PCA3 Test Research Articles

Circulating RNAs in prostate cancer patients.

Growing bodies of evidence have demonstrated that the identification of prostate cancer (PCa) biomarkers in the patients' blood and urine may remarkably improve PCa diagnosis and progression monitoring. Among diverse cancer-derived circulating materials, extracellular RNA molecules (exRNAs) represent a compelling component to investigate cancer-related alterations. Once outside the intracellular environment, exRNAs circulate in biofluids either in association with protein complexes or encapsulated inside extracellular vesicles (EVs). Notably, EV-associated RNAs (EV-RNAs) were used for the development of several assays (such as the FDA-approved Progensa Prostate Cancer Antigen 3 (PCA3 test) aiming at improving early PCa detection. EV-RNAs encompass a mixture of species, including small non-coding RNAs (e.g. miRNA and circRNA), lncRNAs and mRNAs. Several methods have been proposed to isolate EVs and relevant RNAs, and to perform RNA-Seq studies to identify potential cancer biomarkers. However, EVs in the circulation of a cancer patient include a multitude of diverse populations that are released by both cancer and normal cells from different tissues, thereby leading to a heterogeneous EV-RNA-associated transcriptional signal. Decrypting the complexity of such a composite signal is nowadays the major challenge faced in the identification of specific tumor-associated RNAs. Multiple deconvolution algorithms have been proposed so far to infer the enrichment of cancer-specific signals from gene expression data. However, novel strategies for EVs sorting and sequencing of RNA associated to single EVs populations will remarkably facilitate the identification of cancer-related molecules. Altogether, the studies summarized here demonstrate the high potential of using EV-RNA biomarkers in PCa and highlight the urgent need of improving technologies and computational approaches to characterize specific EVs populations and their relevant RNA cargo.

Current biomarkers of prostate cancer

Prostate cancer is one of the most common malignancies in men. Early detection of prostate cancer is largely determined by the widely used prostate specific antigen (PSA) blood test. However, as a diagnostic and prognostic test of prostate cancer, PSA has limited specificity, sensitivity and leads to hyper or underdiagnosis, which, in turn, can lead to excessive treatment. There fore, it is very important to develop diagnostic markers that can be used to determine prostate cancer at an early stage of development, assess the possible progression of the disease and prescribe optimal therapy. Significant progress has been made in the discovery of biomarkers for prostate cancer. For example, biomarkers such as %-free PSA, Prostate Health Index (PHI) or 4K score can be used to increase specificity and reduce the number of unnecessary biopsies, while the PCA3 test can be used to reduce the number of repeated biopsies in men with previously negative biopsy. To determine aggressiveness and predict the outcome of the disease, tissue multigenic tests can be used, such as: T2-ERG, ExoDx, SelectMDx and ConfirmMDx, Prolaris, Oncoytype DX, Decipher. The development of such diagnostic tests opens up new opportunities for improving the diagnosis of prostate cancer, prognosis and decision-making on the appointment of therapy. And with the increase in their availability, finally, the possibility of an individual approach to the appointment of treatment for men with prostate cancer appears on the horizon. This review paper presents the data on the most advanced diagnostic biomarkers of prostate cancer.

The use of molecular biomarker tests: an interview study with healthcare providers about a molecular biomarker test for prostate cancer.

Aim: Investigate why healthcare providers are not always willing to use molecular biomarker tests, even though they promise to personalize disease diagnosis and treatment. Materials & methods: We interviewed 20 Dutch urological healthcare providers to ascertain why they used or did not use SelectMDx, a biomarker test for prostate cancer. Results: Whether and how it was used differed from the developers' expectations, because users and nonusers disagreed aboutits perceived advantages; the scientific and clinical evidence; the advantages of MRI; and the value of PCA3 testing. Financial issues and the absence of SelectMDx in professional guidelines and hospital care pathways also hampered its use. Conclusion: Eliciting users' and nonusers' views is important to better understand how biomarker tests can be embedded in clinical practice.

