Specificity For Detection Of Prostate Cancer Research Articles

B-349 Diagnostic Performance of the Atellica IM High-Sensitivity PSA Assay in Men Undergoing Prostate Cancer Screening

Abstract Background This study evaluated the diagnostic performance of the Atellica® IM High-Sensitivity PSA (hsPSA)* assay in men >50 years undergoing prostate cancer (PC) screening in conjunction with digital rectal exam (DRE). Methods Serum samples were collected prospectively from 2671 subjects >50 years referred to a urologist for evaluation of PC from 26 sites across the United States. To establish PC versus benign disease, all subjects underwent a transrectal prostate biopsy ≤60 days after blood draw. At the cutoff of 4.0 ng/mL for the hsPSA assay, the percentage of PCs detected (sensitivity) and corresponding percentage of biopsies avoided in men without PC (specificity) were determined. Results Cancer prevalence (malignant biopsy) was 58.5% (1562/2671) among the diagnostic population. Preliminary results demonstrated that for DRE alone, sensitivity and specificity were 30.9% (482/1562) and 83.0% (920/1109) compared to biopsy. For hsPSA alone at the cutoff of 4.0 ng/mL, sensitivity was 88.7% (1386/1562). The table provides incidence of cancer and positive biopsies by subgroups defined by DRE and hsPSA. hsPSA detected 61.1% (955/1562) of PCs that DRE did not. Of those DRE+, 71.8% (482/671) had positive biopsy. Of those DRE+ and hsPSA ≥4.0 ng/mL, 78.6% (431/548) had positive biopsy, which significantly increased PC detection by 7.0% (95% CI:1.4%-12.5%). Similarly, in the DRE- population, while 54.0% of subjects had positive biopsy, subjects both DRE- and hsPSA <4.0 ng/mL had only 38.5% positive biopsies, a significant difference of 16.5% (95% CI: 6.3%-27.8%). Conclusions Using DRE alone detected only 3 out of 10 patients with PC. It was observed that when used in conjunction with DRE, the hsPSA assay improved both sensitivity and specificity of PC detection over DRE alone. CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.

Recent Electrochemical Advancements for Liquid-Biopsy Nucleic Acid Detection for Point-of-Care Prostate Cancer Diagnostics and Prognostics.

Current diagnostic and prognostic tests for prostate cancer require specialised laboratories and have low specificity for prostate cancer detection. As such, recent advancements in electrochemical devices for point of care (PoC) prostate cancer detection have seen significant interest. Liquid-biopsy detection of relevant circulating and exosomal nucleic acid markers presents the potential for minimally invasive testing. In combination, electrochemical devices and circulating DNA and RNA detection present an innovative approach for novel prostate cancer diagnostics, potentially directly within the clinic. Recent research in electrochemical impedance spectroscopy, voltammetry, chronoamperometry and potentiometric sensing using field-effect transistors will be discussed. Evaluation of the PoC relevance of these techniques and their fulfilment of the WHO's REASSURED criteria for medical diagnostics is described. Further areas for exploration within electrochemical PoC testing and progression to clinical implementation for prostate cancer are assessed.

Performance of multi-parametric magnetic resonance imaging through PIRADS scoring system in biopsy naïve patients with suspicious prostate cancer

ABSTRACT Background Use of multi-parametric magnetic resonance imaging (mp-MRI) and Prostate Imaging Reporting and Data System (PI-RADS) scoring system allowed more precise detection of prostate cancer (PCa). Our study aimed at evaluating the diagnostic performance of mp-MRI in detection of PCa. Methods Eighty-six patients suspected to have prostate cancer were enrolled. All patients underwent mp-MRI followed by systematic and targeted trans-rectal ultrasound (TRUS) guided prostate biopsies. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of mp-MRI were evaluated. Results Forty-six patients (53.5%) had prostate cancer on targeted and systematic TRUS biopsies. On mp-MRI, 96.6% of lesions with PI-RADS < 3 revealed to be benign by TRUS biopsy, 73.3% of lesions with PI-RADS 4 showed ISUP grades ≥1, whereas all PI-RADS 5 lesions showed high ISUP grades ≥ 3. For PI-RADS 3 lesions, 62.5% of them revealed to be benign and 37.5% showed ISUP grades ≥1 by TRUS biopsy. PI-RADS scores ˃3 had 69.57% sensitivity and 85% specificity for detection of PCa. On adding the equivocal PI-RADS 3 lesions, PI-RADS scores ≥3 had higher sensitivity (97.83%), but at the cost of lower specificity (32.5%). Conclusion Mp-MRI using PI-RADS V2 scoring system categories ≤3 and >3 could help in detection of PCa. PI-RADS 3 lesions are equivocal. Including PI-RADS lesions ≥3 demonstrated higher sensitivity, but at the cost of lower specificity for mp-MRI in diagnosis for Pca. Abbreviations CDR: cancer detection rates; DRE: digital rectal examination; ISUP: international society of urological pathology; mp-MRI: multi-parametric magnetic resonance imaging; NPV: negative predictive value; PCa: prosatate cancer; PI-RADS: Prostate Imaging Reporting and Data System; PPV: Positive predictive value; PSA: prostate specific antigen; TRUS: transrectal ultrasound.

