Elevated HOXC6/DLX1 mRNA biomarker levels in urine to help select patients at increased risk for high-grade prostate cancer detection upon prostate biopsy.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 31-31
Author(s):  
Rianne Hendriks ◽  
Siebren Dijkstra ◽  
Erik Bastiaan Cornel ◽  
Sander Jannink ◽  
Hans de Jong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Score ◽  
Prostate Biopsy ◽  
Area Under The Curve ◽  
Risk Scores ◽  
Grey Zone ◽  
High Grade ◽  
Multicenter Studies ◽  
Biopsy Procedure ◽  
Increased Risk

31 Background: The major challenge in prostate cancer (PCa) diagnostics is to improve the early detection of clinically significant or high-grade PCa, especially in the sPSA "grey-zone" (4-10 ng/ml). Ideally, PCa-specific biomarkers would be obtained non-invasively, for example derived from urine. The aim of this study was to evaluate the expression levels and clinical utility of the recently identified urinary HOXC6-DLX1 mRNA biomarker combination in men at risk of having high-grade PCa. Methods: From two prospective, multicenter studies, a total of 863 post-DRE urine samples were collected from men with elevated sPSA levels before undergoing a prostate biopsy procedure. The HOXC6-DLX1 mRNA biomarkers were measured in urine using RT-qPCR and results were quantified using the Delta DeltaCt method (ΔΔCT), normalized and expressed in a score from 1 to 1421. Results: The HOXC6-DLX1 risk score was significantly higher in urine from patients with high-grade PCa upon prostate biopsy compared to no PCa and PCa Gleason score ≤6. In the sPSA "grey-zone", the HOXC6-DLX1 combination had the highest area-under-the-curve (AUC) of 0.67 (95% confidence interval (CI): 0.58-0.75) for prediction of high-grade PCa upon prostate biopsy in cohort A and 0.68 (95% CI: 0.59-0.76) in cohort B; as compared to sPSA with an AUC of 0.60 (95% CI: 0.51-0.70) and 0.62 (95% CI: 0.52-0.73) respectively. Overall, elevated HOXC6-DLX1 risk scores correlated with an increased risk of high-grade PCa detected on biopsy; 47% of men with a score >108 had significant cancer as compared to 6% with a risk score <17. Using a HOXC6-DLX1 risk score cut-off of 27.5 in the sPSA "grey-zone", 165 biopsies (31%) could have been avoided, and only 4% of patients with high-grade PCa would have been missed. Conclusions: The urine-based HOXC6-DLX1 assay provides a non-invasive solution to improve the selection of patients at increased risk for high-grade PCa who would benefit most from a prostate biopsy procedure, while reducing the number of unnecessary biopsies, particularly in the sPSA "grey-zone".

scholarly journals Clinically significant Prostate Cancer diagnosed using a urinary molecular biomarker-based risk score: two case reports

BMC Urology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Pieter Minnee ◽  
Daphne Hessels ◽  
Jack A. Schalken ◽  
Wim Van Criekinge
Keyword(s):  
Prostate Cancer ◽  
Risk Score ◽  
Prostate Biopsy ◽  
Case Reports ◽  
Randomized Study ◽  
Risk Scores ◽  
High Grade ◽  
Molecular Biomarker ◽  
Life Years ◽  
Clinically Significant

Abstract Background Identifying men for a repeat prostate biopsy is a conundrum to urologists. Risk calculators (RCs) such as the European Randomized Study of Screening for Prostate Cancer (ERSPC) RCs have been developed to predict the outcome of prostate biopsies and have been shown to improve diagnostic accuracy compared to PSA alone. However, it was recently shown that the outcome for high-grade prostate cancer (PCa) upon biopsy tended to be underestimated in men with previous negative biopsies using ERSPC RC model 4. For these men, an individualized approach combining the clinical information with the outcome of biomarker-related urine tests may help to make a more informed decision. Case presentation Two men, aged 66 and 69 respectively when presented in the clinic, show the typical dilemma of urologist and patient for electing repeat prostate biopsy. Both men had normal DRE findings, did not have a family history of PCa, presented with serum PSA values between 3 and 10 ng/ml and the first biopsies were negative for disease. The ERSPC RC4 did not indicate a biopsy in these men. The urinary molecular biomarker-based test for HOXC6 and DLX1, combining biomarker-expression profiling with clinical risk factors, resulted in SelectMDx Risk scores for these men that were higher than the cut-off of the test. Based on this outcome, mpMRI was performed with an outcome of PI-RADS ≥4 in both men. Histopathological evaluation of TRUS-guided biopsies confirmed high-grade PCa. Conclusions The urinary molecular biomarker-based risk score played a pivotal role in the diagnosis of clinically significant PCa whereas ERSPC RC4 outcome would not have indicated further diagnostic follow-up in these two cases. The timely diagnosis was shown to be crucial for the curative treatment by radical retropubic prostatectomy and the potential life-years gained for these two vital males.