Detection of the Prostate Cancer Biomarker PCA3 with Electrochemical and Impedance-Based Biosensors.

Diagnosis of prostate cancer via PCA3 biomarker detection is promising to be much more efficient than with the prostatic specific antigens currently used. In this study, we present the first electrochemical and impedance-based biosensors that are capable of detecting PCA3 down to 0.128 nmol/L. The biosensors were made with a layer of PCA3-complementary single-stranded DNA (ssDNA) probe, immobilized on a layer-by-layer (LbL) film of chitosan (CHT) and carbon nanotubes (MWCNT). They are highly selective to PCA3, which was confirmed in impedance measurements and with polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Using information visualization methods, we could also distinguish between cell lines expressing the endogenous PCA3 long noncoding RNA (lncRNA) from cells that did not contain detectable levels of this biomarker. Since the methods involved in fabrication the biosensors are potentially low cost, one may hope to deploy PCA3 tests in any laboratory of clinical analyses and even for point-of-care diagnostics.

Long Non-Coding RNAs - Current Methods of Detection and Clinical Applications.

Long non-coding RNAs (lncRNA) are more than 200-nucleotide-long RNA molecules that affect multiple physiologic phenomena and have important regulatory functions in cells. Their levels are often altered in various malignancies, thus they represent a potential biomarker for the diagnostics, prognosis or recurrence of cancer. Their importance has recently led to an enormous increase in a number of publications on the subject. The most frequently studied lncRNAs are HOTAIR, MALAT1 and PCA3. Numerous methods are currently being developed for the analysis or detection of lncRNA. They are mostly based on optical methods used for the detection of messenger RNAs, including polymerase chain reaction with reverse transcription, fluorescence in situ hybridisation or next-generation sequencing, but caution must be taken due to their structural differences. Here, we describe not only standard but also novel techniques for lncRNA detection, including chemiluminescent and electrochemical techniques. Despite the great progress and plethora of papers on this topic, there is only one single approved lncRNA-based diagnostic test, a PCA3 test for the diagnosis of prostate cancer from the patients urine. All other tests are only in their research phase and need to be validated. Nevertheless, lncRNA diagnostics offer enormous potential and thus it is highly probable that other diagnostic tests on different lncRNA types will soon appear.

Перспективы совершенствования диагностики рака предстательной железы на основе анализа экспрессии гена РСА3

Prostate cancer is the second leading cause of cancer death. The widespread introduction into the clinical practice of test for prostate specific antigen (PSA) led to an increase in the number of prostate biopsies performed. At the same time, a decrease in the threshold of age-specific PSA standards has resulted in an increase in the number of unnecessary biopsies. In this regard, a need has arisen for new prostate cancer biomarkers. PCA3 is a non-coding mRNA that is exclusively expressed by prostate cells. Currently, three generations of test diagnostic systems based on the quantitative analysis of the PCA3 mRNA in the urine or its cell sediment has already developed, and they differ in the type of material studied and the method for estimating the amount of PCA3 mRNA. Clinical studies of the developed test systems have shown that a high level of PCA3 expression in the patients urine correlates with the probability of detecting prostate cancer. PCA3 test has higher positive and negative predictive values than previously used PSA test. These data are repeatedly confirmed by studies conducted in different clinics. Thus, the introduction of the method of quantitative determination of PCA3 in clinical practice can significantly improve the efficiency of diagnosis of prostate cancer and reduce the number of unnecessary biopsies.

A critical appraisal of biomarkers in prostate cancer.

