2020
DOI: 10.1002/pros.23968
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Development of a multivariable risk model integrating urinary cell DNA methylation and cell‐free RNA data for the detection of significant prostate cancer

Abstract: Background Prostate cancer exhibits severe clinical heterogeneity and there is a critical need for clinically implementable tools able to precisely and noninvasively identify patients that can either be safely removed from treatment pathways or those requiring further follow up. Our objectives were to develop a multivariable risk prediction model through the integration of clinical, urine‐derived cell‐free messenger RNA (cf‐RNA) and urine cell DNA methylation data capable of noninvasively detecting significant… Show more

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Cited by 21 publications
(23 citation statements)
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“…ExoGrail was able to accurately predict the presence of significant (Gs ≥ 7) prostate cancer on biopsy with an AUC of 0.89, comparing favourably to other published tests (AUCs for Gs ≥ 7: PUR = 0.77 [ 46 ], ExoMeth = 0.89 [ 23 ], ExoDX Prostate IntelliScore = 0.77 [ 21 ], SelectMDX = 0.78 [ 20 ], epiCaPture Gs ≥ 4 + 3 AUC = 0.73 [ 49 ]). Furthermore, ExoGrail resulted in accurate predictions even when serum PSA levels alone proved inaccurate; patients with a raised PSA but negative biopsy result possessed ExoGrail scores significantly different from both clinically benign patients and those with low-grade Gleason 6 disease, whilst still able to discriminate between more clinically significant Gleason ≥ 7 cancers ( Figure 4 ).…”
Section: Discussionmentioning
confidence: 87%
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“…ExoGrail was able to accurately predict the presence of significant (Gs ≥ 7) prostate cancer on biopsy with an AUC of 0.89, comparing favourably to other published tests (AUCs for Gs ≥ 7: PUR = 0.77 [ 46 ], ExoMeth = 0.89 [ 23 ], ExoDX Prostate IntelliScore = 0.77 [ 21 ], SelectMDX = 0.78 [ 20 ], epiCaPture Gs ≥ 4 + 3 AUC = 0.73 [ 49 ]). Furthermore, ExoGrail resulted in accurate predictions even when serum PSA levels alone proved inaccurate; patients with a raised PSA but negative biopsy result possessed ExoGrail scores significantly different from both clinically benign patients and those with low-grade Gleason 6 disease, whilst still able to discriminate between more clinically significant Gleason ≥ 7 cancers ( Figure 4 ).…”
Section: Discussionmentioning
confidence: 87%
“…Recent analyses, including those presented here, have demonstrated the added value of integrating multiple prognostic biomarkers within the process of fitting risk models for determining patient risk upon an initial biopsy [23,48]. Urine clearly contains a wealth of useful information concerning the disease status of the prostate through the quantification To assess the benefit of adopting these risk models in a clinically relevant population we used data available from the control arm of the CAP study [42] for proportionally resampling the ExoGrail cohort.…”
Section: Discussionmentioning
confidence: 99%
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“…The cfDNA containing ctDNA has been collected after digital rectal examen or at first void One of the most interesting translational research comes from Brikun et al [4,5] . Using cell-free DNA (cfDNA) from urine after digital rectal examen (DRE) or at first void (FV), they demonstrated, using a panel of 19 targets that the number of methylated markers was statistically higher in PCa cases compared to controls, 10 of 19 vs. 3 of 19, respectively.…”
Section: Methylated Biomarkers In Circulating Cell-free Dna From Urinementioning
confidence: 99%