Lower risk of prostate cancer in patients with sedentary occupations presenting for a prostate biopsy: Analysis of a Veterans Affairs cohort.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 257-257
Author(s):  
Rimaz M. Khadir ◽  
Rashid K. Sayyid ◽  
Martha K. Terris
Keyword(s):  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Statistical Significance ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
High Volume ◽  
Veterans Affairs ◽  
High Grade ◽  
Increased Risk ◽  
Patient Reported

257 Background: Sedentary behavior has been associated with increased serum prostate-specific antigen (PSA) levels. It is currently unknown whether this correlates with an increased risk of underlying prostate cancer (PCa). Our objective was to determine whether patients with sedentary occupations presenting for a prostate biopsy were at increased risk of PCa diagnosis. Methods: A prospectively collected registry of patients undergoing a prostate biopsy between July 1995 and June 2016 at the Veterans Affairs Medical Center in Augusta, GA was utilized. The occupation was classified as sedentary if it was associated with prolonged periods of sitting (i.e. >50% work hours). This was determined via patient reported history at time of biopsy. The associations between a sedentary lifestyle and risk of a positive prostate biopsy, high grade cancer (i.e. Gleason score 8 or higher), and high volume cancer (i.e. at least 50% of total cores were positive) were evaluated using multivariable logistic regression analyses, controlling for age, race, body mass index, PSA level, free PSA ratio, clinical stage, prostate volume, and family history of prostate cancer. Statistical significance was set at p<0.05. All statistical analyses were performed using R version 3.6.1. Results: Our cohort included 1,914 patients. 271 (14.2%) patients had sedentary jobs. Median patient age was 61.0 years (Interquartile range [IQR] 57.0 – 66.0). Median PSA at time of biopsy was 5.7 ng/ml (IQR 4.4 – 8.2). Of the 1,914 initial biopsies performed, 974 (50.9%) were positive for malignancy. Of patients diagnosed with PCa, 229 (23.5%) had high-grade disease and 316 (32.4%) had high volume disease. On multivariable analysis, patients with a sedentary job had a significantly decreased risk of PCa diagnosis (Odds ratio [OR] 0.43, 95% confidence interval [CI] 0.18-1.03, p= 0.058), but no difference in odds of high grade (OR 0.63, 95% CI 0.089-2.99, p= 0.60) or high volume disease (OR 1.07, 95% CI 0.93-1.21, p= 0.89). Conclusions: Patients with sedentary occupations presenting for a prostate biopsy are at a lower apparent risk for a positive prostate biopsy. These results suggest that the serum PSA levels in such patients may be artificially elevated secondary to increased recumbence with no corresponding increase in risk of malignancy. [Table: see text]

Validation of a two-gene mRNA urine test for detection of high-grade prostate cancer in German men.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 96-96
Author(s):  
Derya Tilki ◽  
Daphne Hessels ◽  
Geert Trooskens ◽  
Susan Mulders ◽  
Michael Brawer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Validation Study ◽  
Prostate Biopsy ◽  
Predictive Value ◽  
Clinical Performance ◽  
Unmet Need ◽  
High Grade ◽  
Grade Group ◽  
Increased Risk ◽  
Average Serum