Classification of prostate tumour significance from computed b-value diffusion weighted magnetic resonance using imaging texture analysis

Diffusion-weighted imaging (DWI) reveals microscopic water diffusion. DWI enhances specificity in prostate cancer detection due to morphological changes in tissue and aids the staging of tumours. The aim of this work was to evaluate the effectiveness of texture analysis applied to diffusion-weighted magnetic resonance imaging (MRI) using a wide variety of computed b-values to differentiate malignant and begin tumours in the prostate.

Suitability of PSMA-PET Biology-Guided Radiotherapy for Low Volume Metastases in Newly Diagnosed Prostate Cancer

Biology-guided radiation therapy (BgRT) guides radiation therapy in real time based on positron emissions detected during treatment delivery. Protein specific membrane antigen (PSMA) is a positron emission tomography (PET) tracer with superior sensitivity and specificity for prostate cancer detection compared with conventional imaging. This study aims to quantify the ratio of standard uptake value (SUV) to background SUV for patients with low volume prostate cancer metastases, in the context of determining suitability of these lesions for BgRT. A single institutional patient subset from the ProPSMA prospective clinical trial underwent Ga-68-PSMA-11 at the time of prostate cancer diagnosis with suspected localized disease. From this cohort of 84 patients, 15 had at least one metastatic site disease diagnosed, 1 to 11 lesions per patient, with a total of 43 metastatic lesions (12 bones/31 viscerals). Metastatic gross tumor volume (GTV) were delineated on PSMA-PET images by using a patient-specific fixed SUV threshold method. In order to determine the suitability of various BgRT tracking zones, 3D shells of thickness 5 mm, 10 mm and 20 mm were constructed around the GTV to represent adjacent non-tumor background. Normalized SUV (nSUV) was calculated as the ratio of SUVmax in the GTV to SUVmean of adjacent shell. Sensitivity of nSUV to shell thickness variation was reported as the difference between nSUV values obtained for each thickness. GTV SUVmax ranged from 2.9 to 48.0 (median, 12.0; IQR, 5.1 to 19.5). nSUV ranged from 2.4 to 42.6 for 5 mm shell, 2.7 to 47.5 for 10 mm shell and 2.6 to 36.4 for 20 mm shell. Bone metastases had increased SUVmax compared with visceral metastases (SUVmax min/median/max 2.9/15.0/48.0 for bone compared with 2.9/11.0/40.0 for visceral). Furthermore, 90% of lesions had nSUV greater than 2.9 for a shell thickness of 5 mm, 3.1 for a shell thickness of 10 mm, and 3.2 for a shell thickness of 20 mm. Moreover, 100%/93%/84% of lesions would be suitable for BgRT by using nSUV cut-off of 2/3/4 and a shell thickness of 10 mm. nSUV decreased with increasing shell thickness for 17 lesions, indicating high signal in adjacent non-tumor tissue due to the proximity of bladder (5), bowel (4), other lesion (4), vessel (3) and liver (1). This study demonstrates that it is feasible to identify metabolically defined radiotherapy targets in the setting of BgRT. High lesion to background signal was observed for metastases visible on Ga-PSMA-EPT-11, however a subset of metastases had adjacent non-tumor uptake which may require exclusion from emission tracking during BgRT. Trial ID ACTRN12617000005358.

Prostate cancer assessment using MR elastography of fresh prostatectomy specimens at 9.4 T.

