analysis (DCA). In univariate analysis %p2PSA and PHI were the best predictors of prostate cancer detection in all patients (area under the curve [AUC] 0.72 and 0.73, respectively), at initial (AUC 0.67 and 0.69) and repeat biopsy (AUC 0.74 and 0.74). t-PSA and %f-PSA performed less accurately for all patients (AUC 0.54 and 0.62). For detection of significant prostate cancer (based on Prostate Cancer Research International Active Surveillance [PRIAS] criteria) the %p2PSA and PHI equally demonstrated best performance (AUC 0.70 and 0.73) compared with t-PSA and %f-PSA (AUC 0.54 and 0.59). In multivariate analysis PHI we added to a base model of age, prostate volume, digital rectal examination, t-PSA and %f-PSA. PHI was strongest in predicting prostate cancer in all patients, at initial and repeat biopsy and for significant prostate cancer (AUC 0.73, 0.68, 0.78 and 0.72, respectively). In DCA for all patients the ANN showed the broadest threshold probability and best net benefit. PHI as single parameter and the base model + PHI were equivalent with threshold probability and net benefit nearing those of the ANN. For significant cancers the ANN was the strongest parameter in DCA. The present multicentre study showed that %p2PSA and PHI have a superior diagnostic performance for detecting prostate cancer in the PSA range of 1.6-8.0 ng/mL compared with t-PSA and %f-PSA at initial and repeat biopsy and for predicting significant prostate cancer in men aged ≤65 years. They are equally superior for counselling patients before biopsy. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

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.

Age and total and free prostate-specific antigen levels for predicting prostate volume in patients with benign prostatic hyperplasia.

PubMed

Coban, Soner; Doluoglu, Omer Gokhan; Keles, Ibrahim; Demirci, Hakan; Turkoglu, Ali Riza; Guzelsoy, Muhammet; Karalar, Mustafa; Demirbas, Murat

2016-06-01

To investigate the predictive values of free prostate-specific antigen (fPSA), total PSA (tPSA) and age on the prostate volume. The data of 2148 patients with lower urinary tract symptoms were analyzed retrospectively. The patients who had transrectal ultrasonography guided 10 core biopsies owing to the findings obtained on digital rectal examination and presence of high PSA levels (PSA = 2.5-10 ng/dl), and proven to have BPH histopathologically were included in the study. Age, tPSA, fPSA and the prostate volumes (PV) of the patients were noted. One thousand patients that fulfilled the inclusion criteria were included in the study. The PV of the patients were significantly correlated with age, tPSA and fPSA (p < 0.001 and r = 0.307, p < 0.001 and r = 0.382, p < 0.001 and r = 0.296, respectively). On linear regression model, fPSA was found as a stronger predictive for PV (AUC = 0.75, p < 0.001) when compared to age (AUC = 0.64, p < 0.001), and tPSA (AUC = 0.69, p = 0.013). Although tPSA is an important prognostic factor for predicting PV, the predictive value of fPSA is higher. PV can easily be predicted by using age, and serum tPSA and fPSA levels.

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.

Clinical performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project.

PubMed

Lazzeri, Massimo; Haese, Alexander; Abrate, Alberto; de la Taille, Alexandre; Redorta, Joan Palou; McNicholas, Thomas; Lughezzani, Giovanni; Lista, Giuliana; Larcher, Alessandro; Bini, Vittorio; Cestari, Andrea; Buffi, Nicolòmaria; Graefen, Markus; Bosset, Olivier; Le Corvoisier, Philippe; Breda, Alberto; de la Torre, Pablo; Fowler, Linda; Roux, Jacques; Guazzoni, Giorgio

2013-08-01

To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI. The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed. At a PHI threshold of 25.5 a total of 27 (17.2%) biopsies could have been avoided and two (3.8%) cancers with a GS of 7 would have been missed. In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariable models including PSA and prostate volume by 8.7 and 10%, respectively (P ≤ 0.001). p2PSA, %p2PSA and PHI were directly correlated with Gleason score (ρ: 0.247, P = 0.038; ρ: 0.366, P = 0.002; ρ: 0.464, P < 0.001, respectively). %p2PSA and PHI are more accurate than tPSA, fPSA and %fPSA in predicting PCa in men with a family history of PCa. Consideration of %p2PSA and PHI results in the avoidance of several unnecessary biopsies. p2PSA, %p2PSA and PHI correlate with cancer aggressiveness. © 2013 BJU International.

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.

Health Screening: What Tests You Need and When

MedlinePlus

... cancer screening if you are considering having a prostate-specific antigen (PSA) test or digital rectal examination (DRE). Sexually ... regular colonoscopy for cancer of the colon, serum prostatic-specific antigen (PSA) for prostate cancer, mammography for breast cancer, ...

Incorporating Known Genetic Variants Does Not Improve the Accuracy of PSA Testing to Identify High Risk Prostate Cancer on Biopsy

PubMed Central

Gilbert, Rebecca; Martin, Richard M.; Evans, David M.; Tilling, Kate; Davey Smith, George; Kemp, John P.; Lane, J. Athene; Hamdy, Freddie C.; Neal, David E.; Donovan, Jenny L.; Metcalfe, Chris

2015-01-01

Introduction Prostate-specific antigen (PSA) testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs) principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542). Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels. Materials and Methods Men with PSA between 3-10ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7–10 or stage T2C). We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC) to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men. Results The analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%); High risk: 184 (21.2%)). Receiver operating characteristic (ROC) curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AU C = 59.5% (95% CI: 54.7,64.2) vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5) (p-value = 0.40)). Conclusion We demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10ng/mL). Replication and gaining more accurate estimates of the effects of the 4 PSA-SNPs and additional variants associated with PSA levels and not prostate cancer could be obtained from subsequent GWAS from larger prospective studies. PMID:26431041

Long-distance mountain biking does not disturb the measurement of total, free or complexed prostate-specific antigen in healthy men.

PubMed

Herrmann, Markus; Scharhag, Jürgen; Sand-Hill, Marga; Kindermann, Wilfried; Herrmann, Wolfgang

2004-03-01

Mechanical manipulation of the prostate is a generally accepted interfering factor for the measurement of prostate-specific antigen (PSA). However, only few studies have focused on common daily mechanical manipulations, such as bicycle riding. Furthermore, physical exercise is also supposed to modulate PSA serum concentration. Long-distance mountain biking is an excellent model to study the combined effect of mechanical prostate manipulation by bicycle riding and strenuous endurance exercise on total, free and complexed PSA (tPSA, fPSA, cPSA). We investigated tPSA, fPSA and cPSA in 42 healthy male cyclists (mean age 35+/-6 years) before and after a 120 km off-road mountain bike race. Blood sampling was done before, 15 min and 3 h after the race. Mean race time was 342+/-65 min. All athletes had normal serum levels of tPSA, fPSA or cPSA. None of these parameters was modified by the race. In healthy men the measurement of tPSA, fPSA and cPSA is not disturbed by preceding long distance mountain biking or endurance exercise. Based on the present data, there is no evidence for a recommendation to limit bicycle riding or physical activity before the measurement of tPSA, fPSA or cPSA.

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.

Circulating Prostate-Specific Antigen and Telomere Length in a Nationally Representative Sample of Men Without History of Prostate Cancer.

PubMed

Wulaningsih, Wahyu; Astuti, Yuliana; Matsuguchi, Tetsuya; Anggrandariyanny, Putri; Watkins, Johnathan

2017-01-01

We investigated the association of prostate-specific antigen (PSA) with leukocyte telomere length, which may be altered in preclinical prostate malignancies. This study was based on the 2001-2002 U.S. National Health and Nutrition Examination Survey (NHANES). A subsample of 1,127 men aged 40-85 years without prior history of prostate cancer who provided informed consent and blood samples were selected. Leukocyte telomere length (LTL) relative to standard DNA reference (T/S ratio) was quantified by polymerase chain reaction (PCR). Survey-weighted multivariable linear regression was performed to examine T/S ratio across quintiles of total and free PSA and free-to-total PSA ratio (%fPSA). A sensitivity analysis was performed by excluding men dying from prostate cancer during follow-up through to December 31, 2006. Stratification analyses were carried out to assess any effect modification by age group, race, body mass index (BMI), and levels of C-reactive protein (CRP), a marker of inflammation. Higher total PSA levels were associated to longer LTL, with approximately 8% increase in log-transformed T/S ratio (95% confidence interval [CI]: 2-13%) among men in the highest quintile of total PSA compared to the lowest in the fully adjusted model (P trend  = 0.01). No significant association was found for free PSA or %fPSA, although nonlinearity between all PSA measures and T/S ratio was indicated. Similar results were found after excluding men who died from prostate cancer during follow-up. We also found the associations between total PSA and T/S ratio to be strongest among non-Hispanic blacks, non-obese men (BMI <30 kg/m 2 ), and those with low CRP. However, a significant interaction was only found between total PSA and race/ethnicity (P interaction  = 0.01). Total PSA levels were strongly associated to LTL, particularly among non-Hispanic blacks. Our findings support a potential link between PSA and specific mechanisms contributing to prostate cancer development. Prostate 77:22-32, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

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.

[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.

Serum PSA levels in the Indian population: Is it different?

PubMed

Agrawal, Amit; Karan, Shailesh Chandra

2017-04-01

Serum prostate-specific antigen (PSA) is an important tumour, marker which is widely used to trigger trans-rectal ultrasound (TRUS)-guided prostate biopsy. However, the PSA levels vary with race and ethnicity. Therefore, there is a need to have an Indian reference range. All adult male patients meeting the inclusion and exclusion criteria were enrolled in this study. They were subjected to assessment of serum total PSA, digital rectal examination and trans-abdominal ultrasound. If any one or more of these were found abnormal, then a TRUS-guided 12-core prostate biopsy was done. Patients who were detected to have prostatic cancer were excluded from the final analysis. The data so obtained was grouped among the following three age groups: 40-49, 50-59 and 60-70 years, and the age-specific PSA values, prostatic volume and PSA density were found. A total of 1772 patients were analysed. The mean serum total PSA was 1.76 ng/ml with a standard deviation of 2.566 ng/ml. Group-wise age distribution of the mean serum total PSA was 1.22, 1.97 and 2.08 ng/ml in 40-49, 50-59 and 60-70 years age groups. The mean total PSA and the age-specific PSA range tend to be lower in the Indians than the Western population.

Relationship between prostate-specific antigen and obesity in prostate cancer screening: analysis of a large cohort in Japan.

PubMed

Kubota, Yasuaki; Seike, Kensaku; Maeda, Shinichi; Shinohara, Yuka; Iwata, Masamitsu; Sugimoto, Norio

2011-01-01

Previous studies have shown that lower prostate-specific antigen (PSA) levels in obese men might decrease the sensitivity of prostate cancer screening, leading to delayed diagnosis and unfavorable prognosis. We examined whether the effect of obesity is important in prostate cancer screening of Japanese men, who have a low prevalence of obesity. We analyzed 19,294 male subjects from a large cohort of Toyota Motor Corporation (TMC) employees (aged > 50 years, serum PSA level ≤ 4.0 ng/mL) who underwent physical examinations from August 2006 to December 2009. The relationship between PSA level and obesity-related factors was analyzed by simple and multiple regression analysis. The relationships between six body mass index (BMI) categories, and PSA level and PSA mass (PSA concentration × plasma volume) were analyzed. PSA level decreased significantly with increasing BMI, but the coefficient of determination was very low. Mean PSA values decreased from 1.02 to 0.85 ng/mL as BMI increased from underweight (BMI <18.5) to morbidly obese (BMI >35). However, PSA mass peaked in the overweight category and was slightly reduced with increasing BMI. On multiple regression analysis, PSA level was influenced by age, diastolic blood pressure and high-density lipoprotein as well as BMI. We found an inverse but weak relationship between PSA level and BMI. Obesity seems to have very limited influence on prostate cancer screening in this population. Nonetheless, when considering indications for prostatic biopsy in obese men, we should be aware that the hemodilution effect might reduce PSA levels. © 2010 The Japanese Urological Association.

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.

Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer.

PubMed

Barrabés, Sílvia; Llop, Esther; Ferrer-Batallé, Montserrat; Ramírez, Manel; Aleixandre, Rosa N; Perry, Antoinette S; de Llorens, Rafael; Peracaula, Rosa

2017-07-01

The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

PHI in the Early Detection of Prostate Cancer.

PubMed

Fuchsova, Radka; Topolcan, Ondrej; Windrichova, Jindra; Hora, Milan; Dolejsova, Olga; Pecen, Ladislav; Kasik, Petr; Novak, Jaroslav; Casova, Miroslava; Smejkal, Jiri

2015-09-01

To evaluate changes in the serum levels of prostate specific antigen (PSA), %free PSA and -2proPSA biomarkers, and prostate health index (PHI) in the diagnostic algorithm of early prostate cancer. The Immunoanalytical Laboratory of the University Hospital in Pilsen examined sera from 263 patients being treated at the Hospital's Urology Department with suspected prostate cancer who had undergone biopsies and were divided into a benign and malignant group. The monitored biomarkers were measured using chemiluminescence. All statistical analyses were calculated using the SAS software. We found statistically significantly increased levels of -2proPSA, PHI and PSA and decreased levels of %freePSA in patients diagnosed with prostate cancer by prostate biopsy vs. patients with benign prostatic hypertrophy (median values: -2proPSA: 16 vs. 21 ng/l, PHI: 35 vs. 62, total PSA: 7.2 vs. 7.7 μg/l and %free PSA: 16.7 vs. 11.7%). Receiver operating characteristic curves showed the best performance for PHI compared to other markers. The assessment of -2proPSA and the calculation of PHI appear to be of great benefit for a more accurate differential diagnosis of benign hyperplasia and prostate cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Comparative analysis of prostate-specific antigen by two-dimensional gel electrophoresis and capillary electrophoresis.

PubMed

Barrabés, Sílvia; Farina-Gomez, Noemi; Llop, Esther; Puerta, Angel; Diez-Masa, Jose Carlos; Perry, Antoinette; de Llorens, Rafael; de Frutos, Mercedes; Peracaula, Rosa

2017-02-01

Serum levels of Prostate-Specific Antigen (PSA) are not fully specific for prostate cancer (PCa) diagnosis and several efforts are focused on searching to improve PCa markers through the study of PSA subforms that could be cancer associated. We have previously reported by 2DE a decrease in the sialic acid content of PSA from PCa compared to benign prostatic hyperplasia patients based on the different proportion of the PSA spots. However, faster and more quantitative techniques, easier to automate than 2DE, are desirable. In this study, we examined the potential of CE for resolving PSA subforms in different samples and compared the results with those obtained by 2DE. We first fractionated by OFFGEL the subforms of PSA from seminal plasma according to their pIs and analyzed each separated fraction by 2DE and CE. We also analyzed PSA and high pI PSA, both from seminal plasma, and PSA from urine of a PCa patient. These samples with different PSA spots proportions by 2DE, due to different posttranslational modifications, also presented different CE profiles. This study shows that CE is a useful and complementary technique to 2DE for analyzing samples with different PSA subforms, which is of high clinical interest. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

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.

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."

PSA and Prostate Health Index based prostate cancer screening in a hereditary migration complicated population: implications in precision diagnosis.

PubMed

Akizhanova, Mariyam; Iskakova, Elzira E; Kim, Valdemir; Wang, Xiao; Kogay, Roman; Turebayeva, Aiym; Sun, Qinglei; Zheng, Ting; Wu, Shenghui; Miao, Lixia; Xie, Yingqiu

2017-01-01

Precision diagnosis requires specific markers for differential ethnic populations. Prostate-Specific Antigen (PSA) level (threshold of 4ng/ml) has been widely used to screen prostate cancer and as reference of pro-biopsy but false diagnosis frequently occurs. Prostate health Index (PHI) is a new diagnosis marker which combines PSA, free PSA and p2PSA4. Overall the PCa screening database is lacking in Kazakhstani patients. We analyzed the PSA levels and Gleason scores of 222 biopsies collected in 2015 in Almaty area, Kazakhstan approved by institutional ethics board. We found using PSA of 4ng/ml as threshold, only 25.68% of patients have cancer with Gleason score ranged 6-8 and 65.77% of patients have no character of cancer. Moreover, there is no significant correlation between PSA and cancerous (P=0.266) or Gleason grade (P=0.3046) based on pathological biopsy. In addition, PHI is not correlated to prostate cancer (P=0.4301). Our data suggest that false-positive rate is much higher than the correct-positive diagnosis when using PSA as the first screening. Thus in this cohort study, most patients can not get benefit from the PSA screening for precision PCa diagnosis. As Kazakhstani family trees are unique and complicated because of history and migration, the high rate of over diagnosis might be due to the hyperexpression of PSA via heterosis in Eurasian men. Therefore we should be cautious when using pro-biopsy in precision diagnosis for Eurasian prostate cancer patients.

An endoglycosidase-assisted LC-MS/MS-based strategy for the analysis of site-specific core-fucosylation of low-concentrated glycoproteins in human serum using prostate-specific antigen (PSA) as example.

PubMed

Lang, Robert; Leinenbach, Andreas; Karl, Johann; Swiatek-de Lange, Magdalena; Kobold, Uwe; Vogeser, Michael

2018-05-01

Recently, site-specific fucosylation of glycoproteins has attracted attention as it can be associated with several types of cancers including prostate cancer. However, individual glycoproteins, which might serve as potential cancer markers, often are very low-concentrated in complex serum matrices and distinct glycan structures are hard to detect by immunoassays. Here, we present a mass spectrometry-based strategy for the simultaneous analysis of core-fucosylated and total prostate-specific antigen (PSA) in human serum in the low ng/ml concentration range. Sample preparation comprised an immunoaffinity capture step to enrich total PSA from human serum using anti-PSA antibody coated magnetic beads followed by consecutive two-step on-bead partial deglycosylation with endoglycosidase F3 and tryptic digestion prior to LC-MS/MS analysis. The method was shown to be linear from 0.5 to 60 ng/ml total PSA concentrations and allows the simultaneous quantification of core-fucosylated PSA down to 1 ng/ml and total PSA lower than 0.5 ng/ml. The imprecision of the method over two days ranged from 9.7-23.2% for core-fucosylated PSA and 10.3-18.3% for total PSA depending on the PSA level. The feasibility of the method in native sera was shown using three human specimens. To our knowledge, this is the first MS-based method for quantification of core-fucosylated PSA in the low ng/ml concentration range in human serum. This method could be used in large patient cohorts as core-fucosylated PSA may be a diagnostic biomarker for the differentiation of prostate cancer and other prostatic diseases, such as benign prostatic hyperplasia (BPH). Furthermore, the described strategy could be used to monitor potential changes in site-specific core-fucosylation of other low-concentrated glycoproteins, which could serve as more specific markers ("marker refinement") in cancer research. Copyright © 2018 Elsevier B.V. All rights reserved.

Prostate specific antigen velocity as a measure of the natural history of prostate cancer: defining a 'rapid riser' subset.

PubMed

Nam, R K; Klotz, L H; Jewett, M A; Danjoux, C; Trachtenberg, J

1998-01-01

To study the rate of change in prostate specific antigen (PSA velocity) in patients with prostate cancer initially managed by 'watchful waiting'. Serial PSA levels were determined in 141 patients with prostate cancer confirmed by biopsy, who were initially managed expectantly and enrolled between May 1990 and December 1995. Sixty-seven patients eventually underwent surgery (mean age 59 years) because they chose it (the decision for surgery was not based on PSA velocity). A cohort of 74 patients remained on 'watchful waiting' (mean age 69 years). Linear regression and logarithmic transformations were used to segregate those patients who showed a rapid rise, defined as a > 50% rise in PSA per year (or a doubling time of < 2 years) and designated 'rapid risers'. An initial analysis based on a minimum of two PSA values showed that 31% were rapid risers. Only 15% of patients with more than three serial PSA determinations over > or = 6 months showed a rapid rise in PSA level. There was no advantage of log-linear analysis over linear regression models. Three serial PSA determinations over > or = 6 months in patients with clinically localized prostate cancer identifies a subset (15%) of patients with a rapidly rising PSA level. Shorter PSA surveillance with fewer PSA values may falsely identify patients with rapid rises in PSA level. However, further follow-up is required to determine if a rapid rise in PSA level identifies a subset of patients with an aggressive biological phenotype who are either still curable or who have already progressed to incurability through metastatic disease.

Impact of PSA density of transition zone as a potential parameter in reducing the number of unnecessary prostate biopsies in patients with psa levels between 2.6 and 10.0 ng/mL.

PubMed

Castro, Hugo A Socrates; Iared, Wagner; Santos, José Eduardo Mourão; Solha, Raphael Sandes; Shigueoka, David Carlos; Ajzen, Sergio Aron

2018-04-10

To assess the accuracy of prostate-specific antigen (PSA) adjusted for the transition zone volume (PSATZ) in predicting prostate cancer by comparing the ability of several PSA parameters in predicting prostate cancer in men with intermediate PSA levels of 2.6 - 10.0 ng/mL and its ability to reduce unnecessary biopsies. This study included 656 patients referred for prostate biopsy who had a serum PSA of 2.6 - 10.0 ng/mL. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. The clinical values of PSA, free-to-total (F/T) ratio, PSA density (PSAD) and PSATZ for the detection of prostate cancer were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative (benign) were conducted. Cancer was detected in 172 patients (26.2%). Mean PSA, PSATZ, PSAD and F/T ratio were 7.5 ng/mL, 0.68 ng/mL/cc. 0.25 ng/mL/cc and 0.14 in patients with prostate cancer and 6.29 ng/mL, 0.30 ng/mL/cc, 0.16 ng/mL/cc and 0.22 in patients with benign biopsies, respectively. ROC curves analysis demonstrated that PSATZ had a higher area under curve (0,838) than F/T ratio (0,806) (P<0.001) and PSAD (0,806) (P<0.001). With a cut-off value of 0.22 ng/mL/cc, PSATZ had 100% of sensitivity and could have prevented 24% of unnecessary biopsies. PSATZ may be useful in enhancing the specificity of serum PSA. Compared to other PSA related parameters, it was better in differentiating between prostate cancer and benign prostatic enlargement. Also, PSATZ could reduce a significant number of unnecessary biopsies. Copyright® by the International Brazilian Journal of Urology.

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.

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.

Percentage of free prostate-specific antigen (PSA) is a useful method in deciding to perform prostate biopsy with higher core numbers in patients with low PSA cut-off values.

PubMed

Yilmaz, Hasan; Ciftci, Seyfettin; Yavuz, Ufuk; Ustuner, Murat; Saribacak, Ali; Dillioglugil, Ozdal

2015-06-01

The aim of this study was to evaluate the predictive role of percentage of free prostate-specific antigen (%fPSA) cut-points in prostate cancer (PCa) detection in patients with total PSA (tPSA) levels between 2.5 ng/mL and 10.0 ng/mL. In total, 1321 consecutive initial transrectal ultrasound (TRUS)-guided 12-core biopsies performed between 2005 and 2011 were evaluated retrospectively. Benign pathologies, high-grade prostatic intraepithelial neoplasia, and atypical small acinary proliferations were categorized as noncancerous (benign), and prostate adenocarcinomas were categorized as cancerous (malignant). The patients were categorized according to: Catalona's published %fPSA categories (<10%, 10-15%, 15-20%, 20-25%, or > 25%); digital rectal examination (DRE) results [benign (negative) or suspicious of malignancy (positive)]. There was a significant relationship between the %fPSA cut-points and detection of PCa in DRE-negative patients. The presence of a 10% cut-point increased the probability of PCa threefold. The %fPSA was significantly more related to PCa than the tPSA value in receiver operating characteristic (ROC) curve analyses (p = 0.001). Based on our findings, a lower %fPSA, especially <10%, is an important parameter when deciding whether to perform a biopsy on patients with a tPSA between 2.5 ng/mL and 10 ng/mL. Copyright © 2015. Published by Elsevier Taiwan.

Elevated insulin and reduced insulin like growth factor binding protein-3/prostate specific antigen ratio with increase in prostate size in Benign Prostatic Hyperplasia.

PubMed

Sreenivasulu, Karli; Nandeesha, Hanumanthappa; Dorairajan, Lalgudi Narayanan; Rajappa, Medha; Vinayagam, Vickneshwaran

2017-06-01

Insulin and insulin like growth factor-1 (IGF-1) have growth promoting effects, while insulin like growth factor binding protein-3 (IGFBP-3) has growth inhibitory effects. The present study was designed to assess the concentrations of insulin, IGF-1, IGFBP-3 and their association with prostate size in patients with BPH. Ninety 90 BPH cases and 90 controls were enrolled in the study. Insulin, IGF-1, IGFBP-3, PSA, testosterone and estradiol were estimated in both the groups. Insulin, IGF-1 and estradiol were increased and IGFBP-3/PSA was decreased in BPH cases when compared with controls. Insulin (r=0.64, p=0.001) and IGF-1 (r=0.22, p=0.03) were positively correlated and IGFBP-3/PSA (r=-0.316, p=0.002) were negatively correlated with prostate size in BPH. Multivariate analysis showed that insulin (p=0.001) and IGFBP-3/PSA (p=0.004) predicts the prostate size in patients with BPH. Insulin was increased and IGFBP-3/PSA was reduced in BPH patients with increased prostate size. At a cutoff concentration of 527.52, IGFBP-3/PSA ratio was found to differentiate benign growth of prostate from normal prostate with 96% sensitivity and 96% specificity. Insulin is elevated and IGFBP-3/PSA is reduced with increase prostate size in BPH cases. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer

PubMed Central

Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

2017-01-01

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. PMID:28134773

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.

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

Proteolytic Activity of Prostate-Specific Antigen (PSA) towards Protein Substrates and Effect of Peptides Stimulating PSA Activity

PubMed Central

Mattsson, Johanna M.; Ravela, Suvi; Hekim, Can; Jonsson, Magnus; Malm, Johan; Närvänen, Ale; Stenman, Ulf-Håkan; Koistinen, Hannu

2014-01-01

Prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3) exerts chymotrypsin-like proteolytic activity. The main biological function of PSA is the liquefaction of the clot formed after ejaculation by cleavage of semenogelins I and II in seminal fluid. PSA also cleaves several other substrates, which may explain its putative functions in prostate cancer and its antiangiogenic activity. We compared the proteolytic efficiency of PSA towards several protein and peptide substrates and studied the effect of peptides stimulating the activity of PSA with these substrates. An endothelial cell tube formation model was used to analyze the effect of PSA-degraded protein fragments on angiogenesis. We showed that PSA degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin-3 and IGFBP-3. We identified nidogen-1 as a new substrate for PSA. Peptides B2 and C4 that stimulate the activity of PSA towards small peptide substrates also enhanced the proteolytic activity of PSA towards protein substrates. Nidogen-1, galectin-3 or their fragments produced by PSA did not have any effect on endothelial cell tube formation. Although PSA cleaves several other protein substrates, in addition to semenogelins, the physiological importance of this activity remains speculative. The PSA levels in prostate are very high, but several other highly active proteases, such as hK2 and trypsin, are also expressed in the prostate and may cleave protein substrates that are weakly cleaved by PSA. PMID:25237904

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

PubMed

Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel; Bancroft, Elizabeth; Vertosick, Emily; Dadaev, Tokhir; Brendler, Charles; Page, Elizabeth; Dias, Alexander; Evans, D Gareth; Rothwell, Jeanette; Maehle, Lovise; Axcrona, Karol; Richardson, Kate; Eccles, Diana; Jensen, Thomas; Osther, Palle J; van Asperen, Christi J; Vasen, Hans; Kiemeney, Lambertus A; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Hart, Rachel; Glover, Wayne; Lam, Jimmy; Taylor, Louise; Salinas, Monica; Feliubadaló, Lidia; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A; Oosterwijk, Jan C; Cook, Jackie; Rosario, Derek J; Buys, Saundra S; Conner, Tom; Domchek, Susan; Powers, Jacquelyn; Ausems, Margreet Gem; Teixeira, Manuel R; Maia, Sofia; Izatt, Louise; Schmutzler, Rita; Rhiem, Kerstin; Foulkes, William D; Boshari, Talia; Davidson, Rosemarie; Ruijs, Marielle; Helderman-van den Enden, Apollonia Tjm; Andrews, Lesley; Walker, Lisa; Snape, Katie; Henderson, Alex; Jobson, Irene; Lindeman, Geoffrey J; Liljegren, Annelie; Harris, Marion; Adank, Muriel A; Kirk, Judy; Taylor, Amy; Susman, Rachel; Chen-Shtoyerman, Rakefet; Pachter, Nicholas; Spigelman, Allan; Side, Lucy; Zgajnar, Janez; Mora, Josefina; Brewer, Carole; Gadea, Neus; Brady, Angela F; Gallagher, David; van Os, Theo; Donaldson, Alan; Stefansdottir, Vigdis; Barwell, Julian; James, Paul A; Murphy, Declan; Friedman, Eitan; Nicolai, Nicola; Greenhalgh, Lynn; Obeid, Elias; Murthy, Vedang; Copakova, Lucia; McGrath, John; Teo, Soo-Hwang; Strom, Sara; Kast, Karin; Leongamornlert, Daniel A; Chamberlain, Anthony; Pope, Jenny; Newlin, Anna C; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Castro, Elena; Dearnaley, David; Eyfjord, Jorunn; Falconer, Alison; Foster, Christopher S; Gronberg, Henrik; Hamdy, Freddie C; Johannsson, Oskar; Khoo, Vincent; Lubinski, Jan; Grindedal, Eli Marie; McKinley, Joanne; Shackleton, Kylie; Mitra, Anita V; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Tricker, Karen; Moss, Sue; Kote-Jarai, Zsofia; Vickers, Andrew; Lilja, Hans; Helfand, Brian T; Eeles, Rosalind A

2018-01-01

Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml -l , PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

PubMed Central

Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel; Bancroft, Elizabeth; Vertosick, Emily; Dadaev, Tokhir; Brendler, Charles; Page, Elizabeth; Dias, Alexander; Evans, D Gareth; Rothwell, Jeanette; Maehle, Lovise; Axcrona, Karol; Richardson, Kate; Eccles, Diana; Jensen, Thomas; Osther, Palle J; van Asperen, Christi J; Vasen, Hans; Kiemeney, Lambertus A; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Hart, Rachel; Glover, Wayne; Lam, Jimmy; Taylor, Louise; Salinas, Monica; Feliubadaló, Lidia; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A; Oosterwijk, Jan C; Cook, Jackie; Rosario, Derek J; Buys, Saundra S; Conner, Tom; Domchek, Susan; Powers, Jacquelyn; Ausems, Margreet GEM; Teixeira, Manuel R; Maia, Sofia; Izatt, Louise; Schmutzler, Rita; Rhiem, Kerstin; Foulkes, William D; Boshari, Talia; Davidson, Rosemarie; Ruijs, Marielle; Helderman-van den Enden, Apollonia TJM; Andrews, Lesley; Walker, Lisa; Snape, Katie; Henderson, Alex; Jobson, Irene; Lindeman, Geoffrey J; Liljegren, Annelie; Harris, Marion; Adank, Muriel A; Kirk, Judy; Taylor, Amy; Susman, Rachel; Chen-Shtoyerman, Rakefet; Pachter, Nicholas; Spigelman, Allan; Side, Lucy; Zgajnar, Janez; Mora, Josefina; Brewer, Carole; Gadea, Neus; Brady, Angela F; Gallagher, David; van Os, Theo; Donaldson, Alan; Stefansdottir, Vigdis; Barwell, Julian; James, Paul A; Murphy, Declan; Friedman, Eitan; Nicolai, Nicola; Greenhalgh, Lynn; Obeid, Elias; Murthy, Vedang; Copakova, Lucia; McGrath, John; Teo, Soo-Hwang; Strom, Sara; Kast, Karin; Leongamornlert, Daniel A; Chamberlain, Anthony; Pope, Jenny; Newlin, Anna C; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Castro, Elena; Dearnaley, David; Eyfjord, Jorunn; Falconer, Alison; Foster, Christopher S; Gronberg, Henrik; Hamdy, Freddie C; Johannsson, Oskar; Khoo, Vincent; Lubinski, Jan; Grindedal, Eli Marie; McKinley, Joanne; Shackleton, Kylie; Mitra, Anita V; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Tricker, Karen; Moss, Sue; Kote-Jarai, Zsofia; Vickers, Andrew; Lilja, Hans; Helfand, Brian T; Eeles, Rosalind A

2018-01-01

Background: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. Methods: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. Results: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml−l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. Conclusions: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone. PMID:29301143

An Automated Micro-Total Immunoassay System for Measuring Cancer-Associated α2,3-linked Sialyl N-Glycan-Carrying Prostate-Specific Antigen May Improve the Accuracy of Prostate Cancer Diagnosis

PubMed Central

Ishikawa, Tomokazu; Yoneyama, Tohru; Tobisawa, Yuki; Hatakeyama, Shingo; Kurosawa, Tatsuo; Nakamura, Kenji; Narita, Shintaro; Mitsuzuka, Koji; Duivenvoorden, Wilhelmina; Pinthus, Jehonathan H.; Hashimoto, Yasuhiro; Koie, Takuya; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara

2017-01-01

The low specificity of the prostate-specific antigen (PSA) for early detection of prostate cancer (PCa) is a major issue worldwide. The aim of this study to examine whether the serum PCa-associated α2,3-linked sialyl N-glycan-carrying PSA (S2,3PSA) ratio measured by automated micro-total immunoassay systems (μTAS system) can be applied as a diagnostic marker of PCa. The μTAS system can utilize affinity-based separation involving noncovalent interaction between the immunocomplex of S2,3PSA and Maackia amurensis lectin to simultaneously determine concentrations of free PSA and S2,3PSA. To validate quantitative performance, both recombinant S2,3PSA and benign-associated α2,6-linked sialyl N-glycan-carrying PSA (S2,6PSA) purified from culture supernatant of PSA cDNA transiently-transfected Chinese hamster ovary (CHO)-K1 cells were used as standard protein. Between 2007 and 2016, fifty patients with biopsy-proven PCa were pair-matched for age and PSA levels, with the same number of benign prostatic hyperplasia (BPH) patients used to validate the diagnostic performance of serum S2,3PSA ratio. A recombinant S2,3PSA- and S2,6PSA-spiked sample was clearly discriminated by μTAS system. Limit of detection of S2,3PSA was 0.05 ng/mL and coefficient variation was less than 3.1%. The area under the curve (AUC) for detection of PCa for the S2,3PSA ratio (%S2,3PSA) with cutoff value 43.85% (AUC; 0.8340) was much superior to total PSA (AUC; 0.5062) using validation sample set. Although the present results are preliminary, the newly developed μTAS platform for measuring %S2,3PSA can achieve the required assay performance specifications for use in the practical and clinical setting and may improve the accuracy of PCa diagnosis. Additional validation studies are warranted. PMID:28241428

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

Parameters predicting for prostate specific antigen response rates at one year post low-dose-rate intraoperative prostate brachytherapy

PubMed Central

Meyer, Tyler; Sia, Michael; Angyalfi, Steve; Husain, Siraj

2017-01-01

Purpose To develop a model for prostate specific antigen (PSA) values at one year among patients treated with intraoperatively planned 125I prostate brachytherapy (IOPB). Material and methods Four hundred and deven patients treated with IOPB for prostate adenocarcinoma were divided into four groups: those with PSA values ≥ 3 ng/ml; < 3 and ≥ 2; < 2 and ≥ 1 or PSA < 1 between 10.5 and 14.5 months post implantation (1yPSA). Ordinal regression analysis was then performed between patient, tumor, and treatment characteristics. 1yPSA values were also compared with toxicity outcomes. Results Median 1yPSA was 0.77 (0.04-17.36). Thirty-two patients (8%) had a PSA ≥ 3; 35 (9%) had PSA < 3, ≥ 2; 87 (21%) had PSA < 2, ≥ 1, and most patients 254 (62%) had PSA < 1. PSA response was independent of gland volume, Gleason score, clinical stage, seed activity, V90, V200, D90, or number of needles and seeds used. Older patients had significantly lower 1yPSA; median ages 65.1 (46.5-81.0), 62.1 (50.4-79.5), 60.5 (47.1-80.3), and 58.1 (45.1-74.2) years for each of the 1yPSA groups respectively (p < 0.001). Also, both implant V150 (p < 0.001) and initial PSA values (p = 0.04) were predictive of 1yPSA values. There was no correlation between 1yPSA values and toxicity encountered. Conclusions PSA response at 1 year post IOPB appears to be dependent on patient age, initial PSA, and implant V150. Our results provide reassurance that parameters other than biochemical failure influence 1yPSA values. PMID:28533796

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.

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.

Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

PubMed

Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Kadono, Yoshifumi; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

2016-03-01

To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

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.

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...

Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study.

PubMed

Farrelly, Cormac; Lal, Priti; Trerotola, Scott O; Nadolski, Gregory J; Watts, Micah M; Gorrian, Catherine Mc; Guzzo, Thomas J

2016-05-01

To correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA. In this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1-7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens. Mean PVS PSA was 4.29, range 2.3-6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left-sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events. fPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.

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

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 ...

Evaluation of PSA-age volume score in predicting prostate cancer in Chinese populationArticle Subject.

PubMed

Wu, Yi-Shuo; Wu, Xiao-Bo; Zhang, Ning; Jiang, Guang-Liang; Yu, Yang; Tong, Shi-Jun; Jiang, Hao-Wen; Mao, Shan-Hua; Na, Rong; Ding, Qiang

2018-02-06

This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biopsy from January 2006 to November 2015 in Huashan Hospital were recruited in the current study. The PSA-AV scores were calculated and assessed together with PSA and PSA density (PSAD) retrospectively. Among 2133 patients included in the analysis, 947 (44.4%) were diagnosed with PCa. The mean age, PSA, and positive rates of digital rectal examination result and transrectal ultrasound result were statistically higher in men diagnosed with PCa (all P < 0.05). The values of area under the receiver operating characteristic curves (AUCs) of PSAD and PSA-AV were 0.864 and 0.851, respectively, in predicting PCa in the entire population, both performed better than PSA (AUC = 0.805; P < 0.05). The superiority of PSAD and PSA-AV was more obvious in subgroup with PSA ranging from 2.0 ng ml-1 to 20.0 ng ml-1. A PSA-AV score of 400 had a sensitivity and specificity of 93.7% and 40.0%, respectively. In conclusion, the PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa. This indicated that PSA-AV score could be a useful tool for predicting PCa in Chinese population.

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.

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.

Extreme-Risk Prostate Adenocarcinoma Presenting With Prostate-Specific Antigen (PSA) >40 ng/ml: Prognostic Significance of the Preradiation PSA Nadir

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

Alexander, Abraham S.; University of British Columbia, Vancouver, British Columbia; Mydin, Aminudin

2011-12-01

Purpose: To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml. Methods and Materials: A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration andmore » pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined. Results: Median follow-up time was 6.45 years (range, 0.09-15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level ({<=}0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS (p = 0.033) and OS (p = 0.018) rates, whereas age, T stage, Gleason score, and ADT duration ({<=}6 versus >6 months) were not predictive of outcomes. Conclusion: In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.« less

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.

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.

[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.

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.

PSA velocity does not aid the detection of prostate cancer in men with a prior negative biopsy: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden and Rotterdam, Netherlands

PubMed Central

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

2012-01-01

Purpose Prostate specific antigen (PSA) velocity has been proposed as a marker to aid detection of prostate cancer. We sought to determine whether PSA velocity could predict the results of repeat biopsy in men with persistently elevated PSA after initial negative biopsy. Materials and Methods We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer (ERSPC), and who had one or more subsequent prostate biopsies after an initial negative finding. We evaluated whether PSA velocity improved predictive accuracy beyond that of PSA alone. Results There were a total of 2579 repeat biopsies, of which 363 (14%) were positive for prostate cancer, and 44 (1.7%) were high grade (Gleason score ≥7). Although PSA velocity was statistically associated with cancer risk (p<0.001), it had very low predictive accuracy (area-under-the-curve [AUC] of 0.55). There was some evidence that PSA velocity improved AUC compared to PSA for high grade cancer. However, the small increase in risk associated with high PSA velocity – from 1.7 % to 2.8% as velocity increased from 0 to 1 ng / ml / year - is of questionable clinical relevance. Conclusions Men with a prior negative biopsy have a lower risk for prostate cancer at subsequent biopsies, with high grade disease particularly rare. We found little evidence to support the use of PSA velocity to aid decisions about repeat biopsy for prostate cancer. PMID:20643434

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 ...

Role of PSA density in diagnosis of prostate cancer in obese men.

PubMed

Chiu, Peter Ka-Fung; Teoh, Jeremy Yuen-Chun; Chan, Samson Yun-Sang; Chu, Peggy Sau-Kwan; Man, Chi-Wai; Hou, See-Ming; Ng, Chi-Fai

2014-12-01

To compare the performance of prostate-specific antigen (PSA) density in the diagnosis of prostate cancer in obese and non-obese Chinese men. The results of transrectal ultrasound-guided (TRUS) prostate biopsies of Chinese men with PSA <20 ng/mL were reviewed. Parameters including age, body mass index (BMI), TRUS prostate volume, and TRUS biopsy results were recorded. The diagnostic yields of PSA density (>0.15 ng/mL as positive) in obese and non-obese men with PSA <20 ng/mL were compared. Obesity was defined as BMI ≥ 27 kg/m(2) according to WHO recommendation for Hong Kong Chinese. TRUS biopsy, BMI, and PSA density data were available for 854 men (mean age 65.9 ± 7.3). The mean PSA values for the obese and non-obese patients were 7.9 ± 3.7 and 8.2 ± 4.1 ng/mL, respectively (p = 0.416). TRUS volumes in obese and non-obese men were 63.2 ml and 51.6 ml, respectively (t test, p < 0.001), and PSA density was significantly lower in obese men (0.145 vs. 0.188, p < 0.001). For obese men, positive PSA density was associated with four times (41.1 vs. 9.5 %, p < 0.001) the risk of prostate cancer, compared to only twice the risk (18.8 vs. 9.7 %, p = 0.001) in non-obese men. The specificity and area under the curve of PSA density were 74.2 % and 0.731, respectively, for obese men, and 51.4 % and 0.653, respectively, for non-obese men. Among patients with a diagnosis of prostate cancer, the obese patient group had a significantly higher proportion of patients with Gleason 7-10 prostate cancer than the non-obese patient group (48.9 vs. 32.7 %, Chi-square test, p = 0.035), and a trend toward a higher proportion of bilateral lobe involvement. PSA density had better performance in obese men. Positive PSA density in obese men was associated with four times the risk of prostate cancer.

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

PubMed

Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

2017-05-01

Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients.

PubMed

Washino, Satoshi; Okochi, Tomohisa; Saito, Kimitoshi; Konishi, Tsuzumi; Hirai, Masaru; Kobayashi, Yutaka; Miyagawa, Tomoaki

2017-02-01

To assess the value of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system, for prostate multi-parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate-specific antigen (PSA) level, prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer. Patients who underwent mpMRI at our hospital, and who had their first prostate biopsy between July 2010 and April 2014, were analysed retrospectively. The prostate biopsies were taken transperineally under transrectal ultrasonography guidance. In all, 14 cores were biopsied as a systematic biopsy in all patients. Two cognitive fusion-targeted biopsy cores were added for each lesion in patients who had suspicious or equivocal lesions on mpMRI. The PI-RADS scoring system version 2.0 (PI-RADS v2) was used to describe the MRI findings. Univariate and multivariate analyses were performed to determine significant predictors of prostate cancer and clinically significant prostate cancer. In all, 288 patients were analysed. The median patient age, PSA level, prostate volume and PSA density were 69 years, 7.5 ng/mL, 28.7 mL, and 0.26 ng/mL/mL, respectively. The biopsy results were benign, clinically insignificant, and clinically significant prostate cancer in 129 (45%), 18 (6%) and 141 (49%) patients, respectively. The multivariate analysis revealed that PI-RADS v2 score and PSA density were independent predictors for prostate cancer and clinically significant prostate cancer. When PI-RADS v2 score and PSA density were combined, a PI-RADS v2 score of ≥4 and PSA density ≥0.15 ng/mL/mL, or PI-RADS v2 score of 3 and PSA density of ≥0.30 ng/mL/mL, was associated with the highest clinically significant prostate cancer detection rates (76-97%) on the first biopsy. Of the patients in this group with negative biopsy results, 22% were subsequently diagnosed as prostate cancer. In contrast, a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL yielded no clinically significant prostate cancer and no additional detection of prostate cancer on further biopsies. A combination of PI-RADS v2 score and PSA density can help in the decision-making process before prostate biopsy and in the follow-up strategy in biopsy naïve patients. Patients with a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL may avoid unnecessary biopsies. © 2016 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

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 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.

PSA-selective activation of cytotoxic human serine proteases within the tumor microenvironment as a therapeutic strategy to target prostate cancer.

PubMed

Rogers, Oliver C; Anthony, Lizamma; Rosen, D Marc; Brennen, W Nathaniel; Denmeade, Samuel R

2018-04-27

Prostate cancer is the most diagnosed malignancy and the second leading cause of cancer-related death in American men. While localized therapy is highly curative, treatments for metastatic prostate cancer are largely palliative. Thus, new innovative therapies are needed to target metastatic tumors. Prostate-Specific Antigen (PSA) is a chymotrypsin-like protease with a unique substrate specificity that is secreted by both normal and malignant prostate epithelial cells. Previous studies demonstrated the presence of high levels (μM-mM) of enzymatically active PSA is present in the extracellular fluid of the prostate cancer microenvironment. Because of this, PSA is an attractive target for a protease activated pro-toxin therapeutic strategy. Because prostate cancers typically grow very slowly, a strategy employing a proliferation-independent cytotoxic payload is preferred. Recently, it was shown that the human protease Granzyme B (GZMB), at low micromolar concentrations in the extracellular space, can cleave an array of extracellular matrix (ECM) proteins thus perturbing cell growth, signaling, motility, and integrity. It is also well established that other human proteases such as trypsin can induce similar effects. Because both enzymes require N-terminal proteolytic activation, we propose to convert these proteins into PSA-activated cytotoxins. In this study, we examine the enzymatic and cell targeting parameters of these PSA-activated cytotoxic serine proteases. These pro-enzymes were activated robustly by PSA and induced ECM damage that led to the death of prostate cancer cells in vitro thus supporting the potential use of this strategy as means to target metastatic prostate cancers.

PSA-selective activation of cytotoxic human serine proteases within the tumor microenvironment as a therapeutic strategy to target prostate cancer

PubMed Central

Rogers, Oliver C.; Anthony, Lizamma; Rosen, D. Marc; Brennen, W. Nathaniel; Denmeade, Samuel R.

