A urinary biomarker‐based risk score correlates with multiparametric MRI for prostate cancer detection

The development of more specific biomarkers for prostate cancer and/or high-risk prostate cancer is necessary, because the prostate-specific antigen test lacks specificity for the detection of prostate cancer and can lead to unnecessary prostate biopsies. Urine is a promising source for the development of new biomarkers of prostate cancer. Biomarkers derived from prostate cancer cells are released into prostatic fluids and then into urine. Urine after manipulation of the prostate is enriched with prostate cancer biomarkers, which include prostate cancer cells, DNAs, RNAs, proteins and other small molecules. The urinary prostate cancer antigen 3 test is the first Food and Drug Administration-approved RNA-based urinary marker, and it helps in the detection of prostate cancer on repeat biopsy. The SelectMDx test is based on messenger RNA detection of DLX1 and HOXC6 in urine after prostate massage, and helps in the detection of high-risk prostate cancer on prostate biopsy. Exosomes are extracellular vesicles with a diameter of 30-200 nm that are secreted from various types of cells. Urinary prostate cancer-derived exosomes also contain RNAs and proteins specific for prostate cancer (e.g. PCA3 and TMPRSS2-ERG), and could be promising sources of novel biomarker discovery. The ExoDx Prostate test is a commercially available test based on the detection of three genes (PCA3, ERG and SPDEF) in urinary exosomes. Advancement of comprehensive analysis (microarray, mass spectrometry and next-generation sequencing) has resulted in the discovery of several urinary biomarkers. Non-invasive urinary markers can help in the decision to carry out prostate biopsy or in the design of a therapeutic strategy.

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“…). The SelectMDx score was also associated with multiparametric magnetic resonance imaging outcomes and outperformed the PCA3 test …”

Section: Ergmentioning

confidence: 99%

Urinary biomarkers of prostate cancer

2018

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“…Thus, the authors suggested that this urine test could serve as a urine‐based molecular marker of SPCa and be used to triage men with a clinical suspicion of PCa. Similar studies have been reported for other urine‐based markers, such as the one included in the commercially available SelectMDx test . Nevertheless, in the current study tissue‐based mRNA biomarkers were applied with the aim of improving risk stratification of men undergoing SB.…”

Section: Discussionmentioning

confidence: 60%

Prostate Cancer Risk Stratification in Men With a Clinical Suspicion of Prostate Cancer Using a Unique Biparametric MRI and Expression of 11 Genes in Apparently Benign Tissue: Evaluation Using Machine‐Learning Techniques

Perez

Jambor

Pahikkala

et al. 2019

Magnetic Resonance Imaging

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Background: Accurate risk stratification of men with a clinical suspicion of prostate cancer (cSPCa) remains challenging despite the increasing use of MRI. Purpose: To evaluate the diagnostic accuracy of a unique biparametric MRI protocol (IMPROD bpMRI) combined with clinical and molecular markers in men with cSPCa. Study Type: Prospective single-institutional clinical trial (NCT01864135). Subjects: Eighty men with cSPCa. Field Strength/Sequence: 3T, surface array coils. Two T 2 -weighted and three diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm 2 ; 2) b-values 0,1500 s/mm 2 ; 3) b-values 0, 2000 s/mm 2 . Assessment: IMPROD bpMRI examinations were qualitatively (IMPROD bpMRI Likert score) and quantitatively (DWI-based Gleason grade score) prospectively reported. Men with IMPROD bpMRI Likert 3-5 had two targeted biopsies followed by 12-core systematic biopsies (SB); those with IMPROD bpMRI Likert 1-2 had only SB. Additionally, 2-core from normalappearing prostate areas were obtained for the mRNA expression of ACSM1, AMACR, CACNA1D, DLX1, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 measured by quantitative reverse-transcription polymerase chain reaction. Statistical Tests: Univariate and multivariate analysis using regularized least-squares, feature selection and tournament leave-pair-out cross-validation (TLPOCV), as well as 10 random splits of the data in training-testing sets, were used to evaluate the mRNA, clinical and IMPROD bpMRI parameters in detecting clinically significant prostate cancer (SPCa) defined as Gleason score ≥ 3 + 4. The evaluation metric was the area under the curve (AUC). Results: IMPROD bpMRI Likert demonstrated the highest TLPOCV AUC of 0.92. The tested clinical variables had AUC 0.56-0.73, while the mRNA and additional IMPROD bpMRI parameters had AUC 0.50-0.67 and 0.65-0.89 respectively.View this article online at wileyonlinelibrary.com.

