scholarly journals A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2–10 ng/mL at initial biopsy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ya-Di He ◽  
Wen Tao ◽  
Tao He ◽  
Bang-Yu Wang ◽  
Xiu-Mei Tang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Standard Of Care ◽  
Circular Rna ◽  
Extracellular Vesicle ◽  
High Grade ◽  
Clinical Workflow ◽  
Grade Group ◽  
Training Cohort

AbstractThe aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

A urine exosomal circRNA classifier for detection of high-grade prostate cancer at initial biopsy: A multicenter, retrospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5522-5522
Author(s):  
Liaoyuan Li ◽  
Wen Tao ◽  
Yadi He ◽  
Tao He ◽  
Qing Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Validation Cohort ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Circular Rna ◽  
High Grade ◽  
Training Cohort ◽  
Potential Biomarker ◽  
Initial Biopsy

5522 Background: The low specificity of prostate-specific antigen (PSA) has resulted in the overdiagnosis and overtreatment of clinically indolent prostate cancer (PCa). We aimed to identify a urine exosomal circular RNA (circRNA) classifier that could detect high-grade (Gleason score [GS]7 or greater) PCa. Methods: We did a three-stage study that enrolled eligible participants, including PCa-free men, 45 years or older, scheduled for an initial prostate biopsy due to suspicious digital rectal examination findings and/or PSA levels (limit range, 2.0-20.0 ng/mL), from four hospitals in China. We used RNA sequencing and digital droplet polymerase chain reaction to identify 18 candidate urine exosomal circRNAs that were increased in 11 patients with high-grade PCa compared with 11 case-matched patients with benign prostatic hyperplasia. Using a training cohort of eligible participants, we built a urine exosomal circRNA classifier (Ccirc) to detect high-grade PCa. We then evaluated the classifier in discrimination of GS7 or greater from GS6 and benign disease on initial biopsy in two independent cohorts. We used the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to evaluate diagnostic performance, and compared Ccirc with standard of care (SOC) (ie, PSA level, age, race, and family history). Results: Between June 1, 2016, and July 31, 2019, we recruited 356 participants to the training cohort, and 442 and 325 participants to the two independent validation cohorts. We identified a Ccirc containing five differentially expressed circRNAs (circ_0049335, circ_0056536, circ_0004028, circ_0008475, and circ_0126027) that could detect high-grade PCa. Ccirc showed higher accuracy than SOC to distinguish individuals with high-grade PCa from controls in both the training cohort and the validation cohorts. (AUC 0.831 [95% CI 0.765-0.883] vs 0.724 [0.705-0.852], P = 0.032 in the training cohort; 0.823 [0.762-0.871] vs 0.706 [0.649-0.762], P = 0.007 in validation cohort 1; and 0.878 [0.802-0.943] vs 0.785 [0.701-0.890], P = 0.021 for validation cohort 2). In all three cohorts, Ccirc had higher sensitivity (range 71.6-87.2%) and specificity (82.3-90.7%) than did SOC (sensitivity, 42.3-68.2%; specificity, 40.1-62.3%) to detect high-grade PCa. Using a predefined cut point, 202 of 767 (26.3%) biopsies would have been avoided, missing only 6% of patients with dominant pattern 4 high-risk GS 7 disease. Conclusions: Ccirc is a potential biomarker for high-grade PCa among suspicious men.

scholarly journals Contemporary Distribution of High-Grade Prostate Cancer in the Circumstances of Opportunistic Testing

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Milorad M. Stojadinovic ◽  
Damjan N. Pantic ◽  
Miroslav M. Stojadinovic
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
High Grade ◽  
Average Percentage ◽  
Logistic Analysis ◽  
Positive Biopsy ◽  
Level Data ◽  
Clinical Centre ◽  
The Mean

Abstract Screening has dramatically changed the distribution of the mean age, stage and grade of prostate cancer (PCa) at diagnosis. However, regional-level data that characterize contemporary PCa patients are limited. Th e aim of the study was to ascertain main clinical and pathological characteristics of PCa at the present time in the circumstances of opportunistic testing. High-grade PCa according to age, serum prostate specific antigen (PSA), volume prostate, PSA density (PSAD), digital rectal examination (DRE) number of positive cores biopsies and the average percentage of cancer in biopsy at diagnosis has been retrospectively evaluated in 100 men with biopsyproven PCa, at Clinical Centre Kragujevac, from September 2016 until September 2017. PCa were stratified according to Gleason score (GS) into low/intermediate-grade (GS ≤ 7) and high-grade (GS ≥ 8). To identify the determinants associated with high-grade PCa, we performed univariate and multivariate logistic regression. The most prevalent PCa were the low/intermediategrade (65%), followed by high-grade (35%). The mean age of the patients was 71.5 (range: 56-88) years and median PSA was 14.6 (range: 1.4-935) ng/ml. There were significant differences in age, PSA, PSAD, DRE, number of positive biopsy and average percentage of cancer in biopsy between patients with or without high-grade GS. Logistic analysis demonstrated the PSAD and age have strong prognostic value of high-grade PCa. In conclusion, our study has shown the worrying frequency of high-grade PCa in the circumstances of opportunistic testing. Older men and higher level of PSAD had a much higher probability of high-grade PCa.