2018-01-01

Prostate cancer is the most diagnosed malignancy and the second leading cause of cancer-related death in American men. While localized therapy is highly curative, treatments for metastatic prostate cancer are largely palliative. Thus, new innovative therapies are needed to target metastatic tumors. Prostate-Specific Antigen (PSA) is a chymotrypsin-like protease with a unique substrate specificity that is secreted by both normal and malignant prostate epithelial cells. Previous studies demonstrated the presence of high levels (μM-mM) of enzymatically active PSA is present in the extracellular fluid of the prostate cancer microenvironment. Because of this, PSA is an attractive target for a protease activated pro-toxin therapeutic strategy. Because prostate cancers typically grow very slowly, a strategy employing a proliferation-independent cytotoxic payload is preferred. Recently, it was shown that the human protease Granzyme B (GZMB), at low micromolar concentrations in the extracellular space, can cleave an array of extracellular matrix (ECM) proteins thus perturbing cell growth, signaling, motility, and integrity. It is also well established that other human proteases such as trypsin can induce similar effects. Because both enzymes require N-terminal proteolytic activation, we propose to convert these proteins into PSA-activated cytotoxins. In this study, we examine the enzymatic and cell targeting parameters of these PSA-activated cytotoxic serine proteases. These pro-enzymes were activated robustly by PSA and induced ECM damage that led to the death of prostate cancer cells in vitro thus supporting the potential use of this strategy as means to target metastatic prostate cancers. PMID:29854290

Accuracy of PSA Self-Reports among Low-Income Men with Prostate Cancer after a Public Health Nursing Intervention.

PubMed

Zavala, Mary Wassel; Yule, Arthur; Kwan, Lorna; Lambrechts, Sylvia; Maliski, Sally L; Litwin, Mark S

2016-11-01

To examine accuracy of patient-reported prostate-specific antigen (PSA) levels among indigent, uninsured men in a state-funded prostate cancer treatment program that provides case management, care coordination, and health education. Program evaluation. About 114 men with matched self- and lab-reported PSA levels at program enrollment and another time point within 18 months. Abstraction of self- and lab-reported PSA levels to determine self-report as "accurate" or "inaccurate," and evaluate accuracy change over time, before and after nursing interventions. Chi-square tests compared patients with accurate versus inaccurate PSA values. Nonlinear multivariate analyses explored trends in self-reported accuracy over time. Program enrollees receive prostate cancer education from a Nurse Case Manager (NCM), including significance of PSA levels. Men self-report PSA results to their NCM following lab draws and appointments. The NCM provides ongoing education about PSA levels. Of the sample, 46% (n = 53) accurately reported PSA levels. Accuracy of PSA self-reports improved with increasing time since program enrollment. Compared with men at public facilities, those treated at private facilities showed increasing accuracy in self-reported PSA (p = .038). A targeted nursing intervention may increase specific knowledge of PSA levels. Additionally, the provider/treatment setting significantly impacts a patient's disease education and knowledge. © 2016 Wiley Periodicals, Inc.

Healthy Family 2009: Practicing Healthy Adult Living

MedlinePlus

... doctor the pros and cons of having a prostate-specific antigen (PSA) test or digital rectal examination (DRE) to ... colonoscopies for cancer of the colon, serum prostatin-specific antigen (PSA) tests for prostate cancer, and mammograms for breast cancer. Work out ...

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.

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.

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.

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.

The simultaneous detection of free and total prostate antigen in serum samples with high sensitivity and specificity by using the dual-channel surface plasmon resonance.

PubMed

Jiang, Zhongxiu; Qin, Yun; Peng, Zhen; Chen, Shenghua; Chen, Shu; Deng, Chunyan; Xiang, Juan

2014-12-15

Free/total prostate antigen (f/t-PSA) ratio in serum as a promising parameter has been used to improve the differentiation of benign and malignant prostate disease. In order to obtain the accurate and reliable f/t-PSA ratio, the simultaneous detection of f-PSA and t-PSA with high sensitivity and specificity is required. In this work, the dual-channel surface plasmon resonance (SPR) has been employed to meet the requirement. In one channel, t-PSA was directly measured with a linear range from 1.0 to 20.0 ng/mL. In another channel, due to the low concentration of f-PSA in serum, the asynchronous competitive inhibition immunoassay with f-PSA@Au nanoparticles (AuNPs) was developed. As expected, the detection sensitivity of f-PSA was greatly enhanced, and a linear correlation with wider linear range from 0.010 to 0.40 ng/mL was also achieved. On the other hand, a simple method was explored for significantly reducing the non-specific adsorption of co-existing proteins. On basis of this, the f/t-PSA ratios in serum samples from prostate cancer (PCa) or benign prostatic hyperplasia (BPH) patients were measured. And it was found that there was significant difference between the distributions of f/t-PSA ratio in BPH patients (16.44±1.77%) and those in PCa patients (24.53±4.97%). This present work provides an effective method for distinguishing PCa from BPH, which lays a potential foundation for the early diagnosis of PCa. Copyright © 2014. Published by Elsevier B.V.

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

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.

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.

Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study

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

Farrelly, Cormac, E-mail: farrellycormac@gmail.com; Lal, Priti; Trerotola, Scott O.

PurposeTo correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA.Materials and MethodsIn this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1–7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling resultsmore » were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens.ResultsMean PVS PSA was 4.29, range 2.3–6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left–sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events.ConclusionfPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.« less

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.

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.

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.

First off-time treatment prostate-specific antigen kinetics predicts survival in intermittent androgen deprivation for prostate cancer.

PubMed

Sanchez-Salas, Rafael; Olivier, Fabien; Prapotnich, Dominique; Dancausa, José; Fhima, Mehdi; David, Stéphane; Secin, Fernando P; Ingels, Alexandre; Barret, Eric; Galiano, Marc; Rozet, François; Cathelineau, Xavier

2016-01-01

Prostate-specific antigen (PSA) doubling time is relying on an exponential kinetic pattern. This pattern has never been validated in the setting of intermittent androgen deprivation (IAD). Objective is to analyze the prognostic significance for PCa of recurrent patterns in PSA kinetics in patients undergoing IAD. A retrospective study was conducted on 377 patients treated with IAD. On-treatment period (ONTP) consisted of gonadotropin-releasing hormone agonist injections combined with oral androgen receptor antagonist. Off-treatment period (OFTP) began when PSA was lower than 4 ng/ml. ONTP resumed when PSA was higher than 20 ng/ml. PSA values of each OFTP were fitted with three basic patterns: exponential (PSA(t) = λ.e(αt)), linear (PSA(t) = a.t), and power law (PSA(t) = a.t(c)). Univariate and multivariate Cox regression model analyzed predictive factors for oncologic outcomes. Only 45% of the analyzed OFTPs were exponential. Linear and power law PSA kinetics represented 7.5% and 7.7%, respectively. Remaining fraction of analyzed OFTPs (40%) exhibited complex kinetics. Exponential PSA kinetics during the first OFTP was significantly associated with worse oncologic outcome. The estimated 10-year cancer-specific survival (CSS) was 46% for exponential versus 80% for nonexponential PSA kinetics patterns. The corresponding 10-year probability of castration-resistant prostate cancer (CRPC) was 69% and 31% for the two patterns, respectively. Limitations include retrospective design and mixed indications for IAD. PSA kinetic fitted with exponential pattern in approximately half of the OFTPs. First OFTP exponential PSA kinetic was associated with a shorter time to CRPC and worse CSS. © 2015 Wiley Periodicals, Inc.

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.

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

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.

[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.

Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results.

PubMed

Wenisch, Judith M; Mayr, Florian B; Spiel, Alexander O; Radicioni, Milko; Jilma, Bernd; Jilma-Stohlawetz, Petra

2014-03-01

Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001). LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.

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.

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) 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 ...

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.

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

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.

Impact of poor glycemic control of type 2 diabetes mellitus on serum prostate-specific antigen concentrations in men.

PubMed

Atalay, Hasan Anıl; Akarsu, Murat; Canat, Lutfi; Ülker, Volkan; Alkan, İlter; Ozkuvancı, Unsal

2017-09-01

To evaluate the impact of poor glycemic control of type 2 diabetes mellitus (T2DM) on serum prostate-specific antigen (PSA) concentrations in men. We performed a prospective analysis of 215 consecutive patients affected by erectile dysfunction (ED). ED was evaluated using the IIEF-5 questionnaire and the poor glycemic control (PGC) of T2DM was assessed according to the HbA1c criteria (International Diabetes Federation). Patients were divided into PGC group (HbA1c ≥ 7%) and control group (CG) (HbA1c < 6%). Correlations between serum HbA1c levels and various variables were evaluated and multivariate logistic regression analyses were carried out to identify variables for PGC. We compared 110 cases to 105 controls men ranging from 44 to 81 years of age, lower PSA concentrations were observed in men with PGC (PGC mean PSA: 0.9 ng/dl, CG mean PSA: 2.1 ng/dl, p < 0.001). Also mean prostate volume was 60% was smaller among men with PGC compared with men with CG (PGC mean prostate volume: 26 ml, CG prostate volume: 43 ml, p < 0.001). A strong negative correlation was found between serum HbA1c levels and serum PSA (p < 0.001 and r = -0.665) concentrations in men with PGC. We also found at the multivariate logistic regression model that PSA, prostate volume and peak systolic velocity were independent predictors of PGC. Our results suggest that there is significant impact of PGC on serum PSA levels in T2DM. Poor glycemic control of type 2 diabetes was associated with lower serum PSA levels and smaller prostate volumes.

Proteolysis of complement factors iC3b and C5 by the serine protease prostate-specific antigen in prostatic fluid and seminal plasma.

PubMed

Manning, Michael L; Williams, Simon A; Jelinek, Christine A; Kostova, Maya B; Denmeade, Samuel R

2013-03-15

Prostate-specific Ag (PSA) is a serine protease that is expressed exclusively by normal and malignant prostate epithelial cells. The continued high-level expression of PSA by the majority of men with both high- and low-grade prostate cancer throughout the course of disease progression, even in the androgen-ablated state, suggests that PSA has a role in the pathogenesis of disease. Current experimental and clinical evidence suggests that chronic inflammation, regardless of the cause, may predispose men to prostate cancer. The responsibility of the immune system in immune surveillance and eventually tumor progression is well appreciated but not completely understood. In this study, we used a mass spectrometry-based evaluation of prostatic fluid obtained from diseased prostates after removal by radical prostatectomy to identify potential immunoregulatory proteins. This analysis revealed the presence of Igs and the complement system proteins C3, factor B, and clusterin. Verification of these findings by Western blot confirmed the high-level expression of C3 in the prostatic fluid and the presence of a previously uncharacterized C-terminal C3 cleavage product. Biochemical analysis of this C3 cleavage fragment revealed a putative PSA cleavage site after tyrosine-1348. Purified PSA was able to cleave iC3b and the related complement protein C5. These results suggest a previously uncharacterized function of PSA as an immunoregulatory protease that could help to create an environment hospitable to malignancy through proteolysis of the complement system.

5α-Reductase inhibitor is less effective in men with small prostate volume and low serum prostatic specific antigen level.

PubMed

Lin, Victor C; Liao, Chun-Hou; Wang, Chung-Cheng; Kuo, Hann-Chorng

2015-09-01

Large total prostate volumes (TPVs) or high serum prostate-specific antigen (PSA) levels indicate high-risk clinical progression of benign prostatic hyperplasia. This prospective study investigated the treatment outcome of combined 5α-reductase inhibitor and α-blocker in patients with and without large TPVs or high PSA levels. Men aged ≥ 45 years with International Prostate Symptom scores (IPSS) ≥ 8, TPV ≥ 20 mL, and maximum flow rate ≤ 15 mL/s received a combination therapy (dutasteride plus doxaben) for 2 years. Patients with baseline PSA ≥ 4 ng/mL underwent prostatic biopsy for excluding malignancy. The changes in the parameters from baseline to 24 months after combination therapy were compared in those with and without TPV ≥ 40 mL or PSA levels ≥ 1.5 ng/mL. A total of 285 patients (mean age 72 ± 9 years) completed the study. Combination therapy resulted in significant continuous improvement in IPSS, quality of life index, maximum flow rate, and postvoid residual (all p < 0.0001) regardless of baseline TPV or PSA levels. However, only patients with baseline TPV ≥ 40 mL had significant improvements in IPSS-storage subscore, voided volume, reduction in TPV, transitional zone index, and PSA levels. In addition, patients with baseline TPV < 40 mL and PSA < 1.5 ng/mL had neither a reduction in TPV nor a decrease in serum PSA level. A high TPV indicates more outlet resistance, whereas elevated serum PSA level reflects glandular proliferation. Thus, patients with TPV<40 mL and low PSA levels has less benefit from 5α-reductase inhibitor therapy. The therapeutic effect of combined treatment may arise mainly from the α-blocker in these patients. Copyright © 2013. Published by Elsevier B.V.

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.

Prostate cancer

MedlinePlus

... of prostate cancer. But, it can increase your prostate-specific antigen (PSA) blood test result. Symptoms With early prostate ... 2009 Best Practice Statement. www.auanet.org/guidelines/prostate-specific-antigen-(2009-amended-2013) . Accessed October 9, 2017. Moyer ...

Proteins Annexin A2 and PSA in Prostate Cancer Biopsies Do Not Predict Biochemical Failure.

PubMed

Lamb, David S; Sondhauss, Sven; Dunne, Jonathan C; Woods, Lisa; Delahunt, Brett; Ferguson, Peter; Murray, Judith; Nacey, John N; Denham, James W; Jordan, T William

2017-12-01

We previously reported the use of mass spectrometry and western blotting to identify proteins from tumour regions of formalin-fixed paraffin-embedded biopsies from 16 men who presented with apparently localized prostate cancer, and found that annexin A2 (ANXA2) appeared to be a better predictor of subsequent biochemical failure than prostate-specific antigen (PSA). In this follow-up study, ANXA2 and PSA were measured using western blotting of proteins extracted from biopsies from 37 men from a subsequent prostate cancer trial. No significant differences in ANXA2 and PSA levels were observed between men with and without biochemical failure. The statistical effect sizes were small, d=0.116 for ANXA2, and 0.266 for PSA. ANXA2 and PSA proteins measured from biopsy tumour regions are unlikely to be good biomarkers for prediction of the clinical outcome of prostate cancer presenting with apparently localized disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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 cancer screening using prostate-specific antigen: The views of general and laboratory physicians].

PubMed

Giménez, N; Filella, X; Gavagnach, M; Allué, J A; Pedrazas, D; Ferrer, F

2018-03-21

It is currently recommended to provide individualised information on benefit-risk balance and shared decision-making in prostate cancer screening using prostate-specific antigen (PSA). To determine the usual practice and the views of general and laboratory practitioners in the screening of prostate cancer using PSA. A cross-sectional study based on a questionnaire and on PSA screening requests from Primary Health Care (PHC) in men older than 49 years with no prostatic symptoms. In 2015, PHC in Catalonia requested PSA on 15.2% of males. A total of 114 general practitioners and 227 laboratory practitioners participated in the questionnaire. The mean age of those who responded was 43 years with a mean of 17 years' experience, and included 64% women. According to general practitioners, 61% of PSA was performed at the patient's request. The uncertainty score when requesting PSA was 5 points for general practitioners and 5.7 for laboratory professionals. Interest in having clinical recommendations received 7.2 points in PHC, and 8.8 in the laboratory. Knowledge about the different clinical practice guidelines received was less than 5 points overall. General practitioners requested PSA screening in almost one-sixth of men over the age of 49 without prostate disease, often at the patient's request, and after informing them of the benefits and risks. PHC and laboratory physicians were interested in having recommendations and information, although they did not usually consult clinical practice guidelines immediately. Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Correlation of pretreatment clinical parameters and PSA nadir after high-intensity focused ultrasound (HIFU) for localised prostate cancer.

PubMed

Ganzer, Roman; Bründl, Johannes; Koch, Daniel; Wieland, Wolf F; Burger, Maximilian; Blana, Andreas

2015-01-01

To determine which pretreatment clinical parameters were predictive of a low prostate-specific antigen (PSA) nadir following high-intensity focused ultrasound (HIFU) treatment. Retrospective study of patients with clinically localised prostate cancer undergoing HIFU at a single centre between December 1997 and September 2009. Whole-gland treatment was applied. Patients also included if they had previously undergone transurethral resection of the prostate (TURP). TURP was also conducted simultaneously to HIFU. Biochemical failure based on Phoenix definition (PSA nadir + 2). Univariate and multivariate analysis of pretreatment clinical parameters conducted to assess those factors predictive of a PSA nadir ≤0.2 and >0.2 ng/ml. Mean (SD) follow-up was 6.2 (2.8) years; median (range) was 6.3 (1.1-12.2) years. Kaplan-Meier estimate of biochemical disease-free survival rate at 8 years was 83 and 48 % for patients achieving a PSA nadir of ≤0.2 and >0.2 ng/ml, respectively. Prostate volume and incidental finding of cancer were significant predictors of low PSA nadir (≤0.2 ng/ml). Prostate volume and incidental finding of cancer could be predictors for oncologic success of HIFU based on post-treatment PSA nadir.

Body Mass Index and Prostate-Specific Antigen Failure Following Brachytherapy for Localized Prostate Cancer

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

Efstathiou, Jason A.; Skowronski, Rafi Y.; Coen, John J.

2008-08-01

Purpose: Increasing body mass index (BMI) is associated with prostate-specific antigen (PSA) failure after radical prostatectomy and external beam radiation therapy (EBRT). We investigated whether BMI is associated with PSA failure in men treated with brachytherapy for clinically localized prostate cancer. Patients and Methods: Retrospective analyses were conducted on 374 patients undergoing brachytherapy for stage T1c-T2cNXM0 prostate cancer from 1996-2001. Forty-nine patients (13%) received supplemental EBRT and 131 (35%) received androgen deprivation therapy (ADT). Height and weight data were available for 353 (94%). Cox regression analyses were performed to evaluate the relationship between BMI and PSA failure (nadir + 2more » ng/ml definition). Covariates included age, race, preimplantation PSA, Gleason score, T category, percent of prescription dose to 90% of the prostate, use of supplemental EBRT, and ADT. Results: Median age, PSA, and BMI were 66 years (range, 42-80 years), 5.7 ng/ml (range, 0.4-22.6 ng/ml), and 27.1 kg/m{sup 2} (range, 18.2-53.6 kg/m{sup 2}), respectively. After a median follow-up of 6.0 years (range, 3.0-10.2 years), there were 76 PSA recurrences. The BMI was not associated with PSA failure. Six-year PSA failure rates were 30.2% for men with BMI less than 25 kg/m{sup 2}, 19.5% for BMI of 25 or greater to less than 30 kg/m{sup 2}, and 14.4% for BMI of 30 kg/m{sup 2} or greater (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, using alternative definitions of PSA failure, and excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure (adjusted hazard ratio, 1.12; 95% confidence interval, 1.05-1.20; p 0.0006). Conclusions: Unlike after surgery or EBRT, BMI is not associated with PSA failure in men treated with brachytherapy for prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy in obese patients.« less

Prostate-specific antigen nadir within 12 months as an early surrogate marker of biochemical failure and distant metastasis after low-dose-rate brachytherapy or external beam radiotherapy for localized prostate cancer.

PubMed

Nishimura, Shuichi; Ohashi, Toshio; Momma, Tetsuo; Sakayori, Masanori; Eriguchi, Takahisa; Tanaka, Tomoki; Yamashita, Shoji; Kosaka, Takeo; Oya, Mototsugu; Shigematsu, Naoyuki

2018-05-01

Prostate-specific antigen nadir (nPSA) after radiotherapy for localized prostate cancer has been investigated as a predictor. However, nPSA usually requires several years, limiting its clinical utility. We investigated the significance of nPSA within 12 months (nPSA12) after low-dose-rate prostate brachytherapy (LDR-PB) or external beam radiotherapy (EBRT) on treatment outcomes. Between 2006 and 2014, 663 patients with prostate cancer were treated with LDR-PB or EBRT at two institutions. Four hundred and seventy-four men received LDR-PB and 189 men received EBRT, without androgen deprivation therapy. The Kaplan-Meier method was used for biochemical failure (BF)-free survival (BFFS) and distant metastasis (DM)-free survival (DMFS) analyses, and multivariable Cox regression analysis was performed. The median follow-up was 61.3 months. The median nPSA12 in the LDR-PB and EBRT cohorts was 0.7 and 1.0 ng/mL, respectively. The 7-year BFFS and DMFS rates in LDR-PB patients with nPSA12 ≤ 0.7 ng/mL were 99.1% and 99.5%, respectively; when nPSA12 was >0.7 ng/mL, they were 90.2% and 94.8%, respectively. In EBRT patients with nPSA12 ≤ 1.0 ng/mL, BFFS and DMFS rates were 85.4% and 98.5%, respectively; when nPSA12 was >1.0 ng/mL, they were 67.1% and 87.2%, respectively. nPSA12 was an independent predictor of BF and DM in both cohorts (LDR-PB, P = 0.004 and 0.020, respectively; EBRT, P = 0.005 and 0.041, respectively). The nPSA12 after LDR-PB or EBRT is significantly associated with treatment outcomes of prostate cancer. Higher nPSA12 may identify patients at high risk of relapse who might benefit from salvage treatment. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Serum levels of prostate-specific antigen and vitamin D in peritoneal dialysis patients.

PubMed

Passadakis, Ploumis; Ersoy, Fevzi; Tam, Paul; Memmos, Dimitrios; Siamopoulos, Konstantinos; Ozener, Cetin; Akçiçek, Fehmi; Camsari, Taner; Ates, Kenan; Ataman, Rezzan; Vlachojannis, John; Dombros, Nicholas; Utas, Cengiz; Akpolat, Tekin; Bozfakioglu, Semra; Wu, George G; Karayaylali, Ibrahim; Arinsoy, Tekin; Stathakis, Charalampos; Yavuz, Mahmut; Tsakiris, Dimitrios; Dimitriades, Athanasios; Yilmaz, Mehmet E; Gültekin, Meral; Karayalçin, Binnur; Challa, Anna; Polat, Nese; Oreopoulos, Dimitrios G

2004-01-01

Measuring the free:total ratio of prostate-specific antigen (f/t-PSA) can improve the specificity of single-serum PSA values, distinguishing between benign prostatic hyperplasia (BPH) and prostatic carcinoma (PCa) in men over the age of 50. Additionally, clinical trials have shown that dihydroxyvitamin D3 can slow the rate of PSA rise in PCa patients. However, little is known regarding the applicability of those findings in men undergoing chronic peritoneal dialysis (CPD). In the present study, we investigated the prevalence of increased serum PSA levels among CPD patients and correlated those values with serum levels of vitamin D [25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3]. We undertook a cross-sectional study of 71 male CPD patients without a known history of prostate cancer from 24 centers in Canada, Greece, and Turkey. All of the patients were more than 50 years of age. In these patients, we measured serum concentrations of PSA, free PSA (f-PSA), total PSA (t-PSA), prostate alkaline phosphatase (PAP), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone (iPTH). We recorded serum PSA levels < 4 ng/mL in 62 patients (87.3%, group A) and levels > 4 ng/mL in 9 patients (12.7%, group B). The f/t-PSA ratio was < 0.25 in 16 patients (22.5%). Group B patients were older than those in group A (median: 73 years vs. 65 years, p < 0.01) and had a lower body weight (median: 66.5 kg vs. 76.7 kg, p < 0.05). We observed no statistically significant difference between the two groups for serum 1,25-dihydroxyvitamin D3 (median: 9.8 ng/mL vs. 10.1 ng/mL) or 25-hydroxyvitamin D3 (8 ng/mL vs. 8.2 ng/mL) levels. Also, we observed no correlation between vitamin D levels and f/t-PSA, but iPTH levels were significantly higher in group A (200.5 pg/mL vs. 61.2 pg/mL, p < 0.04). Also, serum PAP levels correlated significantly with PSA (r = 0.49, p = 0.01) and with f-PSA (r = 0.56, p = 0.000). Our results showed no clear relationship between vitamin D and serum levels of PSA or-of f/t-PSA in PD patients. However, further studies are needed to better define the uses of these PSA markers in PD patients because, in such patients, other relevant factors might be implicated in their predictive value.

Predicting prostate biopsy outcome: prostate health index (phi) and prostate cancer antigen 3 (PCA3) are useful biomarkers.

PubMed

Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Marino, Ada; Sorrentino, Alessandra; Di Carlo, Angelina; Autorino, Riccardo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Altieri, Vincenzo; Mariano, Angela; Macchia, Vincenzo; Terracciano, Daniela

2012-08-16

Indication for prostate biopsy is presently mainly based on prostate-specific antigen (PSA) serum levels and digital-rectal examination (DRE). In view of the unsatisfactory accuracy of these two diagnostic exams, research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as phi and PCA3. The purpose of this prospective study was to assess the diagnostic accuracy of phi and PCA3 for prostate cancer using biopsy as gold standard. Phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay) and other established biomarkers (tPSA, fPSA and %fPSA) were assessed before a 18-core prostate biopsy in a group of 251 subjects at their first biopsy. Values of %p2PSA and phi were significantly higher in patients with PCa compared with PCa-negative group (p<0.001) and also compared with high grade prostatic intraepithelial neoplasia (HGPIN) (p<0.001). PCA3 score values were significantly higher in PCa compared with PCa-negative subjects (p<0.001) and in HGPIN vs PCa-negative patients (p<0.001). ROC curve analysis showed that %p2PSA, phi and PCA3 are predictive of malignancy. In conclusion, %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men undergoing their first prostate biopsy. PCA3 score is more useful in discriminating between HGPIN and non-cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

The role of serial free/total prostate-specific antigen ratios in a watchful observation protocol for men with localized prostate cancer.

PubMed

Do, V; Choo, R; De Boer, G; Klotz, L; Danjoux, C; Morton, G; Szumacher, E; Fleshner, N; Bunting, P

2002-05-01

To examine the change in the free/total prostate specific antigen ratio (f/tPSA) with time and to assess the potential value of serial measurements of f/tPSA as a determinant of disease progression in untreated, low-to-intermediate grade prostate cancer (T1b-T2b N0M0, Gleason score < or = 7 and PSA < or = 15 ng/mL). In a prospective single-arm cohort study from November 1995, patients were conservatively managed with watchful observation alone unless they met arbitrarily defined criteria (clinical, histological and biochemical) of disease progression. Patients were followed regularly and underwent blood tests including PSA and f/tPSA. The initial and mean f/tPSA and the rate of change of f/tPSA with time were evaluated against the rate constant for the PSA doubling time (PSATd). Correlation analyses were used to evaluate any association between baseline clinical variables and either the rate of change of f/tPSA or initial f/tPSA. As of December 2000, 161 of a total of 206 accrued patients had three or more f/tPSA measurements and formed the basis of the study (median age 70 years; median follow-up 2.7 years). The median initial f/tPSA was 0.16; there was a significant negative correlation between this value and the initial total PSA. The mean f/tPSA and rate of change of f/tPSA with time were significantly negatively correlated with the rate constant for PSATd. Also, the rate of change of f/tPSA correlated negatively with clinical T stage, but not with other baseline variables, including initial PSA, age and Gleason score. The f/tPSA in men with untreated, clinically localized prostate cancer varied widely. The negative correlation between the rate of change of f/tPSA with time and rate constant for PSATd suggests that both might provide valuable information to allow clinicians to develop a strategy for optimizing the timing of therapeutic intervention for those patients choosing watchful observation alone.

Comparison of two different artificial neural networks for prostate biopsy indication in two different patient populations.

PubMed

Stephan, Carsten; Xu, Chuanliang; Finne, Patrik; Cammann, Henning; Meyer, Hellmuth-Alexander; Lein, Michael; Jung, Klaus; Stenman, Ulf-Hakan

2007-09-01

Different artificial neural networks (ANNs) using total prostate-specific antigen (PSA) and percentage of free PSA (%fPSA) have been introduced to enhance the specificity of prostate cancer detection. The applicability of independently trained ANN and logistic regression (LR) models to different populations regarding the composition (screening versus referred) and different PSA assays has not yet been tested. Two ANN and LR models using PSA (range 4 to 10 ng/mL), %fPSA, prostate volume, digital rectal examination findings, and patient age were tested. A multilayer perceptron network (MLP) was trained on 656 screening participants (Prostatus PSA assay) and another ANN (Immulite-based ANN [iANN]) was constructed on 606 multicentric urologically referred men. These and other assay-adapted ANN models, including one new iANN-based ANN, were used. The areas under the curve for the iANN (0.736) and MLP (0.745) were equal but showed no differences to %fPSA (0.725) in the Finnish group. Only the new iANN-based ANN reached a significant larger area under the curve (0.77). At 95% sensitivity, the specificities of MLP (33%) and the new iANN-based ANN (34%) were significantly better than the iANN (23%) and %fPSA (19%). Reverse methodology using the MLP model on the referred patients revealed, in contrast, a significant improvement in the areas under the curve for iANN and MLP (each 0.83) compared with %fPSA (0.70). At 90% and 95% sensitivity, the specificities of all LR and ANN models were significantly greater than those for %fPSA. The ANNs based on different PSA assays and populations were mostly comparable, but the clearly different patient composition also allowed with assay adaptation no unbiased ANN application to the other cohort. Thus, the use of ANNs in other populations than originally built is possible, but has limitations.

Discordant prostate specific antigen test results despite WHO assay standardization.

PubMed

Boegemann, Martin; Arsov, Christian; Hadaschik, Boris; Herkommer, Kathleen; Imkamp, Florian; Nofer, Jerzy-Roch; Gerß, Joachim; Albers, Peter; Semjonow, Axel

2018-05-01

Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA assays may still produce discordant results. In the present study, we compared four PSA assays calibrated to the WHO standards 96/670 and 96/668 for tPSA and fPSA, respectively. Within the scope of the Prostate Cancer Early Detection Study Based on a ''Baseline'' PSA Value in Young Men (PROBASE), we tested tPSA and fPSA in serum samples from 50 patients in the four different PROBASE sites using four WHO-calibrated assays from Roche (Elecsys, Cobas), Beckman-Coulter (Access-II) and Siemens (ADVIA Centaur). The comparison was performed using the Passing-Bablok regression method. Compared to Access, the median tPSA levels for Centaur, Elecsys, and Cobas were +3%, +11%-20%, and +17%-23%, respectively, while for median fPSA levels the differences for Centaur, Elecsys, and Cobas were +49%, +29%-31%, and +22%, respectively. Despite all investigated assays being WHO-calibrated, the Elecsys and Cobas tPSA assays produced considerably higher results than the Access and Centaur assays. Differences in fPSA-recovery between all investigated assays were even more pronounced. When applying the tPSA cutoff of 3.1 μg/L recommended for WHO-calibrated assays, the use of higher calibrated assays may lead to unnecessary prostate biopsies. Conversely, if the historical threshold of 4 μg/L is applied when using WHO-calibrated assays, it could lead to falsely omitted prostate biopsies.

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.

Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

PubMed

Yamada, Yasutaka; Sakamoto, Shinichi; Amiya, Yoshiyasu; Sasaki, Makoto; Shima, Takayuki; Komiya, Akira; Suzuki, Noriyuki; Akakura, Koichiro; Ichikawa, Tomohiko; Nakatsu, Hiroomi

2018-05-04

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml -1 ), intermediate (100-999 ng ml -1 ), and high (≥1000 ng ml -1 ). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

Decision-making Processes among Prostate Cancer Survivors with Rising PSA Levels: Results from a Qualitative Analysis.

PubMed

Shen, Megan Johnson; Nelson, Christian J; Peters, Ellen; Slovin, Susan F; Hall, Simon J; Hall, Matt; Herrera, Phapichaya Chaoprang; Leventhal, Elaine A; Leventhal, Howard; Diefenbach, Michael A

2015-05-01

Prostate cancer survivors with a rising prostate-specific antigen (PSA) level have few treatment options, experience a heightened state of uncertainty about their disease trajectory that might include the possibility of cancer metastasis and death, and often experience elevated levels of distress as they have to deal with a disease they thought they had conquered. Guided by self-regulation theory, the present study examined the cognitive and affective processes involved in shared decision making between physicians and patients who experience a rising PSA after definitive treatment for prostate cancer. In-depth interviews were conducted with 34 prostate cancer survivors who had been diagnosed with a rising PSA (i.e., biochemical failure) within the past 12 months. Survivors were asked about their experiences and affective responses after being diagnosed with a rising PSA and while weighing potential treatment options. In addition, patients were asked about their decision-making process for the initial prostate cancer treatment. Compared with the initial diagnosis, survivors with a rising PSA reported increased negative affect following their diagnosis, concern about the treatability of their disease, increased planning and health behavior change, heightened levels of worry preceding doctor appointments (especially prior to the discussion of PSA testing results), and a strong reliance on physicians' treatment recommendations. Prostate cancer survivors' decision-making processes for the treatment of a rising PSA are markedly different from those of the initial diagnosis of prostate cancer. Because patients experience heightened distress and rely more heavily on their physicians' recommendations with a rising PSA, interactions with the health care provider provide an excellent opportunity to address and assist patients with managing the uncertainty and distress inherent with rising PSA levels. © The Author(s) 2014.

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.

Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

PubMed

Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

2016-07-01

High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 < 30, 30 < 35 and ≥35 kg/m(2), respectively, compared to the reference (18.5 < 25 kg/m(2)). No statistically significant associations were seen between BMI and prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels. © 2016 UICC.

What does postradiotherapy PSA nadir tell us about freedom from PSA failure and progression-free survival in patients with low and intermediate-risk localized prostate cancer?

PubMed

DeWitt, K D; Sandler, H M; Weinberg, V; McLaughlin, P W; Roach, M

2003-09-01

To determine whether the post-external beam radiotherapy (RT) prostate-specific antigen nadir (nPSA) improves our ability to predict freedom from PSA failure, progression-free survival (PFS), and overall survival. Controversy regarding the importance of nPSA after external beam RT as a prognostic indicator for patients with localized prostate cancer has continued. This analysis was based on the data from 748 patients with low and intermediate-risk localized prostate cancer treated with external beam RT alone. Patients were categorized by nPSA quartile groups with cutpoints of less than 0.3, 0.3 to less than 0.6, 0.6 to less than 1.2, and 1.2 ng/mL or greater. Both univariate and multivariate analyses were used to determine the significance of nPSA on PSA failure (American Society for Therapeutic Radiology Oncology consensus definition), PFS (death after PSA failure), and overall survival (death from any cause). Freedom from PSA failure was strongly associated with nadir quartile groups (P <0.0001). PFS was also significantly different statistically among nadir quartile groups (P = 0.02). No statistically significant difference was found in overall survival associated with nPSA at this point. nPSA is a strong independent predictor of freedom from PSA failure and PFS in patients with low and intermediate-risk localized prostate cancer treated with RT alone. Longer follow-up and larger patient numbers are required to confirm these observations.

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.

Prostate specific antigen based biennial screening is sufficient to detect almost all prostate cancers while still curable.

PubMed

Hugosson, Jonas; Aus, Gunnar; Lilja, Hans; Lodding, Pär; Pihl, Carl Gustaf; Pileblad, Erik

2003-05-01

We evaluated whether biennial screening with prostate specific antigen (PSA) only is sufficient to detect prostate cancer while still curable. In Göteborg, Sweden 9,972 men 50 to 65 years old were randomized to PSA screening. During 1995 and 1996 these men were invited for a first PSA screening and invited during 1997 and 1998 for a second screening. The screening procedure included PSA measurement in all men and in those with a PSA of 3 ng./ml. or greater also it included digital rectal examination, transrectal ultrasound and sextant biopsies. In the first screening 5,854 men participated and 145 cancers were detected. In the second screening 5,267 men participated and 111 cancers were detected. Only 9 interval cancers were diagnosed. In the second screening 102 cancers (92%) were associated with PSA less than 10 ng./ml. Of 465 men with increased PSA and who underwent biopsy with a benign outcome in the first screening 50 had cancer at the second screening. Of 241 men in whom PSA increased between screenings 1 and 2 cancer was detected in 46. None of the 2,950 men with an initial PSA of less than 1 ng./ml. had a PSA of greater than 3 ng./ml. or interval cancer. In men with a PSA of less than 2 ng./ml. it seems safe to offer repeat screening after 2 years with PSA only. Men with a PSA of 2 to 3 ng./ml. or a value of greater than 3 ng./ml. with negative biopsy may be better served by a shorter screening interval. Thus, different screening intervals are implied depending on baseline PSA.

A standard definition of disease freedom is needed for prostate cancer: undetectable prostate specific antigen compared with the American Society of Therapeutic Radiology and Oncology consensus definition.

PubMed

Critz, Frank A

2002-03-01

Freedom from prostate cancer is defined by undetectable prostate specific antigen (PSA) after surgery and the American Society of Therapeutic Radiology and Oncology (ASTRO) criteria are recommended for irradiation. Whether these definitions of disease freedom are comparable was evaluated in this study. From August 1992 to August 1996 simultaneous irradiation with prostate 125iodine implantation followed by external beam irradiation was performed in 591 consecutive men with stage T1T2NX prostate cancer. All patients had a transperineal implant and none received neoadjuvant hormones. Disease freedom was defined by a PSA cutoff of 0.2 ng./ml. and the ASTRO consensus definition. Median followup was 6 years (range 5 to 8). Of the 591 men in this study 65 had recurrence by ASTRO criteria and 93 had recurrence by a PSA cutoff of 0.2 ng./ml., which was a significant difference (p = 0.001). On multivariate analysis of the factors related to disease-free status the definition of disease freedom, pretreatment PSA and Gleason score were highly significant. Of the 528 men with a minimum 5-year PSA followup the 8-year disease-free survival rate by ASTRO criteria was 99% in those who achieved a PSA nadir of 0.2 ng./ml. and 16% in those with a nadir of 0.3 to 1 ng./ml. Of the 469 disease-free patients by ASTRO criteria with a minimum 5-year followup 455 (97%) achieved a PSA nadir of 0.2 ng./ml. or less. The definition of freedom from prostate cancer significantly affects treatment results. A standard definition is needed and a PSA cutoff of 0.2 ng./ml. is suggested as the standard for all curative treatments for localized prostate cancer.

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.

Optimal screening interval for men with low baseline prostate-specific antigen levels (≤1.0 ng/mL) in a prostate cancer screening program.

PubMed

Urata, Satoko; Kitagawa, Yasuhide; Matsuyama, Satoko; Naito, Renato; Yasuda, Kenji; Mizokami, Atsushi; Namiki, Mikio

2017-04-01

To optimize the rescreening schedule for men with low baseline prostate-specific antigen (PSA) levels, we evaluated men with baseline PSA levels of ≤1.0 ng/mL in PSA-based population screening. We enrolled 8086 men aged 55-69 years with baseline PSA levels of ≤1.0 ng/mL, who were screened annually. The relationships of baseline PSA and age with the cumulative risks and clinicopathological features of screening-detected cancer were investigated. Among the 8086 participants, 28 (0.35 %) and 18 (0.22 %) were diagnosed with prostate cancer and cancer with a Gleason score (GS) of ≥7 during the observation period, respectively. The cumulative probabilities of prostate cancer at 12 years were 0.42, 1.0, 3.4, and 4.3 % in men with baseline PSA levels of 0.0-0.4, 0.5-0.6, 0.7-0.8, and 0.9-1.0 ng/mL, respectively. Those with GS of ≥7 had cumulative probabilities of 0.42, 0.73, 2.8, and 1.9 %, respectively. The cumulative probabilities of prostate cancer were significantly lower when baseline PSA levels were 0.0-0.6 ng/mL compared with 0.7-1.0 ng/mL. Prostate cancer with a GS of ≥7 was not detected during the first 10 years of screening when baseline PSA levels were 0.0-0.6 ng/mL and was not detected during the first 2 years when baseline PSA levels were 0.7-1.0 ng/mL. Our study demonstrated that men with baseline PSA levels of 0.0-0.6 ng/mL might benefit from longer screening intervals than those recommended in the guidelines of the Japanese Urological Association. Further investigation is needed to confirm the optimal screening interval for men with low baseline PSA levels.

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.

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.

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

Male Oncology Research and Education program for men at high risk for prostate cancer.

PubMed

Lorentz, J; Liu, S K; Vesprini, D

2018-04-01

Three groups of men are at high risk of developing prostate cancer: men with a strong family history of prostate cancer, men of West African or Caribbean ancestry, and men with a germline pathogenic variant in a prostate cancer-associated gene. Despite the fact that those men constitute a significant portion of the male population in North America, few recommendations for prostate cancer screening specific to them have been developed. For men at general population risk for prostate cancer, screening based on prostate-specific antigen (psa) has remained controversial despite the abundance of literature on the topic. As a result, recommendations made by major screening authorities are inconsistent (ranging from no psa screening to baseline psa screening at age 45), allowing physicians to pick and choose how to screen their patients. The Male Oncology Research and Education (more) program is an observational research program that serves as an academic platform for multiple research foci. For its participants, serum and dna are biobanked, medical information is collected, and contact for relevant research-related opportunities is maintained. This research program is paired with a specialized clinic called the more clinic, where men at high risk are regularly screened for prostate cancer in a standard approach that includes physical examination and serum psa measurement. In this article, we describe the goals, participant accrual to date, and projects specific to this unique program.

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.

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.

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial.

PubMed

Martin, Richard M; Donovan, Jenny L; Turner, Emma L; Metcalfe, Chris; Young, Grace J; Walsh, Eleanor I; Lane, J Athene; Noble, Sian; Oliver, Steven E; Evans, Simon; Sterne, Jonathan A C; Holding, Peter; Ben-Shlomo, Yoav; Brindle, Peter; Williams, Naomi J; Hill, Elizabeth M; Ng, Siaw Yein; Toole, Jessica; Tazewell, Marta K; Hughes, Laura J; Davies, Charlotte F; Thorn, Joanna C; Down, Elizabeth; Davey Smith, George; Neal, David E; Hamdy, Freddie C

2018-03-06

Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality. The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66). Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening. ISRCTN Identifier: ISRCTN92187251.

Prostate cancer diagnosis in a resource-poor setting: the changing role of digital rectal examination.

PubMed

Ahmed, Muhammed

2011-07-01

We undertook this study in order to determine the current role of digital rectal examination (DRE) in the diagnosis of prostate cancer in a resource-poor setting. The diagnosis of prostate cancer has been revolutionized by the introduction of prostate-specific antigen (PSA), transrectal ultrasound (TRUS) for biopsy guidance and more efficient biopsy equipment, but they are not readily available in most developing countries. This is a prospective study of 131 patients with suspected prostate cancer based on clinical presentation, DRE and elevated PSA. The presence or absence of cancer was confirmed by biopsy and histologic examination. Patients with screen- or incidentally-detected prostate cancer were excluded. The most common symptom was the development of lower urinary tract symptoms (LUTS). All patients had abnormal DRE and indurated prostate was the most frequent finding (50%). The mean PSA was 33.9 ng/mL: of the 131 patients, 80 (61.1%) had a malignant histology following biopsy, 47 (35.9%) were benign and four (3.0%) were prostate intraepithelial neoplasia (PIN). The low specificity of DRE in the diagnosis of prostate cancer requires that it should be combined with other diagnostic modalities such as PSA and TRUS-guided prostate biopsy. Thus government and health-care providers in resource-poor countries must strive to make these facilities available in order to improve prostate cancer diagnosis.

The politics of prostate cancer screening.

PubMed

Kaffenberger, Samuel D; Penson, David F

2014-05-01

The controversial recent recommendation by the United States Preventive Services Task Force (USPSTF) against prostate-specific antigen (PSA) screening for early-stage prostate cancer has caused much debate. Whereas USPSTF recommendations against routine screening mammography in younger women resulted in fierce public outcry and eventual alteration in the language of the recommendation, the same public and political response has not been seen with PSA screening for prostate cancer. It is of paramount importance to ensure improved efficiency and transparency of the USPSTF recommendation process, and resolution of concerns with the current USPSTF recommendation against PSA screening for all ages. Published by Elsevier Inc.

Comparative Study of Blood-Based Biomarkers, α2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection.

PubMed

Ferrer-Batallé, Montserrat; Llop, Esther; Ramírez, Manel; Aleixandre, Rosa Núria; Saez, Marc; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2017-04-17

Prostate Specific Antigen (PSA) is the most commonly used serum marker for prostate cancer (PCa), although it is not specific and sensitive enough to allow the differential diagnosis of the more aggressive tumors. For that, new diagnostic methods are being developed, such as PCA-3, PSA isoforms that have resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms. In the present study, we have compared the PHI with our recently developed PSA glycoform assay, based on the determination of the α2,3-sialic acid percentage of serum PSA (% α2,3-SA), in a cohort of 79 patients, which include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH) patients. The % α2,3-SA could distinguish high-risk PCa patients from the rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs. 0.840), although the PHI correlated better with the Gleason score than the % α2,3-SA. The combination of both markers increased the AUC up to 0.985 resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk PCa from the other low and intermediate-risk PCa and BPH patients. These results suggest that both serum markers complement each other and offer an improved diagnostic tool to identify high-risk PCa, which is an important requirement for guiding treatment decisions.

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.

Prostate-specific antigen 1.5-4.0 ng/mL: a diagnostic challenge and danger zone.

PubMed

Crawford, E David; Moul, Judd W; Rove, Kyle O; Pettaway, Curtis A; Lamerato, Lois E; Hughes, Alexa

2011-12-01

What's known on the subject? and What does the study add? Large population screening trials like the ERSPC, PCPT and PLCO have noted that men with seemingly low PSA (even as low as 0.5 ng/dL) still can have prostate cancer. Despite these findings, PSA is still predominantly used as a current indicator for possible presence of prostate cancer rather than also serving as a prognostic marker. This study examines a larger number of men in a diverse US population to determine the prognostic value of a man's baseline or first PSA. • To assess the value of a PSA threshold of 1.5 ng/mL as a predictor of increased prostate cancer risk over a four-year period based on a man's first PSA test, including racial differences. • To review the risk of progression of benign prostatic hyperplasia (BPH) based on a similar PSA threshold. • A retrospective review involving 21,502 men from a large Midwestern health system was performed. • Men at least 40 years old with baseline PSA values between 0 and 4.0 ng/mL and at least four years of follow-up after initial PSA test were included. • Optimal PSA threshold and predictive value of PSA for development of prostate cancer were calculated. • Prostate cancer rates were 15-fold higher in patients with PSA ≥1.5 ng/mL vs patients with PSA <1.5 ng/mL (7.85% vs 0.51%). • African American patients with baseline PSA <1.5 ng/mL faced prostate cancer rates similar to the whole study population (0.54% vs 0.51%, respectively), while African American patients with PSA 1.5-4.0 ng/mL faced a 19-fold increase in prostate cancer. • Both Caucasian and African American men with baseline PSA values between 1.5 and 4.0 ng/mL are at increased risk for future prostate cancer compared with those who have an initial PSA value below the 1.5 ng/mL threshold. • Based on a growing body of literature and this analysis, it is recommended that a first PSA test threshold of 1.5 ng/mL and above, or somewhere between 1.5 and 4.0 ng/mL, represent the Early-Warning PSA Zone (EWP Zone). • This should serve to inform patients and clinicians alike to future clinical activities with respect to prostate cancer and BPH. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

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.

