Specificity Of Prostate Cancer Diagnosis Research Articles

Diagnostic potential of ultrasound elastography in patients with surgical diseases and injuries: Systematic review

In recent years, ultrasound elastography has been introduced into clinical practice. Because of the low availability of this equipment and the short period of operation, professionals are unaware of the technologys potential. Based on the findings of a systematic review of published scientific studies, this study aims to determine the diagnostic use of ultrasound elastography in patients with surgical diseases and injuries. PubMed, Google Scholar, eLibrary, and other information databases were searched for publications in Pediatric Surgery, Russian Bulletin of Pediatric Surgery, Anesthesiology and Intensive Care, Pediatric Surgery, and SonoAce Ultrasound from 2016 to 2022. The total number of sources in the sample is 7,040. The analysis comprised 32 papers that met the PRISMA criteria. The findings are divided into surgical diseases and injuries. The works on space-occupying formations predominated among the surgical diseases (27 publications). A single study was related to vascular problems and ectopic pregnancy, and three articles corresponded to the criteria of injury. The methods specificity was confirmed in the interquartile interval [Q1 77 Q3 95], Me 88.1, with sensitivity in the interval [Q1 81 Q3 94], Me 85.5. The advantages of elastography have been established in terms of the specificity of the method in identifying predictors of rotator cuff rupture, amounting to 96.7% and 61.2%62.5%, respectively, when compared with the B-mode. In pancreatic cysts, elastography had a specificity of 75.0% but only 40.0% in B-mode. The advantage of elastography (84.0%) over grayscale studies (69.0%) in metastatic lymph node lesions was established. Elastography is 15% more effective than standard ultrasonography in treating supraspinatus tendon injury. Elastography raised the specificity of prostate cancer diagnosis from 45.0% to 89.0%.

Robot-assisted technologies for targeted prostate biopsy: a literature review

One key aspect in treating any cancer is timely diagnosis and treatment. Obtaining the right diagnosis depends mainly on running the biopsy algorithm. Most studies show a significant increase in sensitivity and specificity in the targeted tissue sampling method compared to standard biopsy. The human factor can result in more medical errors. This can be solved by replacing the standard biopsy method with a more advanced one. The human factor is excluded from the biopsy sampling process using the semi-automatic robotic biopsy needle guidance. This paper presents a literature review development in robot assisted prostate biopsy. A literature review was performed using PubMed and Scopus databases. Papers reporting on experiments using semi-automatic robotic systems were included. Using the literature, we described the prerequisites for the development the software for semi-automatic targeted biopsy to increase the sensitivity and specificity of prostate cancer diagnosis.

Prostate cancer diagnosis as part of high-tech advanced outpatient medical care

Introduction. The primary focus for improving medical care is introduction of inpatient-replacement forms of healthcare for patients, particularly, with prostate cancer (PCa). Day-care facilities at outpatient institutions and hospitals are considered the most cost-effective and convenient for patients. It is expected that the introduction of new survey methodologies and the optimization of their use in day-hospitals of outpatient clinics will reduce the use of other diagnostic procedures, including invasive ones, and will allow the specialist to determine the treatment tactics and method.Objective. To improve the quality of PCa diagnosis with the use of high-tech advanced outpatient medical care.Materials & methods. To assess the appropriateness and effectiveness of transrectal prostate biopsies (TRPBs) in the day hospital, we have compared the statistics obtained in outpatient clinics with inpatient hospital divisions of the corresponding urban district. A comparative analysis of the data obtained using a standard examination algorithm was carried out: prostate-specific antigen analysis, digital rectal examination and transrectal ultrasound examination with a group of men who used multiparametric magnetic resonance imaging (mpMRI) in the examination algorithm prior to TRPB.Results. The average annual number of TRPBs performed in inpatient urology divisions (three сapital hospitals from Western urban district) was 344, and the PCa detection was 142 (41%). In the outpatient urological unit of the Branch No. 2, Moscow Outpatient Clinics No. 195 for the period from 2010 to 2017, the average annual number of TRPBs was 440, and the PCa detection was 153 (35%) Thus, from the above data, it appears that with inpatient-like PCa detection, one large outpatient urological unit performed on average 24% more TRPBs (440 versus 344) than three inpatient urological divisions in a comparable period of time. When comparing histological data obtained after TRPBs in the absence and presence of pelvic mpMRT, a reliable difference (42% vs 35%) was found in PCa detection, respectively.Conclusion. mpMRI due to its high sensitivity and specificity in PCa diagnosis, which can be recommended as a mandatory diagnostic step before TRPB. In addition, mpMRI can significantly reduce the number of unnecessary TRPBs, increase the effectiveness of timely PCa diagnosis at the early stages.