scholarly journals Predicting high-grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies

2021 ◽  
Author(s):  
Erik Margolis ◽  
Gordon Brown ◽  
Alan Partin ◽  
Ballentine Carter ◽  
James McKiernan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Predictive Value ◽  
Validation Studies ◽  
Characteristic Curve ◽  
Randomized Study ◽  
Specific Antigen ◽  
Low Grade ◽  
High Grade ◽  
Grade Group ◽  
Initial Biopsy

Abstract Background The ability to discriminate indolent from clinically significant prostate cancer (PC) at the initial biopsy remains a challenge. The ExoDx Prostate (IntelliScore) (EPI) test is a noninvasive liquid biopsy that quantifies three RNA targets in urine exosomes. The EPI test stratifies patients for risk of high-grade prostate cancer (HGPC; ≥ Grade Group 2 [GG] PC) in men ≥ 50 years with equivocal prostate-specific antigen (PSA) (2–10 ng/mL). Here, we present a pooled meta-analysis from three independent prospective-validation studies in men presenting for initial biopsy decision. Methods Pooled data from two prospective multi-site validation studies and the control arm of a clinical utility study were analyzed. Performance was evaluated using the area under the receiver-operating characteristic curve (AUC), negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity for discriminating ≥ GG2 from GG1 and benign pathology. Results The combined cohort (n = 1212) of initial-biopsy subjects had a median age of 63 years and median PSA of 5.2 ng/mL. The EPI AUC (0.70) was superior to PSA (0.56), Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) (0.62), and The European Randomized Study of Screening for Prostate Cancer (ERSPC) (0.59), (all p-values <0.001) for discriminating GG2 from GG1 and benign histology. The validated cutoff of 15.6 would avoid 23% of all prostate biopsies and 30% of “unnecessary” (benign or Gleason 6/GG1) biopsies, with an NPV of 90%. Conclusions EPI is a noninvasive, easy-to-use, urine exosome–RNA assay that has been validated across 3 independent prospective multicenter clinical trials with 1212 subjects. The test can discriminate high-grade (≥GG2) from low-grade (GG1) cancer and benign disease. EPI effectively guides the biopsy-decision process independent of PSA and other standard-of-care factors.

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 Can Urinary PCA3 Supplement PSA in the Early Detection of Prostate Cancer?

2014 ◽  
Vol 32 (36) ◽  
pp. 4066-4072 ◽  
Author(s):  
John T. Wei ◽  
Ziding Feng ◽  
Alan W. Partin ◽  
Elissa Brown ◽  
Ian Thompson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Prostate Biopsy ◽  
Predictive Value ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Repeat Biopsy ◽  
Individual Risk ◽  
High Grade ◽  
Initial Biopsy

Purpose Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA. Patients and Methods In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20). Results For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer. Conclusion These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer.

Osteopontin Plasma Level Does Not Detect Prostate Cancer in Patients Referred for Diagnostic Prostate Biopsy

2010 ◽  
Vol 25 (4) ◽  
pp. 200-206 ◽  
Author(s):  
Roberto Puzone ◽  
Laura Paleari ◽  
Franco Montefiore ◽  
Luca Ruggiero ◽  
Matteo Puntoni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Tumor Development ◽  
Digital Rectal Examination ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
High Grade ◽  
Detect Prostate Cancer ◽  
Plasma Marker

Background Prostate cancer is the second most frequent cause of tumor-related deaths in men in Western countries. The selection and evaluation of new markers might help to overcome the limits of the most widely used diagnostic tool, the prostate-specific antigen (PSA) test, often combined with digital rectal examination (DRE). Osteopontin (OPN) is an integrin-binding glycoprotein that has recently been shown to be related to tumor development, progression and metastasis in both experimental and clinical studies. The present study compares plasma OPN levels and tumor presence and grade in a group of PSA/DRE-positive patients referred for diagnostic prostate biopsy. Methods Plasma OPN levels were measured by enzyme-linked immunosorbent assay in blood samples of 194 PSA/DRE-positive patients referred for diagnostic prostate biopsy. OPN measurements were compared with PSA levels and tumor presence and grade as established by needle biopsy. Results Plasma OPN levels were not increased in patients with prostate cancer, and in patients with high-grade prostate cancer the plasma OPN levels were not different from those in patients with low-grade or no prostate cancer. Conclusions In PSA/DRE-positive patients referred for diagnostic prostate biopsy, OPN does not appear to be a plasma marker able to detect prostate cancer or high-grade prostate cancer.