Three-month posttreatment prostate-specific antigen level as a biomarker of treatment response in patients with intermediate-risk or high-risk prostate cancer treated with androgen deprivation therapy and radiotherapy.

PubMed

Bryant, Alex K; D'Amico, Anthony V; Nguyen, Paul L; Einck, John P; Kane, Christopher J; McKay, Rana R; Simpson, Daniel R; Mundt, Arno J; Murphy, James D; Rose, Brent S

2018-05-04

Prostate-specific antigen (PSA) measurement after definitive radiotherapy (RT) and androgen deprivation therapy for localized prostate cancer has been proposed as an early prognostic biomarker. In the current study, the authors investigated the association between 3-month post-RT PSA level and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS), and overall survival (OS). A total of 5783 patients with intermediate-risk or high-risk localized prostate cancer who were diagnosed between 2000 and 2015 and treated with RT and androgen deprivation therapy were identified from Veterans Affairs data. Patients were divided into groups based on 3-month post-RT PSA values: <0.10 ng/mL, 0.10 to 0.49 ng/mL, and ≥0.50 ng/mL. The effect of the 3-month PSA group on bPFS, PCSS, and OS was evaluated in multivariable Cox models adjusting for potential confounders. There were 2651 patients with intermediate-risk and 3132 with high-risk disease; approximately 11% had a 3-month PSA level of ≥0.50 ng/mL. A higher 3-month PSA level was found to be strongly associated with each outcome; compared with patients in the group with a 3-month PSA value <0.10 ng/mL, the authors noted greater hazards for the patients with a 3-month PSA value ≥0.50 ng/mL (hazard ratio for bPFS: 5.23; PCSS: 3.97; and OS: 1.50 [P<.001 for all]) and the patients with a 3-month PSA value of 0.10 to 0.49 ng/mL (hazard ratio for bPFS: 2.41 [P<.001]; PCSS: 2.29 [P<.001]; and OS: 1.21 [P = .003]). When analyzed separately, the 3-month PSA level was found to be predictive of OS in the high-risk group (P<.001) but not the intermediate-risk group (P = .21). The 3-month post-RT PSA level appears to be a strong prognostic biomarker for bPFS, PCSS, and OS in patients with intermediate-risk and high-risk prostate cancer, particularly those with high-risk disease. The 3-month PSA measurement may augment clinical decision making and holds promise as a potential surrogate endpoint in clinical trials. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription.

PubMed

Liu, Youhong; Liu, Yijun; Yuan, Bowen; Yin, Linglong; Peng, Yuchong; Yu, Xiaohui; Zhou, Weibing; Gong, Zhicheng; Liu, Jianye; He, Leye; Li, Xiong

2017-03-07

Androgen/AR is the primary contributor to prostate cancer (PCa) progression by regulating Prostate Specific Antigen (PSA) gene transcription. The disease inevitably evolves to androgen-independent (AI) status. Other mechanisms by which PSA is regulated and develops to AI have not yet been fully determined. FOXM1 is a cell proliferation-specific transcription factor highly expressed in PCa cells compared to non-malignant prostate epithelial cells, suggesting that the aberrant overexpression of FOXM1 contributes to PCa development. In addition to regulating AR gene transcription and cell cycle-regulatory genes, FOXM1 selectively regulates the gene transcription of KLK2 and PSA, typical androgen responsive genes. Screening the potential FOXM1-binding sites by ChIP-PCR, we found that FOXM1 directly binds to the FHK binding motifs in the PSA promoter/enhancer regions. AI C4-2 cells have more FOXM1 binding sites than androgen dependent LNCaP cells. The depletion of FOXM1 by small molecular inhibitors significantly improves the suppression of PSA gene transcription by the anti-AR agent Cadosax. This is the first report showing that FOXM1 promotes PCa progression by regulating PSA gene transcription, particularly in AI PCa cells. The combination of anti-AR agents and FOXM1 inhibitors has the potential to greatly improve therapy for late-stage PCa patients by suppressing PSA levels.

Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement.

PubMed

Grossman, David C; Curry, Susan J; Owens, Douglas K; Bibbins-Domingo, Kirsten; Caughey, Aaron B; Davidson, Karina W; Doubeni, Chyke A; Ebell, Mark; Epling, John W; Kemper, Alex R; Krist, Alex H; Kubik, Martha; Landefeld, C Seth; Mangione, Carol M; Silverstein, Michael; Simon, Melissa A; Siu, Albert L; Tseng, Chien-Wen

2018-05-08

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

Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients.

PubMed

Logozzi, Mariantonia; Angelini, Daniela F; Iessi, Elisabetta; Mizzoni, Davide; Di Raimo, Rossella; Federici, Cristina; Lugini, Luana; Borsellino, Giovanna; Gentilucci, Alessandro; Pierella, Federico; Marzio, Vittorio; Sciarra, Alessandro; Battistini, Luca; Fais, Stefano

2017-09-10

Prostate specific antigen (PSA) test is the most common, clinically validated test for the diagnosis of prostate cancer (PCa). While neoplastic lesions of the prostate may cause aberrant levels of PSA in the blood, the quantitation of free or complexed PSA poorly discriminates cancer patients from those developing benign lesions, often leading to invasive and unnecessary surgical procedures. Microenvironmental acidity increases exosome release by cancer cells. In this study we evaluated whether acidity, a critical phenotype of malignancy, could influence exosome release and increase the PSA expression in nanovesicles released by PCa cells. To this aim, we exploited Nanoparticle Tracking Analysis (NTA), an immunocapture-based ELISA, and nanoscale flow-cytometry. The results show that microenvironmental acidity induces an increased release of nanovesicles expressing both PSA and the exosome marker CD81. In order to verify whether the changes induced by the local selective pressure of extracellular acidity may correspond to a clinical pathway we used the same approach to evaluate the levels of PSA-expressing exosomes in the plasma of PCa patients and controls, including subjects with benign prostatic hypertrophy (BPH). The results show that only PCa patients have high levels of nanovesicles expressing both CD81 and PSA. This study shows that tumor acidity exerts a selective pressure leading to the release of extracellular vesicles that express both PSA and exosome markers. A comparable scenario was shown in the plasma of prostate cancer patients as compared to both BPH and healthy controls. These results suggest that microenvironmental acidity may represent a key factor which determines qualitatively and quantitatively the release of extracellular vesicles by malignant tumors, including prostate cancer. This condition leads to the spill-over of nanovesicles into the peripheral blood of prostate cancer patients, where the levels of tumor biomarkers expressed by exosomes, such as PSA-exosomes, may represent a novel, non-invasive clinical tool for the screening and early diagnosis of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Enzymatic Activity of Free-Prostate-Specific Antigen (f-PSA) Is Not Required for Some of its Physiological Activities

PubMed Central

Chadha, Kailash C.; Nair, Bindukumar B.; Chakravarthi, Srikant; Zhou, Rita; Godoy, Alejandro; Mohler, James L.; Aalinkeel, Ravikumar; Schwartz, Stanley A.; Smith, Gary J.

2015-01-01

BACKGROUND Prostate specific antigen (PSA) is a well known biomarker for early diagnosis and management of prostate cancer. Furthermore, PSA has been documented to have anti-angiogenic and anti-tumorigenic activities in both in vitro and in vivo studies. However, little is known about the molecular mechanism(s) involved in regulation of these processes, in particular the role of the serine-protease enzymatic activity of PSA. METHODS Enzymatic activity of PSA isolated directly from seminal plasma was inhibited specifically (>95%) by incubation with zinc2+. Human umbilical vein endothelial cells (HUVEC) were utilized to compare/contrast the physiological effects of enzymatically active versus inactive PSA. RESULTS Equimolar concentrations of enzymatically active PSA and PSA enzymatically inactivated by incubation with Zn2+ had similar physiological effects on HUVEC, including inhibiting the gene expression of pro-angiogenic growth factors, like VEGF and bFGF, and up-regulation of expression of the anti-angiogenic growth factor IFN-γ; suppression of mRNA expression for markers of blood vessel development, like FAK, FLT, KDR, TWIST-1; P-38; inhibition of endothelial tube formation in the in vitro Matrigel Tube Formation Assay; and inhibition of endothelial cell invasion and migration properties. DISCUSSION Our data provides compelling evidence that the transcriptional regulatory and the anti-angiogenic activities of human PSA are independent of the innate enzymatic activity PMID:21446007

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.

3D MR-Spectroscopic Imaging Assessment of Metabolic Activity in the Prostate During the PSA 'Bounce' Following {sup 125}Iodine Brachytherapy

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

Kirilova, Anna; Damyanovich, Andrei; Crook, Juanita, E-mail: jcrook@bccancer.bc.c

2011-02-01

Purpose: A temporary increase in prostate-specific antigen (PSA) values is observed in 30%-40% of men following {sup 125} I brachytherapy (BT) for prostate cancer. We present the results of a study to characterize prostate metabolic activity during the PSA 'bounce' and to correlate metabolic changes with PSA levels using three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI). Methods and Materials: 3D-MRSI was performed in 24 patients during the PSA bounce. Eight of these had also had a baseline 3D-MRSI scan before BT for the purpose of tumor mapping. The 3D-MRSI was repeated at 6- and 12-month intervals, and PSA levels were monitoredmore » every 3 months. Twenty-one of the patients had favorable-risk prostate cancer, and 3 had intermediate risk. Results: The choline+creatine signal intensity, although markedly reduced, was observable following BT. Diffuse activity not corresponding to original biopsy-positive sites was observed in 22 cases, and 2 cases were documented to have local recurrence. No statistically significant correlation between metabolic activity and PSA levels at each interval was found. Conclusion: Post-BT prostate 3D-MRSI shows evidence of diffuse metabolic activity unrelated to residual malignancy. This supports the benign nature of the PSA bounce and suggests an inflammatory etiology. In the situation of a rising PSA, observation of focal activity on MRI/3D-MRSI could be a useful adjunct to suggest local recurrence at an earlier interval after brachytherapy when prostate biopsies would still be unhelpful. Longer follow-up is necessary to confirm the complex relationship between metabolic activity and PSA levels.« less

Salvage cryotherapy for recurrent prostate cancer after radiation therapy: the Columbia experience.

PubMed

de la Taille, A; Hayek, O; Benson, M C; Bagiella, E; Olsson, C A; Fatal, M; Katz, A E

2000-01-01

Cryotherapy of the prostate represents a potential treatment for localized recurrent prostate cancer after radiation therapy. We report our experience and evaluate the predictive factors for prostate-specific antigen (PSA) recurrence. Between October 1994 and April 1999, 43 patients underwent salvage cryoablation. All patients had biopsy-proven recurrent prostate cancer without seminal vesicle invasion, negative bone scans, and negative lymph node dissection. Patients had received 3 months of combined hormonal therapy before cryosurgery. Biochemical recurrence-free survival (bRFS) was defined as a PSA value less than 0.1 ng/mL. Complications included incontinence (9%), obstruction (5%), urethral stricture (5%), rectal pain (26%), urinary infection (9%), scrotal edema (12%), and hematuria (5%). The mean follow-up was 21.9 months (range 1.2 to 54). Twenty-six patients (60%) reached a serum PSA nadir less than 0.1 ng/mL, 16 (37%) had a PSA less than 4 ng/mL, and 1 (3%) had a PSA less than 10 ng/mL. The bRFS rate was 79% at 6 months and 66% at 12 months. The bRFS rate was higher for patients who had an undetectable postcryotherapy PSA than for patients who did not reach a PSA less than 0. 1 ng/mL (73% versus 30%, P = 0.0076). Using multivariate analysis, a PSA nadir greater than 0.1 ng/mL was an independent predictor of PSA recurrence. Current salvage cryotherapy of the prostate can result in undetectable serum PSA levels with low morbidity. Our data support the current safety and efficacy profile. We believe that cryotherapy is a viable option in the treatment of patients who have biopsy-proven local failure after radiation therapy for prostate cancer. Further refinements in technique and equipment may enhance cryosurgical results.

Current Approaches, Challenges and Future Directions for Monitoring Treatment Response in Prostate Cancer

PubMed Central

Wallace, T.J.; Torre, T.; Grob, M.; Yu, J.; Avital, I.; Brücher, BLDM; Stojadinovic, A.; Man, Y.G.

2014-01-01

Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright. PMID:24396494

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/

A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden

PubMed Central

Vickers, Andrew J; Cronin, Angel M; Aus, Gunnar; Pihl, Carl-Gustav; Becker, Charlotte; Pettersson, Kim; Scardino, Peter T; Hugosson, Jonas; Lilja, Hans

2008-01-01

Background Prostate-specific antigen (PSA) is widely used to detect prostate cancer. The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies. We set out to determine whether a multivariable model including four kallikrein forms (total, free, and intact PSA, and human kallikrein 2 (hK2)) could predict prostate biopsy outcome in previously unscreened men with elevated total PSA. Methods The study cohort comprised 740 men in Göteborg, Sweden, undergoing biopsy during the first round of the European Randomized study of Screening for Prostate Cancer. We calculated the area-under-the-curve (AUC) for predicting prostate cancer at biopsy. AUCs for a model including age and PSA (the 'laboratory' model) and age, PSA and digital rectal exam (the 'clinical' model) were compared with those for models that also included additional kallikreins. Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and clinical models respectively. Using a 20% risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 (57%) and missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers. Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA. A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening, but defer biopsy until there was stronger evidence of malignancy. PMID:18611265

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.

PSA-alpha-2-macroglobulin complex is enzymatically active in the serum of patients with advanced prostate cancer and can degrade circulating peptide hormones.

PubMed

Kostova, Maya B; Brennen, William Nathaniel; Lopez, David; Anthony, Lizamma; Wang, Hao; Platz, Elizabeth; Denmeade, Samuel R

2018-08-01

Prostate cancer cells produce high levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor microenvironment but is presumed to be enzymatically inactive in the blood due to complex formation with serum protease inhibitors α-1-antichymotrypsin and α-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard ELISA assays and are also rapidly cleared from the circulation. Thus the exact magnitude of PSA production by prostate cancer cells is not easily measured. The PSA complexed to A2M is unable to cleave proteins but maintains the ability to cleave small peptide substrates. Thus, in advanced prostate cancer, sufficient PSA-A2M may be in circulation to effect total A2M levels, levels of cytokines bound to A2M and hydrolyze small circulating peptide hormones. Total A2M levels in men with advanced prostate cancer and PSA levels above 1000 ng/mL were measured by ELISA and compared to controls. Additional ELISA assays were used to measure levels of IL-6 and TGF-beta which can bind to A2M. The ability of PSA-A2M complexes to hydrolyze protein and peptide substrates was analyzed ± PSA inhibitor. Enzymatic activity of PSA-A2M in serum of men with high PSA levels was also assayed. Serum A2M levels are inversely correlated with PSA levels in men with advanced prostate cancer. Il-6 Levels are significantly elevated in men with PSA >1000 ng/mL compared to controls with PSA <0.1 ng/mL. PSA-A2M complex in serum of men with PSA levels >1000 ng/mL can hydrolyze small fluorescently labeled peptide substrates but not large proteins that are PSA substrates. PSA can hydrolyze small peptide hormones like PTHrP and osteocalcin. PSA complexed to A2M retains the ability to degrade PTHrP. In advanced prostate cancer with PSA levels >1000 ng/mL, sufficient PSA-A2M is present in circulation to produce enzymatic activity against circulating small peptide hormones. Sufficient PSA is produced in advanced prostate cancer to alter total A2M levels, which can potentially alter levels of a variety of growth factors such as IL-6, TGF-beta, basic FGF, and PDGF. Alterations in levels of these cytokines and proteolytic degradation of small peptide hormones may have profound effect on host-cancer interaction. © 2018 Wiley Periodicals, 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

Predictive value of [-2]propsa (p2psa) and its derivatives for the prostate cancer detection in the 2.0 to 10.0ng/mL PSA range.

PubMed

Vukovic, I; Djordjevic, D; Bojanic, N; Babic, U; Soldatovic, I

2017-01-01

To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated. PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7). New markers, derivates of p2PSA (especially %p2PSA and PHI), represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL. Copyright® by the International Brazilian Journal of Urology.

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.

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.

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

Correlation between the complex PSA/total PSA ratio and the free PSA/total PSA ratio, sensitivity and specificity of both markers for the diagnosis of prostate cancer.

PubMed

Pérez-Lanzac-Lorca, A; Barco-Sánchez, A; Romero, E; Martinez-Peinado, A; López-Elorza, F; Sanchez-Sanchez, E; Alvarez-Ossorio-Fernandez, J L; Castiñeiras-Fernández, J

2013-09-01

To compare the behaviour of the PSAcomplex/PSAtotal percentage (PSAc%) against the PSA free/PSA total (PSAl%) and analyse both markers for their usefulness in diagnosing prostate cancer. We measured total PSA (PSAt), free PSA (PSAl), complex PSA (PSAc), PSAl% and PSAc% levels in 158 patients. Of these, 98 (62%) were biopsied for presenting PSAt≥3 ng/dl and PSAl%<20, PSAt>10, suspicious rectal examination or suspicious ultrasound node. We performed linear regression and Passing-Bablok regression analyses. The ROC curves were calculated to study the sensitivity and specificity of PSAl% and PSAc% and were compared to each other. The prostate cancer diagnoses were analysed by PSAl% and PSAc% by applying the χ(2) test. The correlation coefficient (r) was good (0.7447, P<.0001), and the index of determination (r(2)) was 0,5. The result of the Passing-Bablok analysis was a slope of 1.658 (1.452 to 1.897) and an intersection of 2.044 (-0,936 to 5.393). The optimal cutoff for PSAl% (≤14.7854) showed a sensitivity of 89.29% [95% CI, 0,642-0,823] and a specificity of 54.29% (95% CI, 0,642-0,823). The optimal cutoff for PSAc% (>89.7796) had a sensitivity of 71.43% (95% CI, 0,616-0,802) and a specificity of 71.43% (95% CI, 0,616-0,802). There were no significant differences when comparing the areas under the curve of both markers (P=.59). The PPV of PSAl% was less than that of PSAc% (45.7% vs. 71%). There was a good correlation between PSAl% and PSAc%. PSAc% has demonstrated greater specificity and efficacy than PSAl% in the diagnosis of prostate cancer. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

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

Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

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

Zelefsky, Michael J., E-mail: zelefskm@mskcc.org; Gomez, Daniel R.; Polkinghorn, William R.

2013-07-01

Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5more » years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.« less

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.

Developing Novel Therapeutics Targeting Undifferentiated and Castration-Resistant Prostate Cancer Stem Cells

DTIC Science & Technology

2015-10-01

LNCaP-CRPC cells expressed AR protein and its 4 targets, i.e., PSA, FKBP5, PAP (prostate alkaline phosphatase), and PSMA (prostate-specific membrane...LNCaP GAPDH FKBP5 PSA 75 - 50 - PAP AR *** 100 - 75 - AR-V7100 -75 - PSMA 100 - 250 - 150 - 37 - 25 - 50 - 36 - A B C CDSS CDSS+Bica Re lat ive m

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.

Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.

PubMed

Nonomura, Norio; Takayama, Hitoshi; Nakayama, Masashi; Nakai, Yasutomo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Aozasa, Katsuyuki; Tsujimura, Akira

2011-06-01

• To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

Investigative clinical study on prostate cancer part VI: Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

PubMed

Porcaro, Antonio B; Migliorini, Filippo; Petrozziello, Aldo; Sava, Teodoro; Romano, Mario; Caruso, Beatrice; Cocco, Claudio; Ghimenton, Claudio; Zecchinini Antoniolli, Stefano; Lacola, Vincenzo; Rubilotta, Emanuele; Monaco, Carmelo; Comunale, Luigi

2012-01-01

To evaluate the physiopathology of follicle-stimulating hormone (FSH) along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. The study included 98 patients who were diagnosed with prostate cancer. Age, percentages of positive cores (P+) at transrectal ultrasound scan biopsy, biopsy Gleason score (bGS), luteinizing hormone (LH), FSH, total testosterone, free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had not previously received hormonal manipulations. FSH correlation and multiple linear analyses were computed in the population. The FSH/PSA ratio was computed and then ranked for clustering the population as groups A (0.13≤FSH/PSA≤0.57), B (0.57

Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

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

Lo, Andrea C.; Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia; Morris, W. James, E-mail: JMorris@bccancer.bc.ca

2014-01-01

Purpose: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. Methods and Materials: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72more » months of follow-up and documented PSA values at both 24 and 36 months after implantation. Results: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA ≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. Conclusions: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA ≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA >1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.« less

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.

CCL11 (eotaxin-1): a new diagnostic serum marker for prostate cancer.

PubMed

Agarwal, Manisha; He, Chang; Siddiqui, Javed; Wei, John T; Macoska, Jill A

2013-05-01

The recent recommendation of the U.S. Preventive Services Task Force against PSA-based screening for prostate cancer was based, in part, on the lack of demonstrated diagnostic utility of serum PSA values in the low, but detectable range to successfully predict prostate cancer. Though controversial, this recommendation reinforced the critical need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa. The studies described here were intended to determine whether inflammatory cytokines might augment serum PSA as a diagnostic marker for prostate cancer. Multiplex ELISA assays were performed to quantify CCL1, CCL2, CCL5, CCL8, CCL11, CCL17, CXCL1, CXCL5, CXCL8, CXCL10, CXCL12, and IL-6 protein levels in the serum of 272 men demonstrating serum PSA values of <10 ng/ml and undergoing a 12 core diagnostic needle biopsy for detection of prostate cancer. Logistic regression was used to identify the associations between specific chemokines and prostate cancer status adjusted for prostate volume, and baseline PSA. Serum levels for CCL1 (I-309) were significantly elevated among all men with enlarged prostates (P < 0.04). Serum levels for CCL11 (Eotaxin-1) were significantly elevated among men with prostate cancer regardless of prostate size (P < 0.01). The remaining 10 cytokines examined in this study did not exhibit significant correlations with either prostate volume or cancer status. Serum CCL11 values may provide a useful diagnostic tool to help distinguish between prostatic enlargement and prostate cancer among men demonstrating low, but detectable, serum PSA values. Copyright © 2012 Wiley Periodicals, Inc.

CCL11 (Eotaxin-1): A New Diagnostic Serum Marker for Prostate Cancer

PubMed Central

Agarwal, Manisha; He, Chang; Siddiqui, Javed; Wei, John; Macoska, Jill A.

2012-01-01

Background The recent recommendation of the U.S. Preventive Services Task Force against PSA-based screening for prostate cancer was based, in part, on the lack of demonstrated diagnostic utility of serum PSA values in the low, but detectable range to successfully predict prostate cancer. Though controversial, this recommendation reinforced the critical need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa. The studies described here were intended to determine whether inflammatory cytokines might augment serum PSA as a diagnostic marker for prostate cancer. Methods Multiplex ELISA assays were performed to quantify CCL1, CCL2, CCL5, CCL8, CCL11, CCL17, CXCL1, CXCL5, CXCL8, CXCL10, CXCL12, and IL-6 protein levels in the serum of 272 men demonstrating serum PSA values of < 10 ng/ml and undergoing a 12 core diagnostic needle biopsy for detection of prostate cancer. Logistic regression was used to identify the associations between specific chemokines and prostate cancer status adjusted for prostate volume, and baseline PSA. Results Serum levels for CCL1 (I-309) were significantly elevated among all men with enlarged prostates (p<.04). Serum levels for CCL11 (Eotaxin-1) were significantly elevated among men with prostate cancer regardless of prostate size (p<.01). The remaining 10 cytokines examined in this study did not exhibit significant correlations with either prostate volume or cancer status. Conclusions Serum CCL11 values may provide a useful diagnostic tool to help distinguish between prostatic enlargement and prostate cancer among men demonstrating low, but detectable, serum PSA values. PMID:23059958

Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer.

PubMed

Antwi, Samuel O; Steck, Susan E; Zhang, Hongmei; Stumm, Lareissa; Zhang, Jiajia; Hurley, Thomas G; Hebert, James R

2015-10-01

Although men presenting with clinically localized prostate cancer (PrCA) often are treated with radical prostatectomy or radiation therapy with curative intent, about 25-40% develop biochemically recurrent PrCA within 5 years of treatment, which has no known cure. Studies suggest that carotenoid and tocopherol intake may be associated with PrCA risk and progression. We examined plasma carotenoid and tocopherol levels in relation to prostate-specific antigen (PSA) levels among men with PSA-defined biochemical recurrence of PrCA. Data analyzed were from a 6-month diet, physical activity and stress-reduction intervention trial conducted in South Carolina among biochemically recurrent PrCA patients (n=39). Plasma carotenoids and tocopherol levels were measured using high-performance liquid chromatography (HPLC). Linear regression was used to estimate least-square means comparing PSA levels of men with high versus low carotenoid/tocopherol levels, adjusting for covariates. After adjusting for baseline PSA level, plasma cis-lutein/zeaxanthin level at 3 months was related inversely to PSA level at 3 months (P=0.0008), while α-tocopherol (P=0.01), β-cryptoxanthin (P=0.01), and all-trans-lycopene (P=0.004) levels at 3 months were related inversely to PSA levels at 6-months. Percent increase in α-tocopherol and trans-β-carotene levels from baseline to month 3 were associated with lower PSA levels at 3 and 6 months. Percent increase in β-cryptoxanthin, cis-lutein/zeaxanthin and all-trans-lycopene were associated with lower PSA levels at 6 months only. Certain plasma carotenoids and tocopherols were related inversely to PSA levels at various timepoints, suggesting that greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA recurrence. Copyright © 2015. Published by Elsevier Ltd.

Investigative clinical study on prostate cancer part IV: exploring functional relationships of total testosterone predicting free testosterone and total prostate-specific antigen in operated prostate cancer patients.

PubMed

Porcaro, Antonio B; Petrozziello, Aldo; Migliorini, Filippo; Lacola, Vincenzo; Romano, Mario; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Zecchini Antoniolli, Stefano; Rubilotta, Emanuele; Monaco, Carmelo; Comunale, Luigi

2011-01-01

To explore, in operated prostate cancer patients, functional relationships of total testosterone (tt) predicting free testosterone (ft) and total PSA. 128 operated prostate cancer patients were simultaneously investigated for tt, ft and PSA before surgery. Patients were not receiving 5α-reductase inhibitors, LH-releasing hormone analogues and testosterone replacement treatment. Scatter plots including ft and PSA versus tt were computed in order to assess the functional relationship of the variables. Linear regression analysis of tt predicting ft and PSA was computed. tt was a significant predictor of the response variable (ft) and different subsets of the patient population were assessed according to the ft to tt ratio. PSA was related to tt according to a nonlinear law. tt was a significant predictor of PSA according to an inversely nonlinear law and different significant clusters of the patient population were assessed according to the different constant of proportionality computed from experimental data. In our prostate cancer population, ft was significantly predicted by tt according to a linear law, and the ft/tt ratio was a significant parameter for assessing the different clusters. Also, tt was a significant variable predicting PSA by a nonlinear law and different clusters of the patient population were assessed by the different constants of proportionality. As a theory, we explain the nonlinear relation of tt in predicting PSA as follows: (a) the number of androgen-independent prostate cancer cells increases as tumor volume and PSA serum levels rise, (b) the prevalence of androgen-independent cells producing a substance which inhibits serum LH, and (c) as a result lower levels of serum tt are detected. Copyright © 2011 S. Karger AG, Basel.

Obesity and prostate cancer detection: insights from three national surveys.

PubMed

Parekh, Niyati; Lin, Yong; Dipaola, Robert S; Marcella, Stephen; Lu-Yao, Grace

2010-09-01

Previous studies suggest that obesity is associated with higher prostate cancer progression and mortality despite an association with lower prostate cancer incidence. This study aims to better understand these apparently inconsistent relationships among obese men by combining evidence from 3 nationally representative cross-sectional surveys. We evaluated relationships between obesity and 1) testosterone concentrations in the Third National Health and Nutrition Examination Survey (NHANES III; n=845); 2) prostate-specific antigen (PSA) in NHANES 2001-2004 (n=2458); and 3) prostate biopsy rates in the National Health Interview Survey (NHIS 2000; n=4789) population. Mean testosterone, PSA concentrations, and biopsy rates were computed for Body Mass Index (BMI) categories. Testosterone concentrations were inversely associated with obesity (P-trend <.0001) in NHANES III. In NHANES 2001-2004, obese (BMI >35) versus lean (BMI <25) men were less likely to have PSA concentrations that reached the biopsy threshold of >4 ng/mL (3% vs 8%; P <.0001). Among NHIS participants, all BMI groups had similar rates of PSA testing (P=.24). However, among men who had PSA tests, 11% of men with BMI >30 versus 16% with BMI <25, achieved a PSA threshold of 4 ng/mL; P=.01. Furthermore, biopsy rates were lower among men with BMI >30 versus BMI <25 in NHIS participants (4.6% vs 5.8%; P=.05). Obesity was associated with lower PSA-driven biopsy rates. These data support further studies to test the hypothesis that obesity affects prostate cancer detection independent of prostate cancer risk by decreasing the PSA-driven biopsy rates.

Investigative clinical study on prostate cancer part II: on the role of the pretreatment total PSA to free testosterone ratio as a marker assessing prostate cancer prognostic groups after radical retropubic prostatectomy.

PubMed

Porcaro, Antonio B; Monaco, Carmelo; Romano, Mario; Petrozziello, Aldo; Rubilotta, Emanuele; Lacola, Vincenzo; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Antoniolli, Stefano Zecchini; Migliorini, Filippo; Comunale, Luigi

2010-01-01

To explore the significance of the pretreatment total prostate-specific antigen (PSA) to free testosterone (FT) ratio (PSA/FT) as a marker for assessing the pathologic Gleason sum (pGS) and levels of tumor extension (pT) in prostatectomy specimens. 128 of 135 consecutive patients diagnosed with prostate cancer underwent radical prostatectomy. Simultaneous pretreatment serum samples were obtained to measure serum total testosterone, FT and total PSA levels. The statistical design of the study included 2 sections: the first part trying to explore the role of the PSA/FT ratio in clustering patients with different pathologic prognostic factors, and the second to investigate the PSA/FT ratio distribution in different groups of patients according to the pathologic stage and pGS of the specimen after radical prostatectomy. The average age was 65.80 (range 51.21-77.26) years, mean PSA was 8.88 (range 1.22-44.27) μg/l, mean FT was 35.32 (range 13.70-69.30) pmol/l, and the mean PSA/FT ratio was 0.27 (range 0.04-1.48). The PSA/FT ratio significantly clustered both the pT and pGS groups. Analysis of variance for the distribution of the PSA/FT ratio was significant for the pT model groups. The mean PSA/FT ratio increased as the tumor extended and grew through the prostate gland (high-stage disease). Analysis of variance for the different distributions of the PSA/FT ratio was significant for all model pGS groups. In our investigation we also found (data not shown) that a PSA/FT ratio of ≥0.40 was strongly correlated with large extensive (pT3b+pT4) and high-grade cancers (pGS8+pGS9). Prostate cancer patients may be classified into 3 different pathologic prognostic groups according to the PSA/FT ratio: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40), and high risk (PSA/FT >0.40 and ≤1.5). The PSA/FT ratio may be considered as the marker expressing different biology groups of prostate cancer patients, and it is strongly associated with pT and pGS. Copyright © 2010 S. Karger AG, Basel.

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.

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.

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

PSA levels as a predictor of 68Ga PSMA PET/CT positivity in patients with prostate cancer?

PubMed

Soydal, Cigdem; Urun, Yuksel; Suer, Evren; Nak, Demet; Ozkan, Elgin; Kucuk, Ozlem N

2018-05-10

The aim of this study is to evaluate predictive factors of 68Gallium (68Ga) Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET)/Computed Tomography (CT) positivity. Relationships between serum Prostate Specific Antigen (PSA), Lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels, Gleason Score (GS) and positivity of 68Ga PSMA PET in patients who underwent 68Ga PSMA PET/CT for restaging for PCa were evaluated retrospectively. One hundred and four (median age: 67; range: 51-88) patients were included in this study. Of these patients, PSMA PET was positive in 75 (72%) patients. Mean serum PSA levels for PET negative and positive groups were 0.76±1.00 and 180.85±324.93 ng/ml (p<0.001). The sensitivity and specificity of 68Ga PSMA PET/CT for detection of disease recurrence were calculated as 92% and 80%, respectively, for the 1.4 ng/ml PSA cut-off and 92% and 90%, respectively, for the 2 ng/ml PSA cut-off values. The positivity rates for patients with PSA levels <1.4 ng/ml and ≥1.4 ng/ml were 21% and 90%, respectively (p<0.001). 68Ga PSMA PET/CT seems to be a highly sensitive in patients with early PSA recurrence. Patients with higher GS and early PSA recurrence could benefit from 68Ga PSMA PET/CT.

A novel classification of prostate specific antigen (PSA) biosensors based on transducing elements.

PubMed

Najeeb, Mansoor Ani; Ahmad, Zubair; Shakoor, R A; Mohamed, A M A; Kahraman, Ramazan

2017-06-01

During the last few decades, there has been a tremendous rise in the number of research studies dedicated towards the development of diagnostic tools based on bio-sensing technology for the early detection of various diseases like cardiovascular diseases (CVD), many types of cancer, diabetes mellitus (DM) and many infectious diseases. Many breakthroughs have been developed in the areas of improving specificity, selectivity and repeatability of the biosensor devices. Innovations in the interdisciplinary areas like biotechnology, genetics, organic electronics and nanotechnology also had a great positive impact on the growth of bio-sensing technology. As a product of these improvements, fast and consistent sensing policies have been productively created for precise and ultrasensitive biomarker-based disease diagnostics. Prostate-specific antigen (PSA) is widely considered as an important biomarker used for diagnosing prostate cancer. There have been many publications based on various biosensors used for PSA detection, but a limited review was available for the classification of these biosensors used for the detection of PSA. This review highlights the various biosensors used for PSA detection and proposes a novel classification for PSA biosensors based on the transducer type used. We also highlight the advantages, disadvantages and limitations of each technique used for PSA biosensing which will make this article a complete reference tool for the future researches in PSA biosensing. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictors of Prostate Cancer-Specific Mortality in Elderly Men With Intermediate-Risk Prostate Cancer Treated With Brachytherapy With or Without External Beam Radiation Therapy

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

Nanda, Akash, E-mail: ananda@partners.or; Chen, M.-H.; Moran, Brian J.

2010-05-01

Purpose: To identify clinical factors associated with prostate cancer-specific mortality (PCSM), adjusting for comorbidity, in elderly men with intermediate-risk prostate cancer treated with brachytherapy alone or in conjunction with external beam radiation therapy. Methods and Materials: The study cohort comprised 1,978 men of median age 71 (interquartile range, 66-75) years with intermediate-risk disease (Gleason score 7, prostate-specific antigen (PSA) 20 ng/mL or less, tumor category T2c or less). Fine and Gray's multivariable competing risks regression was used to assess whether prevalent cardiovascular disease (CVD), age, treatment, year of brachytherapy, PSA level, or tumor category was associated with the risk ofmore » PCSM. Results: After a median follow-up of 3.2 (interquartile range, 1.7-5.4) years, the presence of CVD was significantly associated with a decreased risk of PCSM (adjusted hazard ratio, 0.20; 95% CI 0.04-0.99; p = 0.05), whereas an increasing PSA level was significantly associated with an increased risk of PCSM (adjusted hazard ratio 1.14; 95% CI 1.02-1.27; p = 0.02). In the absence of CVD, cumulative incidence estimates of PCSM were higher (p = 0.03) in men with PSA levels above as compared with the median PSA level (7.3 ng/mL) or less; however, in the setting of CVD there was no difference (p = 0.27) in these estimates stratified by the median PSA level (6.9 ng/mL). Conclusions: In elderly men with intermediate-risk prostate cancer, CVD status is a negative predictor of PCSM and affects the prognostic capacity of pretreatment PSA level. These observations support the potential utility of prerandomization stratification by comorbidity to more accurately assess prognostic factors and treatment effects within this population.« less

An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines.

PubMed

Paliouras, Miltiadis; Diamandis, Eleftherios P

2008-06-01

The androgen receptor (AR) plays an important role in early prostate cancer by activating transcription of a number of genes participating in cell proliferation and growth and cancer progression. However, as the cancer progresses, prostate cancer cells transform from an androgen-dependent to an androgen-independent state. Androgen-independent prostate cancer can manifest itself in several forms, including a percentage of cancers that show reduced levels of prostate-specific antigen (PSA) and can progress without the need for the ligand or active receptor. Therefore, our goal was to examine the role of intracellular signaling pathways in an androgen-independent prostate cancer in vitro model. Using the cell line PC3(AR)(2), we stimulated cells with 5-alpha-dihydrotestosterone (DHT) and epidermal growth factor (EGF) and then analyzed PSA expression. We observed lower PSA expression when cells were jointly stimulated with DHT and EGF, and this was associated with an increase in AKT activity. We examined the role of AKT in AR activity and PSA expression by creating stable PC3(AR)(2) cell lines transfected with a PI3K-Ras-effector loop mutant. These cell lines showed lower DHT-stimulated PSA expression that correlated to changes in the phosphorylated state of AR. Therefore, we propose an in vitro androgen-independent model in which a PI3K/AKT activity threshold and subsequent AR transactivation regulate PSA expression.

Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

PubMed

Mubiru, James N; Yang, Alice S; Olsen, Christian; Nayak, Sudhir; Livi, Carolina B; Dick, Edward J; Owston, Michael; Garcia-Forey, Magdalena; Shade, Robert E; Rogers, Jeffrey

2014-01-01

The function of prostate-specific antigen (PSA) is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR) product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas anubis), and African green monkeys (Chlorocebus aethiops). Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS) of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203).

Clinical efficacy of transrectal ultrasound-guided prostate biopsy in men younger than 50 years old with an elevated prostate-specific antigen concentration (>4.0 ng/mL).

PubMed

Lu, Chin-Heng; Lin, Tzu-Ping; Shen, She Huei; Huang, Yi-Hsiu; Chung, Hsiao-Jen; Kuo, Junne-Yih; Huang, William J S; Wu, Howard H H; Chang, Yen-Hwa; Lin, Alex T L; Chen, Kuang-Kuo

2017-07-01

Prostate cancer (PCa) is not commonly found in men younger than 50 years of age. However, serum prostate-specific antigen (PSA) concentration has been examined more frequently at a younger age in Asia partially due to an increased awareness of prostate cancer. The purpose of our study was to investigate the efficacy and complication of PSA-triggered transrectal ultrasonography-guided prostate (TRUSP) biopsies. We retrospectively reviewed TRUSP biopsies in young men with elevated PSA concentration in Taipei Veterans General Hospital. We reviewed the cases of patients younger than 50 years of age with elevated PSA concentration (>4.0 ng/mL), who received 12 cores TRUSP biopsies at TPEVGH from January 2008-December 2013. The age, family history, digital rectal examination (DRE) results, PSA concentration, free/total PSA ratio, total prostate volume, PSA density, lower urinary tract symptoms and complications after the procedure were reviewed. The pathologic findings of TRUSP biopsy and clinical follow-up were reviewed and analyzed according to the Epstein criteria. A total of 77 patients were included and were divided into 2 groups: 1) the younger group consisted of 20 patients <40 years of age; and 2) the elder group had 57 patients who were 40-50 years of age. The overall detection rate of PCa was 11.69% (9/77), and all of the PCa cases were diagnosed in the elder group (group detection rate: 15.8%). There was a significant difference in the severity of lower urinary tract symptoms (LUTS) between these 2 groups. All PCa patients were clinically significant according to the Epstein criteria. Two patients experienced fever (2.60%) after TRUSP biopsy. From our patient cohort, it appears that no benefit was apparent for patients younger than 40 years old who received TRUSP biopsy, even with elevated PSA. However, PCa detected in men between 40 and 50 years of age were all clinically significant. Overall, our results supported current major practice guidelines which recommend an initial PSA checkup at 40 years of age. Copyright © 2017. Published by Elsevier Taiwan LLC.

Long-term longitudinal changes in baseline PSA distribution and estimated prevalence of prostate cancer in male Japanese participants of population-based PSA screening.

PubMed

Oki, Ryo; Ito, Kazuto; Suzuki, Rie; Fujizuka, Yuji; Arai, Seiji; Miyazawa, Yoshiyuki; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

2018-04-26

Japan has experienced a drastic increase in the incidence of prostate cancer (PC). To assess changes in the risk for PC, we investigated baseline prostate specific antigen (PSA) levels in first-time screened men, across a 25-year period. In total, 72,654 men, aged 50-79, underwent first-time PSA screening in Gunma prefecture between 1992 and 2016. Changes in the distribution of PSA levels were investigated, including the percentage of men with a PSA above cut-off values and linear regression analyses comparing log 10 PSA with age. The 'ultimate incidence' of PC and clinically significant PC (CSPC) were estimated using the PC risk calculator. Changes in the age-standardized incidence rate (AIR) during this period were analyzed. The calculated coefficients of linear regression for age versus log 10 PSA fluctuated during the 25-year period, but no trend was observed. In addition, the percentage of men with a PSA above cut-off values varied in each 5-year period, with no specific trend. The 'risk calculator (RC)-based AIR' of PC and CSPC were stable between 1992 and 2016. Therefore, the baseline risk for developing PC has remained unchanged in the past 25 years, in Japan. The drastic increase in the incidence of PC, beginning around 2000, may be primarily due to increased PSA screening in the country. © 2018 UICC.

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.

Evaluation of an Aggressive Prostate Biopsy Strategy in Men Younger than 50 years of Age.

PubMed

Goldberg, Hanan; Klaassen, Zachary; Chandrasekar, Thenappan; Wallis, Christopher J D; Toi, Ants; Sayyid, Rashid; Bhindi, Bimal; Nesbitt, Michael; Evans, Andrew; van der Kwast, Theo; Sweet, Joan; Perlis, Nathan; Hamilton, Robert J; Kulkarni, Girish S; Finelli, Antonio; Zlotta, Alexandre; Fleshner, Neil

2018-05-11

Longitudinal cohort studies and guidelines demonstrate that PSA ≥1 ng/mL in younger patients confer an increased risk of delayed prostate cancer (PC) death. In our institution we have used an aggressive biopsy strategy among younger patients with PSA of>1 ng/ml. Our objective was to determine the proportion of detected cancer and specifically, clinical significant cancer, with this strategy. The prostate biopsy (PB) database at Princess Margaret Cancer Centre was queried for patients younger than 50 who underwent a first PB between 2000 and 2016. We included only patients undergoing PB due to PSA>1 ng/mL, suspicious digital rectal examination, positive family history (PFH), or suspicious lesion on trans-rectal ultrasound. All clinical and pathological parameters were analyzed. Patients were stratified according to their specific PSA values. Multivariable logistic regression was performed to ascertain predictors of any PC diagnosis, and of clinically significant PC. Of 199 patients who met the inclusion criteria, 37 (19%) were diagnosed with PC and 8 (22%) had a Gleason score (GS)>7. Of those diagnosed with PC, 25 (68%) had a PSA>1.5 ng/ml and all men with GS>7 had PSA>1.5 ng/ml. Notably, 19 (51%) patients had PC exceeding Epstein criteria for active surveillance. Factors predicting PC included PFH, rising PSA and lower prostate volumes. Our results justify adopting an aggressive PB strategy for young men<50 years old with a PSA>1.5 ng/ml, while patients with PSAs<1.5 ng/ml are unlikely to have significant cancer. Special attention should be paid to patients with smaller prostates, and PFH. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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.

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.

Tissue polypeptide-specific antigen (TPS) determinations before and during intermittent maximal androgen blockade in patients with metastatic prostatic carcinoma.

PubMed

Kil, P J M; Goldschmidt, H M J; Wieggers, B J A; Kariakine, O B; Studer, U E; Whelan, P; Hetherington, J; de Reijke, Th M; Hoekstra, J W; Collette, L

2003-01-01

To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to clinical progression. Finally to compare TPS with prostate-specific antigen (PSA) measurements in terms of prognostic impact in patients with metastatic prostatic carcinoma. TPS and PSA measurements were performed before start of and monthly during intermittent MAB in 68 patients participating in EORTC protocol 30954. Both TPS and PSA were measured in serum. Fifty-six patients from eight centers were included in the final analysis because at least three TPS values were available. TPS and PSA values were correlated with clinical course of the disease. Median follow-up was 21.3 months. Three patient groups were defined on clinical grounds: (a) clinically progressive disease (n=18); (b) clinically stable disease (n=33); and (c) patients who did not reach a predefined nadir PSA value following 9 months of treatment (n=5). Pretreatment TPS was significantly higher in the clinically progressive patients than in the other patient groups (p=0.0041). When grouping patients according to their pretreatment TPS values (cut-off value of 100 U/l) the pretreatment TPS value (>100 U/l) proved to be a statistically significant prognostic factor with respect to time to progression: elevated TPS was associated with a 3.8 increased risk for progressive disease (p=0.0055). Pretreatment PSA (>100 ng/ml) was of no prognostic value for time to progression. In five patients increase of TPS coincided with or preceded clinical progression during treatment, whereas PSA remained normal. Additional value of pretreatment TPS measurements in metastatic prostate cancer patients is found in defining the patients with rapid clinical progression. Following MAB an increase in TPS signifies clinical progression even if PSA is found to remain normal.

Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter.

