A Four-Group Urine Risk Classifier For Predicting Outcome In Prostate Cancer Patients

Connell, Shea P, Yazbek Hanna, Marcelino, McCarthy, Frank, Hurst, Rachel, Webb, Martyn, Curley, Helen, Walker, Helen, Mills, Robert, Ball, Richard, Sanda, Martin, Pellegrini, Kathryn, Patil, Dattatraya, Perry, Antoinette, Schalken, Jack, Pandha, Hardev, Whitaker, Hayley C, Dennis, Nening, Stuttle, Christine, Mills, Ian, Guldvik, Ingrid, Parker, Christopher C, Brewer, Daniel, Cooper, Colin and Clark, Jeremy (2019) A Four-Group Urine Risk Classifier For Predicting Outcome In Prostate Cancer Patients. BJU International, 124 (4). pp. 609-620. ISSN 1464-4096

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Abstract

Objectives: To develop a risk classifier using urine-derived extracellular vesicle RNA (UEV-RNA) capable of providing diagnostic information of disease status prior to biopsy, and prognostic information for men on active surveillance (AS). Patients and Methods: Post-digital rectal examination UEV-RNA expression profiles from urine (n = 535, multiple centres) were interrogated with a curated NanoString panel. A LASSO-based Continuation-Ratio model was built to generate four Prostate-Urine-Risk (PUR) signatures for predicting the probability of normal tissue (PUR-1), D’Amico Low-risk (PUR-2), Intermediate-risk (PUR-3), and High-risk (PUR-4) PCa. This model was applied to a test cohort (n = 177) for diagnostic evaluation, and to an AS sub-cohort (n = 87) for prognostic evaluation. Results: Each PUR signature was significantly associated with its corresponding clinical category (p<0.001). PUR-4 status predicted the presence of clinically significant Intermediate or High-risk disease, AUC = 0.77 (95% CI: 0.70–0.84). Application of PUR provided a net benefit over current clinical practice. In an AS sub-cohort (n=87), groups defined by PUR status and proportion of PUR-4 had a significant association with time to progression (p<0.001; IQR HR = 2.86, 95% CI:1.83–4.47). PUR4, when utilised continuously, dichotomised patient groups with differential progression rates of 10% and 60% five years post-urine collection (p<0.001, HR = 8.23, 95% CI:3.26–20.81). Conclusion: UEV-RNA can provide diagnostic information of aggressive PCa prior to biopsy, and prognostic information for men on AS. PUR represents a new & versatile biomarker that could result in substantial alterations to current treatment of PCa patients.

Item Type: Article
Uncontrolled Keywords: liquid biopsy,biomarker,urine,active surveillance,prostate cancer
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Depositing User: LivePure Connector
Date Deposited: 23 May 2019 10:30
Last Modified: 11 Jun 2020 01:08
URI: https://ueaeprints.uea.ac.uk/id/eprint/71107
DOI: 10.1111/bju.14811

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