Prostate Cancer Radiotherapy: An Evolving Paradigm

2018 ◽  
Vol 36 (29) ◽  
pp. 2909-2913 ◽  
Author(s):  
Charles N. Catton ◽  
Himu Lukka ◽  
Jarad Martin
Keyword(s):  
Prostate Cancer ◽  
Relevant Literature ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Benign Prostatic Hypertrophy ◽  
Whole Body ◽  
Grade Group ◽  
Ulcer Disease ◽  
Psa Testing ◽  
Adenocarcinoma Of The Prostate

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 urologist referred a 69-year-old man for a radiotherapy opinion regarding a recently diagnosed adenocarcinoma of the prostate. Annual serum prostate-specific antigen (PSA) testing over 7 years demonstrated a rise in PSA from 1.36 ng/mL to 5.8 ng/mL, prompting a transrectal ultrasound that revealed a heterogeneous 37-mL gland containing no visualized hypoechoic nodules. Biopsy disclosed a Gleason score 3+4 (grade group 2) adenocarcinoma of the prostate. The synoptic report stated that six of 14 cores and 17% of the tissue were involved, with the greatest core involvement being 80% at the right apex. Perineural invasion was present without lymphovascular invasion. Disease was present bilaterally at the base, midgland, and apex.His medical history was significant only for treated peptic ulcer disease and he was taking no medication. His International Prostate Symptom Score was six of 35, and he reported being sexually active with good erectile function. There was no family history of prostate cancer. He is retired. Digital rectal examination revealed moderate benign prostatic hypertrophy with no suspicious nodules. A staging computerized tomography (CT) scan of the abdomen and pelvis and a whole-body bone scan ordered by his referring urologist reported no evidence of metastatic disease. The patient had discussed surgical options with his urologist and now wished to consider radiotherapy approaches.

scholarly journals Multiparametric Prostate MRI in Biopsy-Naïve Men: A Prospective Evaluation of Performance and Biopsy Strategies

2021 ◽  
Vol 11 ◽  
Author(s):  
Brage Krüger-Stokke ◽  
Helena Bertilsson ◽  
Sverre Langørgen ◽  
Torill Anita Eidhammer Sjøbakk ◽  
Tone Frost Bathen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Gleason Grade ◽  
Grade Group ◽  
Detection Rates ◽  
Prostate Mri ◽  
Multiparametric Prostate Mri

ObjectivesThis study aims to prospectively estimate the diagnostic performance of multiparametric prostate MRI (mpMRI) and compare the detection rates of prostate cancer using cognitive targeted transrectal ultrasound (TRUS) guided biopsies, targeted MR-guided in-bore biopsies (MRGB), or both methods combined in biopsy-naïve men.MethodsThe biopsy-naïve men referred for mpMRI (including T2-weighted, diffusion-weighted and dynamic contrast enhanced MRI) due to prostate cancer suspicion (elevated prostate-specific antigen or abnormal digital rectal examination) were eligible for inclusion. The images were scored according to Prostate Imaging Reporting and Data System (PI-RADS) v2, and men with PI-RADS 1–2 lesions were referred for routine systematic TRUS, while those with PI-RADS 3–5 lesions were randomized to MRGB or cognitive targeted TRUS. Men randomized to MRGB were referred to a secondary TRUS 2 weeks after MRGB. Gleason grade group ≥2 was defined as clinically significant prostate cancer. The performance of mpMRI was estimated using prostate cancer detected by any biopsy method as the reference test.ResultsA total of 210 men were included. There was no suspicion of prostate cancer after mpMRI (PI-RADS 1–2) in 48% of the men. Among these, significant and insignificant prostate cancer was diagnosed in five and 11 men, respectively. Thirty-five men who scored as PI-RADS 1–2 did not undergo biopsy and were therefore excluded from the calculation of diagnostic accuracy. The overall sensitivity, specificity, negative predictive value, and positive predictive value of mpMRI for the detection of significant prostate cancer were 0.94, 0.63, 0.92, and 0.67, respectively. In patients with PI-RADS 3–5 lesions, the detection rates for significant prostate cancer were not significantly different between cognitive targeted TRUS (68.4%), MRGB (57.7%), and the combination of the two biopsy methods (64.4%). The median numbers of biopsy cores taken per patient undergoing systematic TRUS, cognitive targeted TRUS, and MRGB were 14 [8-16], 12 [6-17], and 2 [1-4] respectively.ConclusionsmpMRI, in a cohort of biopsy-naïve men, has high negative predictive value, and our results support that it is safe to avoid biopsy after negative mpMRI. Furthermore, MRGB provides a similar diagnosis to the cognitive targeted TRUS but with fewer biopsies.

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