PubMed

Ahn, M; Lee, S-J; Li, X; Jiménez, J A; Zhang, Y-P; Bae, K-H; Mohammadi, Y; Kao, C; Gardner, T A

2009-01-01

Enzyme pro-drug suicide gene therapy has been hindered by inefficient viral delivery and gene transduction. To further explore the potential of this approach, we have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK). In our previous Ad-OC-TK/ACV phase I clinical trial, we demonstrated safety and proof of principle with a tissue-specific promoter-based TK/pro-drug therapy using a replication-defective adenovirus for the treatment of prostate cancer metastases. In this study, we aimed to inhibit the growth of androgen-independent (AI), PSA/PSMA-positive prostate cancer cells by AdIU1. In vitro the viability of an AI- PSA/PSMA-expressing prostate cancer cell line, CWR22rv, was significantly inhibited by treatment with AdIU1 plus GCV (10 microg ml(-1)), compared with AdIU1 treatment alone and also cytotoxicity was observed following treatment with AdIU1 plus GCV only in PSA/PSMA-positive CWR22rv and C4-2 cells, but not in the PSA/PSMA-negative cell line, DU-145. In vivo assessment of AdIU1 plus GCV treatment revealed a stronger therapeutic effect against CWR22rv tumors in nude mice than treatment with AdIU1 alone, AdE4PSESE1a alone or in combination with GCV. Our results demonstrate the therapeutic potential of specific-oncolysis and suicide gene therapy for AI-PSA/PSMA-positive prostate cancer gene therapy.

Prostate health index (PHI) and prostate-specific antigen (PSA) predictive models for prostate cancer in the Chinese population and the role of digital rectal examination-estimated prostate volume.

PubMed

Chiu, Peter K F; Roobol, Monique J; Teoh, Jeremy Y; Lee, Wai-Man; Yip, Siu-Ying; Hou, See-Ming; Bangma, Chris H; Ng, Chi-Fai

2016-10-01

To investigate PSA- and PHI (prostate health index)-based models for prediction of prostate cancer (PCa) and the feasibility of using DRE-estimated prostate volume (DRE-PV) in the models. This study included 569 Chinese men with PSA 4-10 ng/mL and non-suspicious DRE with transrectal ultrasound (TRUS) 10-core prostate biopsies performed between April 2008 and July 2015. DRE-PV was estimated using 3 pre-defined classes: 25, 40, or 60 ml. The performance of PSA-based and PHI-based predictive models including age, DRE-PV, and TRUS prostate volume (TRUS-PV) was analyzed using logistic regression and area under the receiver operating curves (AUC), in both the whole cohort and the screening age group of 55-75. PCa and high-grade PCa (HGPCa) was diagnosed in 10.9 % (62/569) and 2.8 % (16/569) men, respectively. The performance of DRE-PV-based models was similar to TRUS-PV-based models. In the age group 55-75, the AUCs for PCa of PSA alone, PSA with DRE-PV and age, PHI alone, PHI with DRE-PV and age, and PHI with TRUS-PV and age were 0.54, 0.71, 0.76, 0.78, and 0.78, respectively. The corresponding AUCs for HGPCa were higher (0.60, 0.70, 0.85, 0.83, and 0.83). At 10 and 20 % risk threshold for PCa, 38.4 and 55.4 % biopsies could be avoided in the PHI-based model, respectively. PHI had better performance over PSA-based models and could reduce unnecessary biopsies. A DRE-assessed PV can replace TRUS-assessed PV in multivariate prediction models to facilitate clinical use.

A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy.

PubMed

Lin, Amy M; Rini, Brian I; Weinberg, Vivian; Fong, Kristen; Ryan, Charles J; Rosenberg, Jonathan E; Fong, Lawrence; Small, Eric J

2006-10-01

To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy. Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly. In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity. Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.

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

Correlation between molecular tumor volume evaluated with 68Ga-PSMA PET/CT and prostatic specific antigen levels.

PubMed

Medina-Ornelas Sevastián, S; García-Pérez Francisco, O; Hernández-Pedro Norma, Y; Arellano-Zarate Angélica, E; Abúndiz-López Blanca, L

2018-02-14

To investigate the association between prostatic-specific antigen (PSA) levels and molecular tumor volume (MTV) measured in the 68 Ga-PSMA PET/CT, both done in a short period of time, in prostate cancer patients with biochemical failure. Eighty-four patients who underwent 68 Ga-PSMA PET/CT and measurement of PSA levels in the same week (trigger-PSA) were studied in this retrospective analysis. MTV was calculated from the sum of the metastatic lesions. To determine the association between trigger-PSA level and PET/CT findings, Spearman rank correlation was used. The median MTV of metastatic bone disease (mBD) was significantly higher than in metastatic lymph-nodes (mLN) (139.5 versus 17.7; P<.05). Disease was limited to the prostate in 8 patients (9.5%), mLN in 21 patients (25%), mBD in 32 patients (38.1%) and the 3 sites (prostate, mLN, and mBD) in 17 patients (20.2%). In 6 patients (6.14%), 68 Ga-PSMA-PET/CT was not capable of detecting disease. The median trigger-PSA levels of patients with disease limited to the prostate (2.8ng/mL), mLN (6.8ng/mL), and for mBD (16.8ng/mL) was statically significant (P<.05). Positive patients had a mean trigger-PSA of 4.3ng/mL vs 1.5ng/mL in negative patients (P<.05). We established 3 threshold-points for trigger-PSA level detection rate:≤1ng/mL (47.3%), 1-4ng/mL (68.4%) and≥4ng/mL (96.7%). When trigger-PSA exceeded 4ng/mL, the MTV was higher (P<.001). The correlation of MTV with trigger-PSA is demonstrated, which may have an impact on management. However, trigger-PSA levels were not capable of distinguishing between localized or distant disease. An accurate detection of disease can lead to a better therapeutic strategy. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Comparison of Digital Rectal Examination and Serum Prostate Specific Antigen in the Early Detection of Prostate Cancer: Results of a Multicenter Clinical Trial of 6,630 Men.

PubMed

Catalona, William J; Richie, Jerome P; Ahmann, Frederick R; Hudson, M'Liss A; Scardino, Peter T; Flanigan, Robert C; DeKernion, Jean B; Ratliff, Timothy L; Kavoussi, Louis R; Dalkin, Bruce L; Waters, W Bedford; MacFarlane, Michael T; Southwick, Paula C

2017-02-01

To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 μg./l. or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 μg./l., 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 μg./l. or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings. Copyright © 1994 American Urological Association, Inc. Published by Elsevier Inc. All rights reserved.

Seven-Month Prostate-Specific Antigen Is Prognostic in Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation With or Without Docetaxel

PubMed Central

Harshman, Lauren C.; Chen, Yu-Hui; Liu, Glenn; Carducci, Michael A.; Jarrard, David; Dreicer, Robert; Hahn, Noah; Garcia, Jorge A.; Hussain, Maha; Shevrin, Daniel; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R.; Cooney, Matthew; Vogelzang, Nicholas J.; Picus, Joel; Dipaola, Robert

2018-01-01

Purpose We evaluated the relationship between prostate-specific antigen (PSA) and overall survival in the context of a prospectively randomized clinical trial comparing androgen-deprivation therapy (ADT) plus docetaxel with ADT alone for initial metastatic hormone-sensitive prostate cancer. Methods We performed a landmark survival analysis at 7 months using the E3805 Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) database (ClinicalTrials.gov identifier: NCT00309985). Inclusion required at least 7 months of follow-up and PSA levels at 7 months from ADT initiation. We used the prognostic classifiers identified in a previously reported trial (Southwest Oncology Group 9346) of PSA ≤ 0.2, > 0.2 to 4, and > 4 ng/mL. Results Seven hundred nineteen of 790 patients were eligible for this subanalysis; 358 were treated with ADT plus docetaxel, and 361 were treated with ADT alone. Median follow-up time was 23.1 months. On multivariable analysis, achieving a 7-month PSA ≤ 0.2 ng/mL was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSAs (all P ≤ .01). Across all patients, median overall survival was significantly longer if 7-month PSA reached ≤ 0.2 ng/mL compared with > 4 ng/mL (median survival, 60.4 v 22.2 months, respectively; P < .001). On multivariable analysis, 7-month PSA ≤ 0.2 and low volume disease were prognostic of longer overall survival (all P < 0.01). The addition of docetaxel increased the likelihood of achieving a PSA ≤ 0.2 ng/mL at 7 months (45.3% v 28.8% of patients on ADT alone). Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/mL had the best survival and were more likely to have low-volume disease (56.7%). Conclusion PSA ≤ 0.2 ng/mL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival. PMID:29261442

Is prostate-specific antigen a valid surrogate end point for survival in hormonally treated patients with metastatic prostate cancer? Joint research of the European Organisation for Research and Treatment of Cancer, the Limburgs Universitair Centrum, and AstraZeneca Pharmaceuticals.

PubMed

Collette, Laurence; Burzykowski, Tomasz; Carroll, Kevin J; Newling, Don; Morris, Tom; Schröder, Fritz H

2005-09-01

The long duration of phase III clinical trials of overall survival (OS) slows down the treatment-development process. It could be shortened by using surrogate end points. Prostate-specific antigen (PSA) is the most studied biomarker in prostate cancer (PCa). This study attempts to validate PSA end points as surrogates for OS in advanced PCa. Individual data from 2,161 advanced PCa patients treated in studies comparing bicalutamide to castration were used in a meta-analytic approach to surrogate end-point validation. PSA response, PSA normalization, time to PSA progression, and longitudinal PSA measurements were considered. The known association between PSA and OS at the individual patient level was confirmed. The association between the effect of intervention on any PSA end point and on OS was generally low (determination coefficient, < 0.69). It is a common misconception that high correlation between biomarkers and true end point justify the use of the former as surrogates. To statistically validate surrogate end points, a high correlation between the treatment effects on the surrogate and true end point needs to be established across groups of patients treated with two alternative interventions. The levels of association observed in this study indicate that the effect of hormonal treatment on OS cannot be predicted with a high degree of precision from observed treatment effects on PSA end points, and thus statistical validity is unproven. In practice, non-null treatment effects on OS can be predicted only from precisely estimated large effects on time to PSA progression (TTPP; hazard ratio, < 0.50).

Independent association between time to prostate-specific antigen (PSA) nadir and PSA progression-free survival in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer receiving abiraterone acetate, but not enzalutamide.

PubMed

Miyake, Hideaki; Hara, Takuto; Tamura, Keita; Sugiyama, Takayuki; Furuse, Hiroshi; Ozono, Seiichiro; Fujisawa, Masato

2017-06-01

The objective of this study was to compare the prognostic effect of time to prostate-specific antigen (PSA) nadir (TTPN) after treatment with abiraterone acetate (AA) and enzalutamide (Enz) in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer (mCRPC). This study included a total of 297 consecutive patients with mCRPC, of whom 125 and 172 received AA and Enz, respectively, without previous treatment with docetaxel and subsequently achieved any degree of PSA reduction after the administration of either agent. The mean values of TTPN in the AA and Enz groups were 19 and 14 weeks, respectively. Despite the lack of significant differences in several parameters according to the mean TTPN in the Enz group, patients with TTPN>19 weeks were characterized by longer duration of androgen deprivation therapy, better performance status, lower incidence of bone metastasis, lower value of nadir PSA, and higher incidence of PSA response than those with TTPN ≤19 weeks in the AA group. The PSA progression-free survival (PFS) in patients with TTPN >19 weeks was significantly superior when compared with TTPN ≤19 weeks in the AA group; however, there was no significant effect of the mean TTPN on the PSA-PFS in the Enz group. Furthermore, TTPN was identified as one of the independent predictors of PSA-PFS in the AA group but not in Enz group. A longer time to reach a PSA nadir after treatment with AA, but not Enz, appeared to be associated with favorable disease control in patients with docetaxel-naïve mCRPC. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimization of PSA screening policies: a comparison of the patient and societal perspectives.

PubMed

Zhang, Jingyu; Denton, Brian T; Balasubramanian, Hari; Shah, Nilay D; Inman, Brant A

2012-01-01

To estimate the benefit of PSA-based screening for prostate cancer from the patient and societal perspectives. A partially observable Markov decision process model was used to optimize PSA screening decisions. Age-specific prostate cancer incidence rates and the mortality rates from prostate cancer and competing causes were considered. The model trades off the potential benefit of early detection with the cost of screening and loss of patient quality of life due to screening and treatment. PSA testing and biopsy decisions are made based on the patient's probability of having prostate cancer. Probabilities are inferred based on the patient's complete PSA history using Bayesian updating. The results of all PSA tests and biopsies done in Olmsted County, Minnesota, from 1993 to 2005 (11,872 men and 50,589 PSA test results). Patients' perspective: to maximize expected quality-adjusted life years (QALYs); societal perspective: to maximize the expected monetary value based on societal willingness to pay for QALYs and the cost of PSA testing, prostate biopsies, and treatment. From the patient perspective, the optimal policy recommends stopping PSA testing and biopsy at age 76. From the societal perspective, the stopping age is 71. The expected incremental benefit of optimal screening over the traditional guideline of annual PSA screening with threshold 4.0 ng/mL for biopsy is estimated to be 0.165 QALYs per person from the patient perspective and 0.161 QALYs per person from the societal perspective. PSA screening based on traditional guidelines is found to be worse than no screening at all. PSA testing done with traditional guidelines underperforms and therefore underestimates the potential benefit of screening. Optimal screening guidelines differ significantly depending on the perspective of the decision maker.

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? ...

Prostate Cancer Predictive Simulation Modelling, Assessing the Risk Technique (PCP-SMART): Introduction and Initial Clinical Efficacy Evaluation Data Presentation of a Simple Novel Mathematical Simulation Modelling Method, Devised to Predict the Outcome of Prostate Biopsy on an Individual Basis.

PubMed

Spyropoulos, Evangelos; Kotsiris, Dimitrios; Spyropoulos, Katherine; Panagopoulos, Aggelos; Galanakis, Ioannis; Mavrikos, Stamatios

2017-02-01

We developed a mathematical "prostate cancer (PCa) conditions simulating" predictive model (PCP-SMART), from which we derived a novel PCa predictor (prostate cancer risk determinator [PCRD] index) and a PCa risk equation. We used these to estimate the probability of finding PCa on prostate biopsy, on an individual basis. A total of 371 men who had undergone transrectal ultrasound-guided prostate biopsy were enrolled in the present study. Given that PCa risk relates to the total prostate-specific antigen (tPSA) level, age, prostate volume, free PSA (fPSA), fPSA/tPSA ratio, and PSA density and that tPSA ≥ 50 ng/mL has a 98.5% positive predictive value for a PCa diagnosis, we hypothesized that correlating 2 variables composed of 3 ratios (1, tPSA/age; 2, tPSA/prostate volume; and 3, fPSA/tPSA; 1 variable including the patient's tPSA and the other, a tPSA value of 50 ng/mL) could operate as a PCa conditions imitating/simulating model. Linear regression analysis was used to derive the coefficient of determination (R 2 ), termed the PCRD index. To estimate the PCRD index's predictive validity, we used the χ 2 test, multiple logistic regression analysis with PCa risk equation formation, calculation of test performance characteristics, and area under the receiver operating characteristic curve analysis using SPSS, version 22 (P < .05). The biopsy findings were positive for PCa in 167 patients (45.1%) and negative in 164 (44.2%). The PCRD index was positively signed in 89.82% positive PCa cases and negative in 91.46% negative PCa cases (χ 2 test; P < .001; relative risk, 8.98). The sensitivity was 89.8%, specificity was 91.5%, positive predictive value was 91.5%, negative predictive value was 89.8%, positive likelihood ratio was 10.5, negative likelihood ratio was 0.11, and accuracy was 90.6%. Multiple logistic regression revealed the PCRD index as an independent PCa predictor, and the formulated risk equation was 91% accurate in predicting the probability of finding PCa. On the receiver operating characteristic analysis, the PCRD index (area under the curve, 0.926) significantly (P < .001) outperformed other, established PCa predictors. The PCRD index effectively predicted the prostate biopsy outcome, correctly identifying 9 of 10 men who were eventually diagnosed with PCa and correctly ruling out PCa for 9 of 10 men who did not have PCa. Its predictive power significantly outperformed established PCa predictors, and the formulated risk equation accurately calculated the probability of finding cancer on biopsy, on an individual patient basis. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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.

SERIAL PERCENT-FREE PSA IN COMBINATION WITH PSA FOR POPULATION-BASED EARLY DETECTION OF PROSTATE CANCER

PubMed Central

Ankerst, Donna Pauler; Gelfond, Jonathan; Goros, Martin; Herrera, Jesus; Strobl, Andreas; Thompson, Ian M.; Hernandez, Javier; Leach, Robin J.

2016-01-01

PURPOSE To characterize the diagnostic properties of serial percent-free prostate-specific antigen (PSA) in relation to PSA in a multi-ethnic, multi-racial cohort of healthy men. MATERIALS AND METHODS 6,982 percent-free PSA and PSA measures were obtained from participants in a 12 year+ Texas screening study comprising 1625 men who never underwent biopsy, 497 who underwent one or more biopsies negative for prostate cancer, and 61 diagnosed with prostate cancer. Area underneath the receiver-operating-characteristic-curve (AUC) for percent-free PSA, and the proportion of patients with fluctuating values across multiple visits were determined according to two thresholds (under 15% versus 25%) were evaluated. The proportion of cancer cases where percent-free PSA indicated a positive test before PSA > 4 ng/mL did and the number of negative biopsies that would have been spared by percent-free PSA testing negative were computed. RESULTS Percent-free PSA fluctuated around its threshold of < 25% (< 15%) in 38.3% (78.1%), 42.2% (20.9%), and 11.4% (25.7%) of patients never biopsied, with negative and positive biopsies, respectively. At the same thresholds, percent-free PSA tested positive earlier than PSA in 71.4% (34.2%) of cancer cases, and among men with multiple negative biopsies and a PSA > 4 ng/mL, percent-free PSA would have tested negative in 31.6% (65.8%) instances. CONCLUSIONS Percent-free PSA should accompany PSA testing in order to potentially spare unnecessary biopsies or detect cancer earlier. When near the threshold, both tests should be repeated due to commonly observed fluctuation. PMID:26979652

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer

PubMed Central

Narang, Amol K.; Trieu, Janson; Radwan, Noura; Ram, Ashwin; Robertson, Scott P.; He, Pei; Gergis, Carol; Griffith, Emily; Singh, Harleen; DeWeese, Tate A.; Honig, Stephanie; Annadanam, Anvesh; Greco, Stephen; DeVille, Curtiland; McNutt, Todd; DeWeese, Theodore L.; Song, Daniel Y.; Tran, Phuoc T.

2016-01-01

Background In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Methods Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993–2006 and who had an EOR PSA (n=688, median follow-up 11.2 years). We analyzed the association of an end-of-radiation (EOR) prostate-specific antigen (PSA) level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ≥0.1 ng ml−1) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. Results At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% vs. 64.4%, p<0.001), 10-year MFS (84.8% vs. 92.0%, p=0.003), 10-year PCSS (94.3% vs. 98.2%, p=0.007), and 10-year OS (75.8% vs. 82.5%, p=0.01), as compared to men with an undetectable EOR PSA. Among NCCN intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37–14.65, p<0.001; NCCN risk level: HR 2.01, 95% CI 0.74–5.42, p=0.168). Main study limitations are retrospective study design and associated biases. Conclusions EOR PSA was significantly associated with survival endpoints in men who received treated with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation. PMID:28094250

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.

Obesity and prostate cancer detection: insights from three national surveys

PubMed Central

Parekh, Niyati; Lin, Yong; DiPaola, Robert S.; Marcella, Stephen; Lu-Yao, Grace

2013-01-01

Background Previous studies suggest that obesity is associated with higher prostate cancer progression and mortality despite an association with lower prostate cancer incidence. This study aims to better understand these apparently inconsistent relationships among obese men, by combining evidence from three nationally representative cross-sectional surveys. Methods We evaluated relationships between obesity and (1) testosterone concentrations in the Third National Health and Nutrition Examination Survey (NHANES III; n=845), (2) prostate-specific antigen (PSA) in NHANES 2001–2004 (n=2,458) and (3) prostate biopsy rates in the National Health Interview Survey (NHIS 2000; n=4,789) population. Mean testosterone, PSA concentrations and biopsy rates were computed for body mass index (BMI) categories. Results Testosterone concentrations were inversely associated with obesity (p-trend<0.0001) in NHANES III. In NHANES 2001–2004 obese (BMI >35) versus lean (BMI <25) men were less likely to have PSA concentrations that reached the biopsy threshold of >4 ng/ml (3% versus 8%; p<0.0001). Among NHIS participants all BMI groups had similar rates of PSA testing (p=0.24). However, among men who had PSA tests, 11% of men with BMI >30 versus 16% with BMI <25, achieved a PSA threshold of 4 ng/ml; p=0.01. Furthermore, biopsy rates were lower among men with BMI >30 versus BMI <25 in NHIS participants (4.6% vs. 5.8%; p=0.05). Conclusions Obesity was associated with lower PSA-driven biopsy rates. These data support further studies to test the hypothesis that obesity affects prostate cancer detection independent of prostate cancer risk by decreasing the PSA-driven biopsy rates. PMID:20800152

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.

Clinical and Biochemical Influence of Prostatic Stones.

PubMed

Soric, Tomislav; Selimovic, Mirnes; Bakovic, Lada; Šimurina, Tatjana; Selthofer, Robert; Dumic, Jerka

2017-01-01

The study aimed to explore clinical influence of prostatic stones on lower urinary tract symptoms (LUTS), seminal plasma cytokines, and serum biomarkers. A total of 70 men aged ≤50 years with LUTS divided into 2 groups: group with stones (GSt) and group without prostatic stones (GNoSt). All subjects completed the International Prostate Symptom Score (IPSS) questionnaire and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scoring questionnaire. Pre- and post-prostate massage test and uroflowmetry were performed. The serum concentration of total prostate specific antigen (PSA), free PSA, and free/total PSA (f/t PSA) ratio, seminal concentration of cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor-alpha were measured. GSt subjects had significantly more severe symptoms based on IPSS answers (p = 0.0289). All domains in NIH-CPSI scores were significantly higher in the GSt group: pain (p = 0.001), urinary symptoms (p = 0.023), quality of life (p = 0.008), and with overall (p = 0.003). GSt subjects also had significantly lower maximum urinary flow (Qmax; p = 0.011), lower f/t PSA ratio (p = 0.048), and higher concentration of IL-1β (p = 0.011) and IL-8 (p = 0.001). Prostatic stones may influence the severity of LUTS and the symptoms of chronic prostatitis. They might reduce Qmax rate and lead to reduction of the f/t PSA ratio and produce more severe inflammation causing increased seminal concentration of IL-1β and IL-8. © 2017 S. Karger AG, Basel.

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

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.

Screening for Prostate Cancer Starting at Age 50-54. A Population-based Cohort Study

PubMed Central

Carlsson, Sigrid; Assel, Melissa; Ulmert, David; Gerdtsson, Axel; Hugosson, Jonas; Vickers, Andrew; Lilja, Hans

2016-01-01

Background Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening. Objective To evaluate the effect of prostate-specific antigen (PSA) screening, versus zero screening, starting at age 50-54, on prostate cancer mortality. Design, Setting, and Participants This is a population-based cohort study comparing 3,479 men aged 50 through 54 randomized to PSA-screening in the Göteborg population-based prostate cancer screening trial, initiated in 1995, versus 4,060 unscreened men aged 51 to 55 providing cryopreserved blood in the population-based Malmö Preventive Project in the pre-PSA era, during 1982-1985. Outcome measures and Statistical Analysis Cumulative incidence and incidence rate ratios of prostate cancer diagnosis, metastasis, and prostate cancer death. Results and Limitation At 17 years, regular PSA-screening in Göteborg of men in their early 50s carried a more than 2-fold higher risk of prostate cancer diagnosis compared to the unscreened men in Malmö (IRR 2.56, 95% CI 2.18, 3.02), but resulted in a substantial decrease in risk of metastases (IRR 0.43, 95% CI 0.22, 0.79) and prostate cancer death (IRR 0.29, 95% CI 0.11, 0.67). There were 57 fewer prostate cancer deaths per 10,000 men (95% CI 22, 92) in the screened group. At 17 years, the number needed to invite to PSA-screening and the number needed to diagnose to prevent one prostate cancer death was 176 and 16, respectively. The study is limited by lack of treatment information and the comparison of two different birth cohorts. Conclusions PSA screening for prostate cancer can decrease prostate cancer mortality among men aged 50–54, with NNI and NND comparable to those previously reported from the European Randomized Study of Screening for Prostate Cancer for men aged 55-69 years, at similar follow-up. Guideline groups could consider whether guidelines for PSA screening should recommend starting no later than at ages 50-54. Trial registration The Göteborg randomized population-based prostate cancer screening trial is registered with the ISRCTN registry (isrctn.com). Identifier: ISRCTN54449243. PMID:27084245

Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study.

PubMed

Jamnagerwalla, Juzar; Howard, Lauren E; Allott, Emma H; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freeman, Michael R; Freedland, Stephen J

2017-12-27

Epidemiologic evidence for a serum cholesterol-prostate cancer link is mixed. Prostate-specific antigen (PSA) is positively correlated with cholesterol, potentially increasing PSA-driven biopsy recommendations in men with high cholesterol, though biopsy compliance may be lower in men with comorbid conditions. These potential biases may affect PSA-driven biopsy rates and subsequent prostate cancer detection in men with high serum cholesterol. Our objective was to test the association between serum cholesterol and prostate cancer risk in men receiving PSA independent, study-mandated prostate biopsies. We conducted a post hoc analysis of data from 4974 non-statin users in REDUCE, a randomized trial in men with elevated PSA and a negative baseline biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies. Associations between baseline serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and prostate cancer risk, overall and by Gleason grade (<7 vs. ≥7), were examined using multivariable logistic regression. High total serum cholesterol was associated with an increased risk of high-grade prostate cancer diagnosis (OR per 10 mg/dL 1.05; 95% CI 1.00-1.09; p = 0.048), but cholesterol was unrelated to either overall or low-grade prostate cancer risk (p-values >0.185). There was no association between serum LDL and overall, low- or high-grade prostate cancer risk (p-values >0.137). In contrast, elevated serum HDL was associated with increased risk of both overall (OR per 10 mg/dL 1.08; 95% CI 1.01-1.16; p = 0.033) and high-grade prostate cancer (OR per 10 mg/dL 1.14; 95% CI 1.01-1.28; p = 0.034). In REDUCE, where all men received PSA independent, trial-mandated biopsies thus ensuring complete prostate cancer ascertainment, high total serum cholesterol and high HDL were associated with increased risk of high-grade prostate cancer, supporting a cholesterol-prostate cancer link.

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.

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.

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 ...

Literacy, race, and PSA level among low-income men newly diagnosed with prostate cancer.

PubMed

Wolf, Michael S; Knight, Sara J; Lyons, E Allison; Durazo-Arvizu, Ramón; Pickard, Simon A; Arseven, Adnan; Arozullah, Ahsan; Colella, Kathleen; Ray, Paul; Bennett, Charles L

2006-07-01

Among men with newly diagnosed prostate cancer, prostate-specific antigen (PSA) levels are higher and the cancer stage more advanced for African Americans than for whites. An earlier study found that after adjustment for literacy, race was no longer a significant predictor of advanced stage at presentation. We investigated whether, after adjusting for literacy, race was a significant independent predictor of greater PSA levels among men with newly diagnosed prostate cancer. Consecutive patients with newly diagnosed prostate cancer from four outpatient care facilities in Chicago were interviewed and given a literacy assessment (n = 308). The PSA level at diagnosis was obtained from the medical charts. Logistic regression models were used to identify predictors of high PSA levels (greater than 20 ng/mL) at presentation. African-American men were three times more likely to have low literacy skills (sixth grade or less: 22.9% versus 7.1%; P <0.001) than were white men. In turn, men with low literacy skills were more than twice as likely to have a PSA level greater than 20 ng/mL at diagnosis (33.3% versus 13.5%; P = 0.009). On multivariate analyses, significant predictors of high PSA levels included low literacy (adjusted odds ratio 2.5, 95% confidence interval 1.5 to 4.2) and older age (age 65 to 74 years, adjusted odds ratio 2.6, 95% confidence interval 2.1 to 3.1 versus older than 74 years, adjusted odds ratio 3.4, 95% confidence interval 1.8 to 6.6), but not African-American race. In the current era in which PSA testing is common, low literacy may be an important and potentially overlooked factor associated with higher PSA levels at prostate cancer diagnosis among African-American and white men.

Positive associations between galectin-3 and PSA levels in prostate cancer patients: a prospective clinical study-I.

PubMed

Nakajima, Kosei; Heilbrun, Lance K; Hogan, Victor; Smith, Daryn; Heath, Elisabeth; Raz, Avraham

2016-12-13

Galectin-3 (Gal-3), an oncogenic pro-inflammatory protein, has been suggested as a possible complementary diagnostic candidate to prostate specific antigen (PSA) blood test for prostate cancer patients. The presence of the proteins in the circulation (biomarkers) may elicit an intrinsic humoral immune reaction by generating autoantibodies, which consequently could alter the detection levels. Here, we report the associations of the two prostate cancer biomarkers, Gal-3 and PSA in patients at different clinical states of prostate cancer while taking into account the autoantibody levels. A blind, prospective, single institution, pilot study was conducted. A total of 95 men were classified into 5 groups: healthy controls (Group1), newly diagnosed patients (Group2), no recurrence after local therapy (Group3), rising PSA after local therapy (Group4), and metastatic patients (Group5). Gal-3 and PSA level were divided by their respective autoantibodies, which yielded relative PSA and relative Gal-3 levels. After the adjustments, Spearman's rank correlations and linear regression modeling revealed the positive associations between relative Gal-3 and relative PSA levels among all 95 men combined (rho = 0.446, P < 0.0001; fitted slope 0.448, P < 0.0001), in Group2 (rho = 0.616, P = 0.0050; fitted slope 0.438, P =0.0011), and Group3 (rho = 0.484, P = 0.0360; fitted slope 0.470, P = 0.0187). The data show positive associations of relative Gal-3 and relative PSA levels in prostate cancer patients, notably at early clinical time course. Allowing for the influence of autoantibodies, Gal-3 level might be considered as a potential biomarker since it is positively associated with PSA level.

Prostate Health Index (PHI) Predicts High-stage Pathology in African American Men.

PubMed

Schwen, Zeyad R; Tosoian, Jeffrey J; Sokoll, Lori J; Mangold, Leslie; Humphreys, Elizabeth; Schaeffer, Edward M; Partin, Alan W; Ross, Ashley E

2016-04-01

To evaluate the association between the Prostate Health Index (PHI) and adverse pathology in a cohort of African American (AA) men undergoing radical prostatectomy. Eighty AA men with prostate-specific antigen (PSA) of 2-10 ng/mL underwent measurement of PSA, free PSA (fPSA), and p2PSA prior to radical prostatectomy. PHI was calculated as [(p2PSA/fPSA) × (PSA)(½)]. Biomarker association with pT3 disease was assessed using logistic regression, and covariates were added to a baseline multivariable model including digital rectal examination. Biomarker ability to predict pT3 disease was measured using the area under the receiver operator characteristic curve. Sixteen men (20%) demonstrated pT3 disease on final pathology. Mean age, PSA, and %fPSA were similar in men with and without pT3 disease (all P  >  .05), whereas PHI was significantly greater in men with pT3 disease (mean 57.2 vs 46.6, P  =  .04). Addition of PHI to the baseline multivariable model improved discriminative ability by 12.9% (P  =. .04) and yielded greater diagnostic accuracy than models, including other individual biomarkers. In AA men with PSA of 2-10 ng/mL, PHI was predictive of pT3 prostate cancer and may help to identify men at increased risk of adverse pathology. Additional studies are needed to substantiate these findings and identify appropriate thresholds for clinical use. Copyright © 2016 Elsevier Inc. All rights reserved.

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., ...

The therapeutic potential of royal jelly in benign prostatic hyperplasia. Comparison with contemporary literature.

PubMed

Pajovic, Bogdan; Radojevic, Nemanja; Dimitrovski, Antonio; Tomovic, Savo; Vukovic, Marko

2016-09-01

The aim of this study is to establish the scientific benefit of royal jelly (RJ) on prostatic-specific antigen (PSA), post-void residual (PVR) volume and International Prostate Symptom Score (IPSS) in benign prostatic hyperplasia. For the study, a group of 40 men were administered 38 mg of RJ over a period of three months, their PSA values, prostate volumes and the volumes of their transitory prostate zones, PVR and IPPS values were measured at the end of the first month, and at the end of the third month. The results of this study confirm the potential of RJ in reducing PSA scores and improving IPSS values. Since the use of RJ did not lead to any significant reduction in PVR, prostate volume, or to any involution of the transitory zone, it appears that it may only affect the blood marker of prostatic hyperplasia and to improve quality-of-life (QoL) in those patients. Overall, in comparison to phytotherapy and conventional therapy, RJ had similar positive effects on QoL in patients with BPH, however it exhibited markedly better effects on reducing PSA levels in blood. The therapeutical use of RJ exhibited no side effects.

Prostate-Specific Antigen: Nonspecific in Deceased Organ Donors.

PubMed

Pabisiak, K; Ostrowski, M; Kram, A; Safranow, K; Myślak, M; Sieńko, J; Sulikowski, T; Ciechanowski, K

2016-06-01

Currently, there is no clear position regarding the donation of organs from donors with prostate carcinoma (CaP) in European countries, except Italy. The lengthening of life expectancy increases the probability of prostate cancer among potential organ donors. The concentration of prostate-specific antigen (PSA) >2 ng/mL at 60 years of age is related to the increasing possibility of identifying an advanced form of CaP. In recent years in Poland, the recommendation has been to determine tumor markers in potential donors. In the first year of the recommendation, 10% of potential male cadaveric donors were disqualified in West Pomerania, Poland, on the basis of elevated PSA levels (>10 ng/mL). To avoid reduction of the actual donor pool, each potential male donor reported to the center since January 2010 undergoes a routine histologic evaluation of the whole prostate, regardless of the PSA level, before organ implantation. In the study group (N = 52), histopathologic evaluation revealed 6 cases of CaP (12%). In CaP positive group Gleason score range from 2+2 to 3+4. In CaP donors PSA level have been noticed in range 1.79 ng/mL - 7.66 ng/mL. There was no correlation between histologically confirmed CaP and the PSA level. Copyright © 2016 Elsevier Inc. All rights reserved.

Transrectal ultrasound (TRUS) findings of the prostate gland in late onset hypogonadism with testosterone supplementation in correlation with clinical outcome.

PubMed

Phongkitkarun, Sith; Rassameepong, Apinan; Permpongkosol, Sompol; Taphey, Mayureewan; Wibulpolprasert, Bussanee

2012-07-01

To determine the TRUS findings of the prostate and correlation of ultrasoundfindings with clinical outcomes in late-onset hypogonadal (LOH) men with testosterone supplementation. Between January 2007 and September 2010, TRUS findings and clinical outcomes of 16 from 226 subjects were studied The demographic data, ultrasound parameters as prostate volume and vascularity, and clinical parameters were evaluated Correlation between ultrasound and clinical parameters were analyzed using Pearson correlation analysis. During mean time follow-up of 6.48 months, the volume of the central gland (CG) significantly increased (p = 0.02), the volume of the total gland (TG) increased, and the volume of the peripheral zone (PZ) slightly decreased. The vascularity of the TG, CG, and PZ were significantly increased. The periurethral region vascularity was not significantly increased (p = 0.06), whereas total serum testosterone, prostate specific antigen (PSA), and PSA density were increased The International Prostate Symptom Score (IPSS) was significantly decreased (p < 0.001). There was a significant correlation between increased prostate volume and increased serum PSA. Testosterone supplementation in LOH men was found to cause an increase in TG volume during the first six months. The preferentially increased CG volume and prostatic vascularity might be due to exogenous testosterone. The authors observed a significantly increased PSA with a strong correlation between serum PSA and prostate volume.

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.

[Survival is associated with time to reach PSA nadir (DAN) and the ratio DAN/nadir value after androgen deprivation for prostate cancer].

PubMed

Gagnat, A; Larré, S; Fromont, G; Pirès, C; Doré, B; Irani, J

2011-05-01

The objective of this study was to assess the prognostic decrease rate of PSA in patients treated with androgen suppression (AS) for prostate cancer (PCa). We identified in our database CaP patients with histologically documented, treated with SA alone and for whom vital status with a minimum follow-up of 6 months (except death beforehand) was established. Patient characteristics and CaP and PSA at baseline, PSA nadir, time of reaching the nadir PSA (DAN) and the ratio of the DAN/nadir value (ratio DAN/Nadir) were analyzed in relation to progression-free survival, specific and overall survival. One hundred ninety eight patients met the inclusion criteria and the median was 61.5 months (range 4.8 to 233). The median PSA at the start of the SA were 37.1 ng/mL and the median nadir PSA was 0.48 ng/mL. The median time to progression was 23.6 months. The median specific and overall survivals were 94 and 78 months, respectively. In univariate analysis, predictors of progression-free survival were PSA before SA, PSA nadir, DAN, DAN ratio/nadir, Gleason score, the percentage of core positive prostate biopsy and the status of bone scintigraphy. Except for PSA before SA which was no longer significant, predictors of specific and overall survival were similar and added the biochemical response (decrease of more than 50% of PSA) to a second hormonal manipulation during the biological progression. In multivariate analysis, the nadir PSA and the ratio DAN/Nadir remained significant predictors. These results have confirmed in one hand the predictive value of survival in patients DAN SA for CaP: achieving faster nadir PSA was associated with shorter survival. They have introduced in the other hand the new concept of DAN/Nadir PSA which provides independent prognostic information. Copyright © 2010 Elsevier Masson SAS. 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.

Development and prospective multicenter evaluation of the long noncoding RNA MALAT-1 as a diagnostic urinary biomarker for prostate cancer

PubMed Central

Lu, Ji; Shi, Xiaolei; Zhu, Yasheng; Zhang, Wei; Jing, Taile; Zhang, Chao; Shen, Jian; Xu, Chuanliang; Wang, Huiqing; Wang, Haifeng; Wang, Yang; Liu, Bin; Li, Yaoming; Fang, Ziyu; Guo, Fei; Qiao, Meng; Wu, Chengyao; Wei, Qiang; Xu, Danfeng; Shen, Dan; Lu, Xin; Gao, Xu; Hou, Jianguo; Sun, Yinghao

2014-01-01

The current strategy for diagnosing prostate cancer (PCa) is mainly based on the serum prostate-specific antigen (PSA) test. However, PSA has low specificity and has led to numerous unnecessary biopsies. We evaluated the effectiveness of urinary metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long noncoding RNA, for predicting the risk of PCa before biopsy. The MALAT-1 score was tested in a discovery phase and a multi-center validation phase. The predictive power of the MALAT-1 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. As an independent predictor of PCa, the MALAT-1 score was significantly higher in men with a positive biopsy than in those with a negative biopsy. The ROC analysis showed a higher AUC for the MALAT-1 score (0.670 and 0.742) vs. the total PSA (0.545 and 0.601) and percent free PSA (0.622 and 0.627) in patients with PSA values of 4.0-10 ng/ml. According to the decision curve analysis, using a probability threshold of 25%, the MALAT-1 model would prevent 30.2%-46.5% of unnecessary biopsies in PSA 4–10 ng/ml cohorts, without missing any high-grade cancers. Our results demonstrate that urine MALAT-1 is a promising biomarker for predicting prostate cancer risk. PMID:25526029

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.

Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer.

PubMed

Fucikova, Jitka; Podrazil, Michal; Jarolim, Ladislav; Bilkova, Pavla; Hensler, Michal; Becht, Etienne; Gasova, Zdenka; Klouckova, Jana; Kayserova, Jana; Horvath, Rudolf; Fialova, Anna; Vavrova, Katerina; Sochorova, Klara; Rozkova, Daniela; Spisek, Radek; Bartunkova, Jirina

2018-01-01

Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population. The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively. No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p < 0.0018). Twelve patients who continued immunotherapy with the second cycle had a median PSADT of 58 months that remained stable after the second cycle. In the peripheral blood, specific PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment. Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

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.

The combination of ovarian volume and outline has better diagnostic accuracy than prostate-specific antigen (PSA) concentrations in women with polycystic ovarian syndrome (PCOs).

PubMed

Bili, Eleni; Bili, Authors Eleni; Dampala, Kaliopi; Iakovou, Ioannis; Tsolakidis, Dimitrios; Giannakou, Anastasia; Tarlatzis, Basil C

2014-08-01

The aim of this study was to determine the performance of prostate specific antigen (PSA) and ultrasound parameters, such as ovarian volume and outline, in the diagnosis of polycystic ovary syndrome (PCOS). This prospective, observational, case-controlled study included 43 women with PCOS, and 40 controls. Between day 3 and 5 of the menstrual cycle, fasting serum samples were collected and transvaginal ultrasound was performed. The diagnostic performance of each parameter [total PSA (tPSA), total-to-free PSA ratio (tPSA:fPSA), ovarian volume, ovarian outline] was estimated by means of receiver operating characteristic (ROC) analysis, along with area under the curve (AUC), threshold, sensitivity, specificity as well as positive (+) and negative (-) likelihood ratios (LRs). Multivariate logistical regression models, using ovarian volume and ovarian outline, were constructed. The tPSA and tPSA:fPSA ratio resulted in AUC of 0.74 and 0.70, respectively, with moderate specificity/sensitivity and insufficient LR+/- values. In the multivariate logistic regression model, the combination of ovarian volume and outline had a sensitivity of 97.7% and a specificity of 97.5% in the diagnosis of PCOS, with +LR and -LR values of 39.1 and 0.02, respectively. In women with PCOS, tPSA and tPSA:fPSA ratio have similar diagnostic performance. The use of a multivariate logistic regression model, incorporating ovarian volume and outline, offers very good diagnostic accuracy in distinguishing women with PCOS patients from controls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

Can Prostate Imaging Reporting and Data System Version 2 reduce unnecessary prostate biopsies in men with PSA levels of 4-10 ng/ml?

PubMed

Xu, Ning; Wu, Yu-Peng; Chen, Dong-Ning; Ke, Zhi-Bin; Cai, Hai; Wei, Yong; Zheng, Qing-Shui; Huang, Jin-Bei; Li, Xiao-Dong; Xue, Xue-Yi

2018-05-01

To explore the value of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) for predicting prostate biopsy results in patients with prostate specific antigen (PSA) levels of 4-10 ng/ml. We retrospectively reviewed multi-parameter magnetic resonance images from 528 patients with PSA levels of 4-10 ng/ml who underwent transrectal ultrasound-guided prostate biopsies between May 2015 and May 2017. Among them, 137 were diagnosed with prostate cancer (PCa), and we further subdivided them according to pathological results into the significant PCa (S-PCa) and insignificant significant PCa (Ins-PCa) groups (121 cases were defined by surgical pathological specimen and 16 by biopsy). Age, PSA, percent free PSA, PSA density (PSAD), prostate volume (PV), and PI-RADS score were collected. Logistic regression analysis was performed to determine predictors of pathological results. Receiver operating characteristic curves were constructed to analyze the diagnostic value of PI-RADS v2 in PCa. Multivariate analysis indicated that age, PV, percent free PSA, and PI-RADS score were independent predictors of biopsy findings, while only PI-RADS score was an independent predictor of S-PCa (P < 0.05). The areas under the receiver operating characteristic curve for diagnosing PCa with respect to age, PV, percent free PSA, and PI-RADS score were 0.570, 0.430, 0.589 and 0.836, respectively. The area under the curve for diagnosing S-PCa with respect to PI-RADS score was 0.732. A PI-RADS score of 3 was the best cutoff for predicting PCa, and 4 was the best cutoff for predicting S-PCa. Thus, 92.8% of patients with PI-RADS scores of 1-2 would have avoided biopsy, but at the cost of missing 2.2% of the potential PCa cases. Similarly, 83.82% of patients with a PI-RADS score ≤ 3 would have avoided biopsy, but at the cost of missing 3.3% of the potential S-PCa cases. PI-RADS v2 could be used to reduce unnecessary prostate biopsies in patients with PSA levels of 4-10 ng/ml.

Impedimetric PSA aptasensor based on the use of a glassy carbon electrode modified with titanium oxide nanoparticles and silk fibroin nanofibers.

PubMed

Benvidi, Ali; Banaei, Maryam; Tezerjani, Marzieh Dehghan; Molahosseini, Hosein; Jahanbani, Shahriar

2017-12-14

This article describes an impedimetric aptasensor for the prostate specific antigen (PSA), a widely accepted prostate cancer biomarker. A glassy carbon electrode (GCE) was modified with titanium oxide nanoparticles (TiO 2 ) and silk fibroin nanofiber (SF) composite. The aptasensor was obtained by immobilizing a PSA-binding aptamer on the AuNP-modified with 6-mercapto-1-hexanol. The single fabrication steps were characterized by cyclic voltammetry and electrochemical impedance spectroscopy. The assay has two linear response ranges (from 2.5 fg.mL -1 to 25 pg.mL -1 , and from 25 pg.mL -1 to 25 ng.mL -1 ) and a 0.8 fg.mL -1 detection limit. After optimization of experimental conditions, the sensor is highly selective for PSA over bovine serum albumin and lysozyme. It was successfully applied to the detection of PSA in spiked serum samples. Graphical abstract Schematic of the fabrication of an aptasensor for the prostate specific antigen (PSA). It is based on the use of a glassy carbon electrode modified with gold nanoparticles and titanium oxide-silk fibroin. The immobilization process of aptamer and interaction with PSA were followed by electrochemical impedance spectroscopy technique.

Correlation of serum androgens and pituitary hormone levels with serum PSA less than 2.5 ng/ml.

PubMed

Sofikerim, Mustafa; Oruç, Ozgür; Eskicorapci, Sadettin; Guliyev, Fuat; Ozen, Haluk

2007-07-27

The aim of this clinical study was to determine whether there is a relationship between total serum testosterone, free testosterone, FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone) and serum prostate specific antigen (PSA) levels. We postulated that such a correlation existed then the use of hormone specific reference ranges might enhance the usefullness of PSA concentrations <2.5 ng/mL as a marker for prostate cancer. Prior to digital rectal examination, serum was obtained from all patients between 8.30-10:00 AM for hormone and PSA concentrations. The study was performed on 210 male patients >40 years of age visiting our urology outpatient clinics. PSA was correlated to age (r = 0.23, p = 0.019), but there none between serum testosterone and age. No significant correlation was noted between testosterone or free testosterone and serum PSA levels, and none between serum FSH or LH and PSA. In age specific reference groups (41-49; 50-59; 60-69 years), we found no significant correlation between PSA and hormone concentrations. In this population of eugonadal men with serum PSA values less than 2.5 ng/ml, serum androgens and pituitary hormones do not appear to correlate with serum PSA.

Investigative clinical study on prostate cancer part III: exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio.

