scholarly journals Performance of a Single Assay for Both Type III and Type VI TMPRSS2:ERG Fusions in Noninvasive Prediction of Prostate Biopsy Outcome

2008 ◽  
Vol 54 (12) ◽  
pp. 2007-2017 ◽  
Author(s):  
Jarrod P Clark ◽  
Kristofer W Munson ◽  
Jessie W Gu ◽  
Katarzyna Lamparska-Kupsik ◽  
Kevin G Chan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Gleason Grade ◽  
Type Iii ◽  
Standard Curve ◽  
Institutional Review

Abstract Background: TMPRSS2:ERG fusions are promising prostate cancer biomarkers. Because they can occur in multiple forms in a single cancer specimen, we developed a quantitative PCR test that detects both type III and type VI TMPRSS2:ERG fusions. The assay is quantified from a standard curve determined with a plasmid-cloned type III TMPRSS2:ERG fusion target. Methods: We collected expressed prostatic secretion (EPS) under an institutional review board-approved, blinded, prospective study from 74 patients undergoing transrectal ultrasound-guided biopsy for prostate cancer. We compared the characteristic performance of the test for type III and type VI TMPRSS2:ERG fusions in predicting biopsy outcome and distinguishing between high and low Gleason scores with similar tests for the expression of PCA3 and DNA methylation levels of the APC, RARB, RASSF1, and GSTP1 genes. We used logistic regression to analyze the effects of multiple biomarkers in linear combinations. Results: Each test provided a significant improvement in characteristic performance over baseline digital rectal examination (DRE) plus serum prostate-specific antigen (PSA); however, the test for type III and type VI TMPRSS2:ERG fusions yielded the best performance in predicting biopsy outcome [area under the curve (AUC) 0.823, 95% CI 0.728–0.919, P < 0.001] and Gleason grade >7 (AUC 0.844, 95% CI 0.740–0.948, P < 0.001). Conclusions: Although each test appears to have diagnostic value, PSA plus DRE plus type III and type VI TMPRSS2:ERG provided the best diagnostic performance in EPS specimens.

scholarly journals Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 188 ◽  
Author(s):  
Jacob Fredsøe ◽  
Anne K. I. Rasmussen ◽  
Peter Mouritzen ◽  
Marianne T. Bjerre ◽  
Peter Østergren ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Minimally Invasive ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Diagnostic Tools ◽  
Test Set ◽  
Localized Disease ◽  
Clinically Significant

Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAs in plasma, we confirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375*miR-33a-5p/miR-16-5p*miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

Optimization of Risk Stratification in Localized Prostate Cancer

2018 ◽  
Vol 36 (6) ◽  
pp. 528-532 ◽  
Author(s):  
Alicia Katherine Morgans
Keyword(s):  
Prostate Cancer ◽  
Relevant Literature ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Localized Prostate Cancer ◽  
Gleason Grade ◽  
Management Options ◽  
Grade Group ◽  
The Right

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 67-year-old retired engineering professor was found to have a prostate-specific antigen (PSA) level of 11 ng/mL on a screening test at his annual physical examination. A digital rectal examination revealed a nodule on the right side. He underwent a transrectal ultrasound-guided prostate biopsy that was notable for prostate adenocarcinoma, Gleason 3 + 4 = 7 (Gleason grade group 2; 30% Gleason 4 component) involving two cores (60% and 20% core involvement). A bone scan and pelvic computed tomography scan were negative for evidence of metastatic disease. (Should he undergo prostate magnetic resonance imaging? That seems rather common these days.) He was diagnosed with cT2b intermediate-risk localized prostate cancer (PCa) by National Comprehensive Cancer Network (NCCN) risk group and was seen in the multidisciplinary clinic to discuss management options (Table 1).

scholarly journals Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3373
Author(s):  
Milena Matuszczak ◽  
Jack A. Schalken ◽  
Maciej Salagierski
Keyword(s):  
Prostate Cancer ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Cost Effective ◽  
Non Invasive ◽  
Diagnosis And Prognosis