96 Background: There is an unmet need for non-invasive methods that can accurately identify patients at increased risk for clinically significant prostate cancer (PCa). SelectMDx is a urine-based molecular test that has been clinically validated for the detection of high-grade PCa. We evaluated SelectMDx clinical performance in a cohort of German men undergoing initial prostate biopsy. Methods: The study population consisted of 443 men sequentially enrolled men who underwent initial prostate biopsy between July 2009 and December 2014 due to suspected PCa. Post-DRE urine was collected from all subjects prior to biopsy, and samples stored at -70C. Urinary HOXC6 and DLX-1 mRNAs were quantified by PCR in May 2018, and RNA results combined with clinical risk factors to determine the likelihood that biopsy would identify ISUP grade group (GG) ≥ 2 (Gleason Score ≥ 7) PCa. We assessed SelectMDx performance for detection of GG ≥ 2 PCa, compared to the PCPT Risk Calculator Version 2.0 (PCPTRC, http://myprostatecancerrisk.com , accessed Oct 7, 2018). Results: For the 443 subjects enrolled, average age was 66 years (median 66, interquartile range 61 to 71), and average serum PSA level 8.8 ng/mL (6.4, 4.8 to 9.7). Cancer was detected in 243/443 (55%) men biopsied (43% GG1, 36% GG2, 9% GG3 and 12% GG4-5). The prevalence of GG2-5 PCa in this population was 31.4% (139/443). For detection of GG2 or higher PCa versus GG1 or no PCa at biopsy, SelectMDx AUC was 0.82 (95% C.I. 0.78-0.86) and the PCPTRC yielded AUC 0.75 (0.70-0.80), P < 0.001. SelectMDx sensitivity was 94% (89-98%), specificity 46% (40-52%), positive predictive value 45% (42-47%) and negative predictive value (NPV) 95% (90-97%). If the initial biopsy had been performed based on SelectMDx results alone, 46% of potentially unnecessary biopsies and 34% of all biopsies would have been avoided, while 5.8% of men with biopsy-detectable high-grade PCa (seven GG2, one GG3) may have had their diagnosis delayed. Conclusions: In this first validation study of SelectMDx in German men, the test’s clinical performance was comparable to the published EU validation study, showing a high NPV for detection of GG2 or higher PCa. These results provide further evidence for the clinical validity of SelectMDx.

scholarly journals Prognostic Index for Predicting Prostate Cancer Survival in a Randomized Screening Trial: Development and Validation

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 435
Author(s):  
Subas Neupane ◽  
Jaakko Nevalainen ◽  
Jani Raitanen ◽  
Kirsi Talala ◽  
Paula Kujala ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Score ◽  
Cancer Survival ◽  
Area Under The Curve ◽  
Prognostic Index ◽  
Risk Groups ◽  
Risk Scores ◽  
Development And Validation ◽  
Screening Trial

We developed and validated a prognostic index to predict survival from prostate cancer (PCa) based on the Finnish randomized screening trial (FinRSPC). Men diagnosed with localized PCa (N = 7042) were included. European Association of Urology risk groups were defined. The follow-up was divided into three periods (0–3, 3–9 and 9–20 years) for development and two corresponding validation periods (3–6 and 9–15 years). A multivariable complementary log–log regression model was used to calculate the full prognostic index. Predicted cause-specific survival at 10 years from diagnosis was calculated for the control arm using a simplified risk score at diagnosis. The full prognostic index discriminates well men with PCa with different survival. The area under the curve (AUC) was 0.83 for both the 3–6 year and 9–15 year validation periods. In the simplified risk score, patients with a low risk score at diagnosis had the most favorable survival, while the outcome was poorest for the patients with high risk scores. The prognostic index was able to distinguish well between men with higher and lower survival, and the simplified risk score can be used as a basis for decision making.

scholarly journals External assessment of the EUROMACS right-sided heart failure risk score

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hirak Shah ◽  
Thomas Murray ◽  
Jessica Schultz ◽  
Ranjit John ◽  
Cindy M. Martin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Risk Score ◽  
Pressure Ratio ◽  
Area Under The Curve ◽  
Left Ventricular ◽  
Right Atrial ◽  
Risk Scores ◽  
External Assessment ◽  
Failure Risk

AbstractThe EUROMACS Right-Sided Heart Failure Risk Score was developed to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) placement. The predictive ability of the EUROMACS score has not been tested in other cohorts. We performed a single center analysis of a continuous-flow (CF) LVAD cohort (n = 254) where we calculated EUROMACS risk scores and assessed for right ventricular heart failure after LVAD implantation. Thirty-nine percent of patients (100/254) had post-operative RVF, of which 9% (23/254) required prolonged inotropic support and 5% (12/254) required RVAD placement. For patients who developed RVF after LVAD implantation, there was a 45% increase in the hazards of death on LVAD support (HR 1.45, 95% CI 0.98–2.2, p = 0.066). Two variables in the EUROMACS score (Hemoglobin and Right Atrial Pressure to Pulmonary Capillary Wedge Pressure ratio) were not predictive of RVF in our cohort. Overall, the EUROMACS score had poor external discrimination in our cohort with area under the curve of 58% (95% CI 52–66%). Further work is necessary to enhance our ability to predict RVF after LVAD implantation.

