scholarly journals Establishing a Urine-Based Biomarker Assay for Prostate Cancer Risk Stratification

2020 ◽  
Vol 8 ◽  
Author(s):  
Jinan Guo ◽  
Dale Liu ◽  
Xuhui Zhang ◽  
Heather Johnson ◽  
Xiaoyan Feng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Stratification ◽  
Gleason Score ◽  
Prospective Cohort ◽  
Lower Risk ◽  
Treatment Decision ◽  
Gene Panel ◽  
Urine Test ◽  
Non Invasive ◽  
Lower Accuracy

One of the major features of prostate cancer (PCa) is its heterogeneity, which often leads to uncertainty in cancer diagnostics and unnecessary biopsies as well as overtreatment of the disease. Novel non-invasive tests using multiple biomarkers that can identify clinically high-risk cancer patients for immediate treatment and monitor patients with low-risk cancer for active surveillance are urgently needed to improve treatment decision and cancer management. In this study, we identified 14 promising biomarkers associated with PCa and tested the performance of these biomarkers on tissue specimens and pre-biopsy urinary sediments. These biomarkers showed differential gene expression in higher- and lower-risk PCa. The 14-Gene Panel urine test (PMP22, GOLM1, LMTK2, EZH2, GSTP1, PCA3, VEGFA, CST3, PTEN, PIP5K1A, CDK1, TMPRSS2, ANXA3, and CCND1) was assessed in two independent prospective and retrospective urine study cohorts and showed high diagnostic accuracy to identify higher-risk PCa patients with the need for treatment and lower-risk patients for surveillance. The AUC was 0.897 (95% CI 0.939–0.855) in the prospective cohort (n = 202), and AUC was 0.899 (95% CI 0.964–0.834) in the retrospective cohort (n = 97). In contrast, serum PSA and Gleason score had much lower accuracy in the same 202 patient cohorts [AUC was 0.821 (95% CI 0.879–0.763) for PSA and 0.860 (95% CI 0.910–0.810) for Gleason score]. In addition, the 14-Gene Panel was more accurate at risk stratification in a subgroup of patients with Gleason scores 6 and 7 in the prospective cohort (n = 132) with AUC of 0.923 (95% CI 0.968–0.878) than PSA [AUC of 0.773 (95% CI 0.852–0.794)] and Gleason score [AUC of 0.776 (95% CI 0.854–0.698)]. Furthermore, the 14-Gene Panel was found to be able to accurately distinguish PCa from benign prostate with AUC of 0.854 (95% CI 0.892–0.816) in a prospective urine study cohort (n = 393), while PSA had lower accuracy with AUC of 0.652 (95% CI 0.706–0.598). Taken together, the 14-Gene Panel urine test represents a promising non-invasive tool for detection of higher-risk PCa to aid treatment decision and lower-risk PCa for active surveillance.

scholarly journals Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Heather Johnson ◽  
Jinan Guo ◽  
Xuhui Zhang ◽  
Heqiu Zhang ◽  
Athanasios Simoulis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Cancer Diagnosis ◽  
Multivariate Logistic Regression Analysis ◽  
Gene Panel ◽  
Urine Test ◽  
Non Invasive ◽  
Clinically Significant ◽  
Benign Prostate

Abstract Background Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. Methods Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRT-PCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. Results The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963–0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929–0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956–0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980–0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947–0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. Conclusions The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.

scholarly journals Non-invasive Urine Test for Molecular Classification of Clinical Significance in Newly Diagnosed Prostate Cancer Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinan Guo ◽  
Xuhui Zhang ◽  
Taolin Xia ◽  
Heather Johnson ◽  
Xiaoyan Feng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Treatment Decision ◽  
Urine Test ◽  
Newly Diagnosed ◽  
Grade Group ◽  
Non Invasive ◽  
Insignificant Cancer ◽  
Clinically Significant

Objective: To avoid over-treatment of low-risk prostate cancer patients, it is important to identify clinically significant and insignificant cancer for treatment decision-making. However, no accurate test is currently available.Methods: To address this unmet medical need, we developed a novel gene classifier to distinguish clinically significant and insignificant cancer, which were classified based on the National Comprehensive Cancer Network risk stratification guidelines. A non-invasive urine test was developed using quantitative mRNA expression data of 24 genes in the classifier with an algorithm to stratify the clinical significance of the cancer. Two independent, multicenter, retrospective and prospective studies were conducted to assess the diagnostic performance of the 24-Gene Classifier and the current clinicopathological measures by univariate and multivariate logistic regression and discriminant analysis. In addition, assessments were performed in various Gleason grades/ISUP Grade Groups.Results: The results showed high diagnostic accuracy of the 24-Gene Classifier with an AUC of 0.917 (95% CI 0.892–0.942) in the retrospective cohort (n = 520), AUC of 0.959 (95% CI 0.935–0.983) in the prospective cohort (n = 207), and AUC of 0.930 (95% 0.912-CI 0.947) in the combination cohort (n = 727). Univariate and multivariate analysis showed that the 24-Gene Classifier was more accurate than cancer stage, Gleason score, and PSA, especially in the low/intermediate-grade/ISUP Grade Group 1–3 cancer subgroups.Conclusions: The 24-Gene Classifier urine test is an accurate and non-invasive liquid biopsy method for identifying clinically significant prostate cancer in newly diagnosed cancer patients. It has the potential to improve prostate cancer treatment decisions and active surveillance.