PubMed

Porcaro, Antonio B; Petrozziello, Aldo; Romano, Mario; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Migliorini, Filippo; Zecchini Antoniolli, Stefano; Rubilotta, Emanuele; Lacola, Vincenzo; Monaco, Carmelo; Comunale, Luigi

2010-01-01

Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≥7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≥7) prostate cancer. Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable (FT) were always highly significant for patients with (1) intraprostate and extraprostate disease, and (2) low-grade and high-grade prostate cancer. According to the prognostic PSA/FT ratio, significantly lower levels of FT are detected in prostate cancer patients with extensive and high-grade disease. Also, significant linear correlations of FT predicting PSA are assessed in the different groups and subgroups of patients clustered according to the prognostic PSA/FT ratio. Confirmatory studies are needed. Copyright © 2010 S. Karger AG, Basel.

Validation of Association of Genetic Variants at 10q with PSA Levels in Men at High Risk for Prostate Cancer

PubMed Central

Chang, Bao-Li; Hughes, Lucinda; Chen, David Y. T.; Gross, Laura; Ruth, Karen; Giri, Veda N.

2013-01-01

Objectives Men with a family history of prostate cancer and African American men are at increased risk for prostate cancer and stand to benefit from individualized interpretation of PSA to guide screening strategies. The purpose of this study was to validate six previously identified markers among high-risk men enrolled in the Prostate Cancer Risk Assessment Program - a prostate cancer screening study. Patients and Methods Eligibility for PRAP includes men ages 35–69 years with a family history of prostate cancer, any African American male regardless of family history, and men with known BRCA gene mutations. GWAS markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12), and rs17632542 (19q13.33). Genotyping methods included either Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders. Results 707 participants (37% Caucasian, 63% African American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) strongly associated with PSA levels among high-risk Caucasian participants (p<0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) demonstrated an association to PSA level (p=0.03) in high-risk Caucasian men, with a 15% increase in PSA with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 is proposed specific to high-risk Caucasian men. Conclusion Genetic variation at 10q may be particularly important in personalizing interpretation of PSA for high-risk Caucasian men. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for high-risk Caucasian men. Further study is warranted. PMID:23937305

Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4-month randomised trial in middle-aged men.

PubMed

Kjaer, Thomas Nordstrøm; Ornstrup, Marie Juul; Poulsen, Morten Møller; Jørgensen, Jens Otto Lunde; Hougaard, David Michael; Cohen, Arieh Sierra; Neghabat, Shadman; Richelsen, Bjørn; Pedersen, Steen Bønløkke

2015-09-01

Resveratrol is a naturally occurring polyphenol with purported inhibitory effects on prostate growth and cancer development. A number of studies have demonstrated that resveratrol reduces prostate growth in animal models and reduces prostate cell growth in vitro. Based on these pre-clinical findings, interest in resveratrol is increasing in relation to the management of benign prostate hyperplasia (BPH) and prostate cancer. So far, no human trials have evaluated the effects of resveratrol on circulating androgens, prostate size, or biochemical markers of prostate size. In a randomized placebo controlled clinical study using two doses of resveratrol (150 mg or 1,000 mg resveratrol daily) for 4 months, we evaluated the effects on prostate size, prostate specific antigen (PSA) and sex steroid hormones in 66 middle-aged men suffering from the metabolic syndrome(MetS). At baseline, prostate size and PSA were positively correlated (R = 0.34, P < 0.007) as was prostate size and age (R = 0.37, P < 0.003). Prostate size did not correlate with testosterone, free testosterone, dihydrotestosterone (DHT), or any other androgen precursor at baseline. The highest dose of resveratrol lowered the serum level of androstenedione 24% (P = 0.052), dehydroepiandrosterone (DHEA) 41% (P < 0.01), and dehydroepiandrosterone-sulphate (DHEAS) 50% (p<0.001), compared to the control group. However, prostate size and levels of PSA, testosterone, free testosterone and DHT remained unchanged. In this population of middle-aged men suffering from MetS, high dose resveratrol (1,000 mg daily) administration for 4 months significantly lowered serum levels of the androgen precursors androstenedione, DHEA and DHEAS, whereas prostate size and circulating levels of PSA, testosterone, free testosterone, and dihydrotestosterone were unaffected. The present study suggests that resveratrol does not affect prostate volume in healthy middle-aged men as measured by PSA levels and CT acquired prostate volumes. Consequently, we find no support for the use of resveratrol in the treatment of benign prostate hyperplasia. © 2015 Wiley Periodicals, Inc.

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.

Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter?

PubMed

Jin, Byung-Soo; Kang, Seok-Hyun; Kim, Duk-Yoon; Oh, Hoon-Gyu; Kim, Chun-Il; Moon, Gi-Hak; Kwon, Tae-Gyun; Park, Jae-Shin

2015-09-01

To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score≤6, PSA≤10 ng/mL, and ≤2 positive biopsy cores). Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL(2), obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.

PSA doubling time of prostate carcinoma managed with watchful observation alone.

PubMed

Choo, R; DeBoer, G; Klotz, L; Danjoux, C; Morton, G C; Rakovitch, E; Fleshner, N; Bunting, P; Kapusta, L; Hruby, G

2001-07-01

To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

Genetic variation in protein specific antigen detected prostate cancer and the effect of control selection on genetic association studies

PubMed Central

Knipe, Duleeka W; Evans, David M; Kemp, John P.; Eeles, Rosalind; Easton, Douglas F; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L.; Hamdy, Freddie C.; Neal, David E

2014-01-01

Background Only a minority of the genetic component of prostate cancer (PrCa) risk has been explained. Some observed associations of single nucleotide polymorphisms (SNPs) with PrCa might arise from associations of these SNPs with circulating prostate specific antigen (PSA) because PSA values are used to select controls. Methods We undertook a genome-wide association study (GWAS) of screen detected PrCa (ProtecT 1146 cases and 1804 controls); meta-analysed the results with those from the previously published UK Genetic Prostate Cancer Study (1854 cases and 1437 controls); investigated associations of SNPs with PrCa using either ‘low’ (PSA <0.5ng/ml) or ‘high’ (PSA ≥3ng/ml, biopsy negative) PSA controls; and investigated associations of SNPs with PSA. Results The ProtecT GWAS confirmed previously reported associations of PrCa at 3 loci: 10q11.23, 17q24.3 and 19q13.33. The meta-analysis confirmed associations of PrCa with SNPs near 4 previously identified loci (8q24.21,10q11.23, 17q24.3 and 19q13.33). When comparing PrCa cases with low PSA controls, alleles at genetic markers rs1512268, rs445114, rs10788160, rs11199874, rs17632542, rs266849 and rs2735839 were associated with an increased risk of PrCa, but the effect-estimates were attenuated to the null when using high PSA controls (p for heterogeneity in effect-estimates<0.04). We found a novel inverse association of rs9311171-T with circulating PSA. Conclusions Differences in effect estimates for PrCa observed when comparing low vs. high PSA controls, may be explained by associations of these SNPs with PSA. Impact These findings highlight the need for inferences from genetic studies of PrCa risk to carefully consider the influence of control selection criteria. PMID:24753544

Decision Aids in Improving Knowledge in Patients With Newly Diagnosed Prostate Cancer

ClinicalTrials.gov

2018-06-08

Stage II Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage I Prostate Cancer; PSA Level Five to Ten; PSA Level Less Than Five; PSA Level Ten to Fifty

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.

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.

Understanding PSA and its derivatives in prediction of tumor volume: Addressing health disparities in prostate cancer risk stratification.

PubMed

Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

2017-03-28

To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives' ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer.

Prostate-Specific Antigen (PSA) Screening and New Biomarkers for Prostate Cancer (PCa)

PubMed Central

Rittenhouse, Harry; Hu, Xinhai; Cammann, Henning; Jung, Klaus

2014-01-01

Abstract PSA screening reduces PCa-mortality but the disadvantages overdiagnosis and overtreatment require multivariable risk-prediction tools to select appropriate treatment or active surveillance. This review explains the differences between the two largest screening trials and discusses the drawbacks of screening and its meta-analysisxs. The current American and European screening strategies are described. Nonetheless, PSA is one of the most widely used tumor markers and strongly correlates with the risk of harboring PCa. However, while PSA has limitations for PCa detection with its low specificity there are several potential biomarkers presented in this review with utility for PCa currently being studied. There is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. From all PSA-based markers, the FDA-approved prostate health index (phi) shows improved specificity over percent free and total PSA. Another kallikrein panel, 4K, which includes KLK2 has recently shown promise in clinical research studies but has not yet undergone formal validation studies. In urine, prostate cancer gene 3 (PCA3) has also been validated and approved by the FDA for its utility to detect PCa. The potential correlation of PCA3 with cancer aggressiveness requires more clinical studies. The detection of the fusion of androgen-regulated genes with genes of the regulatory transcription factors in tissue of ~50% of all PCa-patients is a milestone in PCa research. A combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 shows an improved accuracy for PCa detection. Overall, the field of PCa biomarker discovery is very exciting and prospective. PMID:27683457

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

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.

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

The relationship between early biochemical failure and perineural invasion in pathological T2 prostate cancer.

PubMed

Endrizzi, J; Seay, T

2000-04-01

To evaluate, in patients with pathologically localized prostate cancer, the relationship between early biochemical failure, i.e. an increasing prostate-specific antigen (PSA) level, and perineural invasion (PNI) on final pathology. The records were reviewed of 171 patients with prostate cancer who underwent prostatectomy at one institution between January 1992 and December 1995. Data on the histology, therapy and PSA level were collected and evaluated. Of the 171 patients with pathologically localized (pT2) prostate cancer, 131 were evaluable; 17 (13%) had a detectable PSA level in the first 5 years after surgery and 63 had PNI in the pathological specimen. Of those with PSA recurrence, 14 had PNI, one had no PNI and in two there was no comment on PNI. In comparison, only 10 of the 17 patients with recurrence had a Gleason sum of >/= 7. Perineural invasion seems to be an important predictor of early outcome in patients with organ-confined prostate cancer treated by prostatectomy. In this series it was the most sensitive predictor of biochemical failure. A more detailed pathological evaluation of prostate cancer may allow the clinician to provide closer surveillance and better informed clinical decision-making.

Identifying the Presence of Prostate Cancer in Individuals with PSA Levels <20 ng ml-1 Using Computational Data Extraction Analysis of High Dimensional Peripheral Blood Flow Cytometric Phenotyping Data.

PubMed

Cosma, Georgina; McArdle, Stéphanie E; Reeder, Stephen; Foulds, Gemma A; Hood, Simon; Khan, Masood; Pockley, A Graham

2017-01-01

Determining whether an asymptomatic individual with Prostate-Specific Antigen (PSA) levels below 20 ng ml -1 has prostate cancer in the absence of definitive, biopsy-based evidence continues to present a significant challenge to clinicians who must decide whether such individuals with low PSA values have prostate cancer. Herein, we present an advanced computational data extraction approach which can identify the presence of prostate cancer in men with PSA levels <20 ng ml -1 on the basis of peripheral blood immune cell profiles that have been generated using multi-parameter flow cytometry. Statistical analysis of immune phenotyping datasets relating to the presence and prevalence of key leukocyte populations in the peripheral blood, as generated from individuals undergoing routine tests for prostate cancer (including tissue biopsy) using multi-parametric flow cytometric analysis, was unable to identify significant relationships between leukocyte population profiles and the presence of benign disease (no prostate cancer) or prostate cancer. By contrast, a Genetic Algorithm computational approach identified a subset of five flow cytometry features ( CD 8 + CD 45 RA - CD 27 - CD 28 - ( CD 8 + Effector Memory cells); CD 4 + CD 45 RA - CD 27 - CD 28 - ( CD 4 + Terminally Differentiated Effector Memory Cells re-expressing CD45RA); CD 3 - CD 19 + (B cells); CD 3 + CD 56 + CD 8 + CD 4 + (NKT cells)) from a set of twenty features, which could potentially discriminate between benign disease and prostate cancer. These features were used to construct a prostate cancer prediction model using the k-Nearest-Neighbor classification algorithm. The proposed model, which takes as input the set of flow cytometry features, outperformed the predictive model which takes PSA values as input. Specifically, the flow cytometry-based model achieved Accuracy = 83.33%, AUC = 83.40%, and optimal ROC points of FPR = 16.13%, TPR = 82.93%, whereas the PSA-based model achieved Accuracy = 77.78%, AUC = 76.95%, and optimal ROC points of FPR = 29.03%, TPR = 82.93%. Combining PSA and flow cytometry predictors achieved Accuracy = 79.17%, AUC = 78.17% and optimal ROC points of FPR = 29.03%, TPR = 85.37%. The results demonstrate the value of computational intelligence-based approaches for interrogating immunophenotyping datasets and that combining peripheral blood phenotypic profiling with PSA levels improves diagnostic accuracy compared to using PSA test alone. These studies also demonstrate that the presence of cancer is reflected in changes in the peripheral blood immune phenotype profile which can be identified using computational analysis and interpretation of complex flow cytometry datasets.

Is Serum Prostate-specific Antigen a Diagnostic Marker for Benign and Malignant Breast Tumors in Women.

PubMed

Razavi, Seyed Hasan Emami; Ghajarzadeh, Mahsa; Abdollahi, Alireza; Taran, Ludmila; Shoar, Saeed; Omranipour, Ramesh

2015-06-01

Breast cancer is the most common cancer in women. Prostrate-specific antigen (PSA) is a marker of prostate gland malignancy which has been considered in cases with breast cancer in recent years. The goal of this study was to determine total and free PSA levels in cases with malignant and benign breast lesions. Ninety women with histological proved malignant breast masses and 90 with benign breast masses were enrolled. Total and free PSA levels along with histological grade and conditions of vascular and perinural invasion, status of hormonal tumor receptors, immune-histo-chemistry markers recorded for all cases. Total and free PSA levels were assessed after treatment in cases with malignant masses. Total and free PSA levels were significantly higher in cases with malignant masses. The best cut off point for total PSA to differentiate benign and malignant masses was 0.31 and the best cut off point for free PSA to differentiate benign and malignant masses was 0.19. After treatment, mean free PSA level was significantly lower than free PSA before treatment (0.23 vs 0.3, p<0.001). Serum PSA level could be applied for differentiating benign and malignant breast masses.

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

Alcohol consumption and PSA-detected prostate cancer risk—A case-control nested in the ProtecT study

PubMed Central

Zuccolo, Luisa; Lewis, Sarah J; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Smith, George Davey

2013-01-01

Alcohol is an established carcinogen but not an established risk factor for prostate cancer, despite some recent prospective studies suggesting increased risk among heavy drinkers. The aim of this study was to investigate the role of alcohol on prostate-specific antigen (PSA) levels and prostate cancer risk. Two thousand four hundred PSA detected prostate cancer cases and 12,700 controls matched on age and general practice were identified through a case-control study nested in the PSA-testing phase of a large UK-based randomized controlled trial for prostate cancer treatment (ProtecT). Linear and multinomial logistic regression models were used to estimate ratios of geometric means (RGMs) of PSA and relative risk ratios (RRRs) of prostate cancer by stage and grade, with 95% confidence intervals (CIs), associated with weekly alcohol intake and drinking patterns. We found evidence of lower PSA (RGM 0.98, 95% CI: 0.98–0.99) and decreased risk of low Gleason-grade (RRR 0.96; 95%CI 0.93–0.99) but increased risk of high-grade prostate cancer (RRR 1.04; 95%CI 0.99–1.08; pdifference=0.004) per 10 units/week increase in alcohol consumption, not explained by current BMI, blood pressure, comorbidities, or reverse causation. This is the first large population-based study to find evidence of lower PSA levels for increasing alcohol consumption, with potential public health implications for the detection of prostate cancer. Our results also support a modestly higher risk of high-grade disease for heavy drinkers, but require independent replication to establish the nature of the association of alcohol with low-grade disease, preferably in cohorts with a heterogeneous case-mix. What's new? Alcohol is not an established risk factor for prostate cancer; however, the current work suggests that heavy drinking could cause a small increase in risk of the more aggressive forms. If the results are confirmed to be causal, prostate cancer risk will be added to the many long-term health risks of heavy drinking, and public health strategies will then also reduce high-risk, poorer prognosis prostate cancer. The authors also found that heavy drinkers have lower PSA levels, suggesting that heavy alcohol consumption could be used as a marker to identify men in whom some cancers might be missed. PMID:23024014

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

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.

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.

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.

Diagnostic and prognostic significance of prostate specific antigen and serum interleukin 18 and 10 in patients with locally advanced prostate cancer: a prospective study.

PubMed

Dwivedi, Shailendra; Goel, Apul; Natu, Shanker M; Mandhani, Anil; Khattri, Sanjay; Pant, Kamlesh K

2011-01-01

Prostate cancer is one of the most common cancers afflicting men today. Prostate biopsy, an invasive procedure is generally used for diagnoses but attempts are being made to find accurate and precise non-invasive biomarkers. Diagnostic accuracy of prostate specific antigen (PSA) has been well documented. Serum interleukin-18 (IL-18) and interleukin-10 (IL-10) have shown their diagnostic ability in other cancers but not investigated well in prostate cancer. This study, thus determines the diagnostic and prognostic significance of PSA, IL-18 and IL-10 prospectively in patients with carcinoma prostate. A total of 149 patients, aged 40-84 yrs were investigated during April 2007 to July 2010 and recruited for this study after Institutional ethical approval. Of the total of 149 patients, 71 had biopsy proven prostate cancers (TNM stage: T2=17, T3=26 and T4=28) and 78 clinical benign prostate hyperplasia (BPH). Peripheral blood samples of all patients and 71 age matched control subjects were obtained at baseline and estimation of PSA, IL-18 and IL-10 was done by enzyme linked immunosorbent assay (ELISA). Carcinoma prostate patients were followed for three years. Data were analyzed with ANOVA, ROC curve analysis and survival analysis. The baseline levels of PSA, IL-18 and IL-10 in all groups of carcinoma prostate were found to be significantly (p<0.01) higher than both Control and BPH. The levels of IL-18 and IL-10 also found to be elevated significantly in stage T3 (p<0.05) and T4 (p<0.01) as compared to stage T2. The levels especially of IL-18 is found to be well associated with progression of the disease of various groups (r=0.84, p<0.01). In contrast, IL-10 showed significant direct association with progression of carcinoma (r=0.84, p<0.01) while inverse relation with survival duration (r=-0.48, p<0.01) and survival rate (χ2=8.98, p=0.0027; Hazard ratio=0.37, 95% CI=0.18-0.69). Study concluded that serum IL-18 has potential to be a better diagnostic marker with higher specificity and sensitivity and IL-10 may be valuable as a prognostic marker than PSA in carcinoma prostate.

The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy

PubMed Central

Tokgöz, Hüsnü; Taş, Selim; Giray, Özlem; Yalçınkaya, Soner; Tokgöz, Özlem; Koca, Cemile; Savaş, Murat; Erel, Özcan

2017-01-01

ABSTRACT Objectives The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). Materials and Methods A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Results Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native/total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Conclusion Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted. PMID:28128906

The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy.

PubMed

Tokgöz, Hüsnü; Taş, Selim; Giray, Özlem; Yalçınkaya, Soner; Tokgöz, Özlem; Koca, Cemile; Savaş, Murat; Erel, Özcan

2017-01-01

The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native / total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted. Copyright® by the International Brazilian Journal of Urology.

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.

Clinical outcomes and survival surrogacy studies of prostate-specific antigen declines following enzalutamide in men with metastatic castration-resistant prostate cancer previously treated with docetaxel.

PubMed

Armstrong, Andrew J; Saad, Fred; Phung, De; Dmuchowski, Carl; Shore, Neal D; Fizazi, Karim; Hirmand, Mohammad; Forer, David; Scher, Howard I; Bono, Johann De

2017-06-15

In the AFFIRM trial, enzalutamide significantly increased overall survival (OS) for men with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy versus placebo and significantly decreased prostate-specific antigen (PSA) levels. The goal of this post hoc analysis was to associate levels of PSA decline from baseline after enzalutamide with clinical outcomes in the postchemotherapy mCRPC setting. Men in the AFFIRM trial (n = 1199) were grouped by maximal PSA decline in the first 90 days of treatment. Kaplan-Meier estimates evaluated the association of defined PSA changes from baseline with OS, progression-free survival (PFS), radiographic PFS (rPFS), and pain response. Each PSA decline category was assessed for OS surrogacy using Prentice criteria, proportion of treatment effect explained (PTE), and proportion of variation explained. Men treated with enzalutamide had improved OS (hazard ratio, 0.63; P < .001) and higher rates of PSA decline (odds ratio, >19.0; P < .001) versus placebo. PSA declines of any, ≥30%, ≥50%, and ≥90% with enzalutamide were strongly associated with greater OS, PSA PFS, rPFS (P < .001), and pain response (P < .026) versus PSA increase/no decline. Any, ≥30%, and ≥50% declines in PSA resulted in the PTE range of 1.07-1.29, where treatment was no longer significant after adjustment for decline measures (P > .20). PSA declines of any, ≥30%, and ≥50% following enzalutamide were associated with greater clinical and pain response and improvements in PFS and OS. Surrogacy of PSA decline for OS was not fully established, possibly due to lack of PSA declines with placebo, and discordant results between PSA and imaging responses over time, and because some declines were not durable due to rapid resistance development. However, a lack of PSA decline by 90 days following enzalutamide treatment was a poor prognosis indicator in this setting. Conclusions from sensitivity analyses of maximal PSA decline from baseline over the entire treatment period are consistent with PSA declines restricted to the first 90 days. Cancer 2017;123:2303-2311. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Association between systemic inflammation and serum prostate-specific antigen in a healthy Korean population

PubMed Central

Yun, Jonghyun; Lee, Hyunyoung; Yang, Wonjae

2017-01-01

Objective Serum prostate-specific antigen (PSA) may be elevated in healthy men with systemic inflammation. We aimed to investigate the association between systemic inflammation markers and serum PSA in a healthy Korean population. Material and methods A cohort of 20,151 healthy native Korean men without prostate disease between the ages of 40 and 65 years who underwent medical checkups were studied from January 2007 to December 2013. Serum total PSA and serum C-reactive protein concentrations, neutrophil, lymphocyte, and platelet counts were determined. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were calculated. We checked the correlation between systemic inflammation markers and PSA. Results Data obtained from 18,800 healthy men were analyzed. The mean age of the study subjects was 50.72±7.62 years and the mean NLR was 1.764±0.804. Correlation analysis after adjustment for age and body mass index (BMI) revealed that neutrophil count (coefficient = 0.028, p value <0.001), and NLR (coefficient = 0.027, p value <0.001) correlated with PSA. Multivariate analysis using the full model revealed that age, neutrophil count and NLR were positively correlated with PSA (p<0.001, 0.001, and 0.043 respectively). Multivariate analysis using a stepwise model revealed that age, neutrophil count and NLR were positively correlated with PSA (p<0.001, 0.001, and 0.040, respectively) and BMI was negatively correlated with PSA (p<0.001). Conclusion Systemic inflammation markers are useful with a serum PSA in a healthy Korean population. NLR in particular is significantly associated with serum PSA. PMID:28861299

Prostate health index significantly reduced unnecessary prostate biopsies in patients with PSA 2-10 ng/mL and PSA >10 ng/mL: Results from a Multicenter Study in China.

PubMed

Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Helfand, Brian T; Brendler, Charles B; Conran, Carly A; Packiam, Vignesh; Gong, Jian; Wu, Yishuo; Zheng, Siqun L; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng

2017-08-01

The performance of prostate health index (phi) in predicting prostate biopsy outcomes has been well established for patients with prostate-specific antigen (PSA) values between 2 and 10 ng/mL. However, the performance of phi remains unknown in patients with PSA >10 ng/mL, the vast majority in Chinese biopsy patients. We aimed to assess the ability of phi to predict prostate cancer (PCa) and high-grade disease (Gleason Score ≥7) on biopsy in a Chinese population. This is a prospective, observational, multi-center study of consecutive patients who underwent a transrectal ultrasound guided prostate biopsy at four hospitals in Shanghai, China from August 2013 to December 2014. In the cohort of 1538 patients, the detection rate of PCa was 40.2%. phi had a significantly better predictive performance for PCa than total PSA (tPSA). The areas under the receiver operating characteristic curve (AUC) were 0.90 and 0.79 for phi and tPSA, respectively, P < 0.0001. A considerable proportion of patients in the cohort had PSAs >10 ng/mL (N = 838, 54.5%). The detection rates of PCa were 35.9% and 57.7% in patients with tPSA 10.1-20 and 20.1-50 ng/mL, respectively. The AUCs of phi (0.79 and 0.89, for these two groups, respectively) were also significantly higher than tPSA (0.57 and 0.63, respectively), both P < 0.0001. If a phi ≤35 was used as the cutoff, 599/1538 (39%) biopsies could have been avoided at a cost of missing small numbers of PCa patients: 49 (7.93%) PCa patients, including 18 (3.69%) high-grade tumors. Results from this study suggest that phi can be used to predict PCa and high-grade disease in Chinese men with high PSA levels (>10 ng/mL). © 2017 Wiley Periodicals, Inc.

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.

Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy.

PubMed

Liu, Xiaonan; Li, Jing; Schild, Steven E; Schild, Michael H; Wong, William; Vora, Sujay; Herman, Michael G; Fatyga, Mirek

2017-02-01

A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univa-riate and multivariate linear regression on log PSA values. Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.

A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer screening in Rotterdam, Netherlands.

PubMed

Gupta, A; Roobol, M J; Savage, C J; Peltola, M; Pettersson, K; Scardino, P T; Vickers, A J; Schröder, F H; Lilja, H

2010-08-24

Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>or=3 ng ml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), P<0.001, and high-grade cancer (Gleason >or=7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P=0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.

Non-invasive urinary metabolomic profiling discriminates prostate cancer from benign prostatic hyperplasia.

PubMed

Pérez-Rambla, Clara; Puchades-Carrasco, Leonor; García-Flores, María; Rubio-Briones, José; López-Guerrero, José Antonio; Pineda-Lucena, Antonio

2017-01-01

Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Serum prostate specific antigen (PSA) level has been extensively used as a biomarker to detect PCa. However, PSA is not cancer-specific and various non-malignant conditions, including benign prostatic hyperplasia (BPH), can cause a rise in PSA blood levels, thus leading to many false positive results. In this study, we evaluated the potential of urinary metabolomic profiling for discriminating PCa from BPH. Urine samples from 64 PCa patients and 51 individuals diagnosed with BPH were analysed using 1 H nuclear magnetic resonance ( 1 H-NMR). Comparative analysis of urinary metabolomic profiles was carried out using multivariate and univariate statistical approaches. The urine metabolomic profile of PCa patients is characterised by increased concentrations of branched-chain amino acids (BCAA), glutamate and pseudouridine, and decreased concentrations of glycine, dimethylglycine, fumarate and 4-imidazole-acetate compared with individuals diagnosed with BPH. PCa patients have a specific urinary metabolomic profile. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be useful to discriminate PCa from BPH in a clinical context.

Ever and Annual Use of Prostate Cancer Screening in African American Men

PubMed Central

Halbert, Chanita Hughes; Gattoni-Celli, Sebastiano; Savage, Stephen; Prasad, Sandip M.; Kittles, Rick; Briggs, Vanessa; Delmoor, Ernestine; Rice, LaShanta J.; Jefferson, Melanie; Johnson, Jerry C.

2016-01-01

Since prostate cancer continues to disproportionately affect African American men in terms of incidence, morbidity, and mortality, prostate-specific antigen (PSA) screening plays an important role in early detection, especially when men engage in informed decision making to accept or decline this test. The authors evaluated utilization of PSA testing among African American men based on factors that are important components of making informed decisions. Utilization of PSA testing was evaluated based on whether men had ever had PSA testing and PSA testing during the past year in a community-based sample of African American men ages 50 to 75 (n = 132). Overall, 64% of men (n = 85) reported that they had ever had a PSA test; the mean (SD) age for first use of PSA testing was 47.7 (SD = 7.4). The likelihood of ever having a PSA test increased significantly with physician communication (odds ratio [OR] = 14.2; 95% confidence interval [CI] = 4.20, 48.10; p = .0001) and with having an annual household income that was greater than $20,000 (OR = 9.80; 95% CI = 3.15, 30.51; p = .0001). The odds of ever having a PSA test were also decreased with each unit increase in future temporal orientation (OR = 0.66; 95% CI = 0.47, 0.93; p = .02). Of the men who had ever had PSA testing, 57% were screened during the past year. Only health insurance status had a significant independent association with having annual PSA testing (OR = 5.10; 95% CI = 1.67, 15.60; p = .004). Different factors were associated significantly with ever having PSA testing and annual testing among African American men. African American men may not be making an informed decision about prostate cancer screening. PMID:26240090

Ever and Annual Use of Prostate Cancer Screening in African American Men.

PubMed

Halbert, Chanita Hughes; Gattoni-Celli, Sebastiano; Savage, Stephen; Prasad, Sandip M; Kittles, Rick; Briggs, Vanessa; Delmoor, Ernestine; Rice, LaShanta J; Jefferson, Melanie; Johnson, Jerry C

2015-08-03

Since prostate cancer continues to disproportionately affect African American men in terms of incidence, morbidity, and mortality, prostate-specific antigen (PSA) screening plays an important role in early detection, especially when men engage in informed decision making to accept or decline this test. The authors evaluated utilization of PSA testing among African American men based on factors that are important components of making informed decisions. Utilization of PSA testing was evaluated based on whether men had ever had PSA testing and PSA testing during the past year in a community-based sample of African American men ages 50 to 75 (n = 132). Overall, 64% of men (n = 85) reported that they had ever had a PSA test; the mean (SD) age for first use of PSA testing was 47.7 (SD = 7.4). The likelihood of ever having a PSA test increased significantly with physician communication (odds ratio [OR] = 14.2; 95% confidence interval [CI] = 4.20, 48.10; p = .0001) and with having an annual household income that was greater than $20,000 (OR = 9.80; 95% CI = 3.15, 30.51; p = .0001). The odds of ever having a PSA test were also decreased with each unit increase in future temporal orientation (OR = 0.66; 95% CI = 0.47, 0.93; p = .02). Of the men who had ever had PSA testing, 57% were screened during the past year. Only health insurance status had a significant independent association with having annual PSA testing (OR = 5.10; 95% CI = 1.67, 15.60; p = .004). Different factors were associated significantly with ever having PSA testing and annual testing among African American men. African American men may not be making an informed decision about prostate cancer screening. © The Author(s) 2015.

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.

Unraveling Brazilian Indian population prostate good health: clinical, anthropometric and genetic features

PubMed Central

de Lima, Mario M.; Reis, Leonardo O.; Ferreira, Ubirajara; Cardoso, Ulieme Oliveira; Barbieri, Raquel Bueno; de Mendonça, Gustavo B.; Ward, Laura S.

2015-01-01

Purpose To compare dietary, lifestyle, clinical, anthropometric, genetic and prostatic features of Brazilian Indians and non-Indians (Amazon). Methods 315 men, 228 Indians and 89 non-Indians, ≥40 years old were submitted to digital rectal examination, serum prostate specific antigen (PSA), testosterone, TP53 and GSTP1 genotyping, anthropometric, lifestyle, dietary, personal and familial medical history. Prostatic symptoms were evaluated with the International Prostate Symptom Score (IPSS). Results Macuxis and Yanomamis represented 43.6% and 14.5% of Indians respectively who spontaneously referred no prostate symptoms. Mean IPSS was 7, range 3-19, with only 15% of moderate symptoms (score 8-19); Mean age was 54.7 years, waist circumference 86.6 cm, BMI 23.9 kg/m2. Yanomamis presented both lower BMI (21.4 versus 24.8 and 23.3, p=0,001) and prostate volume than Macuxis and “other ethnic groups” (15 versus 20, p=0.001). Testosterone (414 versus 502 and 512, p=0.207) and PSA (0.48 versus 0.6 and 0.41, p=0.349) were similar with progressive PSA increase with aging. Val/Val correlated with lower PSA (p=0.0361). Indians compared to control population presented: - TP53 super representation of Arg/Arg haplotype, 74.5% versus 42.5%, p<0.0001. -GSTP1 Ile/Ile 35.3% versus 60.9%; Ile/Val 45.9% versus 28.7%; Val/Val 18.8% versus 10.3%; p=0.0003. Conclusions Observed specific dietary, lifestyle, anthropometric and genetic profile for TP53 and GSTP1 may contribute to Brazilian Indian population prostate good health. PMID:26005978

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer

PubMed Central

Hiroshige, Tasuku; Eguchi, Yoshiro; Yoshizumi, Osamu; Chikui, Katsuaki; Kumagai, Hisaji; Kawaguchi, Yoshihiro; Onishi, Rei; Hayashi, Tokumasa; Watanabe, Kouta; Mitani, Tomotaro; Saito, Koujiro; Igawa, Tsukasa

2018-01-01

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC. PMID:29725416

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer.

PubMed

Hiroshige, Tasuku; Eguchi, Yoshiro; Yoshizumi, Osamu; Chikui, Katsuaki; Kumagai, Hisaji; Kawaguchi, Yoshihiro; Onishi, Rei; Hayashi, Tokumasa; Watanabe, Kouta; Mitani, Tomotaro; Saito, Koujiro; Igawa, Tsukasa

2018-05-01

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC.

[Prediction of life expectancy for prostate cancer patients based on the kinetic theory of aging of living systems].

PubMed

Viktorov, A A; Zharinov, G M; Neklasova, N Ju; Morozova, E E

2017-01-01

The article presents a methodical approach for prediction of life expectancy for people diagnosed with prostate cancer based on the kinetic theory of aging of living systems. The life expectancy is calculated by solving the differential equation for the rate of aging for three different stage of life - «normal» life, life with prostate cancer and life after combination therapy for prostate cancer. The mathematical model of aging for each stage of life has its own parameters identified by the statistical analysis of healthcare data from the Zharinov's databank and Rosstat CDR NES databank. The core of the methodical approach is the statistical correlation between growth rate of the prostate specific antigen level (PSA-level) or the PSA doubling time (PSA DT) before therapy, and lifespan: the higher the PSA DT is, the greater lifespan. The patients were grouped under the «fast PSA DT» and «slow PSA DT» categories. The satisfactory matching between calculations and experiment is shown. The prediction error of group life expectancy is due to the completeness and reliability of the main data source. A detailed monitoring of the basic health indicators throughout the each person life in each analyzed group is required. The absence of this particular information makes it impossible to predict the individual life expectancy.

Prostate-specific antigen levels among Chinese, Malays and Indians in Singapore from a community-based study.

PubMed

Chia, Sin-Eng; Lau, Weber Ko; Cheng, Christopher; Chin, Chong Min; Tan, James; Ho, Siew Hong

2007-01-01

The purpose of this study was to examine the distribution of prostate-specific antigen levels among Chinese, Malays and Indians in Singapore, taking the effect of age into consideration. The study was carried out as part of the Singapore Prostate Awareness Week from 23-26th February 2004. Men above 50 years old went to four government-restructured hospitals to participate in the study. Participants filled up a questionnaire and provided 5 ml of blood for measurement of PSA levels using the Abbott IMx Total PSA assay (Abbott Laboratories). 3,486 men responded to the study, comprising 92.8% Chinese, 3.0% Malays, 2.5% Indians and 1.8% Others. 92.7% of them had PSA levels of 4 microg/L or less. There were no significant differences (p<0.05) between the mean PSA levels of Chinese (1.60 microg/L), Malays (1.39 microg/L), Indians (1.23 microg/L) and Others (1.70 microg/L). PSA levels were significantly associated with age (Spearman's r= 0.27, p<0.01). PSA levels increased with each 10-year age group and these trends were significant (p<0.0001) across both PSA group levels and age groupings. In the 50-60 years age groups, the prevalence of PSA levels >4 mug/L were 1.1% and 3.7% respectively. This rose rapidly to 11.3% and 23.5% for age groups >60-70 and >80 years respectively. Our study shows that the median PSA levels in the Caucasian population in the USA are higher than those of Chinese, Malays and Indians in Singapore. PSA levels were positively associated with age. It may be more appropriate to offer PSA testing to men who are >60 years old rather than the current >50 years.

Hybrid Synthetic Receptors on MOSFET Devices for Detection of Prostate Specific Antigen in Human Plasma.

PubMed

Tamboli, Vibha K; Bhalla, Nikhil; Jolly, Pawan; Bowen, Chris R; Taylor, John T; Bowen, Jenna L; Allender, Chris J; Estrela, Pedro

2016-12-06

The study reports the use of extended gate field-effect transistors (FET) for the label-free and sensitive detection of prostate cancer (PCa) biomarkers in human plasma. The approach integrates for the first time hybrid synthetic receptors comprising of highly selective aptamer-lined pockets (apta-MIP) with FETs for sensitive detection of prostate specific antigen (PSA) at clinically relevant concentrations. The hybrid synthetic receptors were constructed by immobilizing an aptamer-PSA complex on gold and subjecting it to 13 cycles of dopamine electropolymerization. The polymerization resulted in the creation of highly selective polymeric cavities that retained the ability to recognize PSA post removal of the protein. The hybrid synthetic receptors were subsequently used in an extended gate FET setup for electrochemical detection of PSA. The sensor was reported to have a limit of detection of 0.1 pg/mL with a linear detection range from 0.1 pg/mL to 1 ng/mL PSA. Detection of 1-10 pg/mL PSA was also achieved in diluted human plasma. The present apta-MIP sensor developed in conjunction with FET devices demonstrates the potential for clinical application of synthetic hybrid receptors for the detection of clinically relevant biomarkers in complex samples.

Understanding PSA and its derivatives in prediction of tumor volume: addressing health disparities in prostate cancer risk stratification

PubMed Central

Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

2017-01-01

Objectives To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Results Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). Materials and Methods We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Conclusions Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives’ ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer. PMID:28160549

Seven-month prostate-specific antigen (PSA) is prognostic in patients with prostate cancer initially diagnosed with distant metastases.

PubMed

Nieder, Carsten; Haukland, Ellinor; Pawinski, Adam; Norum, Jan

2018-03-05

Recent research suggests that prostate-specific antigen (PSA) ≤ 0.2 ng/dl at 7 months is prognostic for better survival with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer regardless of chemotherapy with docetaxel. These results were derived from a group of clinical trial participants. Therefore, we performed a confirmatory analysis in patients treated outside of trials. Furthermore, we limited inclusion to those who presented with metastases at the initial diagnosis of prostate cancer (synchronous metastases). A retrospective analysis of a comprehensive regional database was performed. The oncology care in this region (Nordland County, Northern Norway) was provided by one center. Patients who were diagnosed between January 01, 2004 and December 31, 2016 were included. Of 101 patients, 90 were alive at 7 months and had their PSA value measured. Their median age was 68.5 years. Only six patients (7%) achieved PSA ≤ 0.2 ng/dl at 7 months. The median value was 4.05 ng/dl. Median overall survival was shortest in patients with PSA > 4.0 ng/dl (22 months). For patients with PSA between 0.3 and 4.0 ng/dl, median survival was 54 months (p = 0.0001). No further increase was seen in the small group with lower PSA. Statistical significance was also found for a cutoff of ≤ 1.0 ng/dl (55 vs. 32 months). PSA at 7 months predicts overall survival. Given that only 7% of patients achieved PSA ≤ 0.2 ng/dl, confirmation of this particular cutoff requires additional studies in other populations.

PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

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

McGuire, Sean E., E-mail: semcguir@mdanderson.org; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas; Lee, Andrew K.

2013-01-01

Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specificmore » mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.« less

A System Dynamics Model of Serum Prostate-Specific Antigen Screening for Prostate Cancer.

PubMed

Palma, Anton; Lounsbury, David W; Schlecht, Nicolas F; Agalliu, Ilir

2016-02-01

Since 2012, US guidelines have recommended against prostate-specific antigen (PSA) screening for prostate cancer. However, evidence of screening benefit from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial and the European Randomized Study of Screening for Prostate Cancer has been inconsistent, due partly to differences in noncompliance and contamination. Using system dynamics modeling, we replicated the PLCO trial and extrapolated follow-up to 20 years. We then simulated 3 scenarios correcting for contamination in the PLCO control arm using Surveillance, Epidemiology, and End Results (SEER) incidence and survival data collected prior to the PSA screening era (scenario 1), SEER data collected during the PLCO trial period (1993-2001) (scenario 2), and data from the European trial's control arm (1991-2005) (scenario 3). In all scenarios, noncompliance was corrected using incidence and survival rates for men with screen-detected cancer in the PLCO screening arm. Scenarios 1 and 3 showed a benefit of PSA screening, with relative risks of 0.62 (95% confidence interval: 0.53, 0.72) and 0.70 (95% confidence interval: 0.59, 0.83) for cancer-specific mortality after 20 years, respectively. In scenario 2, however, there was no benefit of screening. This simulation showed that after correcting for noncompliance and contamination, there is potential benefit of PSA screening in reducing prostate cancer mortality. It also demonstrates the utility of system dynamics modeling for synthesizing epidemiologic evidence to inform public policy. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Generalized extracellular molecule sensor platform for programming cellular behavior.

PubMed

Scheller, Leo; Strittmatter, Tobias; Fuchs, David; Bojar, Daniel; Fussenegger, Martin

2018-04-23

Strategies for expanding the sensor space of designer receptors are urgently needed to tailor cell-based therapies to respond to any type of medically relevant molecules. Here, we describe a universal approach to designing receptor scaffolds that enables antibody-specific molecular input to activate JAK/STAT, MAPK, PLCG or PI3K/Akt signaling rewired to transgene expression driven by synthetic promoters. To demonstrate its scope, we equipped the GEMS (generalized extracellular molecule sensor) platform with antibody fragments targeting a synthetic azo dye, nicotine, a peptide tag and the PSA (prostate-specific antigen) biomarker, thereby covering inputs ranging from small molecules to proteins. These four GEMS devices provided robust signaling and transgene expression with high signal-to-noise ratios in response to their specific ligands. The sensitivity of the nicotine- and PSA-specific GEMS devices matched the clinically relevant concentration ranges, and PSA-specific GEMS were able to detect pathological PSA levels in the serum of patients diagnosed with prostate cancer.

Acute prostatitis in middle-aged men: a prospective study.

PubMed

Kravchick, S; Cytron, S; Agulansky, L; Ben-Dor, D

2004-01-01

To determine the clinical outcome of middle-aged men with acute prostatitis, the optimum time for re-assessing their prostate-specific antigen (PSA) levels, and to detect any possible echotextural and vascular changes that remain as a consequence of acute inflammation. Persistent fever prompted a re-evaluation for prostatic abscess formation in 28 middle-aged men, using transrectal ultrasonography (TRUS) colour Doppler imaging, undertaken at the 3-, 6- and 12-month visits. The results of TRUS were compared with laboratory data and clinical outcome. Two abscesses were detected; 19 (68%) of the patients remained infection-free at the 3-month visit. Serum PSA levels were elevated in 11 (39%) of the patients at this visit; three prostate carcinomas were diagnosed. Increased intraprostatic colour flow was detected in 68% and there were hypoechoic areas in 46% of the patients. The re-evaluation for abscess formation should not be postponed for > 48 h. Patients with acute prostatitis tend to have persistent infection. PSA levels could be high even up to 3 months after an acute episode. Middle-aged men with carcinoma could be missed during the acute phase of inflammation. PSA and TRUS monitoring are strongly recommended.

Impact of the United States Preventive Services Task Force 'D' recommendation on prostate cancer screening and staging.

PubMed

Eapen, Renu S; Herlemann, Annika; Washington, Samuel L; Cooperberg, Matthew R

2017-05-01

In 2012, the United States Preventive Services Task Force (USPSTF) issued a grade 'D' recommendation against the use of routine prostate-specific antigen (PSA)-based screening for any men. This recommendation reflects critical misinterpretations of the available evidence base regarding benefits and harms of PSA screening and has influenced the nationwide landscape of prostate cancer screening, diagnosis, and treatment. Following the USPSTF recommendation, a substantial decline in PSA screening was noted for all age groups. Similarly, overall rates of prostate biopsy and prostate cancer incidence have significantly decreased with a shift toward higher grade and stage disease upon diagnosis. Concurrently, the incidence of metastatic prostate cancer has significantly risen in the United States. These trends are concerning particularly for the younger men with occult high-grade disease who are expected to benefit the most from early detection and definitive prostate cancer treatment. These emerging trends in PSA screening and prostate cancer incidence following the USPSTF recommendation may have significant public health implications. Due to the long natural history of the disease, a long-term follow-up is needed to provide a better understanding on the implications of such recommendations on disease progression and mortality rates in prostate cancer patients. The future of US screening policy should reflect a targeted 'smarter' screening strategy rather than dichotomizing the decision between 'screen all' or 'screen none'.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.

PubMed

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-08-30

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

PubMed Central

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-01-01

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer. PMID:27494861

Enhancement of sensitivity using hybrid stimulus for the diagnosis of prostate cancer based on polydiacetylene (PDA) supramolecules.

PubMed

Kwon, Il Kyoung; Kim, Jun Pyo; Sim, Sang Jun

2010-12-15

In this study, hybrid stimulus was initially introduced to improve the sensitivity of PDA vesicle chip for detection of prostate-specific antigen-α1-antichymotrypsin (PSA-ACT) complex. The strategy of hybrid stimulus on PDA vesicle chip offers the amplification method of fluorescent signal which combines a primary response by the immune reaction of antigen-antibody and a secondary response by the mechanical pressure of pAb-conjugated magnetic beads. As the primary response result on PDA vesicle chip, the PSA-ACT complex in PBS buffer was detected at 10 ng/mL. However, this detection sensitivity was insufficient for diagnosis of prostate cancer because the normal human PSA concentration is less than 4.0 ng/mL. To solve this problem, polyclonal PSA antibody-conjugated magnetic beads were used as an amplifying agent after primary immunoresponse. As a result, the PSA-ACT complex concentrations (as low as 0.1 ng/mL) could be detected in the PBS buffer sample. Therefore, this result can be applied to various fields, such as the detection of cells, proteins, and DNA for sensitive and specific biosensing based on PDA supramolecules. Copyright © 2010 Elsevier B.V. All rights reserved.

Experiences of Uncertainty in Men With an Elevated PSA

PubMed Central

Biddle, Caitlin; Brasel, Alicia; Underwood, Willie; Orom, Heather

2016-01-01

A significant proportion of men, ages 50 to 70 years, have, and continue to receive prostate specific antigen (PSA) tests to screen for prostate cancer (PCa). Approximately 70% of men with an elevated PSA level will not subsequently be diagnosed with PCa. Semistructured interviews were conducted with 13 men with an elevated PSA level who had not been diagnosed with PCa. Uncertainty was prominent in men’s reactions to the PSA results, stemming from unanswered questions about the PSA test, PCa risk, and confusion about their management plan. Uncertainty was exacerbated or reduced depending on whether health care providers communicated in lay and empathetic ways, and provided opportunities for question asking. To manage uncertainty, men engaged in information and health care seeking, self-monitoring, and defensive cognition. Results inform strategies for meeting informational needs of men with an elevated PSA and confirm the primary importance of physician communication behavior for open information exchange and uncertainty reduction. PMID:25979635

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

Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia.