Identification of a 24-gene panel and a novel marker of PODXL2 essential for the pathological diagnosis of early prostate cancer

Precise diagnosis of early prostate cancer (PCa) is critical for preventing tumor progression. However, the diagnostic outcomes of currently used markers are far from satisfactory due to the low sensitivity or specificity. Here, we identified a diagnostic subpopulation in PCa tissue with the integrating analysis of single-cell and bulk RNA-seq. The representative markers of this subpopulation were extracted to perform intersection analysis with early-PCa-related gene module generated from weighted correlation network analysis (WGCNA). A total of 24 overlapping genes were obtained, the diagnostic roles of which were validated by distinguishing normal and tumorous prostate samples from the public dataset. A least absolute shrinkage and selection operator (LASSO) model was constructed based on these genes and the obtained 24-gene panel showed high sensitivity and specificity for PCa diagnosis, with better identifying capability of PCa than the commercially used gene panel of Oncotype DX. The top two risk factors, TRPM4 and PODXL2, were verified to be highly expressed in early PCa tissues by multiplex immunostaining, and PODXL2 was more sensitive and specific compared to TRPM4 and the pathologically used marker AMACR for early PCa diagnosis, suggesting a novel and promising pathology marker.

Study on the Diagnostic Value of Contrast-Enhanced Ultrasound and Magnetic Resonance Imaging in Prostate Cancer.

Objective The aim is to study the different roles of single and joint application of magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in prostate malignant tumors. Methods 72 patients with prostate masses who underwent CEUS and MRI examination in our hospital from October 2021 and March 2022 were enrolled in this research. The differentially diagnostic roles of CEUS, MRI, and CEUS combined MRI for prostate cancer was assessed on basis of pathological findings as the reference standard. The specificity and sensitivity of the joint application for prostate malignant tumors with various prostate-specific antigen (PSA) levels were also evaluated. Results The sensitivity of CEUS, MRI, and the joint application for prostate cancer were 72.1%, 74.4%, and 90.7%, respectively. Compared with single application, the sensitivity of CEUS combined with MRI was significantly higher. The specificity of MRI, CEUS, and the combination of the two for prostate cancer were 82.8%, 79.3%, and 89.7%, respectively, and the statistical differences for specificity were not found. The area under ROC curve (AUC) of CEUS combined with MRI in prostate malignant tumor diagnosis was obviously more than that of CEUS and MRI (P < 0.05). CEUS combined with MRI has relative high sensitivity in these patients with different levels of PSA. Conclusions Contrast-enhanced ultrasound combined with MRI can significantly improve the sensitivity and specificity of prostate cancer diagnosis so that patients can be better diagnosed in advance.

Dual electrochemical genosensor for early diagnosis of prostate cancer through lncRNAs detection

