Journal article
A four‐group urine risk classifier for predicting outcomes in patients with prostate cancer
- Abstract:
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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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 981.6KB, Terms of use)
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- Publisher copy:
- 10.1111/bju.14811
Authors
- Publisher:
- Wiley
- Journal:
- BJU International More from this journal
- Volume:
- 124
- Issue:
- 4
- Pages:
- 609-620
- Publication date:
- 2019-06-25
- Acceptance date:
- 2019-05-20
- DOI:
- EISSN:
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1464-410X
- ISSN:
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1464-4096
- Pmid:
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31106513
- Language:
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English
- Keywords:
- Pubs id:
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pubs:1000836
- UUID:
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uuid:eeac3071-ec24-4010-8307-4871a70b6a52
- Local pid:
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pubs:1000836
- Source identifiers:
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1000836
- Deposit date:
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2019-05-22
Terms of use
- Copyright holder:
- Connell, SP et al
- Copyright date:
- 2019
- Rights statement:
- © 2019 The Authors BJU International published by John Wiley and 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 anddistribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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