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A four-group urine risk classifier for predicting outcomes in patients with prostate cancer

Connell, Shea P., Yazbek-Hanna, Marcelino, McCarthy, Frank, Hurst, Rachel, Webb, Martyn, Curley, Helen, Walker, Helen, Mills, Rob, Ball, Richard Y., Sanda, Martin G. , Pellegrini, Kathryn L., Patil, Dattatraya, Perry, Antoinette S., Schalken, Jack, Pandha, Hardev, Whitaker, Hayley, Dennis, Nening, Stuttle, Christine, Mills, Ian G., Guldvik, Ingrid, Parker, Chris, Brewer, Daniel S., Cooper, Colin S., Clark, Jeremy, Bapat, Bharati, Bristow, Rob, Doll, Andreas, Clark, Jeremy, Cooper, Colin, Leung, Hing, Mills, Ian, Neal, David, Olivan, Mireia, Pandha, Hardev, Perry, Antoinette, Parker, Chris, Sanda, Martin, Schalken, Jack and Whitaker, Hayley (2019) A four-group urine risk classifier for predicting outcomes in patients with prostate cancer BJU International.

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Abstract

Objectives

To develop a risk classifier using urine‐derived extracellular vesicle (EV)‐RNA capable of providing diagnostic information on disease status prior to biopsy, and prognostic information for men on active surveillance (AS).

Patients and Methods

Post‐digital rectal examination urine‐derived EV‐RNA expression profiles (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) prostate cancer. 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 (area under the curve = 0.77, 95% confidence interval [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 (interquartile range hazard ratio [HR] 2.86, 95% CI 1.83–4.47; P ˂ 0.001). PUR‐4, when used continuously, dichotomized patient groups with differential progression rates of 10% and 60% 5 years after urine collection (HR 8.23, 95% CI 3.26–20.81; P ˂ 0.001).

Conclusion

Urine‐derived EV‐RNA can provide diagnostic information on aggressive prostate cancer prior to biopsy, and prognostic information for men on AS. PUR represents a new and versatile biomarker that could result in substantial alterations to current treatment of patients with prostate cancer.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Connell, Shea P.
Yazbek-Hanna, Marcelino
McCarthy, Frank
Hurst, Rachel
Webb, Martyn
Curley, Helen
Walker, Helen
Mills, Rob
Ball, Richard Y.
Sanda, Martin G.
Pellegrini, Kathryn L.
Patil, Dattatraya
Perry, Antoinette S.
Schalken, Jack
Pandha, Hardev
Whitaker, Hayley
Dennis, Nening
Stuttle, Christine
Mills, Ian G.
Guldvik, Ingrid
Parker, Chris
Brewer, Daniel S.
Cooper, Colin S.
Clark, Jeremy
Bapat, Bharati
Bristow, Rob
Doll, Andreas
Clark, Jeremy
Cooper, Colin
Leung, Hing
Mills, Ian
Neal, David
Olivan, Mireia
Pandha, HardevH.Pandha@surrey.ac.uk
Perry, Antoinette
Parker, Chris
Sanda, Martin
Schalken, Jack
Whitaker, Hayley
Date : 25 June 2019
Funders : Movember Foundation
DOI : 10.1111/bju.14811
Grant Title : GAP1 Urine Biomarker project
Copyright Disclaimer : © 2019 The Authors BJU International Published by John Wiley & Sons Ltd on behalf of BJU International This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Uncontrolled Keywords : Biomarker; Urine; Active surveillance; Liquid biopsy; Cell free; #ProstateCancer; #PCSM
Depositing User : Clive Harris
Date Deposited : 30 Jul 2019 14:17
Last Modified : 30 Jul 2019 14:17
URI: http://epubs.surrey.ac.uk/id/eprint/852330

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