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

Multiparametric ultrasound and micro-ultrasound in prostate cancer: a comprehensive review

2021 ◽  
Author(s):  
Adriano Basso Dias ◽  
Ciara O’Brien ◽  
Jean-Michel Correas ◽  
Sangeet Ghai
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
High Sensitivity ◽  
Cost Effective ◽  
Cognitive Fusion ◽  
Clinically Significant ◽  
Multiparametric Ultrasound ◽  
Targeted Biopsies

Prostate cancer (PCa) is the most common non-cutaneous cancer diagnosed in males. Traditional tools for screening and diagnosis, such as prostate-specific antigen, digital rectal examination and conventional transrectal ultrasound (TRUS), present low accuracy for PCa detection. Multiparametric MRI has become a game changer in the PCa diagnosis pathway and MRI-targeted biopsies are currently recommended for males at risk of clinically significant PCa, even in biopsy-naïve patients. Recent advances in ultrasound have also emerged with the goal to provide a readily accessible and cost-effective tool for detection of PCa. These newer techniques include elastography and contrast-enhanced ultrasound, as well as improved B-mode and Doppler techniques. These modalities can be combined to define a novel ultrasound approach, multiparametric ultrasound. High frequency Micro-ultrasound has emerged as a promising imaging technology for PCa diagnosis. Initial results have shown high sensitivity of Micro-ultrasound in detecting PCa in addition to its potential in improving the accuracy of targeted biopsies, based on targeting under real-time visualization, rather than relying on cognitive/fusion software MRI-transrectal ultrasound-guided biopsy.

scholarly journals Independent Validation of a Diagnostic Noninvasive 3-MicroRNA Ratio Model (uCaP) for Prostate Cancer in Cell-Free Urine

2019 ◽  
Vol 65 (4) ◽  
pp. 540-548 ◽  
Author(s):  
Jacob Fredsøe ◽  
Anne K I Rasmussen ◽  
Emma B Laursen ◽  
Yunpeng Cai ◽  
Kenneth A Howard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Area Under The Curve ◽  
Extracellular Vesicle ◽  
Urine Samples ◽  
Ratio Model ◽  
Psa Testing ◽  
Diagnostic Potential

Abstract BACKGROUND Detection of prostate cancer (PC) based on serum prostate-specific antigen (PSA) testing leads to many unnecessary prostate biopsies, overdiagnosis, and overtreatment of clinically insignificant tumors. Thus, novel and more accurate molecular biomarkers are required. METHODS Using reverse transcription quantitative PCR, we measured the concentrations of 45 preselected microRNAs (miRNAs) in extracellular vesicle-enriched cell-free urine samples from 4 independent patient cohorts from Spain and Denmark, including 758 patients with clinically localized PC, 289 noncancer controls with benign prostatic hyperplasia (BPH), and 233 patients undergoing initial transrectal ultrasound (TRUS)-guided prostate biopsy owing to PC suspicion (101 with benign and 132 with malignant outcome). Diagnostic potential was assessed by ROC and decision curve analysis. RESULTS We identified and successfully validated 8 upregulated and 21 downregulated miRNAs in urine from PC patients. Furthermore, we validated a previously identified 3-miRNA diagnostic ratio model, uCaP (miR-222–3p*miR-24–3p/miR-30c-5p). High uCaP scores were distinctive of PC in urine samples from BPH vs PC patients in 3 independent cohorts [area under the curve (AUC) = 0.84, 0.71, 0.72]. Additionally, uCaP predicted TRUS biopsy results with greater accuracy than PSA (AUC uCaP = 0.644; AUC PSA = 0.527) for patients within the diagnostic gray zone (PSA ≤ 10 ng/mL). CONCLUSIONS We successfully validated a urine-based diagnostic 3-miRNA signature for PC (uCaP) in 3 independent patient cohorts from 2 countries. In the future, the simple and noninvasive uCaP test may be used to help more accurately select patients for prostate biopsy. Prospective clinical validation is warranted.