Despite its success in the assessment of prostate cancer (PCa), in vivo multiparametric MRI has limitations such as interobserver variability and low specificity. Several MRI methods, among them MR elastography, are currently being discussed as candidates for supplementing conventional multiparametric MRI. This study aims to investigate the detection of PCa in fresh ex vivo human prostatectomy specimens using MR elastography. Fourteen fresh prostate specimens from men with clinically significant PCa without formalin fixation or prior radiation therapy were examined by MR elastography at 500 Hz immediately after radical prostatectomy in a 9.4T preclinical scanner. Specimens were divided into 12 segments for both calculation of storage modulus (G' in kilopascals) and pathology (Gleason score) as reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve were calculated to assess PCa detection. The mean G' and SD were as follows: all segments, 8.74 ± 5.26 kPa; healthy segments, 5.44 ± 4.40 kPa; and cancerous segments, 10.84 ± 4.65 kPa. The difference between healthy and cancerous segments was significant with P ≤ .001. Diagnostic performance assessed with the Youden index was as follows: sensitivity, 69%; specificity, 79%; area under the curve, 0.81; and cutoff, 10.67 kPa. Our results suggest that prostate MR elastography has the potential to improve diagnostic performance of multiparametric MRI, especially regarding its 2 major limitations: interobserver variability and low specificity. Particularly the high value for specificity in PCa detection is a stimulating result and encourages further investigation of this method.

Abstract 690: Improvement of prostate cancer diagnosis using a multiplex test of PSA, GDF-15 (NAG-1) and glycan-binding auto-IgG in plasma

Abstract The blood prostate-specific antigen (PSA) assay is used for prostate cancer diagnosis but specificity of the assay is not satisfactory. Previously a combined PSA and GDF-15 (NAG-1) score was shown to improve specificity of prostate cancer detection. Our hypothesis was that, in prostate cancer, glycoproteins were secreted from tumor tissues into blood and induce autoimmune immunoglobulin G (auto-IgG) production and, thus, measurement of the glycan-auto-IgG in blood would improve prostate cancer diagnosis. The 24 glycan-containing microarray analyses have been carried out with plasma samples obtained from 35 prostate cancer patients and 46 healthy subjects to identify glycan-binding auto-IgG biomarker candidates by incubating the auto-IgG captured by glycans spotted on the slide with biotinylated anti-human secondary IgG/streptavidin-Alexa647. Among the 24 glycans, GlcNAc-polyacrylamide (PAA) (G09) and Fucα1-3GlcNAcβ-PAA (G24) glycans showed lower signals of the auto-IgG in the prostate cancer after quantile normalization. β-D-Galactose-PAA (G04) and L-rhamnose-PAA (G08) glycans showed higher signals of the auto-IgG in prostate cancer. No auto-IgM signal was detected. Subsequently, a 5-glycan subarray analysis was developed and lower signals of G09 and G24 glycan-binding auto-IgG were verified by the subarray analysis using 35 prostate cancer plasma samples compared with 54 controls. A higher signal of Neu5Acα2-8Neu5Acα2-8Neu5Acα-sp-PAA (G81)-binding auto-IgG in prostate cancer was detected by the subarray analysis. When the result obtained with the G81-binding auto-IgG was combined with levels of PSA and NAG-1, the prediction rate of prostate cancer increased to 86.2% from 78.2% with PSA levels alone, improving diagnostic accuracy of prostate cancer. The G81 glycan-binding auto-IgG was isolated from prostate cancer and control plasma samples using G81 glycan-affinity chromatography. Western blot analysis of the auto-IgG eluate with a secondary IgG antibody revealed that the level of the 50 kDa heavy chain of the auto-IgG obtained from the prostate cancer patient was ~3-fold higher than the control sample. The 50 kDa fragment was identified as an IgG heavy chain variable region by N-terminal sequencing (Edman's degradation). Our result demonstrated that a multiplex biomarker diagnostic consisting of glycan-binding auto-IgG, PSA and NAG-1 increased specificity and sensitivity of prostate cancer diagnosis. Supported by NCI SBIR Phase I, CA159721. Citation Format: Hyesook Kim, Julia Matzenbacher Santos, Aby Joiakim, David Kaplan, Ben Rybicki, Alan Dombkowski, David A. Putt. Improvement of prostate cancer diagnosis using a multiplex test of PSA, GDF-15 (NAG-1) and glycan-binding auto-IgG in plasma [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 690.