A number of urine and blood-based biomarker tests have been described for prostate cancer, although to date there has only been a limited exploration of the methodology behind the validation studies that underpin these tests. In this review, a selection of commercially available urine and blood-based biomarker tests for prostate cancer are described, and the underlying key validation studies for each test are critically appraised using the Standards for Reporting Diagnostic Accuracy (STARD) 2015 statement. The ExoDx Prostate Intelliscore, SelectMDx, Progensa PCA3, Mi-Prostate Score, 4K Score, and Prostate Health Index (PHI) tests were reviewed. Most of the validation studies supporting these tests perform exploratory analyses to determine cut-off values in a post hoc manner, comprise cohorts that are primarily Caucasian, report receiver operating characteristic curves that combine the biomarker's result with established clinical nomograms and are based on a reference standard (prostate biopsy) that lacks central pathology review. Deficiencies in STARD reporting guidelines include frequent failure to provide a published study protocol, prospective study registration in a registry, a flow diagram, justification for sample size determination, a discussion of adverse events with testing, and information on how missing or indeterminate test results should be managed. Key validation studies that support many commercially available urine and blood-based biomarkers for prostate cancers have deficiencies in transparency based on STARD reporting guidelines, and limitations in methodology must be considered when deciding when these tests should be applied in clinical practice.

Abstract 651: Development of an RNA in situ hybridization assay for the detection of prostate cancer cells in urine

Abstract Urine-based detection of prostate cancer represents a promising resource for non-invasive diagnostics. The value of urine as a biospecimen in the management of prostate cancer has already been established, but the utility of urine has yet to be fully explored. The objective of our study was to develop a RNA in situ hybridization (RISH) method for detecting prostate cells in urine and to evaluate the feasibility of using this assay for cancer detection in clinical specimens. We hypothesized that robust and specific labeling of prostate cancer cells could be achieved using this approach, providing benefit over existing urine detection methods, namely the FDA-approved PCA3 test, by allowing for the direct visualization and molecular characterization of individual cells. We optimized the following collection, processing, and preparation procedure for detection of prostate cells in fresh urine specimens collected from patients following digital rectal exam (DRE): the entire urine volume was centrifuged to collect the sediment, which was then formalin fixed, cytocentrifuged onto two slides, and slides were stored at -20°C until proceeding to staining and cytological analysis. Cellularity and sample adequacy was assessed by Papanicolaou staining. For identification of prostate cells in post-DRE urine via RISH, single-probe chromogenic labeling for NKX3.1 or HOXB13 was performed. Pretreatment conditions and staining parameters for RISH were optimized using urine samples spiked with 22Rv1 cells prior to staining patient specimens. We were able to readily identify cells of prostate origin in both spiked urines and patient samples. To further discriminate normal prostate cells from cancer cells, fluorescent multiplex RISH was pursued. We screened a candidate panel of prostate-specific RNA targets that included NKX3.1, HOXB13, KLK3, PRAC1, PRAC2, MALAT1, HOXC6, AMACR, and PCA3. Based on detection specificity, NKX3.1 and PRAC1 were selected as markers to identify cells of prostate origin and PCA3 as a marker of malignancy. Multiplex RISH with these three markers was carried out on 19 patient specimens. Prostate cells, classified as those positive for PRAC1 and/or NKX3.1, were identified in 11 samples, 6 of which were also positive for PCA3. These observations demonstrate that multiplex RISH can be used for the specific detection and visualization of prostate cancer cells in post-DRE urine samples. Although further refinement and validation are necessary, this study provides the first evidence supporting the application of a urinary RISH assay as a potential non-invasive method for prostate cancer detection. Ongoing and future studies will include characterizing performance of additional biomarker panels and validating clinical utility of this technique in a diagnostic setting. Citation Format: Jillian N. Eskra, Daniel Rabizadeh, Christian P. Pavlovich, Leslie Mangold, Elizabeth Fabian, William B. Isaacs, Jun Luo. Development of an RNA in situ hybridization assay for the detection of prostate cancer cells in urine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 651.