scholarly journals APTIMA PCA3 Molecular Urine Test: Development of a Method to Aid in the Diagnosis of Prostate Cancer

2006 ◽  
Vol 52 (6) ◽  
pp. 1089-1095 ◽  
Author(s):  
Jack Groskopf ◽  
Sheila MJ Aubin ◽  
Ina Lim Deras ◽  
Amy Blase ◽  
Sharon Bodrug ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Prostate Cancer Risk ◽  
Area Under The Curve ◽  
Roc Curve Analysis ◽  
Cancer Risk Factors ◽  
Specimen Processing ◽  
Whole Urine

Abstract Background: Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA that has shown promise as a prostate cancer diagnostic tool. This report describes the characterization of a prototype quantitative PCA3-based test for whole urine. Methods: Whole-urine specimens were collected after digital rectal examination from 3 groups: men scheduled for prostate biopsy (n = 70), healthy men (<45 years of age with no known prostate cancer risk factors; n = 52), and men who had undergone radical prostatectomy (n = 21). PCA3 and prostate-specific antigen (PSA) mRNAs were isolated, amplified, and quantified by use of Gen-Probe DTS400® Systems. Prostate biopsy results were correlated with the PCA3/PSA mRNA ratio, and PSA mRNA concentrations were used to normalize PCA3 signals and confirm the yield of prostate-specific RNA. Assay precision, specimen stability, and mRNA yield were also evaluated. Results: The specimen informative rate (fraction of specimens yielding sufficient RNA for analysis) was 98.2%. In this clinical research study, ROC curve analysis of prebiopsy specimens yielded an area under the curve of 0.746; sensitivity was 69% and specificity 79%. Serum PSA assay specificity was 28% for this same group. PCA3 and PSA mRNAs were undetectable in postprostatectomy specimens except for one man with recurrent prostate cancer. Assay interrun CVs were ≤12%. Both mRNAs were stable in processed urine up to 5 days at 4 °C and after 5 freeze–thaw cycles. Conclusion: The APTIMA® PCA3 assay combines simple specimen processing with precise assays and existing instruments and could add specificity to the current algorithm for prostate cancer diagnosis.

scholarly journals Evaluation of an RNAseq-Based Immunogenomic Liquid Biopsy Approach in Early-Stage Prostate Cancer

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2567
Author(s):  
Leander Van Neste ◽  
Kirk J. Wojno ◽  
Ricardo Henao ◽  
Shrikant Mane ◽  
Howard Korman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Biology ◽  
Early Stage ◽  
Immune Surveillance ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Primary Objective ◽  
Pathologic Features

The primary objective of this study is to detect biomarkers and develop models that enable the identification of clinically significant prostate cancer and to understand the biologic implications of the genes involved. Peripheral blood samples (1018 patients) were split chronologically into independent training (n = 713) and validation (n = 305) sets. Whole transcriptome RNA sequencing was performed on isolated phagocytic CD14+ and non-phagocytic CD2+ cells and their gene expression levels were used to develop predictive models that correlate to adverse pathologic features. The immune-transcriptomic model with the highest performance for predicting adverse pathology, based on a subtraction of the log-transformed expression signals of the two cell types, displayed an area under the curve (AUC) of the receiver operating characteristic of 0.70. The addition of biomarkers in combination with traditional clinical risk factors (age, serum prostate-specific antigen (PSA), PSA density, race, digital rectal examination (DRE), and family history) enhanced the AUC to 0.91 and 0.83 for the training and validation sets, respectively. The markers identified by this approach uncovered specific pathway associations relevant to (prostate) cancer biology. Increased phagocytic activity in conjunction with cancer-associated (mis-)regulation is also represented by these markers. Differential gene expression of circulating immune cells gives insight into the cellular immune response to early tumor development and immune surveillance.