The prostate specific antigen (PSA) test is the gold standard for the screening of prostate cancer (PCa), despite its limited clinical specificity. Long noncoding RNAs are released from the tumor tissue to the urine and show great potential for improving specificity in PCa diagnosis. This work reports on a sandwich-type hybridization assay to detect both the urinary biomarker prostate cancer antigen 3 (PCA3) and an endogenous control, the PSA mRNA. Multiple fluorescein-tagged hybridization assistant probes are used to promote the selective capture of this long noncoding RNA, and sensitivity by incorporating multiple redox enzymes per target molecule, after addition of antifluorescein Fab fragment-peroxidase conjugate. This strategy alleviates the problems associated with the low natural abundance of this marker, its large size, and complex secondary structure. The individual genosensors exhibit good sensitivity (2.48 ± 0.01 μA nM−1 and 6.4 ± 0.3 μA nM−1 for PCA3 and PSA, respectively), with wide linear ranges (from 25 pM to 10 nM for PCA3 and 1 nM for PSA), and detection limits in the low picomolar range (4.4 pM and 1.5 pM for PCA3 and PSA, respectively). This analytical performance is retained in the dual configuration without significant cross-talk, despite using the same enzyme label. The usefulness of this dual platform was demonstrated by analyzing RNA extracts from the prostate cancer cell line LNCaP and from urine samples of prostate cancer patients.

Levels of plasma glycan-binding auto-IgG biomarkers improve the accuracy of prostate cancer diagnosis.

Strategies to improve the early diagnosis of prostate cancer will provide opportunities for earlier intervention. The blood-based prostate-specific antigen (PSA) assay is widely used for prostate cancer diagnosis but specificity of the assay is not satisfactory. An algorithm based on serum levels of PSA combined with other serum biomarkers may significantly improve prostate cancer diagnosis. Plasma glycan-binding IgG/IgM studies suggested that glycan patterns differ between normal and tumor cells. We hypothesize that in prostate cancer glycoproteins or glycolipids are secreted from tumor tissues into the blood and induce auto-immunoglobulin (Ig) production. A 24-glycan microarray and a 5-glycan subarray were developed using plasma samples obtained from 35 prostate cancer patients and 54 healthy subjects to identify glycan-binding auto-IgGs. Neu5Acα2-8Neu5Acα2-8Neu5Acα (G81)-binding auto-IgG was higher in prostate cancer samples and, when levels of G81-binding auto-IgG and growth differentiation factor-15 (GDF-15 or NAG-1) were combined with levels of PSA, the prediction rate of prostate cancer increased from 78.2% to 86.2% than with PSA levels alone. The G81 glycan-binding auto-IgG fraction was isolated from plasma samples using G81 glycan-affinity chromatography and identified by N-terminal sequencing of the 50kDa heavy chain variable region of the IgG. G81 glycan-binding 25kDa fibroblast growth factor-1 (FGF1) fragment was also identified by N-terminal sequencing. Our results demonstrated that a multiplex diagnostic combining G81 glycan-binding auto-IgG, GDF-15/NAG-1 and PSA (≥ 2.1ng PSA/ml for cancer) increased the specificity of prostate cancer diagnosis by 8%. The multiplex assessment could improve the early diagnosis of prostate cancer thereby allowing the prompt delivery of prostate cancer treatment.

Technetium-99m-MIBI-SPECT for prostate cancer diagnosis

The gold standard method for prostate cancer diagnosis is a transrectal ultrasonography-guided prostate biopsy. The detection rate of prostate cancer using the biopsy is approximately 25-30%. A non-invasive method Technetium-99m methoxy-isobutyl-isonitrile single-photon emission computed tomography (technetium-99m-MIBI-SPECT) could be used in prostate cancer detected.&#x0D; The study aimed to try to show that Tc99m-MIBI-SPECT, which is performed as a non-invasive method before biopsy in patients with prostate biopsy indication, may prevent unnecessary biopsy among these patients.&#x0D; Methods. Fifty-six patients who were admitted to our clinic for any lower urinary tract symptoms or routine control and who had a digital rectal examination or PSA value indication for prostate biopsy were included in this retrospective study. Technetium-99m-MIBI-SPECT our patients before the biopsy was performed, radiopharmaceutical uptake by the intensity and localization of the prostate was detected. Technetium-99m-MIBI-SPECT localization and intensity of involvement by prostate biopsy results were evaluated by nuclear medicine specialists.&#x0D; Results. The patients’ age and PSA level were 62.8 (31-78) years and 11.3 (2.5-100) ng/ml, respectively. Prostate cancer was detected in 27/56 (48.2%) patients. The suspicious diagnosis in technetium-99m-MIBI-SPECT images was observed in 36/56 (64.3%) patients, but prostate cancer was detected in 20 of them only. The sensitivity and specificity of technetium-99m-MIBI-SPECT were 74% and 45%, respectively. The positive and negative predictive values were 55% and 45% respectively. The diagnostic value of technetium-99m-MIBI-SPECT methods was considered as 58%.&#x0D; Conclusıon: The technetium-99m-MIBI-SPECT method in this study had low sensitivity and specificity for prostate cancer diagnosis. Therefore, we came to the conclusion that technetium-99m-MIBI-SPECT cannot be an alternative diagnostic method.