PubMed

Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd; Ludwig, Nicole; Meese, Eckart

2015-01-01

Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients' sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.

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.

Serum complexed and free prostate-specific antigen (PSA) for the diagnosis of the polycystic ovarian syndrome (PCOS).

PubMed

Diamandis, Eleftherios P; Stanczyk, Frank Z; Wheeler, Sarah; Mathew, Anu; Stengelin, Martin; Nikolenko, Galina; Glezer, Eli N; Brown, Marshall D; Zheng, Yingye; Chen, Yen-Hao; Wu, Hsiao-Li; Azziz, Ricardo

2017-10-26

Polycystic ovarian syndrome (PCOS) is a common cause of reproductive and metabolic dysfunction. We hypothesized that serum prostate-specific antigen (PSA) may constitute a new biomarker for hyperandrogenism in PCOS. We conducted a cross-sectional study of 45 women with PCOS and 40 controls. Serum from these women was analyzed for androgenic steroids and for complexed PSA (cPSA) and free PSA (fPSA) with a novel fifth- generation assay with a sensitivity of ~10 fg/mL for cPSA and 140 fg/mL for fPSA. cPSA and fPSA levels were about three times higher in PCOS compared to controls. However, in PCOS, cPSA and fPSA did not differ according to waist-to-hip ratio, Ferriman-Gallwey score, or degree of hyperandrogenemia or oligo-ovulation. In PCOS and control women, serum cPSA and fPSA levels were highly correlated with each other, and with free and total testosterone levels, but not with other hormones. Adjusting for age, body mass index (BMI) and race, cPSA was significantly associated with PCOS, with an odds ratio (OR) of 5.67 (95% confidence interval [CI]: 1.86, 22.0). The OR of PCOS for fPSA was 7.04 (95% CI: 1.65, 40.4). A multivariate model that included age, BMI, race and cPSA yielded an area-under-the-receiver-operating-characteristic curve of 0.89. Serum cPSA and fPSA are novel biomarkers for hyperandrogenism in PCOS and may have value for disease diagnosis.

Using the prostate imaging reporting and data system version 2 (PI-RIDS v2) to detect prostate cancer can prevent unnecessary biopsies and invasive treatment.

PubMed

Liu, Chang; Liu, Shi-Liang; Wang, Zhi-Xian; Yu, Kai; Feng, Chun-Xiang; Ke, Zan; Wang, Liang; Zeng, Xiao-Yong

2018-04-13

Prostate cancer (PCa) is one of the most common cancers among men globally. The authors aimed to evaluate the ability of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) to classify men with PCa, clinically significant PCa (CSPCa), or no PCa, especially among those with serum total prostate-specific antigen (tPSA) levels in the "gray zone" (4-10 ng ml -1 ). A total of 308 patients (355 lesions) were enrolled in this study. Diagnostic efficiency was determined. Univariate and multivariate analyses, receiver operating characteristic curve analysis, and decision curve analysis were performed to determine and compare the predictors of PCa and CSPCa. The results suggested that PI-RADS v2, tPSA, and prostate-specific antigen density (PSAD) were independent predictors of PCa and CSPCa. A PI-RADS v2 score ≥4 provided high negative predictive values (91.39% for PCa and 95.69% for CSPCa). A model of PI-RADS combined with PSA and PSAD helped to define a high-risk group (PI-RADS score = 5 and PSAD ≥0.15 ng ml -1 cm -3 , with tPSA in the gray zone, or PI-RADS score ≥4 with high tPSA level) with a detection rate of 96.1% for PCa and 93.0% for CSPCa while a low-risk group with a detection rate of 6.1% for PCa and 2.2% for CSPCa. It was concluded that the PI-RADS v2 could be used as a reliable and independent predictor of PCa and CSPCa. The combination of PI-RADS v2 score with PSA and PSAD could be helpful in the prediction and diagnosis of PCa and CSPCa and, thus, may help in preventing unnecessary invasive procedures.

Time to PSA rise differentiates the PSA bounce after HDR and LDR brachytherapy of prostate cancer

PubMed Central

Skowronek, Janusz

2018-01-01

Purpose To investigate the differences in prostate-specific antigen (PSA) bounce (PB) after high-dose-rate (HDR-BT) or low-dose-rate (LDR-BT) brachytherapy alone in prostate cancer patients. Materials and methods Ninety-four patients with localized prostate cancer (T1-T2cN0), age ranged 50-81 years, were treated with brachytherapy alone between 2008 and 2010. Patients were diagnosed with adenocarcinoma, Gleason score ≤ 7. The LDR-BT total dose was 144-145 Gy, in HDR-BT – 3 fractions of 10.5 or 15 Gy. The initial PSA level (iPSA) was assessed before treatment, then PSA was rated every 3 months over the first 2 years, and every 6 months during the next 3 years. Median follow-up was 3.0 years. Results Mean iPSA was 7.8 ng/ml. In 58 cases, PSA decreased gradually without PB or biochemical failure (BF). In 24% of patients, PB was observed. In 23 cases (24%), PB was observed using 0.2 ng/ml definition; in 10 cases (11%), BF was diagnosed using nadir + 2 ng/ml definition. The HDR-BT and LDR-BT techniques were not associated with higher level of PB (26 vs. 22%, p = 0.497). Time to the first PSA rise finished with PB was significantly shorter after HDR-BT then after LDR-BT (median, 10.5 vs. 18.0 months) during follow-up. Predictors for PB were observed only after HDR-BT. Androgen deprivation therapy (ADT) and higher Gleason score decreased the risk of PB (HR = 0.11, p = 0.03; HR = 0.51, p = 0.01). The higher PSA nadir and longer time to PSA nadir increased the risk of PB (HR 3.46, p = 0.02; HR 1.04, p = 0.04). There was no predictors for PB after LDR-BT. Conclusions HDR-BT and LDR-BT for low and intermediate risk prostate cancer had similar PB rate. The PB occurred earlier after HDR-BT than after LDR-BT. ADT and higher Gleason score decreased, and higher PSA nadir and longer time to PSA nadir increased the risk of PB after HDR-BT. PMID:29619050

Time to PSA rise differentiates the PSA bounce after HDR and LDR brachytherapy of prostate cancer.

PubMed

Burchardt, Wojciech; Skowronek, Janusz

2018-02-01

To investigate the differences in prostate-specific antigen (PSA) bounce (PB) after high-dose-rate (HDR-BT) or low-dose-rate (LDR-BT) brachytherapy alone in prostate cancer patients. Ninety-four patients with localized prostate cancer (T1-T2cN0), age ranged 50-81 years, were treated with brachytherapy alone between 2008 and 2010. Patients were diagnosed with adenocarcinoma, Gleason score ≤ 7. The LDR-BT total dose was 144-145 Gy, in HDR-BT - 3 fractions of 10.5 or 15 Gy. The initial PSA level (iPSA) was assessed before treatment, then PSA was rated every 3 months over the first 2 years, and every 6 months during the next 3 years. Median follow-up was 3.0 years. Mean iPSA was 7.8 ng/ml. In 58 cases, PSA decreased gradually without PB or biochemical failure (BF). In 24% of patients, PB was observed. In 23 cases (24%), PB was observed using 0.2 ng/ml definition; in 10 cases (11%), BF was diagnosed using nadir + 2 ng/ml definition. The HDR-BT and LDR-BT techniques were not associated with higher level of PB (26 vs. 22%, p = 0.497). Time to the first PSA rise finished with PB was significantly shorter after HDR-BT then after LDR-BT (median, 10.5 vs. 18.0 months) during follow-up. Predictors for PB were observed only after HDR-BT. Androgen deprivation therapy (ADT) and higher Gleason score decreased the risk of PB (HR = 0.11, p = 0.03; HR = 0.51, p = 0.01). The higher PSA nadir and longer time to PSA nadir increased the risk of PB (HR 3.46, p = 0.02; HR 1.04, p = 0.04). There was no predictors for PB after LDR-BT. HDR-BT and LDR-BT for low and intermediate risk prostate cancer had similar PB rate. The PB occurred earlier after HDR-BT than after LDR-BT. ADT and higher Gleason score decreased, and higher PSA nadir and longer time to PSA nadir increased the risk of PB after HDR-BT.

Detection of AR-V7 mRNA in whole blood may not predict the effectiveness of novel endocrine drugs for castration-resistant prostate cancer.

PubMed

Takeuchi, Takumi; Okuno, Yumiko; Hattori-Kato, Mami; Zaitsu, Masayoshi; Mikami, Koji

2016-01-01

A splice variant of androgen receptor (AR), AR-V7, lacks in androgen-binding portion and leads to aggressive cancer characteristics. Reverse transcription-polymerase chain reactions (PCRs) and subsequent nested PCRs for the amplification of AR-V7 and prostate-specific antigen (PSA) transcripts were done for whole blood of patients with prostate cancer and male controls. With primary reverse transcription PCRs, AR-V7 and PSA were detected in 4.5% and 4.7% of prostate cancer, respectively. With nested PCRs, AR-V7 messenger RNA (mRNA) was positive in 43.8% of castration-sensitive prostate cancer and 48.1% of castration-resistant prostate cancer (CRPC), while PSA mRNA was positive in 6.3% of castration-sensitive prostate cancer and 18.5% of CRPC. Whole-blood samples of controls showed AR-V7 mRNA expression by nested PCR. Based on multivariate analysis, expression of AR-V7 mRNA in whole blood was not significantly correlated with clinical parameters and PSA mRNA in blood, while univariate analysis showed a correlation between AR-V7 mRNA and metastasis at initial diagnosis. Detection of AR-V7 mRNA did not predict the reduction of serum PSA in patients with CRPC following abiraterone and enzalutamide administration. In conclusion, AR-V7 mRNA expression in normal hematopoietic cells may have annihilated the manifestation of aggressiveness of prostate cancer and the prediction of the effectiveness of abiraterone and enzalutamide by the assessment of AR-V7 mRNA in blood.

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.

NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

PubMed

Moul, Judd W; Lilja, Hans; Semmes, O John; Lance, Raymond S; Vessella, Robert L; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J; Stevens, Barbara; Klem, Robert E; McDermed, Jonathan E; Triebell, Melissa T; Adams, Thomas H

2012-12-01

To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors. Copyright © 2012 Elsevier Inc. All rights reserved.

The inverse relationship between prostate-specific antigen (PSA) and obesity.

PubMed

Aref, Adel; Vincent, Andrew D; O'Callaghan, Michael; Martin, Sean; Sutherland, Peter; Hoy, Andrew; Butler, Lisa M; Wittert, Gary

2018-06-25

Obese men have lower serum prostate-specific antigen (PSA) than comparably aged lean men, but the underlying mechanism remains unclear. The aim of this study was to determine the effect of obesity on PSA and the potential contributing mechanisms. A cohort of 1195 men aged 35 years and over at recruitment, with demographic, anthropometric (body mass index (BMI), waist circumference (WC)) and serum hormone (serum testosterone (T), estradiol (E2)), PSA and hematology assessments obtained over two waves was assessed. Men with a history of prostate cancer or missing PSA were excluded, leaving 970 men for the final analysis. Mixed-effects regressions and mediation analyses adjusting for hormonal and volumetric factors explore the potential mechanisms relating obesity to PSA. After adjusting for age, PSA levels were lower in men with greater WC (p=0.001). In a multivariable model including WC, age, E2/T and PlasV as predictors, no statistically significant associations were observed between with PSA and either WC (p=0.36) or PlasV (p=0.49), while strong associations were observed with both E2/T (p<0.001) and age (p<0.001). In the mediation analyses with PlasV as the mediator, the average causal mediation effect (ACME) explained roughly 0.2 of the total effect of WC on PSA (p=0.31), while when E2/T is a mediator; the ACME explained roughly 0.5 of the effect (p<0.001). Our findings indicate that lower PSA levels in obese men, as compared to normal weight men, can be explained both by hormonal changes (elevated E2/T ratio) and haemodilution. Hormonal factors therefore represent a substantial but underappreciated mediating pathway.

[PSA testing, biopsy and cancer and benign prostate hyperplasia in France].

PubMed

Tuppin, P; Samson, S; Fagot-Campagna, A; Lukacs, B; Alla, F; Allemand, H; Paccaud, F; Thalabard, J-C; Vicaut, E; Vidaud, M; Millat, B

2014-07-01

Prostate-specific antigen (PSA) testing is high in France. The aim of this study was to estimate their frequency and those of biopsy and newly diagnosed cancer (PCa) according to the presence or absence of treated benign prostatic hyperplasia (BPH). This study concerned men 40 years and older covered by the main French national health insurance scheme (73 % of all men of this age). Data were collected from the national health insurance information system (SNIIRAM). This database comprehensively records all of the outpatient prescriptions and healthcare services reimbursed. This information are linked to data collected during hospitalisations. The frequency of men without diagnosed PCa (10.9 millions) with at least one PSA test was very high in 2011 (men aged 40 years and older: 30 %, 70-74 years: 56 %, 85 years and older: 33 % and without HBP: 25 %, 41 % and 19 %). Men with treated BPH totalized 9 % of the study population, but 18 % of the men with at least one PSA test, 44 % of those with at least one prostate biopsy and 40 % of those with newly managed PCa. Over a 3-year period, excluding men with PCa, 88 % of men with BPH had at least one PSA test and 52 % had three or more PSA tests versus 52 % and 15 % for men without BPH. One year after PSA testing, men of 55-69 years with BPH more frequently underwent prostate biopsy than those without BPH (5.4 % vs 1.8 %) and presented PCa (1.9 % vs 0.9 %). PSA testing frequencies in France are very high even after exclusion of men with BPH, who can be a group with more frequent managed PCa. 4. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Diagnostic performance of expression of PCA3, Hepsin and miR biomarkers inejaculate in combination with serum PSA for the detection of prostate cancer.

PubMed

Roberts, Matthew J; Chow, Clement W K; Schirra, Horst Joachim; Richards, Renee; Buck, Marion; Selth, Luke A; Doi, Suhail A R; Samaratunga, Hema; Perry-Keene, Joanna; Payton, Diane; Yaxley, John; Lavin, Martin F; Gardiner, Robert A

2015-04-01

Here, we report on the evaluation of the diagnostic performance of ejaculate-derived PCA3, Hepsin, and miRNAs to complement serum PSA to detect prostate cancer. cDNA was prepared from 152 candidate specimens following RNA isolation and amplification for PSA, PCA3 and Hepsin qPCR, with 66 having adequate RNA for all three assays. Small RNA sequencing and examination of PCa-associated miRNAs miR-200b, miR-200c, miR-375 and miR-125b was performed on 20 specimens. We compared findings from prostate biopsies using D'Amico and PRIAS classifications and in relation to whole gland histopathology following radical prostatectomy. Multivariate logistic regression modeling and clinical risk (incorporating standard clinicopathological variables) were performed for all ejaculate-based markers. While Hepsin alone was not of predictive value, the Hepsin:PCA3 ratio together with serum PSA, expressed as a univariate composite score based on multivariate logistic regression, was shown to be a better predictor than PSA alone of prostate cancer status (AUC 0.724 vs. 0.676) and risk, using D'Amico (AUC 0.701 vs. 0.680) and PRIAS (AUC 0.679 vs. 0.659) risk stratification criteria as classified using prostate biopsies. It was also possible to analyse a subgroup of patients for miRNA expression with miR-200c (AUC 0.788) and miR-375 (AUC 0.758) showing best single marker performance, while a combination of serum PSA, miR-200c, and miR-125b further improved prediction for prostate cancer status when compared to PSA alone determined by biopsy (AUC 0.869 vs. 0.672; P < 0.05), and risk (D'Amico/PRIAS) as well as by radical prostatectomy histology (AUC 0.809 vs. 0.690). For prostate cancer status by biopsy, at a sensitivity of 90%, the specificity of the test increased from 11% for PSA alone to 67% for a combination of PSA, miR-200c, and miR-125b. These results show that use of a combination of different types of genetic markers in ejaculate together with serum PSA are at least as sensitive as those reported in DRE urine. Furthermore, a combination of serum PSA and selected miRNAs improved prediction of prostate cancer status. This approach may be helpful in triaging patients for MRI and biopsy, when confirmed by larger studies. © 2015 Wiley Periodicals, Inc.

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.

Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

PubMed

Hayman, Jonathan; Phillips, Ryan; Chen, Di; Perin, Jamie; Narang, Amol K; Trieu, Janson; Radwan, Noura; Greco, Stephen; Deville, Curtiland; McNutt, Todd; Song, Daniel Y; DeWeese, Theodore L; Tran, Phuoc T

2018-06-01

Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men. © 2018 Wiley Periodicals, Inc.

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.

Cranberry intervention in patients with prostate cancer prior to radical prostatectomy. Clinical, pathological and laboratory findings.

PubMed

Student, Vladimir; Vidlar, Ales; Bouchal, Jan; Vrbkova, Jana; Kolar, Zdenek; Kral, Milan; Kosina, Pavel; Vostalova, Jitka

2016-12-01

Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.

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

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.

Pretreatment prostate-specific antigen velocity is associated with freedom from biochemical recurrence of prostate cancer after low-dose-rate prostate brachytherapy alone.

PubMed

Rossi, Peter J; Urbanic, James; Clark, Peter E; McCullough, David L; Lee, W Robert

2008-01-01

This report examines the relationship between pretreatment prostate-specific antigen (PSA) velocity (PSAV) and freedom from biochemical recurrence (FFBR) in men with prostate cancer treated with low-dose-rate prostate brachytherapy (LDRPB). This is a report of 51 men treated with LDRPB between 1997 and 1999. two or more evaluable PSA values >3 months apart and <18 months before treatment. PSAV is calculated using a linear regression equation. All patients had biopsy confirmed, clinically localized prostate cancer. All men were treated with (125)I LDRPB. The prescription dose was 144Gy. Biochemical failure is determined from PSA values over time using the ASTRO Consensus Definition. FFBR is estimated using Kaplan-Meier method. Pretreatment variables analyzed include percentage positive biopsy cores, D(90), risk group, and PSAV. All p values are two-sided. The median followup is 60 months. The median pretreatment PSA is 6.5, 75% of men were Stage T1c, and 88% had Gleason score > or =6; 10% developed evidence of biochemical recurrence at a median of 13 months (range, 6-36). The 6-year estimate of FFBR is 90% for the entire cohort. On univariate analysis, pretreatment PSAV and risk group are associated with FFBR. The 6-year estimate of FFBR in patients with a PSAV <2 ng/mL/yr is 100% vs. 80% (95% confidence interval: 64-96%) when the pretreatment PSAV is > or =2 ng/mL/yr before LDRPB (p = 0.017). Pretreatment PSAV is a predictor of FFBR after LDRPB in this population of men with prostate cancer. Men with a pretreatment PSAV > or =2 ng/mL/yr may warrant more aggressive treatment.

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.

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

PSA predicts development of incident lower urinary tract symptoms: results from the REDUCE study.

PubMed

Patel, Devin N; Feng, Tom; Simon, Ross M; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Roehrborn, Claus; Andriole, Gerald L; Freedland, Stephen J

2018-05-23

The relationship between baseline prostate-specific antigen (PSA) and development of lower urinary tract symptoms (LUTS) in asymptomatic and mildly symptomatic men is unclear. We sought to determine if PSA predicts incident LUTS in these men. A post-hoc analysis of the 4-year REDUCE study was performed to assess for incident LUTS in 1534 men with mild to no LUTS at baseline. The primary aim was to determine whether PSA independently predicted incident LUTS after adjusting for the key clinical variables of age, prostate size, and baseline International prostate symptom score (IPSS). Incident LUTS was defined as the first report of medical treatment, surgery, or sustained clinically significant symptoms (two IPSS >14). Cox proportional hazards, cumulative incidence curves, and the log-rank test were used to test our hypothesis. A total of 1534 men with baseline IPSS <8 were included in the study cohort. At baseline, there were 335 men with PSA 2.5-4 ng/mL, 589 with PSA 4.1-6 ng/mL, and 610 with PSA 6-10 ng/mL. During the 4-year study, 196 men progressed to incident LUTS (50.5% medical treatment, 9% surgery, and 40.5% new symptoms). As a continuous variable, higher PSA was associated with increased incident LUTS on univariable (HR 1.09, p = 0.019) and multivariable (HR 1.08, p = 0.040) analysis. Likewise, baseline PSA 6-10 ng/mL was associated with increased incident LUTS vs. PSA 2.5-4 ng/mL in adjusted models (HR 1.68, p = 0.016). This association was also observed in men with PSA 4.1-6 ng/mL vs. PSA 2.5-4 ng/mL (HR 1.60, p = 0.032). Men with mild to no LUTS but increased baseline PSA are at increased risk of developing incident LUTS presumed due to benign prostatic hyperplasia.

Feasibility of metronomic chemotherapy with tegafur-uracil, cisplatin, and dexamethasone for docetaxel-refractory prostate cancer

PubMed Central

Kubota, Hiroki; Fukuta, Katsuhiro; Yamada, Kenji; Hirose, Masahito; Naruyama, Hiromichi; Yanai, Yoshimasa; Yamada, Yasuyuki; Watase, Hideki; Kawai, Noriyasu; Tozawa, Keiichi; Yasui, Takahiro

2017-01-01

Objectives: To evaluate the efficacy of tegafur–uracil (UFT), a prodrug of 5-fluorouracil, plus cisplatin and dexamethasone in patients with docetaxel-refractory prostate cancers. Methods: Twenty-five patients with docetaxel-refractory prostate cancer were administered oral UFT plus intravenous cisplatin (UFT-P therapy) and dexamethasone. Treatment responses were assessed monthly via prostate-specific antigen (PSA) level measurements. Treatment-related adverse events and overall survival were also assessed. Results: UFT-P therapy resulted in decreased PSA levels in 14 (56%) patients and increased PSA levels in 11 (44%). In patients with increased PSA levels, 7 (64%) of the 11 patients displayed decreased PSA doubling times. The UFT-P therapy response rate was 84% (21/25 patients). Imaging studies revealed that tumor shrinkage during UFT-P therapy occurred in 1 patient in whom bilateral hydronephrosis caused by lymph node metastasis improved. The median survival time from docetaxel initiation was 36 months. In UFT-P-treated patients, the median PSA progression and overall survival times were 6 and 14 months, respectively. UFT-P treatment-related adverse events were mild diarrhea, general fatigue, and anorexia. Treatment was not discontinued for any of the patients. UFT-P therapy did not cause serious hepatic or renal dysfunction or pancytopenia. Conclusions: UFT-P therapy is a safe and effective treatment for patients with docetaxel-refractory prostate cancer, although large-scale, multicenter, prospective studies are needed to validate these findings. PMID:29255528

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.

Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study.

PubMed

Thomsen, F B; Brasso, K; Berg, K D; Gerds, T A; Johansson, J-E; Angelsen, A; Tammela, T L J; Iversen, P

2016-03-01

The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting. Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml. We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values. NCT00672282. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A comparative Study of Aptasensor Vs Immunosensor for Label-Free PSA Cancer Detection on GQDs-AuNRs Modified Screen-Printed Electrodes.

PubMed

Srivastava, Monika; Nirala, Narsingh R; Srivastava, S K; Prakash, Rajiv

2018-01-31

Label-free and sensitive detection of PSA (Prostate Specific Antigen) is still a big challenge in the arena of prostate cancer diagnosis in males. We present a comparative study for label-free PSA aptasensor and PSA immunosensor for the PSA-specific monoclonal antibody, based on graphene quantum dots-gold nanorods (GQDs-AuNRs) modified screen-printed electrodes. GQDs-AuNRs composite has been synthesized and used as an electro-active material, which shows fast electron transfer and catalytic property. Aptamer or anti-PSA has immobilized onto the surface of modified screen printed electrodes. Three techniques are used simultaneously, viz. cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedence spectroscopy (EIS) to investigate the analytical performance of both PSA aptasensor and PSA immunosensor with its corresponding PSA antigen. Under optimum conditions, both sensors show comparable results with an almost same limit of detection (LOD) of 0.14 ng mL -1 . The results developed with aptasensor and anti-PSA is also checked through the detection of PSA in real samples with acceptable results. Our study suggests some advantages of aptasensor in terms of better stability, simplicity and cost effectiveness. Further our present work shows enormous potential of our developed sensors for real application using voltammetric and EIS techniques simultaneous to get reliable detection of the disease.

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.

Construction of novel electrochemical immunosensor for detection of prostate specific antigen using ferrocene-PAMAM dendrimers.

PubMed

Çevik, Emre; Bahar, Özlem; Şenel, Mehmet; Abasıyanık, M Fatih

2016-12-15

In this study, an immunosensor was designed to utilize for the detection of prostate specific antigen (PSA) based on three different generations (G1, G2 and G3) of ferrocene (Fc) cored polyamidiamine dendrimers (Fc-PAMAM) gold (Au) electrode. The self-assembled monolayer principle (SAM) was used to fabricate the sensitive, selective and disposable immunosensor electrodes. In electrode fabrication cysteamine (Cys) was the first agent covalently linked on the Au electrode surface. Immobilized redox center (ferrocene) cored PAMAM dendrimers served as a layer for the further binding of biological components. The monoclonal antibody of PSA (anti-PSA) was covalently immobilized on dendrimers which were attached onto the modified Au surface (Au/Cys/Fc-PAMAMs/anti-PSA). PSA levels were quantitatively analyzed by using electrochemical differential pulse voltammetry (DPV) whose lowest detection limit was calculated as 0.001ngmL(-1). The Au/Cys/FcPAMAM/anti-PSA immunosensor showed excellent performance for PSA at the pulse amplitude; 50mV and the scan rate; 10mV/s in a wide linear concentration range of 0.01ng-100ngmL(-1). Analytical performance and specificity assays were carried out using human serum and different proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

A dramatic, objective antiandrogen withdrawal response: case report and review of the literature.

PubMed

Lau, Yiu-Keung; Chadha, Manpreet K; Litwin, Alan; Trump, Donald L

2008-11-05

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation.

A Sol-gel Integrated Dual-readout Microarray Platform for Quantification and Identification of Prostate-specific Antigen.

PubMed

Lee, SangWook; Lee, Jong Hyun; Kwon, Hyuck Gi; Laurell, Thomas; Jeong, Ok Chan; Kim, Soyoun

2018-01-01

Here, we report a sol-gel integrated affinity microarray for on-chip matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) that enables capture and identification of prostate?specific antigen (PSA) in samples. An anti-PSA antibody (H117) was mixed with a sol?gel, and the mixture was spotted onto a porous silicon (pSi) surface without additional surface modifications. The antibody easily penetrates the sol-gel macropore fluidic network structure, making possible high affinities. To assess the capture affinity of the platform, we performed a direct assay using fluorescein isothiocyanate-labeled PSA. Pure PSA was subjected to on-chip MALDI-TOF-MS analysis, yielding three clear mass peptide peaks (m/z = 1272, 1407, and 1872). The sol-gel microarray platform enables dual readout of PSA both fluorometric and MALDI-TOF MS analysis in biological samples. Here we report a useful method for a means for discovery of biomarkers in complex body fluids.

Use of selenium-silymarin mix reduces lower urinary tract symptoms and prostate specific antigen in men.

PubMed

Vostalova, Jitka; Vidlar, Ales; Ulrichova, Jitka; Vrbkova, Jana; Simanek, Vilim; Student, Vladimir

2013-12-15

The aim of this double-blind, placebo controlled clinical trial was to assess the effects of a combination of selenium and silymarin in men with lower urinary tract symptoms, benign prostatic hyperplasia and a prostate specific antigen (PSA) ≤2.5ng/ml. The volunteers were randomized to two groups: the first one (n=26) received 240μg selenium (in the form of yeast l-selenomethionine) plus 570mg silymarin daily for 6 months and the second (n=29) received placebo. Outcome measures were changes in the International Prostate Symptom Score (IPSS), bladder volume (V), urinary flow rate, ultrasound estimated postvoid residual urine volume (RV), serum PSA, testosterone and selenium levels, safety clinical biochemistry, hematology and oxidative stress parameters at baseline and on day 180. The results showed statistically significant differences (p<0.05) between treatment and control groups for the following parameters: IPSS score, urodynamic parameters: maximal rate of urine flow (Qmax), average flow (Qave), V and RV, total PSA value and serum selenium levels. There was a significant reduction in PSA in the selenium-silymarin group but no effect on blood testosterone level. Overall the treatment was well-tolerated with no adverse effects. Copyright © 2013 Elsevier GmbH. All rights reserved.

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.

[Cost analysis of ultrasound-guided transrectal needle biopsy in prostatic carcinoma].

PubMed

Bissoli, E; Fandella, A; La Torre, E; Faggiano, L; Anselmo, G; Frasson, F

1998-04-01

The literature mortality and morbidity rates from prostatic carcinoma prompt to the better use of some routine diagnostic tools such as transrectal ultrasound-guided biopsy. We evaluated the overall cost of transrectal ultrasound biopsy (TRUSB) of the prostate and investigated the economic impact of the procedures currently used to diagnose prostatic carcinoma. The total cost of TRUSB was calculated with reference to 247 procedures performed in 1996. The following cost factors were evaluated: personnel, materials, maintenance-equipment depreciation, energy consumption and hospital overheads. A literature review was also carried out to check if our extrapolated costs corresponded to those of other authors worldwide and to consider them in the wider framework of the cost effectiveness of the strategies for the early diagnosis of prostatic cancer. The overall cost of TRUSB was Itl. 249,000, obtained by adding together the costs of: personnel (Itl. 160,000); materials (Itl. 59,000); equipment maintenance and depreciation (Itl. 12,400); energy consumption (Itl. 100); hospital overheads (Itl. 17,500). The literature review points out TRUSB as a clinically invasive tool for diagnosing prostatic carcinoma whose cost-effectiveness is debated. Cadaver studies report the presence of cancer cells in the prostate of 50% of 70-year-old men, while extrapolations calculate a morbidity from prostatic carcinoma in 9.5% of 50-year-old men. It is therefore obvious that randomized prostatic biopsies, methods apart, are very likely to be positive. This probability varies with the patient's age, the level of prostate specific antigen (PSA), the density of PSA/cm3 of prostate volume (PSAD), and the positivity of exploration and/or transrectal ultrasound findings. Despite the strict application of all these criteria and the critical assessment of the patient's general conditions, TRUSB is indicated for 16% of the male population over 50, with obvious implications. It has been recently suggested that the ratio between free PSA (antigen fraction of the total serum PSA) and total PSA could be clinically useful as an effective predict of TRUSB positivity or negativity. Free PSA evaluation might thus help reduce the number of TRUSB.

Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy in Japanese patients with locally advanced prostate cancer.

PubMed

Sakamoto, Masato; Mizowaki, Takashi; Mitsumori, Michihide; Takayama, Kenji; Sasai, Keisuke; Norihisa, Yoshiki; Kamoto, Toshiyuki; Nakamura, Eijiro; Ogawa, Osamu; Hiraoka, Masahiro

2010-12-01

The outcomes of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with locally advanced prostate cancer who initiated salvage hormonal therapy (SHT) at a relatively early phase were evaluated. Between April 1998 and April 2003, 70 Japanese patients with T3N0M0 prostate cancer who received radical 3D-CRT treatment were evaluated. The median age, initial prostate-specific antigen (PSA) level, and duration of NAHT were 73 years old, 26.3 ng/ml, and 4 months, respectively. Seventy grays were given in 35 fractions that were confined to the prostate and seminal vesicles. Adjuvant hormonal therapy was not administered after 3D-CRT in any of the cases. The median follow-up period was 64.9 months. The median PSA value at the time of initiation of SHT was 5.0 ng/ml (range 0.1-21.6 ng/ml). Overall, disease-specific, PSA failure-free (based on the Phoenix definition) and SHT-free survival rates at 5 years were 90.3% (95% CI 86.5-94.0), 96.5% (94.0-98.9), 60.5% (48.2-72.7), and 63.5% (57.2-69.8), respectively. Therefore, two-thirds of the patients were still hormone-free at 5 years. PSA control rates in our series of Japanese patients with stage T3N0M0 prostate cancer treated with the standard dose of 3D-CRT combined with NAHT seemed higher than expected. This approach involving 3D-CRT combined with NAHT with the initiation of SHT at PSA values of around 5 ng/ml may be one option for Japanese patients with locally advanced prostate cancer, although further prospective study is required to confirm the validity.

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.

Prognostic role of prostate-specific antigen and prostate volume for the risk of invasive therapy in patients with benign prostatic hyperplasia initially managed with alpha1-blockers and watchful waiting.

PubMed

Mochtar, C A; Kiemeney, L A L M; Laguna, M P; van Riemsdijk, M M; Barnett, G S; Debruyne, F M J; de la Rosette, J J M C H

2005-02-01

To investigate the prognostic role of prostate-specific antigen (PSA) level and prostate volume (PV) for the need for benign prostatic hyperplasia (BPH)-related invasive therapy among patients initially treated with an alpha1-blocker or watchful waiting (WW) in real-life clinical practice. Data were collected from 2264 consecutive patients with clinical BPH. Patients initially treated with an alpha1-blocker or WW were included in this study. They were stratified by baseline PSA level (less than 1.5, 1.5 to less than 3.0, 3.0 to 10.0 ng/mL) and PV (less than 30 and 30 to 200 cm3), and analyzed for the time to BPH-related invasive therapy. Of the 2264 patients, 389 treated with alpha1-blockers and 553 who chose WW were included. Across the PSA and PV strata, the alpha1-blocker group had worse symptoms, peak flow, postvoid residual urine volumes, and obstruction than did the WW group. Increasing PSA levels produced an increase in the 5-year cumulative risk of invasive treatment: 20%, 34%, and 44% in the alpha1-blocker and 8%, 9%, and 15% in the WW group for a PSA level of less than 1.5, 1.5 to less than 3.0, and 3.0 to 10.0 ng/mL, respectively. The hazard ratio for the highest compared with the lowest PSA strata was 2.8 for alpha1-blocker and 2.7 for WW patients. An increasing PV increased the 5-year cumulative risk from 21% to 35% in the alpha1-blocker group and 8% to 11% in the WW group. The hazard ratio for the large versus small prostates in the alpha1-blocker group was 1.8 and in the WW group was 1.0. A higher PSA level and larger PV resulted in a greater risk of BPH-related invasive therapy that was more pronounced in the alpha1-blocker than in the WW patients. However, symptom severity, flow parameters, and obstruction grade may have contributed to the difference in risk between the two treatment groups.

Consequences of an Early PSA Response to Enzalutamide Treatment for Japanese Patients with Metastatic Castration-resistant Prostate Cancer.

PubMed

Kato, Haruo; Furuya, Yosuke; Miyazawa, Yoshiyuki; Miyao, Takeshi; Syuto, Takahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro

2016-11-01

Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population. Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide. The PSA progression-free survival (PFS), radiographic PFS (rPFS) and overall survival (OS) were assessed. The association of rPFS and OS in patients with an early PSA response at 4 weeks after commencement of enzalutamide was studied. Early PSA responses were significantly associated with a longer rPFS (median of 47.9 vs. 20.1 weeks, p<0.001, in patients exhibiting a 50% PSA response; median of 40.9 vs. 20.1 weeks, p=0.016, in patients exhibiting a 30% PSA response). OS was also significantly associated with an early PSA response (p=0.002 for patients exhibiting a 50% PSA response, p=0.003 for patients exhibiting a 30% PSA response). Multivariate analysis showed that the predictors of a 50% PSA response were an interval to mCRPC and a docetaxel treatment history, while the predictor of a 30% PSA response was a docetaxel treatment history. Furthermore, a 50% PSA response was independently prognostic of rPFS. An early PSA response to enzalutamide was significantly associated with a longer rPFS and OS. This information will aid in the management of patients treated with enzalutamide. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[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.

PSA Nadir of <0.5 ng/mL Following Brachytherapy for Early-Stage Prostate Adenocarcinoma is Associated With Freedom From Prostate-Specific Antigen Failure

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

Ko, Eric C.; Stone, Nelson N.; Department of Urology, Mount Sinai Medical Center, New York, NY

2012-06-01

Purpose: Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. Methods and Materials: We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk ({<=}T2a), 126 were intermediate risk (T2b), and 20 were high riskmore » (>T2b). By Gleason score, 840 were low risk ({<=}6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Results: Absence of high-risk factors in clinical stage ({<=}T2b), Gleason score ({<=}7), and pretreatment PSA ({<=}20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 {+-} 0.8% vs. 71.5 {+-} 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in {<=}5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 {+-} 0.7% vs. 80.8 {+-} 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in {<=}5 years had significantly higher FFBF than other patients. Conclusions: Pretreatment risk factors (clinical tumor stage, Gleason score, pretreatment PSA) strongly predict for patients achieving nPSA <0.5 ng/mL following brachytherapy, and this cohort had significantly higher long-term FFBF.« less

PSA nadir of <0.5 ng/mL following brachytherapy for early-stage prostate adenocarcinoma is associated with freedom from prostate-specific antigen failure.

PubMed

Ko, Eric C; Stone, Nelson N; Stock, Richard G

2012-06-01

Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk (≤ T2a), 126 were intermediate risk (T2b), and 20 were high risk (>T2b). By Gleason score, 840 were low risk (≤ 6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Absence of high-risk factors in clinical stage (≤ T2b), Gleason score (≤ 7), and pretreatment PSA (≤ 20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 ± 0.8% vs. 71.5 ± 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in ≤ 5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 ± 0.7% vs. 80.8 ± 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in ≤ 5 years had significantly higher FFBF than other patients. Pretreatment risk factors (clinical tumor stage, Gleason score, pretreatment PSA) strongly predict for patients achieving nPSA <0.5 ng/mL following brachytherapy, and this cohort had significantly higher long-term FFBF. Copyright © 2012 Elsevier Inc. All rights reserved.

Screening for prostate cancer: are digital rectal examinations being performed?

PubMed

Federman, Daniel G; Pitkin, Patricia; Carbone, Vera; Concato, John; Kravetz, Jeffrey D

2014-04-01

Prostate cancer is common and prostate cancer screening is controversial; this retrospective observational study was conducted to determine the prevalence of digital rectal examination (DRE) in those in whom a prostate-specific antigen (PSA) test was performed. A manual review was performed of the electronic medical record for male veterans in the VA Connecticut Healthcare System without a history of known prostate cancer aged between 50 and 74 years who underwent PSA testing. Documentation of DRE (or refusal) within 12 months before or after the performance of a PSA test. Less than half (47.6%) of patients underwent DRE. An additional 6.9% were offered DRE and refused. Although the provider gender was not associated with DRE, resident physicians were less likely to perform DRE than nonresidents; P = 0.01. Patients whose PSA was > 4.0 ng/mL were more likely to undergo DRE than those whose PSA was ≤ 4.0 ng/mL; P = 0.002. Those with body mass index (BMI) > 40 kg/m 2 were less likely to undergo DRE than those with BMI < 30 kg/m 2 ; P = 0.04. Screening for prostate cancer remains controversial. We found a low rate of DRE among veterans in whom prostate cancer screening was entertained. Although the provider gender does not seem to influence DRE, resident physicians were less likely to perform DRE than other providers. Our finding that BMI > 40 kg/m 2 is associated with a lower rate of DRE than those with BMI < 30 kg/m 2 is consistent with screening for other cancers and should be explored further.

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.

Prostate specific antigen (PSA) kinetic as a prognostic factor in metastatic prostate cancer receiving androgen deprivation therapy: systematic review and meta-analysis.

PubMed

Afriansyah, Andika; Hamid, Agus Rizal Ardy Hariandy; Mochtar, Chaidir Arif; Umbas, Rainy

2018-01-01

Aim: Metastatic prostate cancer (mPCa) has a poor outcome with median survival of two to five years. The use of androgen deprivation therapy (ADT) is a gold standard in management of this stage.  Aim of this study is to analyze the prognostic value of PSA kinetics of patient treated with hormonal therapy related to survival from several published studies Method: Systematic review and meta-analysis was performed using literature searching in the electronic databases of MEDLINE, Science Direct, and Cochrane Library. Inclusion criteria were mPCa receiving ADT, a study analyzing Progression Free Survival (PFS), Overall Survival (OS), or Cancer Specific Survival (CSS) and prognostic factor of survival related to PSA kinetics (initial PSA, PSA nadir, and time to achieve nadir (TTN)). The exclusion criteria were metastatic castration resistant of prostate cancer (mCRPC) and non-metastatic disease. Generic inverse variance method was used to combine hazard ratio (HR) within the studies. Meta-analysis was performed using Review Manager 5.2 and a p-value <0.05 was considered statistically significant. Results: We found 873 citations throughout database searching with 17 studies were consistent with inclusion criteria. However, just 10 studies were analyzed in the quantitative analysis. Most of the studies had a good methodological quality based on Ottawa Scale. No significant association between initial PSA and PFS. In addition, there was no association between initial PSA and CSS/ OS. We found association of reduced PFS (HR 2.22; 95% CI 1.82 to 2.70) and OS/ CSS (HR 3.31; 95% CI 2.01-5.43) of patient with high PSA nadir. Shorter TTN was correlated with poor result of survival either PFS (HR 2.41; 95% CI 1.19 - 4.86) or CSS/ OS (HR 1.80; 95%CI  1.42 - 2.30) Conclusion: Initial PSA before starting ADT do not associated with survival in mPCa.  There is association of PSA nadir and TTN with survival.

Prostate specific antigen (PSA) kinetic as a prognostic factor in metastatic prostate cancer receiving androgen deprivation therapy: systematic review and meta-analysis

PubMed Central

Afriansyah, Andika; Hamid, Agus Rizal Ardy Hariandy; Mochtar, Chaidir Arif; Umbas, Rainy

2018-01-01

Aim: Metastatic prostate cancer (mPCa) has a poor outcome with median survival of two to five years. The use of androgen deprivation therapy (ADT) is a gold standard in management of this stage.  Aim of this study is to analyze the prognostic value of PSA kinetics of patient treated with hormonal therapy related to survival from several published studies Method: Systematic review and meta-analysis was performed using literature searching in the electronic databases of MEDLINE, Science Direct, and Cochrane Library. Inclusion criteria were mPCa receiving ADT, a study analyzing Progression Free Survival (PFS), Overall Survival (OS), or Cancer Specific Survival (CSS) and prognostic factor of survival related to PSA kinetics (initial PSA, PSA nadir, and time to achieve nadir (TTN)). The exclusion criteria were metastatic castration resistant of prostate cancer (mCRPC) and non-metastatic disease. Generic inverse variance method was used to combine hazard ratio (HR) within the studies. Meta-analysis was performed using Review Manager 5.2 and a p-value <0.05 was considered statistically significant. Results: We found 873 citations throughout database searching with 17 studies were consistent with inclusion criteria. However, just 10 studies were analyzed in the quantitative analysis. Most of the studies had a good methodological quality based on Ottawa Scale. No significant association between initial PSA and PFS. In addition, there was no association between initial PSA and CSS/ OS. We found association of reduced PFS (HR 2.22; 95% CI 1.82 to 2.70) and OS/ CSS (HR 3.31; 95% CI 2.01-5.43) of patient with high PSA nadir. Shorter TTN was correlated with poor result of survival either PFS (HR 2.41; 95% CI 1.19 – 4.86) or CSS/ OS (HR 1.80; 95%CI  1.42 – 2.30) Conclusion: Initial PSA before starting ADT do not associated with survival in mPCa.  There is association of PSA nadir and TTN with survival PMID:29904592

Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis–Free Survival and Prostate Cancer–Specific Mortality

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

Naik, Mihir, E-mail: naikm@ccf.org; Reddy, Chandana A.; Stephans, Kevin L.

Objectives/Background: To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis–free survival (DMFS), and prostate cancer–specific mortality (PCSM). Methods: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, andmore » cumulative incidence was used to estimate PCSM. Results: 532 patients were identified. The median follow-up time was 7.5 years (range, 1-16.25 years). The median initial PSA (iPSA) was 13.0 ng/mL (range, 0.37-255 ng/mL), and the median duration of ADT was 6 months (range, 1-78 months). The median PSA 6 months after EBRT was 0.1 ng/mL (range, 0-19 ng/mL), and 310 patients (58.3%) had a 6-month PSA ≤0.1 ng/mL. Multivariable analysis (MVA) demonstrated that a 6-month post-EBRT PSA of >0.1 ng/mL was an independent predictor of worse bRFS (hazard ratio [HR] = 2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6 months) was not predictive of any clinical endpoint. Conclusions: A 6-month posttreatment PSA >0.1 ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early salvage therapy on future clinical trials.« less

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

PubMed

Narang, A K; Trieu, J; Radwan, N; Ram, A; Robertson, S P; He, P; Gergis, C; Griffith, E; Singh, H; DeWeese, T A; Honig, S; Annadanam, A; Greco, S; DeVille, C; McNutt, T; DeWeese, T L; Song, D Y; Tran, P T

2017-06-01

In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml -1 ) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

Prostate cancer screening

MedlinePlus

Prostate cancer screening - PSA; Prostate cancer screening - digital rectal exam; Prostate cancer screening - DRE ... level of PSA could mean you have prostate cancer. But other conditions can also cause a high ...

Cost implications of PSA screening differ by age.

PubMed

Rao, Karthik; Liang, Stella; Cardamone, Michael; Joshu, Corinne E; Marmen, Kyle; Bhavsar, Nrupen; Nelson, William G; Ballentine Carter, H; Albert, Michael C; Platz, Elizabeth A; Pollack, Craig E

2018-05-09

Multiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups-including the costs of screening and subsequent diagnosis, treatment, and adverse events-remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios. We determined the prevalence of PSA screening among men aged 50 and higher using 2013-2014 data from a large, multispecialty group, obtained reimbursed costs associated with screening, diagnosis, and treatment from a commercial health plan, and identified transition probabilities for biopsy, diagnosis, treatment, and complications from the literature to generate a cost model. We estimated annual total costs for groups of men ages 50-54, 55-69, and 70+ years, and varied annual prostate cancer screening prevalence in each group from 5 to 50% and tested hypothetical examples of different test characteristics (e.g., true/false positive rate). Under the baseline screening patterns, costs of the PSA screening represented 10.1% of the total costs; costs of biopsies and associated complications were 23.3% of total costs; and, although only 0.3% of all screen eligible patients were treated, they accounted for 66.7% of total costs. For each 5-percentage point decrease in PSA screening among men aged 70 and older for a single calendar year, total costs associated with prostate cancer screening decreased by 13.8%. For each 5-percentage point decrease in PSA screening among men 50-54 and 55-69 years old, costs were 2.3% and 7.3% lower respectively. With constrained financial resources and with national pressure to decrease use of clinically unnecessary PSA-based prostate cancer screening, there is an opportunity for cost savings, especially by focusing on the downstream costs disproportionately associated with screening men 70 and older.