scholarly journals Identification of a novel non-invasive biological marker to overcome the shortcomings of PSA in diagnosis and risk stratification for prostate cancer: Initial prospective study of developmental endothelial locus-1 protein

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250254
Author(s):  
Jae-Wook Chung ◽  
Hyun Tae Kim ◽  
Yun-Sok Ha ◽  
Eun Hye Lee ◽  
So Young Chun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Risk Stratification ◽  
Prospective Study ◽  
Gleason Score ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Biological Marker ◽  
Clinicopathological Characteristics ◽  
Non Invasive

Objective This prospective study sought to clarify the developmental endothelial locus-1 (Del-1) protein as values of diagnosis and risk stratification of prostate cancer (PCa). Design From February 2017 to December 2019, a total 458 patients who underwent transrectal ultrasound guided prostate biopsy or surgery of benign prostatic hyperplasia agreed to research of Del-1 protein. We prospectively compared and analyzed the Del-1 protein and prostate specific antigen (PSA) in relation to the patients’ demographic and clinicopathological characteristics. Results Mean age was 68.86±8.55 years. Mean PSA and Del-1 protein was 21.72±89.37, 0.099±0.145, respectively. Two hundred seventy-six (60.3%) patients were diagnosed as PCa. Among them, 181 patients underwent radical prostatectomy (RP). There were significant differences in Del-1 protein between benign and PCa group (0.066±0.131 vs 0.121±0.149, respectively, p<0.001). When we set the cut-off value of del-1 protein as 0.120, in patients with 3≤PSA≤8, positive predictive value and specificity of Del-1 protein (≥0.120) for predicting PCa were 88.9% (56/63) and 93.5% (101/108), respectively. Among 181 patients who underwent RP, there were significant differences in Del-1 protein according to stage (pT2 vs pT3a vs ≥pT3b) (0.113±0.078, 0.171±0.121, 0.227±0.161, respectively, p<0.001) and to Gleason score (6 (3+3) or 7 (3+4) vs 7 (4+3) or 8 (4+4) vs 9 or 10) (0.134±0.103, 0.150±0.109, 0.212±0.178, respectively, P = 0.044). Multivariate analysis showed that PSA, Del-1 protein and high Gleason score (≥9) were the independent prognostic factors for predicting higher pT stage (≥3b). Furthermore, age, PSA and Del-1 protein were independent prognostic factors for predicting significant PCa. Conclusion Patients with PCa showed higher expression of Del-1 protein than benign patients. Del-1 protein increased with the stage and Gleason score of PCa. Collaboration with PSA, Del-1 protein can be a non-invasive useful marker for diagnosis and risk stratification of PCa.

Association of time from definitive therapy (DT) to start of androgen deprivation therapy (ADT) for metastatic disease and survival outcomes in men with new metastatic hormone-sensitive prostate cancer (mHSPC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 265-265
Author(s):  
David Michael Gill ◽  
David D. Stenehjem ◽  
Heather H. Cheng ◽  
Elizabeth Riley Kessler ◽  
Andrew W. Hahn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Decision Making ◽  
Risk Stratification ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Treatment Decision ◽  
Localized Prostate Cancer ◽  
Prior History ◽  
Treatment Decision Making ◽  
Definitive Therapy

265 Background: Few objective criteria are considered for risk stratification for treatment decision making in men with new mHSPC. Time between DT for localized disease, and start of ADT for new mHSPC may predict response to ADT, and prognosticate outcomes in this setting. Methods: In this multicenter study, men with newly diagnosed mHSPC with prior history of definite therapy for localized prostate cancer were included. Kaplan-Meier and Cox proportional hazard methods assessed time to castration resistance (CRPC) and overall survival (OS) from initiation of ADT, and correlated with the time elapsed from DT to initiation of ADT for new mHSPC. Results: A total of 112 men with new mHSPC initiating ADT, with prior definitive therapy were eligible (all median: age 68 yrs, Gleason score 7, PSA 14 ng/ml, ECOG 0, median time from DT to start of ADT for new mHSPC 54 months). In the univariate analysis, time from DT to start of ADT of < 60 months vs ≥ 60 months significantly correlated with duration of response to ADT and outcomes (Table). After adjustment for Gleason score and log PSA, time from DT to start of ADT for new mHSPC (<60 vs ≥60 months) remained an independent and a significant predictor of time to CRPC (HR 1.92 95% CI 1.02-3.90, p=0.044), and showed trends towards predicting OS (HR 1.77 95% CI 0.60-6.19, p=0.33). Conclusions: Time from DT for localized prostate cancer to initiation of ADT for new mHSPC independently predicts response to ADT, and may aid in risk stratification for treatment decision making in men with new mHSPC. These hypothesis-generating data require validation in a larger cohort. [Table: see text]

scholarly journals Pre-treatment risk stratification of prostate cancer patients:A critical review