PCA3 as a second-line biomarker in a prospective controlled randomized opportunistic prostate cancer screening programme

ObjectivesPCA3 performance as a single second line biomarker is compared to the European Randomized Study of Screening for Prostate Cancer risk calculator model 3 (ERSPC RC-3) in an opportunistic screening in prostate cancer (PCa). Material and methods5199 men, aged 40–75 years, underwent prostate-specific antigen (PSA) screening and digital rectal examination (DRE). Men with a normal DRE and PSA ≥3ng/ml had a PCA3 test done. All men with PCA3 ≥35 underwent an initial biopsy (IBx) – 12 cores. Men with PCA3 <35 were randomized 1:1 to either IBx or observation. We compared them to those obtained with ERSPC RC-3. ResultsPCA3 test was performed on 838 men (16.1%). In PCA3(+) and PCA3(–) groups, global PCa detection rates were 40.9% and 14.7% with a median follow-up (FU) of 21.7 months (p<0.001). In the PCA3(+) arm (n=301, 35.9%), PCa was identified in 115 men at IBx (38.2%). In the randomized arm, 256 underwent IBx and PCa was found in 46 (18.0%) (p<0.001). The biopsy-sparing potential would have been 64.1% as opposed to 76.6% if we had used ERSPC RC-3. However, the estimated false negative cases for HGPCa would have been reduced by 37.1% (89–56 patients). Moreover, if we had applied PCA3 -35 to avoid IBx, 14.7% PCa and 9.1% of clinical significant PCa patients would not have been diagnosed during this FU. ConclusionsWhen PCA3 -35 is used as a second-line biomarker when PSA ≥3ng/ml and DRE is normal, IBx could be avoided in 12.5% less than if ERSPC RC-3 is used and would reduce the false negative cases by 36.2%. At a FU of 21.7 months, this dual protocol would miss 9.1% of clinically significant PCa, so strict FU is mandatory with established biopsy criteria based on PSA and DRE in cases with PCA3 <35.

PCA3 como biomarcador de segunda línea en un programa de screening oportunista prospectivo, aleatorizado y controlado

ObjectivesPCA3 performance as a single second line biomarker is compared to the European Randomised Study of Screening for Prostate Cancer risk calculator model 3 (ERSPC RC-3) in an opportunistic screening in prostate cancer (PCa). Material and methods5,199 men, aged 40-75y, underwent prostate-specific antigen (PSA) screening and digital rectal examination (DRE). Men with a normal DRE and PSA ≥3ng/ml had a PCA3 test done. All men with PCA3 ≥35 underwent an initial biopsy (IBx) —12 cores—. Men with PCA3 <35 were randomized 1:1 to either IBx or observation. We compared them to those obtained with ERSPC RC-3. ResultsPCA3 test was performed on 838 men (16.1%). In PCA3(+) and PCA3(–) groups, global PCa detection rates were 40.9% and 14.7% with a median follow-up (FU) of 21.7 months (P<.001). In the PCA3(+) arm (n=301, 35.9%), PCa was identified in 115 men at IBx (38.2%). In the randomized arm, 256 underwent IBx and PCa was found in 46 (18.0%) (P<.001). The biopsy-sparing potential would have been 64.1% as opposed to 76.6% if we had used ERSPC RC-3. However, the estimated false negative cases for HGPCa would have been reduced by 37.1% (89 to 56 patients). Moreover, if we had applied PCA3-35 to avoid IBx, 14.7% PCa and 9.1% of clinical significant PCa patients would not have been diagnosed during this FU. ConclusionsWhen PCA3-35 is used as a second-line biomarker when PSA ≥3ng/ml and DRE is normal, IBx could be avoided in 12.5% less than if ERSPC RC-3 is used and would reduce the false negative cases by 36.2%. At a FU of 21.7 months, this dual protocol would miss 9.1% of clinically significant PCa, so strict FU is mandatory with established biopsy criteria based on PSA and DRE in cases with PCA3 <35.

PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer.

The incidence of prostate cancer (PCa) is rising steadily among males in many countries. Serum prostate-specific antigen (PSA) is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PCA3 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.