Cytokine profiling identifies an interaction of IL-6 and IL-1α to drive PSMA-PSA prostate clones.

PubMed

Jemaa, Awatef Ben; Bouraoui, Yosra; Rais, Nawfel Ben; Nouira, Yassine; Oueslati, Ridha

2016-12-01

Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear. We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups. 27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20ng/mL or >20ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups. Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones. Copyright © 2016 Elsevier GmbH. All rights reserved.

CWR22: the first human prostate cancer xenograft with strongly androgen-dependent and relapsed strains both in vivo and in soft agar.

PubMed

Nagabhushan, M; Miller, C M; Pretlow, T P; Giaconia, J M; Edgehouse, N L; Schwartz, S; Kung, H J; de Vere White, R W; Gumerlock, P H; Resnick, M I; Amini, S B; Pretlow, T G

1996-07-01

Most patients' prostate cancers respond to androgen deprivation but relapse after periods of several months to years. Only two prostate cancer xenografts, LNCaP and PC-346, have been reported to be responsive to androgen deprivation and to relapse subsequently. Both of these tumors shrink slightly, if at all, and relapse less than 5 weeks after androgen withdrawal. After androgen withdrawal, the human primary prostate cancer xenograft CWR22 regresses markedly, and prostate-specific antigen (PSA) falls up to 3000-fold in the blood of mice. PSA usually returns to normal. In some animals, the tumor relapses and is then designated CWR22R. In these animals, PSA starts to rise approximately 2-7 months, and tumor begins to grow 3-10 months after castration. Animals with CWR22 need to be euthanized because of large tumors 6-12 weeks after the transplantation of CWR22. Androgen withdrawal prolongs life approximately 3-4-fold.

C-reactive protein haplotype is associated with high PSA as a marker of metastatic prostate cancer but not with overall cancer risk

PubMed Central

Eklund, C M; Tammela, T L J; Schleutker, J; Hurme, M

2009-01-01

Growing evidence points to a role for inflammation in prostate carcinogenesis. The significance of C-reactive protein (CRP), an inflammatory and innate immunity molecule, has not been evaluated thoroughly in prostate cancer (PC). In this study of 739 Finnish patients with PC and 760 healthy men, we evaluated the associations of CRP genotypes and haplotypes with total PC risk and PC progression, using prostate-specific antigen (PSA) as a marker of metastatic disease. Although the haplotype frequencies were similar in patients and controls, an association between haplotype ACCCA and patients' PSA levels was found. The carriers more often had a high PSA than non-carriers (P=0.0002) and the SNP rs2794521 A-allele and rs1800947 C-allele carriers had a higher PSA than non-carriers (P=0.009 and P=0.0004, respectively). A trend for a younger age at diagnosis was found among the carriers of ACCCA (P=0.07) and the rs1800947 C-allele (P=0.06), as well as a trend for the latter to have more likely metastases (P=0.06), but not after Bonferroni correction (α=0.00208). This is the first study to suggest association between PSA and CRP variants in PC and, therefore, further studies are warranted. CRP alleles previously found to protect against increased CRP levels are now suggested to be associated with metastatic PC, indicated by elevated PSA. PMID:19436291

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.

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 ...

Frequency of Propionibacterium acnes Infection in Prostate Glands with Negative Biopsy Results Is an Independent Risk Factor for Prostate Cancer in Patients with Increased Serum PSA Titers.

PubMed

Kakegawa, Tomoya; Bae, Yuan; Ito, Takashi; Uchida, Keisuke; Sekine, Masaki; Nakajima, Yutaka; Furukawa, Asuka; Suzuki, Yoshimi; Kumagai, Jiro; Akashi, Takumi; Eishi, Yoshinobu

2017-01-01

Propionibacterium acnes has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular P. acnes infection in prostate glands and the higher frequency of P. acnes-positive glands in radical prostatectomy specimens from patients with prostate cancer (PCa) than in those from patients without PCa led us to examine whether the P. acnes-positive gland frequency can be used to assess the risk for PCa in patients whose first prostate biopsy, performed due to an increased prostate-specific antigen (PSA) titer, was negative. We retrospectively collected the first and last prostate biopsy samples from 44 patients that were diagnosed PCa within 4 years after the first negative biopsy and from 36 control patients with no PCa found in repeated biopsy for at least 3 years after the first biopsy. We evaluated P. acnes-positive gland frequency and P. acnes-positive macrophage number using enzyme-immunohistochemistry with a P. acnes-specific monoclonal antibody (PAL antibody). The frequency of P. acnes-positive glands was higher in PCa samples than in control samples in both first biopsy samples and in combined first and last biopsy samples (P < 0.001). A frequency greater than the threshold (18.5 and 17.7, respectively) obtained by each receiver operating characteristic curve was an independent risk factor for PCa (P = 0.003 and 0.001, respectively) with odds ratios (14.8 and 13.9, respectively) higher than those of serum PSA titers of patients just before each biopsy (4.6 and 2.3, respectively). The number of P. acnes-positive macrophages did not differ significantly between PCa and control samples. These results suggested that the frequency of P. acnes-positive glands in the first negative prostate biopsy performed due to increased PSA titers can be supportive information for urologists in planning repeated biopsy or follow-up strategies.

Influence of Long-Distance Bicycle Riding on Serum/Urinary Biomarkers of Prostate Cancer

PubMed Central

Heger, Zbynek; Gumulec, Jaromir; Ondrak, Ales; Skoda, Jan; Zitka, Zdenek; Cernei, Natalia; Masarik, Michal; Zitka, Ondrej; Adam, Vojtech

2016-01-01

Herein, we present a study focused on the determination of the influence of long-distance (53 km) bicycle riding on levels of chosen biochemical urinary and serum prostate cancer (PCa) biomarkers total prostate-specific antigen (tPSA), free PSA (fPSA) and sarcosine. Fourteen healthy participants with no evidence of prostate diseases, in the age range from 49–57 years with a median of 52 years, underwent physical exercise (mean race time of 150 ± 20 min, elevation increase of 472 m) and pre- and post-ride blood/urine sampling. It was found that bicycle riding resulted in elevated serum uric acid (p = 0.001, median 271.76 vs. 308.44 µmol/L pre- and post-ride, respectively), lactate (p = 0.01, median 2.98 vs. 4.8 mmol/L) and C-reactive protein (p = 0.01, 0.0–0.01 mg/L). It is noteworthy that our work supports the studies demonstrating an increased PSA after mechanical manipulation of the prostate. The subjects exhibited either significantly higher post-ride tPSA (p = 0.002, median 0.69 vs. 1.1 ng/mL pre- and post-ride, respectively) and fPSA (p = 0.028, median 0.25 vs. 0.35 ng/mL). Contrary to that, sarcosine levels were not significantly affected by physical exercise (p = 0.20, median 1.64 vs. 1.92 µmol/mL for serum sarcosine, and p = 0.15, median 0.02 µmol/mmol of creatinine vs. 0.01 µmol/mmol of creatinine for urinary sarcosine). Taken together, our pilot study provides the first evidence that the potential biomarker of PCa—sarcosine does not have a drawback by means of a bicycle riding-induced false positivity, as was shown in the case of PSA. PMID:26999116

68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour.

PubMed

Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Fritz, Josef; von Guggenberg, Elisabeth; Kendler, Dorota; Scarpa, Lorenza; di Santo, Gianpaolo; Roig, Llanos Geraldo; Maffey-Steffan, Johanna; Horninger, Wolfgang; Virgolini, Irene Johanna

2017-06-01

Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by 68 Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of 68 Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related 68 Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level. Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6-10; median PSA: 9.7 ng/ml) referred for 68 Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUV max ). The SUV max of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUV max of the primary tumour was assessed in relation to both PSA level and GS. Eighty-two patients (91.1%) demonstrated pathologic tracer accumulation in the primary tumour that exceeded physiologic tracer uptake in normal prostate tissue (median SUV max : 12.5 vs. 3.9). Tumours with GS of 6, 7a (3+4) and 7b (4+3) showed significantly lower 68 Ga-PSMA-11 uptake, with median SUV max of 5.9, 8.3 and 8.2, respectively, compared to patients with GS >7 (median SUV max : 21.2; p < 0.001). PC patients with PSA ≥10.0 ng/ml exhibited significantly higher uptake than those with PSA levels <10.0 ng/ml (median SUV max : 17.6 versus 7.7; p < 0.001). In 24 patients (26.7%), 82 lymph nodes with pathologic tracer accumulation consistent with metastases were detected (median SUV max : 10.6). Eleven patients (12.2%) revealed 55 pathologic osseous lesions suspicious for bone metastases (median SUV max : 11.6). The GS and PSA level correlated with the intensity of tracer accumulation in the primary tumours of PC patients on 68 Ga-PSMA-11 PET/CT. As PC tumours with GS 6+7 and patients with PSA values ≤10 ng/ml showed significantly lower 68 Ga-PSMA-11 uptake, 68 Ga-PSMA-11 PET/CT should be preferentially applied for primary staging of PC in patients with GS >7 or PSA levels ≥10 ng/ml.

Experiences of Uncertainty in Men With an Elevated PSA.

PubMed

Biddle, Caitlin; Brasel, Alicia; Underwood, Willie; Orom, Heather

2015-05-15

A significant proportion of men, ages 50 to 70 years, have, and continue to receive prostate specific antigen (PSA) tests to screen for prostate cancer (PCa). Approximately 70% of men with an elevated PSA level will not subsequently be diagnosed with PCa. Semistructured interviews were conducted with 13 men with an elevated PSA level who had not been diagnosed with PCa. Uncertainty was prominent in men's reactions to the PSA results, stemming from unanswered questions about the PSA test, PCa risk, and confusion about their management plan. Uncertainty was exacerbated or reduced depending on whether health care providers communicated in lay and empathetic ways, and provided opportunities for question asking. To manage uncertainty, men engaged in information and health care seeking, self-monitoring, and defensive cognition. Results inform strategies for meeting informational needs of men with an elevated PSA and confirm the primary importance of physician communication behavior for open information exchange and uncertainty reduction. © The Author(s) 2015.

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

Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer.

PubMed

Ecke, Thorsten H; Huang-Tiel, Hui-Juan; Golka, Klaus; Selinski, Silvia; Geis, Berit Christine; Koswig, Stephan; Bathe, Katrin; Hallmann, Steffen; Gerullis, Holger

2016-11-10

High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D'Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis ( p = 0.009), PSA on date of first HDR-BT ( p = 0.033), and PSA on date of first follow-up after one year ( p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

Detection of prostate specific antigen (PSA) in human saliva using an ultra-sensitive nanocomposite of graphene nanoplatelets with diblock-co-polymers and Au electrodes.

PubMed

Khan, M S; Dighe, K; Wang, Z; Srivastava, I; Daza, E; Schwartz-Dual, A S; Ghannam, J; Misra, S K; Pan, D

2018-02-26

Prostate-specific antigen (PSA) is a commonly used biomarker for the detection of prostate cancer (PCa) and there are numerous data available for its invasive detection in the serum and whole blood. In this work, an electrochemical sensing method was devised to detect traces of PSA in human saliva using a hybrid nanocomposite of graphene nanoplatelets with diblock co-polymers and Au electrodes (GRP-PS 67 -b-PAA 27 -Au). The pure graphitic composition on filter paper provides significantly high electrical and thermal conductivity while PS 67 -b-PAA 27 makes an amphiphilic bridge between GRP units. The sensor utilizes the binding of an anti-PSA antibody with an antigen-PSA to act as a resistor in a circuit providing an impedance change that in turn allows for the detection and quantification of PSA in saliva samples. A miniaturized electrical impedance analyzer was interfaced with a sensor chip and the data were recorded in real-time using a Bluetooth-enabled module. This fully integrated and optimized sensing device exhibited a wide PSA range of detection from 0.1 pg mL -1 to 100 ng mL -1 (R 2 = 0.963) with a lower limit of detection of 40 fg mL -1 . The performance of the biosensor chip was validated with an enzyme-linked immunosorbent assay technique with a regression coefficient as high as 0.940. The advantages of the newly developed saliva-PSA electrical biosensor over previously reported serum-PSA electrochemical biosensors include a faster response time (3-5 min) to achieve a stable electrical signal for PSA detection, high selectivity, improved sensitivity, no additional requirement of a redox electrolyte for electron exchange and excellent shelf life. The presented sensor is aimed for clinical commercialization to detect PSA in human saliva.

A dramatic, objective antiandrogen withdrawal response: case report and review of the literature

PubMed Central

Lau, Yiu-Keung; Chadha, Manpreet K; Litwin, Alan; Trump, Donald L

2008-01-01

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation. PMID:18986533

Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis in Biopsy-naive Men with Suspected Prostate Cancer Based on Elevated Prostate-specific Antigen Values: Results from a Randomized Prospective Blinded Controlled Trial.

PubMed

Tonttila, Panu P; Lantto, Juha; Pääkkö, Eija; Piippo, Ulla; Kauppila, Saila; Lammentausta, Eveliina; Ohtonen, Pasi; Vaarala, Markku H

2016-03-01

Multiparametric magnetic resonance imaging (MP-MRI) may improve the detection of clinically significant prostate cancer (PCa). To compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided random biopsy for overall and clinically significant PCa detection among patients with suspected PCa based on prostate-specific antigen (PSA) values. This institutional review board-approved, single-center, prospective, randomized controlled trial (April 2011 to December 2014) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values (PSA <20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA <10 ng/ml). Patients were randomized 1:1 to the MP-MRI or control group. Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided random biopsy and cognitive MRI/TRUS fusion targeted biopsy. The control group underwent TRUS-guided random biopsy alone. MP-MRI 3-T phased-array surface coil. The primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups. Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinically significant PCa in the MP-MRI and control groups. Between-group analyses were performed. Overall, 53 and 60 patients were evaluable in the MP-MRI and control groups, respectively. The overall PCa detection rate and the clinically significant cancer detection rate were similar between the MP-MRI and control groups, respectively (64% [34 of 53] vs 57% [34 of 60]; 7.5% difference [95% confidence interval (CI), -10 to 25], p=0.5, and 55% [29 of 53] vs 45% [27 of 60]; 9.7% difference [95% CI, -8.5 to 27], p=0.8). The PCa detection rate was higher than assumed during the planning of this single-center trial. MP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values. In this randomized clinical trial, additional prostate magnetic resonance imaging (MRI) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound-guided random biopsy in the diagnosis of prostate cancer. Similar numbers of cancers were detected with and without MRI. ClinicalTrials.gov identifier: NCT01357512. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A comparison of US and Australian men's values and preferences for PSA screening.

PubMed

Howard, Kirsten; Brenner, Alison T; Lewis, Carmen; Sheridan, Stacey; Crutchfield, Trisha; Hawley, Sarah; Nielsen, Matthew E; Pignone, Michael P

2013-10-05

Patient preferences derived from an assessment of values can help inform the design of screening programs, but how best to do so, and whether such preferences differ cross-nationally, has not been well-examined. The objective of this study was to compare the values and preferences of Australian and US men for PSA (prostate specific antigen) screening. We used an internet based survey of men aged 50-75 with no personal or family history of prostate cancer recruited from on-line panels of a survey research organization in the US and Australia. Participants viewed information on prostate cancer and prostate cancer screening with PSA testing then completed a values clarification task that included information on 4 key attributes: chance of 1) being diagnosed with prostate cancer, 2) dying from prostate cancer, 3) requiring a biopsy as a result of screening, and 4) developing impotence or incontinence as a result of screening. The outcome measures were self reported most important attribute, unlabelled screening test choice, and labelled screening intent, assessed on post-task questionnaires. We enrolled 911 participants (US:456; AU:455), mean age was 59.7; 88.0% were white; 36.4% had completed at least a Bachelors' degree; 42.0% reported a PSA test in the past 12 months. Australian men were more likely to be white and to have had recent screening. For both US and Australian men, the most important attribute was the chance of dying from prostate cancer. Unlabelled post-task preference for the PSA screening-like option was greater for Australian (39.1%) compared to US (26.3%) participants (adjusted OR 1.68 (1.28-2.22)). Labelled intent for screening was high for both countries: US:73.7%, AUS:78.0% (p = 0.308). There was high intent for PSA screening in both US and Australian men; fewer men in each country chose the PSA-like option on the unlabelled question. Australian men were somewhat more likely to prefer PSA screening. Men in both countries did not view the increased risk of diagnosis as a negative aspect, suggesting more work needs to be done on communicating the concept of overdiagnosis to men facing a PSA screening decision. This trial was registered at ClinicalTrials.gov (NCT01558583).

Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

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

Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin

2013-03-15

Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likelymore » to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.« less

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 ...

Prebiopsy biparametric MRI: differences of PI-RADS version 2 in patients with different PSA levels.

PubMed

Choi, M H; Lee, Y J; Jung, S E; Rha, S E; Byun, J Y

2018-06-09

To validate the diagnostic accuracy of Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in detecting clinically significant prostate cancer (csPCa, Gleason score ≥7) on prebiopsy biparametric MRI (bpMRI) in patients with different prostate-specific antigen (PSA) levels. This retrospective study included 184 patients who underwent prebiopsy bpMRI followed by transrectal ultrasonography-guided biopsy between June 2015 and February 2017. Reader 1 performed a combination of systematic and targeted biopsy with cognitive fusion after reviewing bpMRI and reader 2 reviewed the bpMRIs retrospectively. PI-RADS categories 4 and 5 were considered positive, and the results of the biopsy were considered the reference standard. Diagnostic performance of PI-RADS of bpMRI was evaluated in two PSA groups with a PSA cut-off level of 10 ng/ml and compared to PSA and the PSA density using receiver operating characteristics (ROC) curve analysis. csPCa was diagnosed in 24 of 123 patients (19.5%) and 26 of 61 patients (42.6%) in the low and high PSA groups, respectively. A PI-RADS v2 category by either readers 1 or 2 had a significantly better performance to detect csPCa than PSA in both PSA groups. In the high PSA group, only one csPCa was missed by reader 2, but none by reader 1. In the low PSA group, readers 1 and 2 were unable to detect seven and five of the 24 csPCas, respectively. Prebiopsy bpMRI has good performance for detecting csPCa in the high PSA group but may miss small-volume csPCa in the low PSA group. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Extent of disease in recurrent prostate cancer determined by [(68)Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and Gleason score.

PubMed

Verburg, Frederik A; Pfister, David; Heidenreich, Axel; Vogg, Andreas; Drude, Natascha I; Vöö, Stefan; Mottaghy, Felix M; Behrendt, Florian F

2016-03-01

To examine the relationship between the extent of disease determined by [(68)Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score. We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [(68)Ga]PSMA-HBED-CC PET/CT. PET/CT was positive in 44%, 79% and 89% of patients with PSA levels of ≤1, 1-2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (p < 0.001), and extrapelvic lymph node (p = 0.037) and bone metastases (p = 0.013). A shorter PSAdt was significantly associated with pelvic lymph node (p = 0.026), extrapelvic lymph node (p = 0.001), bone (p < 0.001) and visceral (p = 0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases (p = 0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases (p = 0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95%) had a positive scan and 12 (60%) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36%) had a positive scan and 1 (7%) had M1a disease. [(68)Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for [(68)Ga]PSMA-HBED-CC PET/CT.

The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients

PubMed Central

Maxeiner, Andreas; Kilic, Ergin; Matalon, Julia; Friedersdorff, Frank; Miller, Kurt; Jung, Klaus; Stephan, Carsten; Busch, Jonas

2017-01-01

The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p < 0.05) for cancer aggressiveness: Gleason-score <7 or ≥7 (ISUP grade 1 or ≥2) . Concerning pathological tumor stage discrimination and prediction, variables as PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages

The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients.

PubMed

Maxeiner, Andreas; Kilic, Ergin; Matalon, Julia; Friedersdorff, Frank; Miller, Kurt; Jung, Klaus; Stephan, Carsten; Busch, Jonas

2017-10-03

The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p < 0.05) for cancer aggressiveness: Gleason-score <7 or ≥7 (ISUP grade 1 or ≥2) . Concerning pathological tumor stage discrimination and prediction, variables as PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages

Performance characteristics and relationship of PSA value/kinetics on carbon-11 acetate PET/CT imaging in biochemical relapse of prostate cancer.

PubMed

Almeida, Fabio D; Yen, Chi-Kwan; Scholz, Mark C; Lam, Richard Y; Turner, Jeffrey; Bans, Larry L; Lipson, Robert

2017-01-01

An elevated serum prostate-specific antigen (PSA) level alone cannot distinguish between local-regional recurrences and distant metastases after treatment with curative intent. With available salvage treatments, it has become important to localize the site of recurrence. 11 C-Acetate PET/CT was performed in patients with rising PSA, with statistical analysis of detection rates, sites/location of detection, PSA kinetics and comparison with other tracers (FDG and Choline). Correlation to biopsy, subsequent imaging and PSA response to focal treatment was also performed. 88% (637) of 721 11 C-Acetate PET/CT scans performed were positive. There was a statistically significant difference in PSA values between the positive and negative scans (P < 0.001 for mean difference) with the percentage of positive scans and PSA having a positive correlation. A PSA of 1.09 ng/mL was found to be an optimal cutoff. PSAdT was significantly correlated with a positive scan only when the PSA was < 1.0 ng/mL. For this subgroup, a PSAdT of < 3.8 months appeared significant (P < 0.05) as an optimal cutoff point. 11 C-Acetate PET/CT demonstrates a high detection rate for the site of recurrence/metastasis in biochemical relapsed prostate cancer (88% overall detection rate, PPV 90.8%). This analysis suggests an optimal PSA threshold of > 1.09 ng/mL or a PSAdT of < 3.8 months when the PSA is below 1.0 ng/mL as independent predictors of positive findings.

Vaccine Immunotherapy for Prostate Cancer

DTIC Science & Technology

2012-05-01

adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols have been used in the trial: #1 - Phase II study of Adenovirus/PSA...this award is to conduct a Phase II clinical trial (Study) of an adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols...suddenly prior to study treatment . And one patient previously reported as a screen failure became eligible and was treated. This subject was not

Determine of the optimal number of cycles of docetaxel in the treatment of metastatic castration-resistant prostate cancer.

PubMed

Shen, Yuan-Chi; Chiang, Po-Hui; Luo, Hao-Lun; Chuang, Yao-Chi; Chen, Yen-Ta; Kang, Chih-Hsiung; Hsu, Chun-Chien; Lee, Wei-Ching; Cheng, Yuan-Tso

2016-09-01

To determine the optimal number of cycles of docetaxel for metastatic castration-resistant prostate cancer, we retrospectively collected 73 patients receiving varying numbers of docetaxel plus prednisolone and analyzed the clinical outcomes including overall survival, prostate-specific antigen (PSA) response, and adverse events. The study included 33 patients receiving ≤ 10 cycles of docetaxel and 40 patients receiving > 10 cycles. Patients receiving > 10 cycles were younger than those who received ≤ 10 cycles. There was no statistical significant difference in overall survival between the two groups (log-rank test, p = 0.75). Adverse effects were more common among patients receiving ≥ 10 cycles of treatment. A PSA flare-up was observed among six patients (8.2%); the median duration of the PSA surge was 3 weeks (range, 3-12 weeks). The overall survival rates in patients with PSA flare-up were comparable with the patients having PSA response. We concluded that at least four cycles of docetaxel should be administered in metastatic castration-resistant prostate cancer patients in order not to cease treatment prematurely from potentially beneficial chemotherapy. However, administering > 10 cycles does not result in any further improvement in survival and is associated with more adverse effects. Copyright © 2016. Published by Elsevier Taiwan.

Ten-core versus 16-core transrectal ultrasonography guided prostate biopsy for detection of prostatic carcinoma: a prospective comparative study in Indian population

PubMed Central

Prakash, V. Surya; Mohan, G. Chandra; Krishnaiah, S. Venkata; Vijaykumar, V.; Babu, G. Ramesh; Reddy, G. Vijaya Bhaskar; Mahaboob, V. S.

2013-01-01

Purpose: To compare the cancer detection rate in patients with raised serum prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE) results between the 10-core and the 16-core biopsy techniques in an Indian population. Methods: Between November 2010 and November 2012, 95 men aged >50 years who presented to the Urology Department with lower urinary tract symptoms, elevated serum PSA, and/or abnormal DRE findings underwent transrectal ultrasonography (TRUS)-guided prostate biopsy. A total of 53 patients underwent 10-core biopsy and 42 patients underwent 16-core biopsy. Results: Of the 53 men in the 10-core group, 8 had cancer, whereas in the 16-core biopsy group, 23 of 42 men had cancer. Detection of prostate cancer was significantly higher in patients who underwent 16-core biopsy than in those who underwent 10-core biopsy (P<0.001). Among the 95 men, 44 men had abnormal DRE findings (46.3%), of whom 23 showed cancer (52.27%). Of 51 men with normal DRE findings and elevated PSA, 8 men had malignancy with a cancer detection rate of 15.68%. Among 20 men with PSA between 4.1 and 10 ng/mL, 2 (10%) had cancer. In 31 men with PSA between 10.1 and 20 ng/mL, 3 cancers (9.67%) were detected, and in 44 men with PSA >20 ng/mL, 26 cancers were detected (59.09%). Conclusions: The cancer detection rate with 16-core TRUS-guided biopsy is significantly higher than that with 10-core biopsy (54.76% vs. 15.09%, P<0.001). In patients with both normal and abnormal DRE findings, 16-core biopsy has a better detection rate than the 10-core biopsy protocol. With increasing PSA, there is a high rate of detection of prostate cancer in both 10-core and 16-core biopsy patients. PMID:24392441

Ten-core versus 16-core transrectal ultrasonography guided prostate biopsy for detection of prostatic carcinoma: a prospective comparative study in Indian population.

PubMed

Prakash, V Surya; Mohan, G Chandra; Krishnaiah, S Venkata; Vijaykumar, V; Babu, G Ramesh; Reddy, G Vijaya Bhaskar; Mahaboob, V S

2013-01-01

To compare the cancer detection rate in patients with raised serum prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE) results between the 10-core and the 16-core biopsy techniques in an Indian population. Between November 2010 and November 2012, 95 men aged >50 years who presented to the Urology Department with lower urinary tract symptoms, elevated serum PSA, and/or abnormal DRE findings underwent transrectal ultrasonography (TRUS)-guided prostate biopsy. A total of 53 patients underwent 10-core biopsy and 42 patients underwent 16-core biopsy. Of the 53 men in the 10-core group, 8 had cancer, whereas in the 16-core biopsy group, 23 of 42 men had cancer. Detection of prostate cancer was significantly higher in patients who underwent 16-core biopsy than in those who underwent 10-core biopsy (P<0.001). Among the 95 men, 44 men had abnormal DRE findings (46.3%), of whom 23 showed cancer (52.27%). Of 51 men with normal DRE findings and elevated PSA, 8 men had malignancy with a cancer detection rate of 15.68%. Among 20 men with PSA between 4.1 and 10 ng/mL, 2 (10%) had cancer. In 31 men with PSA between 10.1 and 20 ng/mL, 3 cancers (9.67%) were detected, and in 44 men with PSA >20 ng/mL, 26 cancers were detected (59.09%). The cancer detection rate with 16-core TRUS-guided biopsy is significantly higher than that with 10-core biopsy (54.76% vs. 15.09%, P<0.001). In patients with both normal and abnormal DRE findings, 16-core biopsy has a better detection rate than the 10-core biopsy protocol. With increasing PSA, there is a high rate of detection of prostate cancer in both 10-core and 16-core biopsy patients.

Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

PubMed

Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

2017-12-01

The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

Impact of United States Preventive Services Task Force Recommendations on Utilization of Prostate-specific Antigen Screening in Medicare Beneficiaries.

PubMed

Khairnar, Rahul; Mishra, Mark V; Onukwugha, Eberechukwu

2018-02-16

Previous studies assessing the impact of United States Preventive Services Task Force (USPSTF) recommendations on utilization of prostate-specific antigen (PSA) screening have not investigated longer-term impacts of 2008 recommendations nor have they investigated the impact of 2012 recommendations in the Medicare population. This study aimed to evaluate change in utilization of PSA screening, post-2008 and 2012 USPSTF recommendations, and assessed trends and determinants of receipt of PSA screening in the Medicare population. This retrospective study of male Medicare beneficiaries utilized Medicare Current Beneficiary Survey data and linked administrative claims from 2006 to 2013. Beneficiaries aged ≥65 years, with continuous enrollment in parts A and B for each year they were surveyed were included in the study. Beneficiaries with self-reported/claims-based diagnosis of prostate cancer were excluded. The primary outcome was receipt of PSA screening. Other measures included age groups (65 to 74 and ≥75), time periods (pre-2008/post-2008 and 2012 recommendations), and sociodemographic variables. The study cohort consisted of 11,028 beneficiaries, who were predominantly white (87.56%), married (69.25%), and unemployed (84.4%); 52.21% beneficiaries were aged ≥75. Declining utilization trends for PSA screening were observed in men aged ≥75 after 2008 recommendations and in both age groups after 2012 recommendations. The odds of receiving PSA screening declined by 17% in men aged ≥75 after 2008 recommendations and by 29% in men aged ≥65 after 2012 recommendations. The 2008 and 2012 USPSTF recommendations against PSA screening were associated with declines in utilization of PSA screening during the study period. USPSTF recommendations play a significant role in affecting utilization patterns of health services.

Prostate cancer marker panel with single cell sensitivity in urine.

PubMed

Nickens, Kristen P; Ali, Amina; Scoggin, Tatiana; Tan, Shyh-Han; Ravindranath, Lakshmi; McLeod, David G; Dobi, Albert; Tacha, David; Sesterhenn, Isabell A; Srivastava, Shiv; Petrovics, Gyorgy

2015-06-15

Over one million men undergo prostate biopsies annually in the United States, a majority of whom due to elevated serum PSA. More than half of the biopsies turn out to be negative for prostate cancer (CaP). The limitations of both the PSA test and the biopsy procedure have led to the development for more precise CaP detection assays in urine (e.g., PCA3, TMPRSS2-ERG) or blood (e.g., PHI, 4K). Here, we describe the development and evaluation of the Urine CaP Marker Panel (UCMP) assay for sensitive and reproducible detection of CaP cells in post-digital rectal examination (post-DRE) urine. The cellular content of the post-DRE urine was captured on a translucent filter membrane, which is placed on Cytoclear slides for direct evaluation by microscopy and immuno-cytochemistry (ICC). Cells captured on the membrane were assayed for PSA and Prostein expression to identify prostate epithelial cells, and for ERG and AMACR to identify prostate tumor cells. Immunostained cells were analyzed for quantitative and qualitative features and correlated with biopsy positive and negative status for malignancy. The assay was optimized for single cell capture sensitivity and downstream evaluations by spiking a known number of cells from established CaP cell lines, LNCaP and VCaP, into pre-cleared control urine. The cells captured from the post-DRE urine of subjects, obtained prior to biopsy procedure, were co-stained for ERG, AMACR (CaP specific), and Prostein or PSA (prostate epithelium specific) rendering a whole cell based analysis and characterization. A feasibility cohort of 63 post-DRE urine specimens was assessed. Comparison of the UCMP results with blinded biopsy results showed an assay sensitivity of 64% (16 of 25) and a specificity of 68.8% (22 of 32) for CaP detection by biopsy. This pilot study assessing a minimally invasive CaP detection assay with single cell sensitivity cell-capture and characterization from the post-DRE urine holds promise for further development of this novel assay platform. Prostate 75: 969-975, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

Levels of beta-microseminoprotein in blood and risk of prostate cancer in multiple populations.

PubMed

Haiman, Christopher A; Stram, Daniel O; Vickers, Andrew J; Wilkens, Lynne R; Braun, Katharina; Valtonen-André, Camilla; Peltola, Mari; Pettersson, Kim; Waters, Kevin M; Marchand, Loic Le; Kolonel, Laurence N; Henderson, Brian E; Lilja, Hans

2013-02-06

A common genetic variant (rs10993994) in the 5' region of the gene encoding β-microseminoprotein (MSP) is associated with circulating levels of MSP and prostate cancer risk. Whether MSP levels are predictive of prostate cancer risk has not been evaluated. We investigated the prospective relationship between circulating plasma levels of MSP and prostate cancer risk in a nested case-control study of 1503 case subjects and 1503 control subjects among black, Latino, Japanese, Native Hawaiian, and white men from the Multiethnic Cohort study. We also examined the ability of MSP to serve as a biomarker for discriminating prostate cancer case subjects from control subjects. All statistical tests are two-sided. In all racial and ethnic groups, men with lower MSP levels were at greater risk of developing prostate cancer (odds ratio = 1.02 per one unit decrease in MSP, P < .001 in the prostate-specific antigen [PSA]-adjusted analysis). Compared with men in the highest decile of MSP, the multivariable PSA-adjusted odds ratio was 3.64 (95% confidence interval = 2.41 to 5.49) for men in the lowest decile. The positive association with lower MSP levels was observed consistently across racial and ethnic populations, by disease stage and Gleason score, for men with both high and low levels of PSA and across all genotype classes of rs10993994. However, we did not detect strong evidence of MSP levels in improving prostate cancer prediction beyond that of PSA. Regardless of race and ethnicity or rs10993994 genotype, men with low blood levels of MSP have increased risk of prostate cancer.

‘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

A novel urinary long non-coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy.

PubMed

Zhang, Wei; Ren, Shan-Cheng; Shi, Xiao-Lei; Liu, Ya-Wei; Zhu, Ya-Sheng; Jing, Tai-Le; Wang, Fu-Bo; Chen, Rui; Xu, Chuan-Liang; Wang, Hui-Qing; Wang, Hai-Feng; Wang, Yan; Liu, Bing; Li, Yao-Ming; Fang, Zi-Yu; Guo, Fei; Lu, Xin; Shen, Dan; Gao, Xu; Hou, Jian-Guo; Sun, Ying-Hao

2015-05-01

Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis. © 2015 Wiley Periodicals, Inc.

Post-treatment PSA < or = 0.2 ng/mL defines disease freedom after radiotherapy for prostate cancer using modern techniques.

PubMed

Critz, F A; Williams, W H; Holladay, C T; Levinson, A K; Benton, J B; Holladay, D A; Schnell, F J; Maxa, L S; Shrake, P D

1999-12-01

The prostate-specific antigen (PSA) definition of disease freedom after radiotherapy for prostate cancer is still in dispute. This report focuses on the PSA nadir achieved in men treated by modern radiotherapy techniques. From 1984 to 1994, 489 consecutive men with clinical Stage T1 -T2 prostate cancer were treated by simultaneous radiation: prostate iodine-125 implant followed by external beam radiation. A transperineal implant was performed on 143 men with Stage T1-T2NX, the focus of this study; 346 men with Stage T1-T2N0 had a retropubic implant. The median pretreatment PSA was 8.3 ng/mL (range 0.3 to 188). A rising PSA was defined as one that rose on three consecutive occasions above whatever nadir was achieved. A minimum 5-year follow-up (range 5 to 15) was reached by 453 men. After a minimum 5-year follow-up, 336 men had a nonrising PSA, and of this group, 107 had undergone simultaneous radiation by the transperineal implant technique. A PSA nadir of 0.2 ng/mL or less was achieved by 97% of the transperineally implanted men, and 3% had a nadir of 0.3 to 1.0 ng/mL. Of the 489 men, those who had a nadir of 0.2 ng/mL or less had a 92% nonrising PSA rate (P = 0.001) 10 years after treatment compared with a 41% rate for men who had a nadir of 0.3 to 1.0 ng/mL. All men whose nadir was greater than 1.0 ng/mL had recurrence. The median time to achieve the PSA nadir of 0.2 ng/mL was 27 months (range 3 to 102). Primarily on the basis of the results from men treated with simultaneous radiation using the transperineal technique, the definition of disease freedom for radiotherapy should be men who achieve and maintain a PSA nadir of 0.2 ng/mL or less.

Development of Interpretable Predictive Models for BPH and Prostate Cancer.

PubMed

Bermejo, Pablo; Vivo, Alicia; Tárraga, Pedro J; Rodríguez-Montes, J A

2015-01-01

Traditional methods for deciding whether to recommend a patient for a prostate biopsy are based on cut-off levels of stand-alone markers such as prostate-specific antigen (PSA) or any of its derivatives. However, in the last decade we have seen the increasing use of predictive models that combine, in a non-linear manner, several predictives that are better able to predict prostate cancer (PC), but these fail to help the clinician to distinguish between PC and benign prostate hyperplasia (BPH) patients. We construct two new models that are capable of predicting both PC and BPH. An observational study was performed on 150 patients with PSA ≥3 ng/mL and age >50 years. We built a decision tree and a logistic regression model, validated with the leave-one-out methodology, in order to predict PC or BPH, or reject both. Statistical dependence with PC and BPH was found for prostate volume (P-value < 0.001), PSA (P-value < 0.001), international prostate symptom score (IPSS; P-value < 0.001), digital rectal examination (DRE; P-value < 0.001), age (P-value < 0.002), antecedents (P-value < 0.006), and meat consumption (P-value < 0.08). The two predictive models that were constructed selected a subset of these, namely, volume, PSA, DRE, and IPSS, obtaining an area under the ROC curve (AUC) between 72% and 80% for both PC and BPH prediction. PSA and volume together help to build predictive models that accurately distinguish among PC, BPH, and patients without any of these pathologies. Our decision tree and logistic regression models outperform the AUC obtained in the compared studies. Using these models as decision support, the number of unnecessary biopsies might be significantly reduced.

A polymorphism in the glucokinase gene that raises plasma fasting glucose, rs1799884, is associated with diabetes mellitus and prostate cancer: findings from a population-based, case-control study (the ProtecT study)

PubMed Central

Murad, Ali S; Smith, George Davey; Lewis, Sarah J; Cox, Angela; Donovan, Jenny L; Neal, David E; Hamdy, Freddie C; Martin, Richard M

2010-01-01

Epidemiological studies have identified a positive association between prostate cancer and recent onset type 2 diabetes mellitus but an increasingly inverse association with greater duration of type 2 diabetes. The mecha- nisms underlying these paradoxical associations are not clear. A single nucleotide polymorphism in the glucokinase gene, rs1799884, is associated with higher circulating plasma fasting glucose and with an increased risk of type 2 diabetes. We report a case-control study nested within the population-based Prostate testing for cancer and Treatment (ProtecT) study ISRCTN20141297. Men aged 50-69 years based around 9 UK cities were invited for a prostate specific antigen (PSA) test between June 2002 and November 2006. 1,551 cases and 2,993 controls were geno-typed. We observed suggestive evidence for a positive association between the AA variant rs1799884 and PSA-detected prostate cancer (ORAA V GG= 1.40, 95% CI= 0.95 to 2.07). There was little evidence that this effect was greater for more advanced stage/ grade cancers (ORAA V GG= 1.78, 95% CI= 0.99 to 3.21) versus less advanced cancers (ORAA V GG= 1.23, 95% CI= 0.77 to 1.94) (p for interaction = 0.33). The rs1799884 genotype was not associated with PSA concentration, suggesting that any effect on prostate cancer risk is not attributable to PSA detection bias. Our results provide suggestive evidence for a link between a genotype associated with type 2 diabetes mellitus and PSA-detected prostate cancer. We hypothesize that hyperglycaemia may be important in mediating this relationship. PMID:21537389

Serum markers for prostate cancer: a rational approach to the literature.

PubMed

Steuber, Thomas; O'Brien, Matthew Frank; Lilja, Hans

2008-07-01

Due to its universal applicability for early detection and prediction of cancer stage and disease recurrence, widespread implementation of serum-based prostate-specific antigen (PSA) measurements has a significant influence on current treatment strategies for men with prostate cancer (PCa). However, over-detection and the resultant over-treatment of indolent cancers have been strongly implicated to occur. Using current recommended guidelines, the PSA test suffers from both limited sensitivity and specificity to enable efficacious population-based cancer detection. Therefore, novel biomarkers are much needed to complement PSA by enhancing its diagnostic and prognostic performance. The present literature on serum markers for PCa was reviewed. PSA derivatives, molecular PSA isoforms, and novel molecular targets in blood were summarized and weighted against their potential to improve decision-making of men with PCa. Current evidence suggests that no single analyte is likely to achieve the desired level of diagnostic and prognostic accuracy for PCa. However, the combination of biomarkers with clinical and demographic data, for example, using established standard nomograms, has produced progress toward the goal of both optimal screening and risk assessment. Furthermore, potential candidate molecular markers for PCa can be derived from high-throughput technologies. Current studies demonstrate that understanding dynamic PSA changes over time may offer diagnostic and prognostic information. Bridging the gap between basic science and clinical practice represents the main goal in the near future to enable physicians to tailor risk-adjusted screening and treatment strategies for current patients with PCa.

Anisotropic In Situ-Coated AuNPs on Screen-Printed Carbon Surface for Enhanced Prostate-Specific Antigen Impedimetric Aptasensor

NASA Astrophysics Data System (ADS)

Do, Tram T. N.; Van Phi, Toan; Nguy, Tin Phan; Wagner, Patrick; Eersels, Kasper; Vestergaard, Mun'delanji C.; Truong, Lien T. N.

2017-06-01

An impedimetric aptasensor has been used to study the effect of charge transfer on the binding of prostate-specific antigen (PSA) to its aptamer. Full understanding of this mechanism will be beneficial to further improve its sensitivity for PSA detection in human semen at physiologically relevant concentrations. Bare gold electrodes (SPAuEs) and gold nanoparticles (AuNPs)-coated screen-printed carbon ink electrodes (AuNPs/SPCEs) were coated with aptamer solution at various concentrations and the sensor response to increasing PSA concentration in buffer solution examined. AuNPs were deposited onto carbon electrodes in 10 cycles. AuNPs/SPCEs were then coated with a self-assembled monolayer (SAM) of 16-mercaptohexadecanoic acid prior to aptamer immobilization at dose of 5 μg mL-1. The results indicate that anisotropic AuNPs/SPCEs outperform bare gold electrodes in terms of decreased amount of aptamer bunches as well as the number of intermediate PSA-aptamer complexes formed on the electrode surface. The key finding is that the fabricated aptasensor is sensitive enough [limit of detection (LoD) 1.95 ng mL-1] for early diagnosis of prostate cancer and displays linear response in the physiologically relevant concentration range (0 ng mL-1 to 10 ng mL-1), as shown by the calibration curve of the relative change in electron transfer resistance (Δ R CT) versus PSA concentration when aptamer/SAM/AuNPs/SPCEs were exposed to buffer containing PSA at different concentrations.

The role of BPH, lower urinary tract symptoms, and PSA levels on erectile function of Brazilian men who undergo prostate cancer screening.

PubMed

Antunes, Alberto A; Srougi, Miguel; Dall'oglio, Marcos F; Vicentini, Fabio; Paranhos, Mario; Freire, Geraldo C

2008-07-01

Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are common problems in middle-aged and older men. Recently, epidemiologic studies have shown significant associations between severity of LUTS and male sexual dysfunction. We analyzed the role of prostate enlargement, LUTS, and prostate specific antigen (PSA) levels in the erectile function of Brazilian men who underwent prostate cancer (PCa) screening. We analyzed data from 1,008 consecutive patients enrolled in a PCa screening program. Benign prostatic hyperplasia (BPH) was defined as a prostate weight greater than 30 g as defined by digital rectal examination. For statistical analysis, we used the chi-squared and analysis of variance tests. The odds ratios (OR) for correlation of ED with prostate volume LUTS and PSA were estimated using logistic regression models. The American Urological Association (AUA) symptom score for LUTS and the International Index of Erectile Function. Mean patient age was 61.2 years (45-87) and median PSA value was 1.9 ng/mL. BPH was identified in 48.5% of patients. Mild, moderate, and severe LUTS were found in 52.3%, 30.9%, and 16.8% of cases, respectively. ED was classified as absent, mild, mild to moderate, moderate, and severe in 18.6%, 23.1%, 18.6%, 15.2%, and 24.5%, respectively. While only 5.4% of the patients with no ED presented severe LUTS, this finding was observed in 27.1% of patients with severe ED (P < 0.001). Univariate logistic regression analysis demonstrated that age, prostate volume, AUA symptom score, and PSA levels were significant predictors of ED. However, when controlled for patient age, only LUTS remained as an independent predictor of ED. Controlling for patient age, LUTS are independent risk factors for the development of ED among Brazilian men who undergo PCa screening. Antunes AA, Srougi M, Dall'Oglio MF, Vicentini F, Paranhos M, and Freire GC. The role of BPH, lower urinary tract symptoms, and PSA levels on erectile function of Brazilian men who undergo prostate cancer screening.

First postoperative PSA is associated with outcomes in patients with node positive prostate cancer: Results from the SEARCH database.

PubMed

McDonald, Michelle L; Howard, Lauren E; Aronson, William J; Terris, Martha K; Cooperberg, Matthew R; Amling, Christopher L; Freedland, Stephen J; Kane, Christopher J

2018-05-01

To analyze factors associated with metastases, prostate cancer-specific mortality, and all-cause mortality in pN1 patients. We analyzed 3,642 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Pathologic Gleason grade, number of lymph nodes (LN) removed, and first postoperative prostate-specific antigen (PSA) (<0.2 ng/ml or ≥0.2 ng/ml) were among covariates assessed. Cox regression was used to analyze the association between characteristics and survival outcomes. Kaplan-Meier was used to estimate survival in pN1 patients stratified by first postoperative PSA. Of 3,642 patients, 124 (3.4%) had pN1. There were 71 (60%) patients with 1 positive LN, 32 (27%) with 2 positive LNs, and 15 (13%) with ≥3. Among men with pN1, first postoperative PSA was<0.2ng/ml in 46 patients (51%) and ≥0.2ng/ml in 44 patients (49%). Univariable Cox regression determined pathological Gleason grade (P = 0.021), seminal vesicle invasion (P = 0.010), and first postoperative PSA ≥0.2 ng/ml (P = 0.005) were associated with metastases. First postoperative PSA ≥0.2ng/ml was associated with metastasis on multivariable analysis (P = 0.046). Log-rank analysis revealed a more favorable metastases-free survival in patients with a first postoperative PSA<0.2ng/ml (P = 0.001). Estimated 5-year metastases-free survival rate was 99% for patients with a first postoperative PSA<0.2ng/ml and 87% for ≥0.2ng/ml. pN1 patients with a first postoperative PSA ≥0.2ng/ml were more likely to develop metastases. First postoperative PSA may be useful in identifying pN1 patients who harbor distant disease and aid in secondary treatment decisions. Copyright © 2018 Elsevier Inc. All rights reserved.