A multivariate index analyte (MIA) assay for differentiating aggressive from nonaggressive prostate cancer.

e588 Background: Biomarkers that can assist clinicians and patients to proceed when PSA and /or DRE are equivocal. Such biomarkers should establish both sensitivity and specificity for prostate cancer detection in order to improve go-forward decisions to perform prostate biopsy. Following the successful use of a three-protein marker panel to increase the specificity of prostate cancer detection1 we have now used the same technology to examine whether an MIA assay can assist in differentiating aggressive from non-aggressive cancer in prostate cancer patients. Methods: Samples from patients with either aggressive prostate cancer or non- aggressive prostate cancer were obtained from two sources. The cohort criteria comprised of serum samples where blood was drawn from patients with adenocarcinoma and a PSA greater than or equal to 2ng/mL. All men were Caucasian with the exception of 3 who were African American. Non-aggressive prostate cancer was defined as having a Gleason score of 6 (n = 35) and aggressive prostate cancer was characterized as Gleason score 7 and above (n = 69). Biomarker levels were determined using a plate based ELISA for GPC-12 and a bead-based MIA assay for the other markers. Results: By using biostatistical analysis (Simplicity Bio, Switzerland) two models were identified that were able to differentiate between aggressive and non-aggressive prostate cancer. One consisted of a combination of 5 analytes and the other used 6 analytes. Model 1 containing PSA and GPC-1 plus 4 analytes produced a combined sensitivity of 81% and specificity of 78% (AUC 0.81). The second model comprising of GPC-1 with an additional 4 analytes achieved a sensitivity of 72% with a specificity of 76% (AUC 0.76). Both models had a p value of less than 0.05. By itself PSA was a poor predictor of prostate cancer with a sensitivity of 58% and specificity of 43% (AUC 0.55). Conclusions: The analytes identified by the two statistical models demonstrate potential utility for using the combined markers as a new means of differentiating aggressive prostate cancer from non-aggressive cancer. An additional study to further validate these models is currently being constructed.

Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer.

Rapid and reliable diagnosis of prostate cancer (PCa) is highly desirable as current used methods lack specificity. In addition, identification of PCa biomarkers that can classify patients into high- and low-risk groups for disease progression at early stage will improve treatment decision-making. Here, we describe a set of protein-combination panels in urinary extracellular vesicles (EVs), defined by targeted proteomics and immunoblotting techniques that improve early non-invasive detection and stratification of PCa patients.We report a two-protein combination in urinary EVs that classifies benign and PCa patients (ADSV-TGM4), and a combination of five proteins able to significantly distinguish between high- and low-grade PCa patients (CD63-GLPK5-SPHM-PSA-PAPP). Proteins composing the panels were validated by immunohistochemistry assays in tissue microarrays (TMAs) confirming a strong link between the urinary EVs proteome and alterations in PCa tissues. Moreover, ADSV and TGM4 abundance yielded a high diagnostic potential in tissue and promising TGM4 prognostic power. These results suggest that the proteins identified in urinary EVs distinguishing high- and low grade PCa are a reflection of histological changes that may be a consequence of their functional involvement in PCa development. In conclusion, our study resulted in the identification of protein-combination panels present in urinary EVs that exhibit high sensitivity and specificity for PCa detection and patient stratification. Moreover, our study highlights the potential of targeted proteomic approaches–such as selected reaction monitoring (SRM)–as diagnostic assay for liquid biopsies via urinary EVs to improve diagnosis and prognosis of suspected PCa patients.

Multiparametric MRI and targeted prostate biopsy: Improvements in cancer detection, localization, and risk assessment.

IntroductionMultiparametric-MRI (mp-MRI) is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer at the time of MRI targeted biopsy, thereby enhancing clinical risk assessment, and improving the ability to appropriately counsel patients regarding therapy.Material and methodsWe used MEDLINE/PubMed to conduct a comprehensive search of the English medical literature. Articles were reviewed, data was extracted, analyzed, and summarized. In this review, we discuss the mp-MRI prostate exam, its role in targeted prostate biopsy, along with clinical applications and outcomes of MRI targeted biopsies.ResultsMp-MRI, consisting of T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and possibly MR spectroscopy, has demonstrated improved specificity in prostate cancer detection as compared to conventional T2-weighted images alone. An MRI suspicion score has been developed and is depicted using an institutional Likert or, more recently, a standardized reporting scale (PI-RADS). Techniques of MRI-targeted biopsy include in-gantry MRI guided biopsy, TRUS-guided visual estimation biopsy, and software co-registered MRI-US guided biopsy (MRI-US fusion). Among men with no previous biopsy, MRI-US fusion biopsy demonstrates up to a 20% increase in detection of clinically significant cancers compared to systematic biopsy while avoiding a significant portion of low risk disease. These data suggest a potential role in reducing over-detection and, ultimately, over-treatment. Among men with previous negative biopsy, 72–87% of cancers detected by MRI targeted biopsy are clinically significant. Among men with known low risk cancer, repeat biopsy by MR-targeting improves risk stratification in selecting men appropriate for active surveillance secondarily reducing the need for repetitive biopsy during surveillance.ConclusionsUse of mp-MRI for targeting prostate biopsies has the potential to reduce the sampling error associated with conventional biopsy by providing better disease localization and sampling. MRI-ultrasound fusion-targeted prostate biopsy may improve the identification of clinically significant prostate cancer while limiting detection of indolent disease, ultimately facilitating more accurate risk stratification. Literature supports the clinical applications of MRI-targeted biopsy in men who have never been biopsied before, those with a prior negative biopsy, and those with low risk disease considering active surveillance.