Abstract 1293: A high through approach to delineate protein complexes in adenocarcinoma tissues

Abstract Although it is well known that prostate cancer (PCa) is a progressive disease involving multiple gene alterations, little is known at the proteome level. Most of the functional information of the cancer-associated genes relies in the proteome, an exceptionally complex biological system involving several proteins that function through dynamic protein-protein interactions and post-translational modifications. To identify potential PCa protein biomarkers, we carried out an in depth proteomic analysis (ESI-MS/MS) using human PCa and BPH tissue. Samples were obtained using phase-transfer surfactant-aided extraction/tryptic digestion of formalin-fixed and paraffin-embedded sections mounted on microscope slides. We identified 1331 and 1239 proteins in PCa and BPH tissue proteomes respectively. 71 proteins were present in at least 50% of PCa samples and not in BPH samples, while 122 proteins where present in at least 50% of BPH samples and not in carcinoma samples. In order to prioritize candidate markers for PCa, we compared the differential protein expression based on normalized spectral counts between tissue samples. We set as cut-offs proteins that were found with a minimum of three peptides within our PCa proteomes. This filter resulted in the selection of 11 proteins. The list contained proteins that were previously studied in the context of prostate cancer progression, including SSBP1, GDF15, NDRG1, C4A &amp; APOE, thus providing further confirmation for the robustness of our quantification method. Bioinformatics analysis (Oncomine) showed that the proteins aforementioned were significant up-regulated (fold change &amp;gt;1.5, P≤0.05) in prostate adenocarcinoma vs. normal prostate gland. Whole exome analysis (cBioportal), revealed amplification as the most frequent genetic alteration and RNASeq data also confirmed a significant up-regulation for these proteins (P≤0.05). To contextualize the proteomic data, we utilized protein complexes information from CORUM database. Utilizing biological complexes as a cluster vector, we calculate a Proteomics Signature Profile (PSP) for each sample based on the hit rates of its reported proteins, against the cluster vector. We identified 25 complexes differentially expressed between PCa and BPH. Among those, the top ranked cluster upregulated in PCa was EIF3 (p-value= 4,37x10-5), a protein complex that functions during the initiation phase of eukaryotic translation, composed of EIF3B, EIF3J and EIF3I. We hereby report and offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis. Citation Format: Sofia Lage Vickers, Juan Bizzotto, Emiliano Ortiz, Alejandra Paez, Nicolás Anselmino, Javier Brandani, Mercedes Abbate, Javier Cotignola, Maria Pía Valacco, Elba Vazquez, Geraldine Gueron. A high through approach to delineate protein complexes in adenocarcinoma tissues [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 1293.

Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers.

Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient’s serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet’s serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10−6 in Fischer’s exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis.

Improved sensitivity and specificity for prostate cancer diagnosis based on the urine PCA3/PSA ratio acquired by sequence‑specific RNA capture.