2012 ◽  
Vol 6 (2) ◽  
Author(s):  
George Rodrigues ◽  
Padraig Warde ◽  
Tom Pickles ◽  
Juanita Crook ◽  
Michael Brundage ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Cancer Risk ◽  
Risk Stratification ◽  
Gleason Score ◽  
Critical Review ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Original Research ◽  
Pre Treatment

Introduction:  The use of accepted prostate cancer risk stratification groups based on prostate-specific antigen, T stage and Gleason score assists in therapeutic treatment decision-making, clinical trial design and outcome reporting. The utility of integrating novel prognostic factors into an updated risk stratification schema is an area of current debate. The purpose of this work is to critically review the available literature on novel pre-treatment prognostic factors and alternative prostate cancer risk stratification schema to assess the feasibility and need for changes to existing risk stratification systems. Methods:  A systematic literature search was conducted to identify original research publications and review articles on prognostic factors and risk stratification in prostate cancer. Search terms included risk stratification, risk assessment, prostate cancer or neoplasms, and prognostic factors. Abstracted information was assessed to draw conclusions regarding the potential utility of changes to existing risk stratification schema. Results:  The critical review identified three specific clinically relevant potential changes to the most commonly used three-group risk stratification system: (1) the creation of a very-low risk category; (2) the splitting of intermediate-risk into a low- and highintermediate risk groups; and (3) the clarification of the interface between intermediate- and high-risk disease. Novel pathological factors regarding high-grade cancer, subtypes of Gleason score 7 and percentage biopsy cores positive were also identified as potentially important risk-stratification factors. Conclusions:  Multiple studies of prognostic factors have been performed to create currently utilized prostate cancer risk stratification systems. We propose potential changes to existing systems.

Abstract 899: TMPRSS2:ERG urine test identifies Gleason score upgrading and significant prostate cancer

2011 ◽  
Author(s):  
Sheila M. Aubin ◽  
Scott Tomlins ◽  
Sarah Meyer ◽  
Yvonne Penabella ◽  
Javed Siddiqui ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Urine Test

CCP score and risk stratification for prostate cancer patients at biopsy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 47-47 ◽  
Author(s):  
E. David Crawford ◽  
Neal Shore ◽  
Peter T. Scardino ◽  
John W. Davis ◽  
Jonathan D. Tward ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Risk Stratification ◽  
Gleason Score ◽  
Cell Cycle Progression ◽  
Specific Antigen ◽  
Risk Category ◽  
Cycle Progression ◽  
Aggressive Cancer ◽  
Cancer Aggressiveness

47 Background: New prognostic markers for prostate cancer play an important role in addressing the controversies of over diagnosis and treatment. The cell cycle progression score (CCP) (Prolaris, Myriad Genetic Laboratories, Inc.) is a new RNA-based marker, which improved the prediction of prostate cancer aggressiveness in eight separate cohorts. Each one-unit increase in CCP score corresponds with approximately a doubling of the risk of the studied event (recurrence or death from prostate cancer). In this analysis, we characterized the CCP score distribution from our initial CCP signature commercial testing. Methods: Our current laboratory database was evaluated for patients whose biopsy was analyzed with the CCP test and whose clinicopathologic data was collected by the ordering physician. Formalin fixed, prostate biopsy tissue from 1,648 patients diagnosed with adenocarcinoma ordered by more than 300 physicians were analyzed. The CCP score was calculated by measuring the RNA expression of 31 cell cycle progression genes normalized to 15 housekeeping genes. Results: Of the 1,648 samples that contained sufficient carcinoma (more than 0.5mm linear extent), 1,604 (97.3%) provided quality RNA for analysis. This retrospective analysis showed a normal distribution for the CCP score ranging from −2.9 to 3.1. Correlation with Gleason score was r=0.35. A relative classification of cancer aggressiveness based on CCP of approximately1,200 patients from multiple cohorts was developed to interpret how the patient’s CCP score compared to that of patients within the same AUA risk category. The thresholds between each of the five intervals are one unit of CCP score apart, with the "consistent" interval centered at the median CCP score. Based on the CCP score, 27.9% of men had a less aggressive cancer compared to the clinicopathologic prediction and were assigned to a lower risk group while 27.6% of patients had a more aggressive cancer. Conclusions: The CCP signature test is a novel assay that can improve risk stratification for men with prostate adenocarcinoma independent of the Gleason score and prostate-specific antigen level. Over 50% of men initially tested in the commercial assay were assigned to a different risk category than predicted by clinicopathologic features alone.

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