The Case for Tailored Prostate Cancer Screening: An NCCN Perspective.

A preponderance of clinical evidence supports a significant public health benefit for screening and early detection of prostate cancer in selected men. The challenge lies in maximizing early diagnosis of potentially aggressive but curable disease while minimizing diagnosis and treatment of indolent disease. A tailored approach to population screening in appropriately counseled men, using an evidence-based strategy with judicious prostate-specific antigen (PSA) testing, will reduce prostate-cancer mortality yet limit overdetection of clinically insignificant disease. Use of newer biomarkers that increase specificity for prostate cancer detection, including percentage of free PSA, 4Kscore, prostate health index, prostate cancer antigen 3, and multiparametric MRI may be considered under certain circumstances.

Proteomics analysis of urine reveals acute phase response proteins as candidate diagnostic biomarkers for prostate cancer.

Despite the overall success of prostate specific antigen (PSA) in screening and detection of prostate cancer (PCa), its use has been limited due to the lack of specificity. The principal driving goal currently within PCa research is to identify non-invasive biomarker(s) for early detection of aggressive tumors with greater sensitivity and specificity than PSA. In this study, we focused on identification of non-invasive biomarkers in urine with higher specificity than PSA. We tested urine samples from PCa and benign prostatic hyperplasia (BPH) patients by 2-D DIGE coupled with MS and bioinformatics analysis. Statistically significant (p < 0.05), 1.8 fold variation or more in abundance, showed 41 spots, corresponding to 23 proteins. The Ingenuity Pathway Analysis showed significant association with the Acute Phase Response Signaling pathway. Nine proteins with differential abundances were included in this pathway: AMBP, APOA1, FGA, FGG, HP, ITIH4, SERPINA1, TF and TTR. The expression pattern of 4 acute phase response proteins differed from the defined expression in the canonical pathway. The urine levels of TF, AMPB and HP were measured by immunoturbidimetry in an independent validation set. The concentration of AMPB in urine was significantly higher in PCa while levels of TF and HP were opposite (p < 0.05). The AUC for the individual proteins ranged from 0.723 to 0.754. The combination of HP and AMBP yielded the highest accuracy (AUC = 0.848), greater than PSA. The proposed biomarker set is quickly quantifiable and economical with potential to improve the sensitivity and specificity of PCa detection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12953-014-0059-9) contains supplementary material, which is available to authorized users.

MP67-04 MULTIPARAMETRIC MRI CAN IMPROVE THE DETECTION RATE OF PROSTATE CANCER AND UPGRADE THE GLEASON SCORE AT REPEATED BIOPSY