Prostate cancer antigen3 (PCA3) is a non-coding RNA fragment that is overexpressed in prostate cancer cells. However, the clinical applications of PCA3 are highly limited due to the instability of RNA and the lack of reliable and efficient RNA extraction and purification methods. Thus, in the present study, we compared three different methods of RNA extraction to further confirm the higher yield of commercial magnetic beads with poly-T functionalization and a capturer strand. The current protocols for RNA extraction of i) the phenol-chloroform method, ii) the affinity column method and iii) magnetic beads with poly-T functionalization and a capturer strand were applied separately for RNA extraction in urine samples. Reverse transcription‑quantitative polymerase chain reaction was performed to evaluate the yield of the three methods of RNA extraction. Furthermore, 52urine samples after prostate massage from patients suspected of a diagnosis of prostate cancer were collected. The Mag-Cap method and RT-PCR were applied to obtain the PCA3 score. The clinical value of the PCA3 score was investigated by comparison with the pathology of the prostate biopsy. The yield of the Mag-Cap method was higher than that of the phenol‑chloroform method and commercial kits. Thirty‑four patients were pathologically diagnosed with prostate cancer and 18with benign prostatic hyperplasia (BPH). It was confirmed that the median PCA3 score was higher among the prostate cancer patients than those with benign disease (53.5vs.17, p=0.000). A sensitivity of 82.4% and a specificity of 77.8% were obtained when the cut-off value for the PCA3 score was 28.5. The Mag-Cap method was found to be more efficient for RNA extraction. The urinary PCA3 score is a promising method for prostate cancer screening, detection and diagnosis, and has the potential to reduce unnecessary prostate biopsies.

Prostate specific antigen. Current clinical application and future prospects.

Prostate-specific antigen (PSA) is a glycoprotein produced by the prostate gland and its production can be enhanced in benign and malignant diseases. The introduction of PSA testing has greatly increased the detection of prostate cancer. However there is continuing controversy and confusion over the most appropriate application of the PSA test. PubMed and Web of Science databases were used to search original and review articles on the historical aspects, clinical utilization and possible future directions in PSA. After its discovery, PSA was quickly established as an exquisitely sensitive tumor marker for prostate cancer detection, assessment of treatment responses and follow-up among patients with prostate cancer. Nevertheless, controversy exists about the proper threshold for recommending prostate biopsy. If this limit is lowered to improve the sensitivity even more, patients with low-risk prostate cancer would be subsequently detected. Post-treatment PSA levels can certainly provide valuable information about the effectiveness of the therapy given. Recently introduced ultrasensitive PSA detection techniques are offering new insight into the changes in serum PSA at very low concentrations. This has resulted in identification of valuable postoperative prognostic variables together with the possibility of earlier cancer relapse detection. The development of assays that may show superior sensitivity and specificity in prostate cancer diagnosis is focused on proteins possibly complexed with PSA and other potential markers detectable both in serum and urine. The goal of newly discovered prostate cancer biomarkers is greater cancer specificity in order to reduce the overdiagnosis, overtreatment and financial cost.

PSA, PSA derivatives, proPSA and prostate health index in the diagnosis of prostate cancer

Currently, prostate- specific antigen (PSA) is the most common oncological marker used for prostate cancer screening. However, high levels of PSA in benign prostatic hyperplasia and prostatitis decrease the specificity of PSA as a cancer marker. To increase the specificity of PSA, PSA derivatives and PSA kinetics have been used. However, these new techniques were not able to increase the diagnostic specificity for prostate cancer. Therefore, the search for new molecules and derivatives of PSA continues. With the aim of increasing the specificity of prostate cancer diagnosis, proPSA and the Prostate Health Index have been introduced. In this review, the roles of PSA, PSA derivatives, proPSA and the Prostate Health Index in Prostate Cancer diagnosis are examined.

Plasma Low-Molecular-Weight Proteome Profiling Identified Neuropeptide-Y as a Prostate Cancer Biomarker Polypeptide

In prostate cancer diagnosis, PSA test has greatly contributed to the early detection of prostate cancer; however, expanding overdiagnosis and unnecessary biopsies have emerged as serious issues. To explore plasma biomarkers complementing the specificity of PSA test, we developed a unique proteomic technology QUEST-MS (Quick Enrichment of Small Targets for Mass Spectrometry). The QUEST-MS method based on 96-well formatted sequential reversed-phase chromatography allowing efficient enrichment of <20 kDa proteins quickly and reproducibly. Plasma from 24 healthy controls, 19 benign prostate hypertrophy patients, and 73 prostate cancer patients were purified with QUEST-MS and analyzed by LC/MS/MS. Among 153 057 nonredundant peptides, 189 peptides showed prostate cancer specific detection pattern, which included a neurotransmitter polypeptide neuropeptide-Y (NPY). We further validated the screening results by targeted multiple reaction monitoring technology using independent sample set (n = 110). The ROC curve analysis revealed that logistic regression-based combination of NPY, and PSA showed 81.5% sensitivity and 82.2% specificity for prostate cancer diagnosis. Thus QUEST-MS technology allowed comprehensive and high-throughput profiling of plasma polypeptides and had potential to effectively uncover very low abundant tumor-derived small molecules, such as neurotransmitters, peptide hormones, or cytokines.