Prostate-Specific Antigen Halving Time While on Neoadjuvant Androgen Deprivation Therapy Is Associated With Biochemical Control in Men Treated With Radiation Therapy for Localized Prostate Cancer

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

Malik, Renuka; Jani, Ashesh B.; Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.ed

2011-03-15

Purpose: To assess whether the PSA response to neoadjuvant androgen deprivation therapy (ADT) is associated with biochemical control in men treated with radiation therapy (RT) for prostate cancer. Methods and Materials: In a cohort of men treated with curative-intent RT for localized prostate cancer between 1988 and 2005, 117 men had PSA values after the first and second months of neoadjuvant ADT. Most men had intermediate-risk (45%) or high-risk (44%) disease. PSA halving time (PSAHT) was calculated by first order kinetics. Median RT dose was 76 Gy and median total duration of ADT was 4 months. Freedom from biochemical failuremore » (FFBF, nadir + 2 definition) was analyzed by PSAHT and absolute PSA nadir before the start of RT. Results: Median follow-up was 45 months. Four-year FFBF was 89%. Median PSAHT was 2 weeks. A faster PSA decline (PSAHT {<=}2 weeks) was associated with greater FFBF (96% vs. 81% for a PSAHT >2 weeks, p = 0.0110). Those within the fastest quartile of PSAHTs ({<=} 10 days) achieved a FFBF of 100%. Among high-risk patients, a PSAHT {<=}2 weeks achieved a 4-yr FFBF of 93% vs. 70% for those with PSAHT >2 weeks (p = 0.0508). Absolute PSA nadir was not associated with FFBF. On multivariable analysis, PSAHT (p = 0.0093) and Gleason score (p = 0.0320) were associated with FFBF, whereas T-stage (p = 0.7363) and initial PSA level (p = 0.9614) were not. Conclusions: For men treated with combined ADT and RT, PSA response to the first month of ADT may be a useful criterion for prognosis and treatment modification.« less

The role of IGF-1 and the distribution of body fat in decreasing the number of prostate rebiopsies.

PubMed

Morán, E; Martínez, M; Budía, A; Broseta, E; Cámara, R; Boronat, F

2017-03-01

To assess the usefulness of IGF-1 and internal organ fat measured by bioelectrical impedance audiometry to avoid rebiopsies in patients with persistently high prostate-specific antigen (PSA) levels. A prospective study was conducted with 92 patients who underwent prostate rebiopsy due to high PSA levels with negative results in the rectal examination and a lack of preneoplastic lesions. The patients previously had their IGF-1 levels measured and had undergone an impedance audiometry test using the abdominal Fat Analyser AB-140 TANITA system. We calculated the receiver operating characteristic (ROC) curves for the PSA levels, %PSA, internal organ fat and IGF-1 and PSA density. Twenty-five patients were diagnosed with prostate cancer. These patients had significantly higher PSA, PSAd and IGF-1 values and a tendency towards higher internal organ fat levels and lower %PSA readings (p=.001, p=.003, p=.001, p=.24 and P=0.28, respectively). The ROC curve showed an area under the curve for IGF-1 and PSA of .82 and .81, respectively. Using the cutoff points for 95% sensitivity and using the 3 criteria as an indication of rebiopsy, 74% of the biopsies would have been spared, leaving undiagnosed only 1 patient with clinically significant cancer -Gleason score>7 (4+3)-. The positive and negative predictive values for the set of variables were higher than for each one separately (PPV: 66/NPV: 63). The cost of both determinations was 82 euros. Our results suggest that measuring IGF-1 could significantly decrease the number of unnecessary rebiopsies in an inexpensive and safe manner. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Prostate-Specific Antigen (PSA)–Based Population Screening for Prostate Cancer: An Evidence-Based Analysis

PubMed Central

Pron, G

2015-01-01

Background Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer in men and their second or third leading cause of cancer death. Prostate-specific antigen (PSA) testing for PC has been in common practice for more than 20 years. Objectives A systematic review of the scientific literature was conducted to determine the effectiveness of PSA-based population screening programs for PC to inform policy decisions in a publicly funded health care system. Data Sources A systematic review of bibliographic databases was performed for systematic reviews or randomized controlled trials (RCT) of PSA-based population screening programs for PC. Review Methods A broad search strategy was employed to identify studies reporting on key outcomes of PC mortality and all-cause mortality. Results The search identified 5 systematic reviews and 6 RCTs. None of the systematic reviews found a statistically significant reduction in relative risk (RR) of PC mortality or overall mortality with PSA-based screening. PC mortality reductions were found to vary by country, by screening program, and by age of men at study entry. The European Randomized Study of Screening for Prostate Cancer found a statistically significant reduction in RR in PC mortality at 11-year follow-up (0.79; 95% CI, 0.67–0.92), although the absolute risk reduction was small (1.0/10,000 person-years). However, the primary treatment for PCs differed significantly between countries and between trial arms. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a statistically non-significant increase in RR for PC mortality with 13-year follow-up (1.09; 95% CI, 0.87–1.36). The degree of opportunistic screening in the control arm of the PLCO trial, however, was high. None of the RCTs found a reduction in all-cause mortality and all found a statistically significant increase in the detection of mainly low-risk, organ-confined PCs in the screening arm. Conclusions There was no evidence of a PC mortality reduction in the American PLCO trial, which investigated a screening program in a setting where opportunistic screening was already common practice. Given that opportunistic PSA screening practices in Canada are similar, it is unlikely that the introduction of a formal PSA screening program would reduce PC mortality. PMID:26366236

Prostate-Specific Antigen (PSA)-Based Population Screening for Prostate Cancer: An Evidence-Based Analysis.

PubMed

Pron, G

2015-01-01

Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer in men and their second or third leading cause of cancer death. Prostate-specific antigen (PSA) testing for PC has been in common practice for more than 20 years. A systematic review of the scientific literature was conducted to determine the effectiveness of PSA-based population screening programs for PC to inform policy decisions in a publicly funded health care system. A systematic review of bibliographic databases was performed for systematic reviews or randomized controlled trials (RCT) of PSA-based population screening programs for PC. A broad search strategy was employed to identify studies reporting on key outcomes of PC mortality and all-cause mortality. The search identified 5 systematic reviews and 6 RCTs. None of the systematic reviews found a statistically significant reduction in relative risk (RR) of PC mortality or overall mortality with PSA-based screening. PC mortality reductions were found to vary by country, by screening program, and by age of men at study entry. The European Randomized Study of Screening for Prostate Cancer found a statistically significant reduction in RR in PC mortality at 11-year follow-up (0.79; 95% CI, 0.67-0.92), although the absolute risk reduction was small (1.0/10,000 person-years). However, the primary treatment for PCs differed significantly between countries and between trial arms. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a statistically non-significant increase in RR for PC mortality with 13-year follow-up (1.09; 95% CI, 0.87-1.36). The degree of opportunistic screening in the control arm of the PLCO trial, however, was high. None of the RCTs found a reduction in all-cause mortality and all found a statistically significant increase in the detection of mainly low-risk, organ-confined PCs in the screening arm. There was no evidence of a PC mortality reduction in the American PLCO trial, which investigated a screening program in a setting where opportunistic screening was already common practice. Given that opportunistic PSA screening practices in Canada are similar, it is unlikely that the introduction of a formal PSA screening program would reduce PC mortality.

Differential blood-based diagnosis between benign prostatic hyperplasia and prostate cancer: miRNA as source for biomarkers independent of PSA level, Gleason score, or TNM status.

PubMed

Leidinger, Petra; Hart, Martin; Backes, Christina; Rheinheimer, Stefanie; Keck, Bastian; Wullich, Bernd; Keller, Andreas; Meese, Eckart

2016-08-01

Since the benefit of prostate-specific antigen (PSA) screening remains controversial, new non-invasive biomarkers for prostate carcinoma (PCa) are still required. There is evidence that microRNAs (miRNAs) in whole peripheral blood can separate patients with localized prostate cancer from healthy individuals. However, the potential of blood-based miRNAs for the differential diagnosis of PCa and benign prostatic hyperplasia (BPH) has not been tested. We compared the miRNome from blood of PCa and BPH patients and further investigated the influence of the tumor volume, tumor-node-metastasis (TNM) classification, Gleason score, pretreatment risk status, and the pretreatment PSA value on the miRNA pattern. By microarray approach, we identified seven miRNAs that were significantly deregulated in PCa patients compared to BPH patients. Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221-5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH. Clinical parameters like PSA level, Gleason score, or TNM status seem to have only limited impact on the overall abundance of miRNAs in patients' blood, suggesting a no influence of these factors on the expression of deregulated miRNAs.

Prostate cancer-related anxiety in long-term survivors after radical prostatectomy.

PubMed

Meissner, Valentin H; Herkommer, Kathleen; Marten-Mittag, Birgitt; Gschwend, Jürgen E; Dinkel, Andreas

2017-12-01

Knowledge of the psychological distress of long- and very long-term (>10 years) prostate cancer (PC) survivors is limited. This study intended to examine the parameters influencing anxiety related to prostate-specific antigen (PSA) and PC in long-term survivors after radical prostatectomy. We surveyed 4719 PC survivors from the German multicenter prospective database "Familial Prostate Cancer." We evaluated the association of PC-related anxiety (MAX-PC) with sociodemographic characteristics, family history of PC, global health status/quality of life (EORTC QLQ-C30), depression and anxiety (PHQ-2; GAD-2), latest PSA level, time since radical prostatectomy, and current therapy. The survey participants' mean age was 75.2 years (SD = 6.5). Median follow-up was 11.5 years, and 19.5% of participants had survived more than 15 years since the initial treatment. The final regression analysis found that younger age, lower global health status/quality of life, higher depression and anxiety scores, higher latest PSA level, and shorter time since radical prostatectomy predicted increased PSA-related anxiety and PC anxiety. Familial PC was predictive only of PSA anxiety (all p < 0.05). The final model explained 12% of the variance for PSA anxiety and 24% for PC anxiety. PC-related anxiety remained relevant many years after prostatectomy and was influenced by younger age, psychological status, rising PSA level, and shorter time since initial treatment. Survivors with these characteristics are at increased risk of PC-related anxieties, which should be considered by the treating physician during follow-up.

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.

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.

Deliberative democracy and cancer screening consent: a randomised control trial of the effect of a community jury on men's knowledge about and intentions to participate in PSA screening.

PubMed

Thomas, Rae; Glasziou, Paul; Rychetnik, Lucie; Mackenzie, Geraldine; Gardiner, Robert; Doust, Jenny

2014-12-24

Prostate-specific antigen (PSA) screening is controversial. A community jury allows presentation of complex information and may clarify how participants view screening after being well-informed. We examined whether participating in a community jury had an effect on men's knowledge about and their intention to participate in PSA screening. Random allocation to either a 2-day community jury or a control group, with preassessment, postassessment and 3-month follow-up assessment. Participants from the Gold Coast (Australia) recruited via radio, newspaper and community meetings. Twenty-six men aged 50-70 years with no previous diagnosis of prostate cancer. The control group (n=14) received factsheets on PSA screening. Community jury participants (n=12) received the same factsheets and further information about screening for prostate cancer. In addition, three experts presented information on PSA screening: a neutral scientific advisor provided background information, one expert emphasised the potential benefits of screening and another expert emphasised the potential harms. Participants discussed information, asked questions to the experts and deliberated on personal and policy decisions. Our primary outcome was change in individual intention to have a PSA screening test. We also assessed knowledge about screening for prostate cancer. Analyses were conducted using intention-to-treat. Immediately after the jury, the community jury group had less intention-to-screen for prostate cancer than men in the control group (effect size=-0.6 SD, p=0.05). This was sustained at 3-month follow-up. Community jury men also correctly identified PSA test accuracy and considered themselves more informed (effect size=1.2 SD, p<0.001). Evidence-informed deliberation of the harms and benefits of PSA screening effects men's individual choice to be screened for prostate cancer. Community juries may be a valid method for eliciting target group input to policy decisions. Australian and New Zealand Clinical Trials Registry (ACTRN12612001079831). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Deliberative democracy and cancer screening consent: a randomised control trial of the effect of a community jury on men's knowledge about and intentions to participate in PSA screening

PubMed Central

Thomas, Rae; Glasziou, Paul; Rychetnik, Lucie; Mackenzie, Geraldine; Gardiner, Robert; Doust, Jenny

2014-01-01

Objective Prostate-specific antigen (PSA) screening is controversial. A community jury allows presentation of complex information and may clarify how participants view screening after being well-informed. We examined whether participating in a community jury had an effect on men's knowledge about and their intention to participate in PSA screening. Design Random allocation to either a 2-day community jury or a control group, with preassessment, postassessment and 3-month follow-up assessment. Setting Participants from the Gold Coast (Australia) recruited via radio, newspaper and community meetings. Participants Twenty-six men aged 50–70 years with no previous diagnosis of prostate cancer. Intervention The control group (n=14) received factsheets on PSA screening. Community jury participants (n=12) received the same factsheets and further information about screening for prostate cancer. In addition, three experts presented information on PSA screening: a neutral scientific advisor provided background information, one expert emphasised the potential benefits of screening and another expert emphasised the potential harms. Participants discussed information, asked questions to the experts and deliberated on personal and policy decisions. Main outcome and measures Our primary outcome was change in individual intention to have a PSA screening test. We also assessed knowledge about screening for prostate cancer. Results Analyses were conducted using intention-to-treat. Immediately after the jury, the community jury group had less intention-to-screen for prostate cancer than men in the control group (effect size=−0.6 SD, p=0.05). This was sustained at 3-month follow-up. Community jury men also correctly identified PSA test accuracy and considered themselves more informed (effect size=1.2 SD, p<0.001). Conclusions Evidence-informed deliberation of the harms and benefits of PSA screening effects men's individual choice to be screened for prostate cancer. Community juries may be a valid method for eliciting target group input to policy decisions. Trial registration number Australian and New Zealand Clinical Trials Registry (ACTRN12612001079831). PMID:25539779

Effects of increasing the PSA cutoff to perform additional biomarker tests before prostate biopsy.

PubMed

Nordström, Tobias; Adolfsson, Jan; Grönberg, Henrik; Eklund, Martin

2017-10-03

Multi-step testing might enhance performance of the prostate cancer diagnostic pipeline. Using PSA >1 ng/ml for first-line risk stratification and the Stockholm 3 Model (S3M) blood-test >10% risk of Gleason Score > 7 prostate cancer to inform biopsy decisions has been suggested. We aimed to determine the effects of changing the PSA cutoff to perform reflex testing with S3M and the subsequent S3M cutoff to recommend prostate biopsy while maintaining the sensitivity to detect Gleason Score ≥ 7 prostate cancer. We used data from the prospective, population-based, paired, diagnostic Stockholm 3 (STHLM3) study with participants invited by date of birth from the Swedish Population Register during 2012-2014. All participants underwent testing with PSA and S3M (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms, and clinical variables [age, family, history, previous prostate biopsy, prostate exam]). Of 47,688 men in the STHLM3 main study, we used data from 3133 men with S3M >10% and prostate biopsy data. Logistic regression models were used to calculate prostate cancer detection rates and proportion saved biopsies. 44.2%, 62.5% and 67.9% of the participants had PSA <1, <1.5 and <1.7 ng/ml, respectively. Increasing the PSA cut-off for additional work-up from 1 ng/ml to 1.5 ng/ml would thus save 18.3% of the performed tests, 4.9% of the biopsies and 1.3% (10/765) of Gleason Grade ≥ 7 cancers would be un-detected. By lowering the S3M cutoff to recommend biopsy, sensitivity to high-grade prostate cancer can be restored, to the cost of increasing the number of performed biopsies modestly. The sensitivity to detect prostate cancer can be maintained when using different PSA cutoffs to perform additional testing. Biomarker cut-offs have implications on number of tests and prostate biopsies performed. A PSA cutoff of 1.5 ng/ml to perform additional testing such as the S3M test might be considered. ISRCTN84445406 .

[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

Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes.

PubMed

Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M; Aleixandre, Rosa N; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2016-01-01

New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic.

Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes

PubMed Central

Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M.; Aleixandre, Rosa N.; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2016-01-01

New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic. PMID:27279911

Improved porous silicon (P-Si) microarray based PSA (prostate specific antigen) immunoassay by optimized surface density of the capture antibody

PubMed Central

Lee, SangWook; Kim, Soyoun; Malm, Johan; Jeong, Ok Chan; Lilja, Hans; Laurell, Thomas

2014-01-01

Enriching the surface density of immobilized capture antibodies enhances the detection signal of antibody sandwich microarrays. In this study, we improved the detection sensitivity of our previously developed P-Si (porous silicon) antibody microarray by optimizing concentrations of the capturing antibody. We investigated immunoassays using a P-Si microarray at three different capture antibody (PSA - prostate specific antigen) concentrations, analyzing the influence of the antibody density on the assay detection sensitivity. The LOD (limit of detection) for PSA was 2.5ngmL−1, 80pgmL−1, and 800fgmL−1 when arraying the PSA antibody, H117 at the concentration 15µgmL−1, 35µgmL−1 and 154µgmL−1, respectively. We further investigated PSA spiked into human female serum in the range of 800fgmL−1 to 500ngmL−1. The microarray showed a LOD of 800fgmL−1 and a dynamic range of 800 fgmL−1 to 80ngmL−1 in serum spiked samples. PMID:24016590

The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer.

PubMed

Wilt, Timothy J; Brawer, Michael K; Barry, Michael J; Jones, Karen M; Kwon, Young; Gingrich, Jeffrey R; Aronson, William J; Nsouli, Imad; Iyer, Padmini; Cartagena, Ruben; Snider, Glenn; Roehrborn, Claus; Fox, Steven

2009-01-01

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. Ninety percent of men with prostate cancer are over aged 60 years, diagnosed by early detection with the prostate specific antigen (PSA) blood test and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting surgery to remove the prostate gland (radical prostatectomy), external beam radiation therapy and interstitial radiation therapy (brachytherapy) and androgen deprivation. Little is known about the relative effectiveness and harms of treatments due to the paucity of randomized controlled trials. The VA/NCI/AHRQ Cooperative Studies Program Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy versus watchful waiting conducted in Scandinavia. We screened 13,022 men with prostate cancer at 52 United States medical centers for potential enrollment. From these, 5023 met initial age, comorbidity and disease eligibility criteria and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African-American. Approximately 85% reported they were fully active. The median prostate specific antigen (PSA) was 7.8 ng/mL (mean 10.2 ng/mL). In three-fourths of men the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade and tumor stage, approximately 43% had low risk, 36% had medium risk and 20% had high-risk prostate cancer. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the U.S. and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared to watchful waiting for men with predominately PSA detected clinically localized prostate cancer.

A Serum miR Signature Specific to Low-Risk Prostate Cancer

DTIC Science & Technology

2017-09-01

useful pre-treatment risk calculators that use clinical parameters (age, biopsy grade, PSA ). These calculators accurately identify high-risk patients...aggressive disease. There are several useful pre-treatment risk calculators that use clinical parameters (age, biopsy grade, PSA ). These calculators

Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

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

Wiegel, Thomas, E-mail: thomas.wiegel@uniklinik-ulm.de; Bartkowiak, Detlef; Bottke, Dirk

2015-02-01

Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6,more » range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups will benefit most from which treatment option.« less

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.

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.

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

PubMed Central

Hellwinkel, Olaf J. C.; Sellier, Christina; Sylvester, Yu-Mi Jessica; Brase, Jan C.; Isbarn, Hendrik; Erbersdobler, Andreas; Steuber, Thomas; Sültmann, Holger; Schlomm, Thorsten; Wagner, Christina

2013-01-01

We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ. PMID:23459235

Effects of the somatostatin analog lanreotide on the circulating levels of chromogranin-A, prostate-specific antigen, and insulin-like growth factor-1 in advanced prostate cancer patients.

PubMed

Berruti, A; Dogliotti, L; Mosca, A; Tarabuzzi, R; Torta, M; Mari, M; Gorzegno, G; Fontana, D; Angeli, A

2001-05-15

The concept that neuroendocrine cells detected within prostate adenocarcinoma produce paracrine factors, that may exert a proliferative effect on exocrine prostate tumor cells, provides a rationale for the use of somatostatin analogs with the aim to counteract or delay the tumor progression. This study was designed to provide preliminary information on the effect of the administration of a long-acting somatostatin analog, lanreotide, on plasma levels of chromogranin A (CgA). Secondary aims were the evaluation of changes in circulating prostate-specific antigen (PSA) and insulin-like growth factor-1 (IGF-1). Lanreotide (Ipstyl 30 mg; Ipsen, Milan, Italy) was administered intramuscularly every 14 days for 2 months to nine heavily pretreated prostate cancer patients with hormone refractory disease. All patients had, at baseline conditions, CgA values above the normal range. Androgen deprivation was maintained during the study period, while other concomitant antineoplastic treatments were not allowed. Serum PSA levels and plasma CgA and IGF-1 values were measured every week. Lanreotide treatment was very well tolerated and no patient experienced major toxicity. Plasma CgA values at baseline: mean 109 U/liter, standard deviation +/- 85 decreased significantly after treatment as follows: 42 U/liter, +/- 17.8; 27.2 U/liter +/- 13.6; 31.4 U/liter, +/- 17.8 and 27.6 U/liter, +/- 17.0; after 7, 14, 21, and 28 days, respectively (P < 0.01, Friedman ANOVA). Serum PSA did not change. Baseline IGF-1 was found to be above the detection limit in four cases, all of them showing a decrease after lanreotide. Lanreotide administration to prostate cancer patients induces a decrease in plasma CgA and IGF-1 levels, without any influence on serum PSA values. Prostate 47:205-211, 2001. Copyright 2001 Wiley-Liss, Inc.

Sirolimus, Docetaxel, and Carboplatin in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

ClinicalTrials.gov

2018-05-25

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Level Greater Than or Equal to Two; PSA Progression; Stage IV Prostate Cancer AJCC v7

Metformin Has a Positive Therapeutic Effect on Prostate Cancer in Diabetes Mellitus 2 Patients

PubMed Central

Chong, R. William; Vasudevan, Vijaya; Zuber, Jeffrey; Solomon, Solomon S.

2016-01-01

Objective Prostate cancer and type 2 diabetes mellitus are both common diseases found in the elderly male population. The diabetic drug, metformin, has been shown to have anti-neoplastic properties and demonstrated better treatment outcomes when used as adjuvant therapy in breast cancer patients. The hormonally-sensitive cancer analogous to breast in men is prostate. We investigated improved survival, lower risks of recurrences, and lower, more stable levels of prostate specific antigen (PSA) in DM2 patients with prostate cancer on metformin. Methods Prostate cancer patients with type 2 diabetes that remained on metformin were compared to controls not on metformin matched by age, weight, race, and Gleason score cancer staging. The endpoints of our study included final PSA values, number of recurrences, metastases and number living for each group. Results There were significantly fewer deaths (23% vs 10%), fewer recurrences (15% vs 8%), and fewer metastases (5% vs 0%), and fewer secondary cancers (17% vs 6%) in the metformin group (p<0.004). The final PSA value was lower in the metformin-treated group with a result approaching significance (p=0.067). The primary treatments for prostate cancer (i.e. surgery, radiation, androgen depletion) were found to be comparable in both groups. Conclusions Our retrospective study shows that adjuvant metformin therapy leads to a better prognosis in prostate cancer. Not only are PSA levels controlled for several years, but there are significantly fewer cancer recurrences in metformin treated patients. Overall, these results are promising and should be followed up with a prospective study to assess long-term survival. PMID:27079349

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: |

Low testosterone at first prostate-specific antigen failure and assessment of risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.

PubMed

Atkins, Katelyn M; Chen, Ming-Hui; Wu, Jing; Renshaw, Andrew A; Loffredo, Marian; Kantoff, Philip W; Small, Eric J; D'Amico, Anthony V

2018-04-01

Low testosterone at the time of diagnosis of prostate cancer has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at the time of first prostate-specific antigen (PSA) failure to the authors' knowledge has not been elucidated to date and was studied herein. Between 1995 and 2001, a total of 58 men with unfavorable-risk PC who were treated on clinical trials with radiotherapy and androgen deprivation therapy (ADT) had available testosterone levels at the time of PSA failure. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone was associated with the risk of PC-specific mortality, other-cause mortality, and all-cause mortality adjusting for age, salvage ADT, and known PC prognostic factors. After a median follow-up of 6.68 years after PSA failure, 31 men (53.4%) had died; 10 of PC (32.3%), of which 8 of 11 (72.7%) versus 2 of 47 (4.3%) deaths occurred in men with low versus normal testosterone at the time of PSA failure, respectively. A significant increase in the risk of all-cause mortality (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [95% CI], 1.04-6.21 [P = .04]) and PC-specific mortality (AHR, 13.71; 95% CI, 2.4-78.16 [P = .003]), with a reciprocal trend toward a decreased risk of other-cause mortality (AHR, 0.18; 95% CI, 0.02-1.55 [P = .12]) was observed in men with low versus normal testosterone. Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis. These observations provide evidence to support testosterone testing at the time of PSA failure. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic PC and possibly localized high-risk PC provides a rationale supporting their use with ADT in men with low testosterone in the setting of a phase 2 trial. Cancer 2018;124:1383-90. © 2017 American Cancer Society. © 2017 American Cancer Society.

Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy.

PubMed

Fossati, Nicola; Karnes, R Jeffrey; Cozzarini, Cesare; Fiorino, Claudio; Gandaglia, Giorgio; Joniau, Steven; Boorjian, Stephen A; Goldner, Gregor; Hinkelbein, Wolfgang; Haustermans, Karin; Tombal, Bertrand; Shariat, Shahrokh; Karakiewicz, Pierre I; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas; Briganti, Alberto

2016-04-01

Early salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear. To test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics. The study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤ 0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥ 0.2 ng/ml. Multivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤ 6, 7, or ≥ 8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥ 8, and negative surgical margins. Median follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27-105). At 5 yr after eSRT, BCR-free survival rate was 82% (95% confidence interval [CI], 78-85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95% CI, 1.40-22.9; p < 0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors. In this retrospective study, cancer control after eSRT greatly depended on pretreatment PSA. The absolute PSA level had a different prognostic value depending on the pathologic characteristics of the tumour. In patients with more adverse pathologic features, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Conversely, the benefit of eSRT was less evident in men with favourable disease at RP. In this retrospective study, cancer control after early salvage radiation therapy (eSRT) was influenced by pretreatment prostate-specific antigen (PSA) level. This effect was highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥ 8, and negative surgical margins. In these patients, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Do Men Receive Information Required for Shared Decision Making About PSA Testing? Results from a National Survey.

PubMed

Leyva, Bryan; Persoskie, Alexander; Ottenbacher, Allison; Hamilton, Jada G; Allen, Jennifer D; Kobrin, Sarah C; Taplin, Stephen H

2016-12-01

Most professional organizations, including the American College of Physicians and U.S. Preventive Services Task Force, emphasize that screening for prostate cancer with the prostate-specific antigen (PSA) test should only occur after a detailed discussion between the health-care provider and patient about the known risks and potential benefits of the test. In fact, guidelines strongly advise health-care providers to involve patients, particularly those at elevated risk of prostate cancer, in a "shared decision making" (SDM) process about PSA testing. We analyzed data from the National Cancer Institute's Health Information National Trends Survey 2011-2012-a nationally representative, cross-sectional survey-to examine the extent to which health professionals provided men with information critical to SDM prior to PSA testing, including (1) that patients had a choice about whether or not to undergo PSA testing, (2) that not all doctors recommend PSA testing, and (3) that no one is sure if PSA testing saves lives. Over half (55 %) of men between the ages of 50 and 74 reported ever having had a PSA test. However, only 10 % of men, regardless of screening status, reported receiving all three pieces of information: 55 % reported being informed that they could choose whether or not to undergo testing, 22 % reported being informed that some doctors recommend PSA testing and others do not, and 14 % reported being informed that no one is sure if PSA testing actually saves lives. Black men and men with lower levels of education were less likely to be provided this information. There is a need to improve patient-provider communication about the uncertainties associated with the PSA test. Interventions directed at patients, providers, and practice settings should be considered.

Baseline PSA in a Spanish male population aged 40-49 years anticipates detection of prostate cancer.

PubMed

Angulo, J C; Viñas, M A; Gimbernat, H; Fata, F Ramón de; Granados, R; Luján, M

2015-12-01

We researched the usefulness of optimizing prostate cancer (PC) screening in our community using baseline PSA readings in men between 40-49 years of age. A retrospective study was performed that analyzed baseline PSA in the fifth decade of life and its ability to predict the development of PC in a population of Madrid (Spain). An ROC curve was created and a cutoff was proposed. We compared the evolution of PSA from baseline in patients with consecutive readings using the Friedman test. We established baseline PSA ranges with different risks of developing cancer and assessed the diagnostic utility of the annual PSA velocity (PSAV) in this population. Some 4,304 men aged 40-49 years underwent opportunistic screening over the course of 17 years, with at least one serum PSA reading (6,001 readings) and a mean follow-up of 57.1±36.8 months. Of these, 768 underwent biopsy of some organ, and 104 underwent prostate biopsy. Fourteen patients (.33%) were diagnosed with prostate cancer. The median baseline PSA was .74 (.01-58.5) ng/mL for patients without PC and 4.21 (.76-47.4) ng/mL for those with PC. The median time from the reading to diagnosis was 26.8 (1.5-143.8) months. The optimal cutoff for detecting PC was 1.9ng/mL (sensitivity, 92.86%; specificity, 92.54%; PPV, 3.9%; NPV, 99.97%), and the area under the curve was 92.8%. In terms of the repeated reading, the evolution of the PSA showed no statistically significant differences between the patients without cancer (p=.56) and those with cancer (P=.64). However, a PSAV value >.3ng/mL/year revealed high specificity for detecting cancer in this population. A baseline PSA level ≥1.9ng/mL in Spanish men aged 40-49 years predicted the development of PC. This value could therefore be of use for opportunistic screening at an early age. An appropriate follow-up adapted to the risk of this population needs to be defined, but an annual PSAV ≥.3ng/mL/year appears of use for reaching an early diagnosis. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer.

PubMed

Heath, Elisabeth I; Hillman, David W; Vaishampayan, Ulka; Sheng, Shijie; Sarkar, Fazlul; Harper, Felicity; Gaskins, Melvin; Pitot, Henry C; Tan, Winston; Ivy, S Percy; Pili, Roberto; Carducci, Michael A; Erlichman, Charles; Liu, Glenn

2008-12-01

17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with antiproliferative activity in several mouse xenograft models, including prostate cancer models. A two-stage phase II study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer. Patients with at least one prior systemic therapy and a rising prostate-specific antigen (PSA) were eligible. Patients received 17-AAG at a dose of 300 mg/m2 i.v. weekly for 3 of 4 weeks. The primary objective was to assess the PSA response. Secondary objectives were to determine overall survival, to assess toxicity, and to measure interleukin-6, interleukin-8, and maspin levels and quality of life. Fifteen eligible patients were enrolled. The median age was 68 years and the median PSA was 261 ng/mL. Patients received 17-AAG for a median number of two cycles. Severe adverse events included grade 3 fatigue (four patients), grade 3 lymphopenia (two patients), and grade 3 back pain (two patients). The median PSA progression-free survival was 1.8 months (95% confidence interval, 1.3-3.4 months). The 6-month overall survival was 71% (95% confidence interval, 52-100%). 17-AAG did not show any activity with regard to PSA response. Due to insufficient PSA response, enrollment was stopped at the end of first stage per study design. The most significant severe toxicity was grade 3 fatigue. Further evaluation of 17-AAG at a dose of 300 mg/m2 i.v. weekly as a single agent in patients with metastatic, hormone-refractory prostate cancer who received at least one prior systemic therapy is not warranted.

Prostate-specific antigen levels in hypertensive patients suffering from a non-ST elevation myocardial infarction or a new-onset atrial fibrillation.

PubMed

Patanè, Salvatore; Marte, Filippo

2012-07-26

Increasing evidence suggests that prostate-specific antigen kallikrein (PSA) relates to the cardiovascular system. Recently, an association between PSA levels and aortic stiffness has been also reported in untreated essential hypertensive males. Elevated pulse pressure, a surrogate measure for increased proximal aortic stiffness, predisposes to myocardial infarction and atrial fibrillation. No studies, to date, have evaluated the relationship between PSA levels and the occurrence of AMI or new-onset atrial fibrillation in hypertensive male patients. Herein, we conducted a study to investigate this question. This work is a retrospective, observational, study. Consecutive male patients were enrolled and divided in two groups: 58 patients with non-ST elevation myocardial infarction (NSTEMI) and 59 patients with new-onset atrial fibrillation. PSA levels gradually change with age and we prefer to use the percentage of age-specific PSA ranges (a.s. PSA) instead of the simple PSA levels. At multivariate analysis DM [0.263 (0.105-0.662); P=0.005], dyslipidemia [0.301 (0.105-0.863); P=0.025] and a higher percentage of a.s. PSA [0.908 (0.895-0.970); P=0.000] were significantly associated with the occurrence of NSTEMI. The main results of this study showed that a higher percentage of a.s. PSA significantly relates with the occurrence of NSTEMI. In addition, the results of our investigation, also, demonstrate that the significant correlation between higher percentage of a.s. PSA and the occurrence of NSTEMI persisted after adjustment for traditional CAD risk factors (age, DM, dyslipidemia, and smoking). Large studies are needed to further confirm our findings and to elucidate the causes and effects. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

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

Mitchell, Darren M.; McAleese, Jonathan; Park, Richard M.

2007-12-01

Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapymore » was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.« less

Screening men for prostate and colorectal cancer in the United States: does practice reflect the evidence?

PubMed

Sirovich, Brenda E; Schwartz, Lisa M; Woloshin, Steven

2003-03-19

The debate about the efficacy of prostate-specific antigen (PSA) screening for prostate cancer has received substantial attention in the medical literature and the media, but the extent to which men are actually screened is unknown. If practice were evidence-based, PSA screening would be less common among men than colorectal cancer screening, a preventive service of broad acceptance and proven efficacy. To compare the prevalences of PSA and colorectal cancer screening among US men. The 2001 Behavioral Risk Factor Surveillance System, an annual population-based telephone survey of US adults conducted by the Centers for Disease Control and Prevention, was used to gather data on a representative sample of men aged 40 years or older from all 50 states and the District of Columbia (n = 49 315). Proportions of men ever screened and up to date on screening for prostate cancer (with PSA testing) and colorectal cancer (with fecal occult blood testing, flexible sigmoidoscopy, or colonoscopy). Overall, men are more likely to report having ever been screened for prostate cancer than for colorectal cancer; 75% of those aged 50 years or older have had a PSA test vs 63% for any colorectal cancer test (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.18-1.21). Up-to-date PSA screening is also more common than colorectal cancer screening for men of all ages. Among men aged 50 to 69 years (those for whom there is the greatest consensus in favor of screening), 54% reported an up-to-date PSA screen, while 45% reported up-to-date testing for colorectal cancer (RR, 1.19; 95% CI, 1.16-1.21). In state-level analyses of this age group, men were significantly more likely to be up to date on prostate cancer screening compared with colorectal cancer screening in 27 states, while up-to-date colorectal cancer screening was more common in only 1 state. Among men in the United States, prostate cancer screening is more common than colorectal cancer screening. Physicians should ensure that men who choose to be screened for cancer are aware of the known mortality benefit of colorectal cancer screening and the uncertain benefits of screening for prostate cancer.

Carbidopa abrogates L-dopa decarboxylase coactivation of the androgen receptor and delays prostate tumor progression.

PubMed

Wafa, Latif A; Cheng, Helen; Plaa, Nathan; Ghaidi, Fariba; Fukumoto, Takahiro; Fazli, Ladan; Gleave, Martin E; Cox, Michael E; Rennie, Paul S

2012-06-15

The androgen receptor (AR) plays a central role in prostate cancer progression to the castration-resistant (CR) lethal state. L-Dopa decarboxylase (DDC) is an AR coactivator that increases in expression with disease progression and is coexpressed with the receptor in prostate adenocarcinoma cells, where it may enhance AR activity. Here, we hypothesize that the DDC enzymatic inhibitor, carbidopa, can suppress DDC-coactivation of AR and retard prostate tumor growth. Treating LNCaP prostate cancer cells with carbidopa in transcriptional assays suppressed the enhanced AR transactivation seen with DDC overexpression and decreased prostate-specific antigen (PSA) mRNA levels. Carbidopa dose-dependently inhibited cell growth and decreased survival in LNCaP cell proliferation and apoptosis assays. The inhibitory effect of carbidopa on DDC-coactivation of AR and cell growth/survival was also observed in PC3 prostate cancer cells (stably expressing AR). In vivo studies demonstrated that serum PSA velocity and tumor growth rates elevated ∼2-fold in LNCaP xenografts, inducibly overexpressing DDC, were reverted to control levels with carbidopa administration. In castrated mice, treating LNCaP tumors, expressing endogenous DDC, with carbidopa delayed progression to the CR state from 6 to 10 weeks, while serum PSA and tumor growth decreased 4.3-fold and 5.4-fold, respectively. Our study is a first time demonstration that carbidopa can abrogate DDC-coactivation of AR in prostate cancer cells and tumors, decrease serum PSA, reduce tumor growth and delay CR progression. Since carbidopa is clinically approved, it may be readily used as a novel therapeutic strategy to suppress aberrant AR activity and delay prostate cancer progression. Copyright © 2011 UICC.

Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

PubMed Central

MOMOZONO, HIROYUKI; MIYAKE, HIDEAKI; TEI, HIROMOTO; HARADA, KEN-ICHI; FUJISAWA, MASATO

2016-01-01

The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC. PMID:27123292

Selective and augmented β-glucuronidase expression combined with DOX-GA3 application elicits the potent suppression of prostate cancer.

PubMed

Wang, Longxin; Dong, Jie; Wei, Ming; Wen, Weihong; Gao, Jianping; Zhang, Zhengyu; Qin, Weijun

2016-03-01

The present study was carried out to evaluate the specific and amplified β-glucuronidase (βG) expression in prostate cancer cells by using a prostate‑specific antigen (PSA) promoter-controlled bicistronic adenovirus and to evaluate the specific killing of prostate cancer cells after the application of the prodrug DOX‑GA3. Bicistronic adenoviral expression vectors were constructed, and the effectiveness of specific and amplified expression was evaluated using luciferase and EGFP as reporter genes. βG expression was detected in LNCaP cells after they were infected with the βG‑expressing PSA promoter-controlled bicistronic adenovirus. MTT assays were conducted to evaluate the cytoxicity on the infected cells after the application of the prodrug DOX‑GA3. Tumor growth inhibition was also evaluated in nude mice after treatment with the βG‑expressing adenovirus and DOX‑GA3. Selective and amplified expression was observed in the PSA-producing LNCaP cells, but not in the PSA‑non‑producing DU145 cells. Potent cytotoxity and a strong bystander effect were observed in the LNCaP cells after infection with the βG‑expressing adenovirus and the application of DOX‑GA3. Intravenous injection of a GAL4 regulated bicistronic adenovirus vector constructed to express βG under the control of the PSA promoter (Ad/PSAP‑GV16‑βG) and the application of DOX‑GA3 strongly inhibited tumor growth and prolonged the survival time of tumor‑bearing nude mice. Selective and amplified βG expression together with the prodrug DOX‑GA3 had an increased antitumor effect, showing great potential for prostate cancer therapy.

Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer

PubMed Central

Ahmadzadehfar, Hojjat; Eppard, Elisabeth; Kürpig, Stefan; Fimmers, Rolf; Yordanova, Anna; Schlenkhoff, Carl Diedrich; Gärtner, Florian; Rogenhofer, Sebastian; Essler, Markus

2016-01-01

Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with 177Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64–82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17–2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients. PMID:26871285

A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer.

PubMed

Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

2017-09-01

We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa -high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa -low PSA and non PCa -high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa.

A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer

PubMed Central

Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

2017-01-01

Objective We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). Material and methods We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. Results The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa –high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa –low PSA and non PCa –high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. Conclusion According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa. PMID:28861298

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

Frequency of Propionibacterium acnes Infection in Prostate Glands with Negative Biopsy Results Is an Independent Risk Factor for Prostate Cancer in Patients with Increased Serum PSA Titers

PubMed Central

Ito, Takashi; Uchida, Keisuke; Sekine, Masaki; Nakajima, Yutaka; Furukawa, Asuka; Suzuki, Yoshimi; Kumagai, Jiro; Akashi, Takumi

2017-01-01

Background Propionibacterium acnes has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular P. acnes infection in prostate glands and the higher frequency of P. acnes-positive glands in radical prostatectomy specimens from patients with prostate cancer (PCa) than in those from patients without PCa led us to examine whether the P. acnes-positive gland frequency can be used to assess the risk for PCa in patients whose first prostate biopsy, performed due to an increased prostate-specific antigen (PSA) titer, was negative. Methods We retrospectively collected the first and last prostate biopsy samples from 44 patients that were diagnosed PCa within 4 years after the first negative biopsy and from 36 control patients with no PCa found in repeated biopsy for at least 3 years after the first biopsy. We evaluated P. acnes-positive gland frequency and P. acnes-positive macrophage number using enzyme-immunohistochemistry with a P. acnes-specific monoclonal antibody (PAL antibody). Results The frequency of P. acnes-positive glands was higher in PCa samples than in control samples in both first biopsy samples and in combined first and last biopsy samples (P < 0.001). A frequency greater than the threshold (18.5 and 17.7, respectively) obtained by each receiver operating characteristic curve was an independent risk factor for PCa (P = 0.003 and 0.001, respectively) with odds ratios (14.8 and 13.9, respectively) higher than those of serum PSA titers of patients just before each biopsy (4.6 and 2.3, respectively). The number of P. acnes-positive macrophages did not differ significantly between PCa and control samples. Conclusions These results suggested that the frequency of P. acnes-positive glands in the first negative prostate biopsy performed due to increased PSA titers can be supportive information for urologists in planning repeated biopsy or follow-up strategies. PMID:28081259

Prognostic grouping of metastatic prostate cancer using conventional pretreatment prognostic factors.

PubMed

Mikkola, Arto; Aro, Jussi; Rannikko, Sakari; Ruutu, Mirja

2009-01-01

To develop three prognostic groups for disease specific mortality based on the binary classified pretreatment variables age, haemoglobin concentration (Hb), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), prostate-specific antigen (PSA), plasma testosterone and estradiol level in hormonally treated patients with metastatic prostate cancer (PCa). The present study comprised 200 Finnprostate 6 study patients, but data on all variables were not known for every patient. The patients were divided into three prognostic risk groups (Rgs) using the prognostically best set of pretreatment variables. The best set was found by backward stepwise selection and the effect of every excluded variable on the binary classification cut-off points of the remaining variables was checked and corrected when needed. The best group of variables was ALP, PSA, ESR and age. All data were known in 142 patients. Patients were given one risk point each for ALP > 180 U/l (normal value 60-275 U/l), PSA > 35 microg/l, ESR > 80 mm/h and age < 60 years. Three risk groups were formed: Rg-a (0-1 risk points), Rg-b (2 risk points) and Rg-c (3-4 risk points). The risk of death from PCa increased statistically significantly with advancing prognostic group. Patients with metastatic PCa can be divided into three statistically significantly different prognostic risk groups for PCa-specific mortality by using the binary classified pretreatment variables ALP, PSA, ESR and age.

Predictors of participation in prostate cancer screening at worksites.

PubMed

Weinrich, S P; Greiner, E; Reis-Starr, C; Yoon, S; Weinrich, M

1998-01-01

Unfortunately, African American men have a higher incidence of and a higher mortality rate for prostate cancer than White men but are less likely to participate in prostate cancer screening. This correlational survey research identifies predictors for participation in a free prostate cancer screening in 179 men, 64% of whom are African American. Each man was invited to see his personal physician for a free prostate cancer screening following a prostate cancer educational program given at his worksite. Forty-seven percent of the African American men went to their personal physician following the educational program and received a digital rectal examination (DRE) and a prostate specific antigen (PSA) screening. In the original cohort of educational program attendees, only 16% of the African Americans had obtained a DRE in the previous 12 months. However, 44% subsequently did participate in free DRE screening. Similarly, only 6% of the African American men had received a PSA screening in the previous 12 months, yet 42% obtained a PSA screening after the educational program, a sevenfold increase. Implications for allocating limited resources for education and screening to the high-risk group of African American men are discussed. This study's model of a prostate cancer educational program at worksites followed by attendees visiting their personal physician for screening could be replicated throughout the United States to increase African American men's participation in prostate cancer screening.

Watchful waiting and factors predictive of secondary treatment of localized prostate cancer.

PubMed

Wu, Hongyan; Sun, Leon; Moul, Judd W; Wu, Hong Yu; McLeod, David G; Amling, Christopher; Lance, Raymond; Kusuda, Leo; Donahue, Timothy; Foley, John; Chung, Andrew; Sexton, Wade; Soderdahl, Douglas

2004-03-01

Watchful waiting remains an important treatment option for some patients with localized prostate cancer. We defined the demographic, clinical and outcome features of men selecting watchful waiting as an initial treatment strategy, and determined factors predictive of eventual progression to secondary treatment. Of 8390 patients diagnosed with prostate cancer from 1990 to 2001 in the Department of Defense Center for Prostate Disease Research Database, 1158 patients chose watchful waiting as initial treatment. The demographic and clinical differences between patients on watchful waiting and those choosing other initial treatments were compared using the chi-square test. Secondary treatment-free survival according to various prognostic factors was plotted using the Kaplan-Meier method and differences were tested using the log rank test. A multivariate Cox proportional hazards regression analysis was performed to determine which factors were independent predictors of secondary treatment. Compared to other patients, those selecting watchful waiting were older, had lower prostate specific antigen (PSA) at diagnosis, and were more likely to have lower stage (cT1) and lower grade (Gleason sum 7 or less) cancers. Age, PSA and clinical stage were all significant and independent predictors of secondary treatment. The relative risk of secondary treatment can be expressed as EXP (-0.034 x age at diagnosis + 0.284 x LOG (diagnostic PSA) + 0.271 x clinical stage T2 + 0.264 x clinical stage T3). Men who elect watchful waiting as initial management for prostate cancer are older with lower Gleason sums and serum PSA. In these men, age at diagnosis, serum PSA and clinical stage are the most significant predictors of requiring or selecting secondary treatment.