Transrectal Ultrasonography in the Diagnosis of Prostatic Carcinoma: Our Study on 365 Patients

1994 ◽  
Vol 61 (4) ◽  
pp. 270-276
Author(s):  
M. Calò ◽  
I. Malavolti ◽  
G. Cuscianna ◽  
F. Baldari ◽  
C.A. Pollastri ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Needle Biopsy ◽  
Prostatic Carcinoma ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
High Sensitivity ◽  
Transrectal Ultrasonography ◽  
Prostatic Specific Antigen ◽  
Clinical Exam

To evaluate the usefulness of transrectal ultrasound associated with needle biopsy of the prostate, 365 patients, with age ranging between 50 and 80 years, were studied for a total of 412 biopsies; the ultrasound exam was performed when the clinical or the prostate specific antigen findings were pathological. Our experience confirms the high sensitivity and specificity of transrectal ultrasonography in detecting prostate cancer. It is our opinion that all the patients with positive or negative digital rectal examination but altered prostatic specific antigen or clinical exam should undergo transrectal ultrasonography associated with needle biopsy. The elevated operability of the studied patients shows the capability of ultrasound to detect the pathology in the early stages and its value in screening diagnosis should therefore be considered.

Randomised Trial of Prostate Cancer Screening in the Netherlands: Assessment of Acceptance and Motives for Attendance

1997 ◽  
Vol 4 (2) ◽  
pp. 102-106 ◽  
Author(s):  
H G T Nijs ◽  
D M R Tordoir ◽  
J H Schuurman ◽  
W J Kirkels ◽  
F H Schroder
Keyword(s):  
Prostate Cancer ◽  
Cancer Screening ◽  
Prostate Specific Antigen ◽  
Prostate Cancer Screening ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Population Based ◽  
Personal Benefit ◽  
Screening Procedures

Abstract Objectives— To assess motives for attending a randomised population based prostate cancer screening trial, and to assess acceptance of screening and invitation procedures. Methods— First pilot of the European Randomised Study of Screening for Prostate Cancer (ERSPC; 1992/1993). Men aged 55–75 years, randomly selected from the population register of four city districts of Rotterdam, were invited by a single invitation for screening. Screening consisted of prostate specific antigen prescreening followed by either (1) digital rectal examination, transrectal ultrasound, and, on indication, biopsy, or (2) no additional screening. After screening, or in the case of non-attendance, a questionnaire was sent to a random sample of 600 attenders and 400 non-attenders, with a reminder after three weeks. Outcome measures— In both attenders and non-attenders: Knowledge of prostate cancer, attitudes towards screening, motives for attending, procedural aspects and sociodemographic characteristics. In attenders, acceptance of screening procedures. Results— The response rate for the questionnaire was 76%: 94% in attenders and 42% in non-attenders. The main reasons for attending were expected personal benefit (76%) and scientific value (39%), and those for not attending were the absence of urological complaints (41%) and anticipated pain or discomfort (24%). Uptake of screening was 32%, which increased to a sustained 42% in following years. Attenders, compared with non-attenders, were significantly younger, more often married, better educated, and had higher perceived health status, more knowledge about prostate cancer, and a more positive attitude towards screening. Information materials and invitation procedure were adequate. Screening procedures were well accepted (high report marks and satisfaction, and 95% would attend for rescreening). A single prostate specific antigen determination was liked less than a combination of all three screening modalities. Conclusions— (1) The main reasons for attending are personal benefit and science, and those for not attending were absence of urological complaints and anticipated pain or discomfort; (2) knowledge, attitudes, and motives for attending are comparable with other screening programmes; hence, for population based prostate cancer screening, known health promotional aspects should be carefully considered; (3) prostate specific antigen, digital rectal examination and transrectal ultrasound are acceptable to attenders.

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