The use of PCA3 in the diagnosis of prostate cancer

Although the routine use of serum PSA testing has undoubtedly increased prostate cancer detection, one of its main drawbacks has been its lack of specificity, which results in a high negative biopsy rate. Consequently, a large population of men with chronically elevated serum PSA and one or more negative biopsies has emerged. More accurate tests are needed that can help identify which patients are at high risk of developing prostate cancer, and for whom repeat prostate biopsies are mandatory. To improve the specificity of prostate cancer diagnosis, prostate-cancer-specific markers, such as prostate cancer gene 3 (PCA3), are needed. The strong association between PCA3 mRNA overexpression and malignant transformation of prostate epithelium indicates its potential as a diagnostic biomarker. Quantification of PCA3 mRNA levels in urine was found to help predict the outcome of prostate biopsies. The intensive and time-consuming reverse-transcriptase polymerase chain reaction PCA3 urine test has been translated successfully into the fast and easy transcription-mediated amplification (TMA)-based PCA3 test. This test is the first RNA-based molecular diagnostic assay in body fluids for prostate cancer that is available to urologists. This Review describes the translation of the molecular marker PCA3 from the research laboratory to clinical practice.

WDR19 Expression is Increased in Prostate Cancer Compared with Normal Cells, but Low-Intensity Expression in Cancers is Associated with Shorter Time to Biochemical Failures and Local Recurrence

Prostate cancer is the third leading cause of cancer death in the United States, following lung and colorectal cancer. We previously identified WDR19 as a prostate-specific, androgen-regulated gene. Here, we evaluate its utility as a prostate cancer tissue marker for diagnosis and prognostic evaluation. Real-time quantitative PCR was done on a panel of prostate tissue isolated by laser capture microdissection. After generating antibodies against WDR19, tissue microarrays (TMA) were employed to compare WDR19 expression between normal, benign prostatic hyperplasia, and prostate cancer tissue. Using microarrays and real-time quantitative PCR, we showed that WDR19 mRNA expression was increased in cancer. We further showed that WDR19 protein is localized to cytoplasmic subcellular granules and is expressed exclusively in prostate epithelia. Large-scale immunohistochemical staining using TMAs reveals a significant percentage of increase in intensely staining tissue cores in cancer tissue when compared with normal or benign prostatic hyperplastic tissue. Based on the analysis of a separate TMA for which clinical follow-up information was available, low-intensity WDR19 staining was significantly associated with decreased time to biochemical failure (P = 0.006) and with decreased time to locoregional recurrence (P = 0.050). WDR19 should be added to the list of prostate cancer tissue markers. The continued expansion of a multiple-marker panel will conceivably increase the sensitivity and specificity of prostate cancer diagnosis and prognosis.

Significance of different molecular forms of prostate-specific antigen in prostate cancer diagnosis

Prostate-specifeic antigen is an important tumor marker in the detection of prostate cancer. Various molecular forms of prostate-specific antigen and their related indexes can improve the sensitivity and specificity of prostate cancer diagnosis.