You have accessJournal of UrologyProstate Cancer: Detection & Screening IV1 Apr 2014MP67-04 MULTIPARAMETRIC MRI CAN IMPROVE THE DETECTION RATE OF PROSTATE CANCER AND UPGRADE THE GLEASON SCORE AT REPEATED BIOPSY Lars Boesen, Nis Nørgaard, Elizaveta Chabanova, Vibeke Løgager, Ingegerd Balslev, Kari Mikines, and Henrik Thomsen Lars BoesenLars Boesen More articles by this author , Nis NørgaardNis Nørgaard More articles by this author , Elizaveta ChabanovaElizaveta Chabanova More articles by this author , Vibeke LøgagerVibeke Løgager More articles by this author , Ingegerd BalslevIngegerd Balslev More articles by this author , Kari MikinesKari Mikines More articles by this author , and Henrik ThomsenHenrik Thomsen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2071AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) is traditionally diagnosed by histological examination of 10-12 transrectal ultrasound guided biopsies (TRUS-bx) from standard zones in the prostate. TRUS-bx has limited sensitivity and specificity in PCa detection and repeated biopsy (re-biopsy)-strategies are therefore often necessary in patients with persistent suspicion of PCa after negative TRUS-bx due to the high false-negative rates. In addition, there is also a risk that the most pathological aggressive part of the tumour can be missed at TRUS-bx leading to an incorrect Gleason score and diagnosis. Scientific work support the growing use of multiparametric MRI (mp-MRI) as the most sensitive and specific imaging tool for detection of PCa where mp-MRI suspicious lesions can be targeted by biopsies towards the most aggressive part. METHODS Patients scheduled for repeated biopsies due to persistent suspicion of PCa after standard TRUS-bx with negative findings were prospectively enrolled. Mp-MRI (T2W-, DWI- and DCE-imaging) was performed prior to re-biopsy. All identified lesions were scored by the ESUR guidelines, classified overall on a five-point scale according to the probability of clinically significant malignancy to be present and divided into 3 groups – low, moderate and high suspicion of PCa. All patients underwent systematic TRUS-bx (10 cores) and visual mp-MRI-targeted biopsies (mp-MRI-bx) under TRUS-guidance of any mp-MRI-suspicious lesion not hit on systematic TRUS-bx. RESULTS 83 patients with median 2(1-5) prior negative TRUS-Bx and median PSA 11(2-97) underwent mp-MRI before re-biopsy. PCa was found in 39/83 (47%) patients. Mp-MRI identified at least one PCa positive lesion in all 39 patients with median 2 (0-5) identified lesions per patient. Biopsies positive for PCa correlated to suspicion of malignancy and Gleason score are shown in Table 1. 5 patients (13%) had cancer detected only on mp-MRI-bx (p=0.025) and another 7 patients (21%) had an overall Gleason score upgrade (p=0.037) based on the mp-MRI-bx. 37/39 cancer patients were classified as clinically significant according to the Epstein criteria (2004). CONCLUSIONS Multiparametric MRI can improve the detection rate of clinically significant prostate cancer at repeated biopsy and allows for a more accurate Gleason grading. Table 1: Biopsy results correlated to mp-MRI suspicion of malignancy and the relation to Gleason score MRI suspicion Positive biopsy Negative biopsy Lesions(n) Gleason score 6(3+3) Gleason score 7(3+4) Gleason score 7(4+3) Gleason score 8-10 High 43(77%) 13(23%) 56 10 14 7 12 Moderate 8(15%) 44(85%) 52 4 4 Low 1(2%) 47(98%) 48 1 Total 52 104 156 15 18 7 12 © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e749-e750 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Lars Boesen More articles by this author Nis Nørgaard More articles by this author Elizaveta Chabanova More articles by this author Vibeke Løgager More articles by this author Ingegerd Balslev More articles by this author Kari Mikines More articles by this author Henrik Thomsen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MALDI-MS tissue imaging identification of biliverdin reductase B overexpression in prostate cancer

New biomarkers are needed to improve the specificity of prostate cancer detection and characterisation of individual tumors. In a proteomics profiling approach using MALDI-MS tissue imaging on frozen tissue sections, we identified discriminating masses. Imaging analysis of cancer, non-malignant benign epithelium and stromal areas of 15 prostatectomy specimens in a test and 10 in a validation set identified characteristic m/z peaks for each tissue type, e.g. m/z 10775 for benign epithelial, m/z 6284 and m/z 6657.5 for cancer and m/z 4965 for stromal tissue. A 10-fold cross-validation analysis showed highest discriminatory ability to separate tissue types for m/z 6284 and m/z 6657.5, both overexpressed in cancer, and a multicomponent mass peak cluster at m/z 10775-10797.4 overexpressed in benign epithelial tissue. ROC AUC values for these three masses ranged from 0.85 to 0.95 in the discrimination of malignant and non-malignant tissue. To identify the underlying proteins, prostate whole tissue extract was separated by nano-HPLC and subjected to MALDI TOF/TOF analysis. Proteins in fractions containing discriminatory m/z masses were identified by MS/MS analysis and candidate marker proteins subsequently validated by immunohistochemistry (IHC). Biliverdin reductase B (BLVRB) turned out to be overexpressed in PCa tissue. In this study on cryosections of radical prostatectomies of prostate cancer patients, we performed a MALDI-MS tissue imaging analysis and a consecutive protein identification of significant m/z masses by nano-HPLC, MALDI TOF/TOF and MS/MS analysis. We identified BLVRB as a potential biomarker in the discrimination of PCa and benign tissue, also suggesting BVR as a feasible therapeutic target.