scholarly journals Multi-cohort modeling strategies for scalable globally accessible prostate cancer risk tools

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Johanna Tolksdorf ◽  
Michael W. Kattan ◽  
Stephen A. Boorjian ◽  
Stephen J. Freedland ◽  
Karim Saba ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Family History ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Prostate Biopsy ◽  
Prostate Cancer Risk ◽  
High Grade ◽  
Prediction Tools ◽  
History Of

Abstract Background Online clinical risk prediction tools built on data from multiple cohorts are increasingly being utilized for contemporary doctor-patient decision-making and validation. This report outlines a comprehensive data science strategy for building such tools with application to the Prostate Biopsy Collaborative Group prostate cancer risk prediction tool. Methods We created models for high-grade prostate cancer risk using six established risk factors. The data comprised 8492 prostate biopsies collected from ten institutions, 2 in Europe and 8 across North America. We calculated area under the receiver operating characteristic curve (AUC) for discrimination, the Hosmer-Lemeshow test statistic (HLS) for calibration and the clinical net benefit at risk threshold 15%. We implemented several internal cross-validation schemes to assess the influence of modeling method and individual cohort on validation performance. Results High-grade disease prevalence ranged from 18% in Zurich (1863 biopsies) to 39% in UT Health San Antonio (899 biopsies). Visualization revealed outliers in terms of risk factors, including San Juan VA (51% abnormal digital rectal exam), Durham VA (63% African American), and Zurich (2.8% family history). Exclusion of any cohort did not significantly affect the AUC or HLS, nor did the choice of prediction model (pooled, random-effects, meta-analysis). Excluding the lowest-prevalence Zurich cohort from training sets did not statistically significantly change the validation metrics for any of the individual cohorts, except for Sunnybrook, where the effect on the AUC was minimal. Therefore the final multivariable logistic model was built by pooling the data from all cohorts using logistic regression. Higher prostate-specific antigen and age, abnormal digital rectal exam, African ancestry and a family history of prostate cancer increased risk of high-grade prostate cancer, while a history of a prior negative prostate biopsy decreased risk (all p-values < 0.004). Conclusions We have outlined a multi-cohort model-building internal validation strategy for developing globally accessible and scalable risk prediction tools.

scholarly journals A urine-based Exosomal gene expression test stratifies risk of high-grade prostate Cancer in men with prior negative prostate biopsy undergoing repeat biopsy

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
James McKiernan ◽  
Mikkel Noerholm ◽  
Vasisht Tadigotla ◽  
Sonia Kumar ◽  
Phillipp Torkler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Repeat Biopsy ◽  
High Grade ◽  
Negative Prostate Biopsy

scholarly journals Diagnostic accuracy of prostate cancer antigen 3 (PCA3) prior to first prostate biopsy: A systematic review and meta-analysis

2019 ◽  
Vol 14 (5) ◽  
Author(s):  
Sandra Viviana Muñoz Rodríguez ◽  
Herney Andrés García-Perdomo
Keyword(s):  
Prostate Cancer ◽  
Diagnostic Accuracy ◽  
Prostate Biopsy ◽  
Reference Lists ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Diagnostic Odds Ratio ◽  
Cancer Antigen ◽  
Prostate Cancer Antigen

Introduction: We aimed to determine the diagnostic accuracy of the prostate cancer antigen 3 (PCA3) test before performing the first biopsy compared with prostate biopsy for the diagnosis of prostate cancer. Methods: A systematic search was performed in MEDLINE, EMBASE, CENTRAL, LILACS, reference lists, specialized journals in urology and cancer, and unpublished literature. The population was adults with suspected prostate cancer, and the intervention was the measurement of PCA3 in urine samples for the diagnosis of prostate cancer. The quality of studies was evaluated with the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The operative characteristics were determined, and a meta-analysis was performed. Results: Nine studies of diagnostic tests were included based on a cutoff value of 35. The following overall values were obtained: the sensitivity was 0.69 (95% confidence interval [CI] 0.61–0.75); specificity was 0.65 (95% CI 0.553–0.733); the diagnostic odds ratio (DOR) was 4.244 (95% CI 3.487–5.166); and the area under the curve was 0.734 (95% CI 0.674–0.805) with a heterogeneity of 0%. Conclusions: Urinary PCA3 has an acceptable diagnostic accuracy, aids in the study of patients with suspected prostate cancer, and can be used as a guide for directing the performance of the first prostate biopsy and decreasing unnecessary biopsies.

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