Les formes moléculaires du PSA

Molecular forms of serum PSA (prostate specific antigen) have been developped to improve total PSA sensitivity and specificity in prostate cancer diagnosis and staging. Total PSA is measured in bound (complexed PSA) and unbound (free PSA) molecular forms. Their levels in absolute values and in relation to total PSA (f/t PSA and c/t PSA) have been evaluated. The percentage of free PSA is more specific but less sensitive than tPSA and it is not recommended as a first line diagnostic test. It may be useful as a second-line test, prescribed by the urologist after a first series of negative biopsies. There is general agreement that at high sensitivity, cPSA provides higher specificity compared with tPSA in the gray zone (2-10 ng/ml). Nevertheless the widespread use of tPSA an the small benefit in terms of specificity explains why cPSA is not generally recommanded. Molecular derivates of free PSA have been identified: proPSA (precursor inactive form of PSA), intact PSA (an additionnal form of proPSA that is found intact and inactive), human Kallikrein 2 and BPSA (for benign PSA wich is associated to BPH) have been evaluated. Preliminary studies did not have demonstrate their ability to discriminate between cancer and BPH, and did not define cutoff values.

114 THE TIME RESOLVED FLUORESCENCE-BASED PCA3 TEST ON URINARY SEDIMENTS AFTER EXTENDED DIGITAL RECTAL EXAMINATION; A DUTCH MULTICENTER VALIDATION OF THE DIAGNOSTIC PERFORMANCE

Purpose: To improve the specificity in prostate cancer diagnosis and to prevent unnecessary prostate biopsies, especially in the serum prostate-specific antigen (PSA) ''gray zone'' between 3 and 15 ng/mL, the implementation of prostate cancer ^ specific markers is urgently needed. The recently discovered prostate cancer antigen 3 (PCA3) is such a promising prostate cancer marker. In a previous single institution study, the PCA3 urine test clearly proved to be of diagnostic value.Therefore, the diagnostic performance of the PCA3 urine test was validated in a multicenter study. Experimental Design:The first voided urine after digital rectal examination was collected from a total of 583 men with serum PSA levels between 3 and 15 ng/mL who were to undergo prostate biopsies. We determined the PCA3 score in these samples and correlated the results with the results of the prostate biopsies. Results: A total of 534 men (92%) had an informative sample. The area under the receiver- operating characteristic curve, a measure of the diagnostic accuracy of a test, was 0.66 for the PCA3 urine test and 0.57 for serum PSA. The sensitivity for the PCA3 urine test was 65%, the specificity was 66% (versus 47% for serum PSA), and the negative predictive value was 80%. Conclusions: In this multicenter study, we validated the diagnostic performance of the PCA3 urine test in the largest group studied thus far using a PCA3 gene-based test. This study shows that the PCA3 urine test, when used as a reflex test, can improve the specificity in prostate cancer diagnosis and could prevent many unnecessary prostate biopsies.

The Time-Resolved Fluorescence-Based PCA3 Test on Urinary Sediments after Digital Rectal Examination; a Dutch Multicenter Validation of the Diagnostic Performance

To improve the specificity in prostate cancer diagnosis and to prevent unnecessary prostate biopsies, especially in the serum prostate-specific antigen (PSA) "gray zone" between 3 and 15 ng/mL, the implementation of prostate cancer-specific markers is urgently needed. The recently discovered prostate cancer antigen 3 (PCA3) is such a promising prostate cancer marker. In a previous single institution study, the PCA3 urine test clearly proved to be of diagnostic value. Therefore, the diagnostic performance of the PCA3 urine test was validated in a multicenter study. The first voided urine after digital rectal examination was collected from a total of 583 men with serum PSA levels between 3 and 15 ng/mL who were to undergo prostate biopsies. We determined the PCA3 score in these samples and correlated the results with the results of the prostate biopsies. A total of 534 men (92%) had an informative sample. The area under the receiver-operating characteristic curve, a measure of the diagnostic accuracy of a test, was 0.66 for the PCA3 urine test and 0.57 for serum PSA. The sensitivity for the PCA3 urine test was 65%, the specificity was 66% (versus 47% for serum PSA), and the negative predictive value was 80%. In this multicenter study, we validated the diagnostic performance of the PCA3 urine test in the largest group studied thus far using a PCA3 gene-based test. This study shows that the PCA3 urine test, when used as a reflex test, can improve the specificity in prostate cancer diagnosis and could prevent many unnecessary prostate biopsies.