Seminal Plasma as a Source of Prostate Cancer Peptide Biomarker Candidates for Detection of Indolent and Advanced Disease

BackgroundExtensive prostate specific antigen screening for prostate cancer generates a high number of unnecessary biopsies and over-treatment due to insufficient differentiation between indolent and aggressive tumours. We hypothesized that seminal plasma is a robust source of novel prostate cancer (PCa) biomarkers with the potential to improve primary diagnosis of and to distinguish advanced from indolent disease.Methodology/Principal FindingsIn an open-label case/control study 125 patients (70 PCa, 21 benign prostate hyperplasia, 25 chronic prostatitis, 9 healthy controls) were enrolled in 3 centres. Biomarker panels a) for PCa diagnosis (comparison of PCa patients versus benign controls) and b) for advanced disease (comparison of patients with post surgery Gleason score <7 versus Gleason score >7) were sought. Independent cohorts were used for proteomic biomarker discovery and testing the performance of the identified biomarker profiles. Seminal plasma was profiled using capillary electrophoresis mass spectrometry. Pre-analytical stability and analytical precision of the proteome analysis were determined. Support vector machine learning was used for classification. Stepwise application of two biomarker signatures with 21 and 5 biomarkers provided 83% sensitivity and 67% specificity for PCa detection in a test set of samples. A panel of 11 biomarkers for advanced disease discriminated between patients with Gleason score 7 and organ-confined (<pT3a) or advanced (≥pT3a) disease with 80% sensitivity and 82% specificity in a preliminary validation setting. Seminal profiles showed excellent pre-analytical stability. Eight biomarkers were identified as fragments of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase, prostatic acid phosphatase, stabilin-2, GTPase IMAP family member 6, semenogelin-1 and -2. Restricted sample size was the major limitation of the study.Conclusions/SignificanceSeminal plasma represents a robust source of potential peptide makers for primary PCa diagnosis. Our findings warrant further prospective validation to confirm the diagnostic potential of identified seminal biomarker candidates.

Assays for Prostate Cancer

Prostate cancer (PCa) screening and detection have changed dramatically since the introduction of serum prostate-specific antigen (PSA) testing. Despite the resulting improvement in early PCa detection and stage migration, in clinical practice the use of PSA testing may cause overdetection and ultimately overtreatment. As a consequence, novel biomarkers are needed to increase the specificity of PCa detection. The aim of this article is to present an overview of novel blood- and urine-based biomarkers that may optimize PCa detection, with improved identification of patients with significant PCa and avoidance of unnecessary prostate biopsies. A systematic and comprehensive PubMed search was performed using the MeSH search terms 'prostate cancer', 'biomarker', 'marker', and 'detection'. Results were restricted to the English language. Several blood- and urine-based biomarkers have the potential to improve prediction of the presence and/or significance of PCa. Ideally, biomarkers should be used in combination within multivariate models, leading to superior accuracy for prediction of any PCa or clinically significant PCa, compared with the use of a single marker.

Development of a New Optical Device and Its Feasibility in Prostate Cancer Detection

Aim: To develop a new optical device (prostate optical device, POD) for assessment of prostate tissue stiffness and evaluate its sensitivity and specificity in prostate cancer detection. Patients and Methods: POD was tested in prostate phantoms and in patients with indications for prostate biopsy. Its sensitivity and specificity were compared to digital rectal examination (DRE) and transrectal ultrasonography (TRUS). Results: POD was able to identify stiffness differences on each prostate phantom. 45 patients were included in the study. Sensitivity of TRUS (40%) was significantly lower to POD (85.7%) and DRE (74.3%) (p = 0.000 and p = 0.003, respectively). There was no statistical difference between POD and DRE (p = 0.221). The combination of POD and DRE showed the highest sensitivity (88.6%), positive predictive value (81.6%), and negative predictive value (42.9%) among all diagnostic tests. Conclusions: POD identified prostatic stiffness differences with the same sensitivity of DRE performed by an experienced urologist providing an objective indication for prostate biopsy and early prostate cancer detection.