Urinary PCA3 to predict prostate cancer in a cohort of 1015 patients

Summary Aim To evaluate the performance of urinary PCA3 test to predict prostate biopsy outcome in a large French cohort. Patients and methods A urine sample was prospectively obtained from 1015 patients undergoing prostate biopsies to determine the PCA3 score. The predictive value of PCA3 was explored using receiver operating characteristic curve analysis (ROC), multivariable logistic regression analysis and decision curve analysis. Results The median PCA3 score was significantly higher in patients with positive biopsies. The PCA3 score AUC was 0.76 (0.73–0.79), significantly higher than that of PSA (0.55; 0.51–0.58). At the cutoff of 35, sensitivity was 68%, specificity 71%, positive and negative predictive values 67% and 71%, and accuracy 69%. Using multivariate analysis, PCA3 score appeared as an independent predictor of biopsy outcome and its addition to a base model including usual clinicobiological parameters resulted in a significant increase in predictive accuracy. At the cutoff of 20, about 1/2 of the ultimately unnecessary biopsies would have been avoided while ignoring 7% of cancers with Gleason score ≥ 7. PCA3 score did not correlate with Gleason score but did correlate with tumor volume (proportion of positive cores). Conclusion Urinary PCA3 is a useful test with high diagnostic performances for early prostate cancer diagnosis. Its correlation with cancer aggressiveness seems rather represented by a link to prostate volume than Gleason score. Level of evidence 5.

Test urinaire PCA3 et diagnostic du cancer prostatique : étude à partir de 1015 patients

To evaluate the performance of urinary PCA3 test to predict prostate biopsy outcome in a large French cohort. A urine sample was prospectively obtained in 1015 patients undergoing prostate biopsies to determine the PCA3 score. The predictive value of PCA3 was explored using receiver operating characteristic curve analysis (ROC), multivariable logistic regression analysis and decision curve analysis. The median PCA3 score was significantly higher in patients with positive biopsies. The PCA3 score AUC was 0.76 (0.73-0.79), significantly higher than that of PSA (0.55; 0.51-0.58). At the cut-off of 35, sensitivity was 68 %, specificity 71 %, positive and negative predictive values 67 % and 71 %, and accuracy 69 %. Using multivariate analysis, PCA3 score appeared as an independent predictor of biopsy outcome and its addition to a base model including usual clinico-biological parameters resulted in a significant increase in predictive accuracy. At the cut-off of 20, about 1/2 of the eventual useless biopsies would have been avoided while ignoring 7 % of cancers with Gleason score ≥ 7. PCA3 score did not correlate to Gleason score but correlated to tumor volume (proportion of invaded cores). Urinary PCA3 is a useful test with high diagnostic performance for early prostate cancer diagnosis. Its correlation with cancer aggressiveness seems rather represented by a link to prostate volume than Gleason score.

Processing of voided urine for prostate cancer RNA biomarker analysis.

Voided urine samples have been shown to contain cells released from prostate tumors. Could good quality RNA from cells in urine be obtained from every donor for multimarker analysis? In addition, could urine donation be as simple as possible, a practical consideration for a lab test, without involving a prostate massage (as indicated for PCA3 testing), which precludes frequent collection; needing it done at a specific time of day (e.g., first or second urine); and requiring prompt processing of samples in clinics with limited molecular biology capability? Collected urine samples were pelleted, and the RNA isolated was processed for cDNA synthesis and in vitro transcription to generate amplified sense aRNA. The resultant aRNA was rigorously analyzed for possible introduced changes. DMSO was used as a cell preservative for frozen storage of urine samples. Good quality aRNA was obtained for over 100 samples collected at two different institutions. The process of RNA amplification removed co-isolated DNA in some samples, which did not affect RNA amplification. Amplification did not amplify genes that were absent and produce other expression alterations. The sense aRNA could be used to generate urinary transcriptomes specific to individual patients. No chaotropic agents for RNA preservation were added to the urine samples so that the supernatant could be used for analysis of secreted protein biomarkers. The time of donation was not important since patients were seen during the entire day. DMSO was an effective cell preservative for freezing urine. Urinary RNA can be readily isolated and amplified for prostate cancer biomarker analysis. Individual patients had unique set of transcripts derived from their tumor.

