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

Shea P. Connell (Lead Author), Marcelino Yazbek Hanna, Frank McCarthy, Rachel Hurst, Martyn Webb, Helen Curley, Helen Walker, Robert Mills, Richard Ball, Martin Sanda, Kathryn Pellegrini, Dattatraya Patil, Antoinette Perry, Jack Schalken, Hardev Pandha, Hayley C Whitaker, Nening Dennis, Christine Stuttle, Ian Mills, Ingrid GuldvikChristopher C. Parker, Daniel Brewer, Colin Cooper, Jeremy Clark

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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.
Original languageEnglish
Pages (from-to)609-620
Number of pages12
JournalBJU International
Issue number4
Early online date25 Jun 2019
Publication statusPublished - Oct 2019


  • liquid biopsy
  • biomarker
  • urine
  • active surveillance
  • Prostate Cancer

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