PCA3 sensitivity and specificity for prostate cancer detection in patients with abnormal PSA and/or suspicious digital rectal examination. First Latin American experience

IntroductionProstate Cancer Gene 3 (PCA3) is a recently described and highly specific urinary marker for prostate cancer (CaP). Its introduction in clinical practice to supplement low specificity of prostate specific antigen (PSA) can improve CaP diagnosis and follow-up. However, before its introduction, it is necessary to validate the method of PCA3 detection in distinct geographic populations. ObjectivesOur aim was to describe for the first time in Latin America, the application of the PROGENSA PCA3 assay for PCA3 detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate biopsy. Materials and methodsSixty-four Chilean patients (mean age, 64 years) with indication of prostate biopsy because of elevated PSA and/or suspicious digital rectal examination (DRE) were prospectively recruited. PCA3 scores were assessed from urine samples obtained after DRE, before biopsy, and compared with PSA levels and biopsy outcome. ResultsThe median PSA value and mean PCA3 score were 5.8 ng/ml and 31.7, respectively. Using a cutoff PCA3 score of 35, the sensitivity and specificity for detecting CaP were 52% and 87%, respectively. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA, for the same group of patients. In patients with previous negative biopsy, PCA3 specificity increased by 2.2%. ConclusionsThis is the first report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those reported in other populations in the literature, demonstrating the reproducibility of the test. PCA3 score was highly specific and we specially recommend its use in patients with persistent elevated PSA and prior negative biopsies.

Influence of the Prostate Volume, Prostate Specific Antigen Density and Number of Biopsy Samples on Prostate Cancer Detection

Establish the main differences in the prostate volume, prostate specific antigen density (PSAD), number of biopsy samples in patients with primarily or rebiopsy detected prostate cancer. In the 2007-2009 period, at the KCUS Urology Clinic, there were 379 TRUS guided prostate biopsies in 323 patients with known prostate volume. The total of 56 patients (17.3%) underwent the first rebiopsy, primarily due to precancerous lesions. The mean prostate volume, ranges of prostate size, PSAT, PSAD and the number of biopsy samples were analysed retrospectively, and the main characteristics in patients with primarily and rebiopsy diagnosed Pca were evaluated as well. The first biopsy cancer detection rate was 29.6% (112/379). The rebiopsy detection rate was 30.3%. There was no statistically significant difference in the prostate volume and the number of biopsy samples among the total number of patients with prostate cancer against the group with benign (suspected) findings. There was a higher Pca detection rate in patients with the prostate volume < 40 cm3 and 40-60 cm3, against the group with the prostate volume > 60 cm3. PSAD was significantly higher in patients with PCa (0.24 vs. 0.18; p = 0.013). The total of 27.2% of the patients with negative biopsy findings and 48% of the patients with diagnosed Pca had PSAD > 0.15. PSAD showed sensitivity and specificity in prostate cancer detection of 50% and 75%, with PPV of 48%. Furthermore, the patients with PSAD >0.15 had a higher Gleason score versus the patients with PSAD < 0.15 (6.7 +/- 2.4 vs. 5.9 +/- 1.7; p < 0.003). A comparison of the main characteristics in patients with primarily and rebiopsy detected prostate cancer gave a statistically significant difference only in the number of biopsy samples (10.9 vs. 14.1, p <.0000). Patients with a smaller prostate volume, lower PSAD and a higher number of biopsy samples in rebiopsy have a higher chance of prostate cancer detection. PSAD carries a higher specificity in rebiopsy decision, and a higher PSAD is related to a higher Gleason score.

Neue Ultraschalltechnologien für die Diagnostik des Prostatakarzinoms

Prostate cancer is the most common cancer in men. The diagnosis is based on prostate-specific antigen (PSA), digital rectal examination (DRE) and transrectal ultrasound (TRUS) guided biopsy. These techniques have considerable limitations, which result in unnecessary biopsies. Furthermore the biopsies are associated with morbidity and costs. Standard gray-scale ultrasound has a low sensitivity and specificity for prostate cancer detection. New ultrasound technologies, including color- and power Doppler ultrasound, contrast enhanced US and real-time sonoelastography have shown to improve prostate cancer diagnosis. Contrast-enhanced ultrasound has shown a sensitivity of 100% (95% CI, 95%), a negative predictive value (NPV) of 99.8% and a positive predictive value (PPV) of 88.8% for prostate cancer detection. Real-time sonoelastography has shown a sensitivity of 86%, a specificity of 81% and NPV of 91% for prostate cancer diagnosis. Most studies show that these new ultrasound modalities demonstrate a 1.5 to 2.5 times higher detection of prostate cancer per biopsy specimen compared with systematic biopsy. Multicenter studies results are at present lacking but are, however ongoing. In patients with suspected prostate cancer (elevated PSA, suspicious DRE) these new ultrasound techniques should be used. These techniques can detect prostate cancer and allow a targeted biopsy approach.