315 Prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program for early diagnosis of prostate cancer

315 Prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program for early diagnosis of prostate cancer

Editorial Comment

The challenge of trying to reduce additional biopsies in men with an elevated prostate-specific antigen (PSA) level and an initial negative biopsy result is nothing new to the clinical urologist. Plausible approaches currently include the use of additional markers (such as free PSA, urinary PCA3, OPKO 4Kscore, or Prostate Health Index testing) and/or magnetic resonance imaging of the prostate. PSA velocity (PSAV) has been shown to be unreliable in untreated men, whereas in men receiving 5α-reductase inhibitor (5ARI), PSAV has been shown to be beneficial. 1 Marberger M. Freedland S.J. Andriole G.L. et al. Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study. BJUI. 2011; 109: 1162-1169 Crossref PubMed Scopus (39) Google Scholar In this study, the authors reanalyzed data from the REDUCE trial to further define the benefit of PSA and PSAV in this group of men. 2 Andriole G.L. Bostwick D.G. Brawley O.W. et al. Effect of dutasteride on the risk of prostate cancer. NEJM. 2010; 362: 1192-1202 Crossref PubMed Scopus (879) Google Scholar Unfortunately, their analysis is not ideal as their assumption that serum PSA level will nadir within 6 months of initiating dutasteride therapy is inaccurate. In fact, only 13% of dutasteride-treated men in REDUCE achieved nadir by 6 months. 1 Marberger M. Freedland S.J. Andriole G.L. et al. Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study. BJUI. 2011; 109: 1162-1169 Crossref PubMed Scopus (39) Google Scholar It is for this reason that our prior analysis of the utility of PSA in dutasteride-treated men considered rise from nadir rather than as rise from a specific time point after initiating therapy. In our analysis, a PSA rise from nadir in a dutasteride-treated man was superior to the then (2011) relevant National Comprehensive Cancer Network PSAV guideline for untreated men. Decision Analysis of Dutasteride Use for Patients With Negative Prostate BiopsyUrologyVol. 85Issue 2PreviewTo determine whether the additional benefits of improved prostate cancer detection associated with 5α-reductase inhibitors are sufficient to warrant chemoprevention in the case where the degree of prostate cancer risk reduction is deemed inadequate. Full-Text PDF ReplyUrologyVol. 85Issue 2PreviewIt may well be true that our analysis “is not ideal” (after all, is any?). The key question is whether taking an alternative approach would change our conclusions. We repeated all analyses measuring change in prostate-specific antigen (PSA) level from nadir instead of change from 6 months. As the authors of the letter point out, this led to different estimates for many individual patients. However, this did not affect our conclusions at the group level. In no case did measuring from nadir instead of from 6 months lead to consistent changes in either inference or estimation. Full-Text PDF

Expression of PCA3 and PSA genes as a biomarker for differential diagnosis of nodular hyperplasia and prostate cancer.

We evaluated the expression of the PCA3 gene in urine from patients with nodular hyperplasia/benign prostatic hyperplasia (PNH) or adenocarcinoma type prostate cancer (PCa).The study included 59 men: 22 with PCa, 26 with PNH, and 11 with no alterations (controls). Patients' urine was collected following prostatic massage and quantified by quantitative real-time PCR for prostate cancer antigen 3 gene (PCA3) and prostate-specific antigen gene (PSA) expression with the ACTB gene for normalization. PCA3 gene expression was detected in 16 patients with PCa and 4 with PNH; in the control group, there was no expression of the gene. No significant difference was observed in the mean levels of PCA3 and PSA expression, the PCA3/PSA ratio, and the total PSA levels when the groups of patients with PCa and PNH were compared. The area under the receiver operating characteristic (ROC) curve was 0.625, 0.596, 0.559, and 0.503 for PCA3 and PSA expression, the PCA3/PSA ratio, and total PSA levels, respectively. The sensitivity and specificity of the PCA3 test were 73 and 85%, respectively. Considering the estimated cutoff values (0.2219 and 0.5007 for PCA3 and PCA3/PSA, respectively), we observed a significant difference between the frequency of individuals with values above in the PCa group compared with the PNH group (P < 0.001). We conclude that the qualitative PCA3 test could be applied to initial screening for differentiation between individuals with PCa or PNH and those without prostate changes.