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“…Haese recently reported in systematic sextant biopsies patients that HOXC6 and DLX1 measurements improved the calibration of the model, compared to the clinical risk factors alone. The net benefit of the biomarkers was mainly observed for low-risk situations [15]-a condition shown by Hendricks to be most prevalent in low PI-RADS scores [6]. However, in this series, only a minority was imaged prior to biopsies and none received IGB, thereby questioning the practical value of this observation.…”

Section: Discussionmentioning

confidence: 71%

“…This proprietary model of prediction combines biomarker expressions in prostatic epithelium with clinical risk factors and was recently mentioned in the EAU guidelines to avoid unnecessary biopsies. Hendriks reported a strong correlation with MRIs secondarily performed for persistent clinical suspicion or for cancer staging-a double-edged result as it simultaneously vindicated MDx-2 as a proxy for significant cancer that constitutes the bulk of PI-RADS scores 4 and 5, but also questioned the value that it might have retained in the reverse situation of upfront MRI [6].…”

Section: Introductionmentioning

confidence: 99%

Independent Evaluation of the Respective Predictive Values for High-Grade Prostate Cancer of Clinical Information and RNA Biomarkers after Upfront MRI and Image-Guided Biopsies

Roumiguié¹,

Ploussard²,

Nogueira

et al. 2020

Cancers

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Upfront MRI is taking the lead in the diagnosis of clinically significant prostate cancer, while few image-guided biopsies (IGBs) fail to demonstrate clinically significant prostate cancer. The added value of innovative biomarkers is not confirmed in this context. We analysed SelectMDx-v2 (MDx-2) in a cohort of upfront MRI and image-guided biopsy patients. Participants included patients who received a trans-rectal elastic-fusion registration IGB on the basis of DRE, PSA, PCA3, and PCPT-2.0 risk evaluation. Pre-biopsy MRI DICOM archives were reviewed according to PI-RADS-v2. Post-massage first-void urine samples stored in the institutional registered bio-repository were commercially addressed to MDxHealth to obtain MDx-2 scores. Univariate and multivariate analyses were conducted with the detection on IGB of high-grade (ISUP 2 and higher) as the dependent variable. High-grade cancer was demonstrated in 32/117 (27.4%) patients (8/2010–8/2018). Age, prostate volume, biopsy history, MDx-2, and PI-RADS-v2 scores significantly related to the detection of high-grade cancer. MDx-2 scores and the clinical variables embedded into MDx-2 scores were analysed in multivariate analysis to complement PI-RADS-v2 scores. The two combinations outperformed PI-RADS-v2 alone (AUC-ROC 0.67 vs. 0.73 and 0.80, respectively, p < 0.05) and calibration curves confirmed an adequate prediction. Similar discrimination (C-statistics, p = 0.22) was observed in the prediction of high-grade cancer, thereby questioning the respective inputs and added values of biomarkers and clinical predictors in MDx-2 scores. Based on the results of this study, we can conclude that instruments of prediction developed for systematic prostate biopsies, including those that incorporate innovative biomarkers, must be reassessed and eventually confirmed in the context of upfront MRI and IGB.

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A urinary biomarker‐based risk score correlates with multiparametric MRI for prostate cancer detection

Cited by 66 publications

References 21 publications

Urinary biomarkers of prostate cancer

Urinary biomarkers of prostate cancer

Prostate Cancer Risk Stratification in Men With a Clinical Suspicion of Prostate Cancer Using a Unique Biparametric MRI and Expression of 11 Genes in Apparently Benign Tissue: Evaluation Using Machine‐Learning Techniques

Independent Evaluation of the Respective Predictive Values for High-Grade Prostate Cancer of Clinical Information and RNA Biomarkers after Upfront MRI and Image-Guided Biopsies

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