Role of PCA3 test in clinical decision making for prostate cancer diagnosis

Role of PCA3 test in clinical decision making for prostate cancer diagnosis

Prognostic and predictive molecular biological markers in prostate cancer - significance of expression of genes PCA3 and TMPRSS2.

Prostatespecific antigen and digital rectal examination have low specificity for detectingprostate cancerand they poorly predict the presence of aggressive disease. We present recent findings onPCA3and TMPRSS:ERG fusion and assessed the relationship between PSA, urinePCA3and TMPRSS2:ERG and corelation with pathological findings. We tested the PCA3 score in two groups. The first comprised 96 men treated in urology out-patient units with suspicion of prostate cancer, who had elevated PSA and/or positive DRE. The second group comprised 28 patients, who were treated by radiation for localised prostate cancer, and whose PCA3 was regularly monitored. Afurther cohort comprised patients with already-diagnosed tumors, who had undergone radical prostatectomy. With these, using histopathological samples, we examined samples of the TMPRSS2:ERG fusion gene and compared the results with Gleason score values and level of PSA. We also examined the TMPRSS2:ERG gene in patients who had positive biopsy. Part of the genetical analysis was also an examination of the MSMB gene.The sensitivity of PCA3 testing was 66.7% and the specificity 78.5%. TMPRSS2:ERG gene was correllated with the Gleason score. Neither the TMPRSS2:ERG (p=0.13) nor the MSMB (p=0.556) genotype had an influence on the value of the Gleason score. However adifference was found between the homozygote and wild type (WT) in the TMPRSS2 gene.FISH analysis of TMPRSS/ERG gene fusion was evaluated as positive in 8 (36.8%) of the biopsically verified tumors and in 20 (37.3%) of the evaluated patients after RAPE of parafin slicing.We did not confirm acorellation between fusion and Gleason score (p=0.29).PCA3, with its higher sensitivity in comparison with PSA, is more useful for eventual screening examination. Identification of further molecular markers such as TMPRSS2, may be very promising ways to determine further prognosis of patients with prostate cancer. prostate cancer, PSA, PCA3.

Impact of the 2012 United States Preventive Services Task Force statement on prostate-specific antigen screening: analysis of urologic and primary care practices.

To identify the effect of the 2012 United States Preventive Services Task Force (USPSTF) prostate-specific antigen (PSA) recommendation statement on primary care referral patterns and urologists' decision making. Men referred to our institution for newly elevated PSA level from June 2011 to June 2013 were identified. Patients with a prior history of prostate cancer or biopsy were excluded. Clinical and management parameters were compared between those presenting in the year before vs the year after the USPSTF statement. Factors predictive of receiving a prostate biopsy were identified using multivariate regression analysis. A total of 201 men were identified in the pre-USPSTF period and 212 men, thereafter. The groups were comparable in age, race, prostate cancer family history, PSA values, and digital rectal examination findings. At the initial evaluation, patients presenting after the statement were more likely to undergo PCA3 testing (27% vs 11%; P <.01) and repeat PSA testing (82% vs 72%; P = .02) and less likely to undergo immediate biopsy (16% vs 24%; P = .03). The proportion of patients ultimately receiving a biopsy was equivalent. The groups were similar in the percentage of positive biopsies, Gleason distribution, and D'Amico risk. African American race and family history were predictors for receiving a biopsy in the post-USPSTF group but not in the pre-USPSTF group. The 2012 USPSTF recommendation statement has not affected the number or clinical characteristics of patients referred to a tertiary center for elevated PSA level. After recommendation, urologists ordered significantly more PCA3 and repeat PSA tests and recommended fewer biopsies at the initial visit. The fraction of patients ultimately receiving a biopsy remained the same.