A Four-Group Urine Risk Classifier for Predicting Outcome in Prostate Cancer Patients

Movember GAP1 Urine Biomarker Consortium

Research output: Contribution to journalArticle

2 Citations (Scopus)

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). PUR-4, 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. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalBJU International
DOIs
Publication statusEarly online date - 20 May 2019

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Prostatic Neoplasms
Urine
Prostate
RNA
Biopsy
Digital Rectal Examination
Urine Specimen Collection
Area Under Curve
Biomarkers

Bibliographical note

This article is protected by copyright. All rights reserved.

Cite this

@article{cf6cad5c3eb64a3db26f2dbb4bd3fa0c,
title = "A Four-Group Urine Risk Classifier for Predicting Outcome in Prostate Cancer Patients",
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). PUR-4, 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. This article is protected by copyright. All rights reserved.",
author = "{Movember GAP1 Urine Biomarker Consortium} and Connell, {Shea P} and Marcel Hanna and Frank McCarthy and Rachel Hurst and Martyn Webb and Helen Curley and Helen Walker and Rob Mills and Ball, {Richard Y} and Sanda, {Martin G} and Pellegrini, {Kathryn L} and Dattatraya Patil and Perry, {Antoinette S} and Jack Schalken and Hardev Pandha and Hayley Whitaker and Nening Dennis and Christine Stuttle and Mills, {Ian G} and Ingrid Guldvik and Chris Parker and Brewer, {Daniel S} and Cooper, {Colin S} and Jeremy Clark",
note = "This article is protected by copyright. All rights reserved.",
year = "2019",
month = "5",
day = "20",
doi = "10.1111/bju.14811",
language = "English",
journal = "BJU International",
issn = "1464-4096",
publisher = "Wiley-Blackwell",

}

A Four-Group Urine Risk Classifier for Predicting Outcome in Prostate Cancer Patients. / Movember GAP1 Urine Biomarker Consortium.

In: BJU International, 20.05.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Four-Group Urine Risk Classifier for Predicting Outcome in Prostate Cancer Patients

AU - Movember GAP1 Urine Biomarker Consortium

AU - Connell, Shea P

AU - Hanna, Marcel

AU - McCarthy, Frank

AU - Hurst, Rachel

AU - Webb, Martyn

AU - Curley, Helen

AU - Walker, Helen

AU - Mills, Rob

AU - Ball, Richard Y

AU - Sanda, Martin G

AU - Pellegrini, Kathryn L

AU - Patil, Dattatraya

AU - Perry, Antoinette S

AU - Schalken, Jack

AU - Pandha, Hardev

AU - Whitaker, Hayley

AU - Dennis, Nening

AU - Stuttle, Christine

AU - Mills, Ian G

AU - Guldvik, Ingrid

AU - Parker, Chris

AU - Brewer, Daniel S

AU - Cooper, Colin S

AU - Clark, Jeremy

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/5/20

Y1 - 2019/5/20

N2 - 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). PUR-4, 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. This article is protected by copyright. All rights reserved.

AB - 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). PUR-4, 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. This article is protected by copyright. All rights reserved.

U2 - 10.1111/bju.14811

DO - 10.1111/bju.14811

M3 - Article

C2 - 31106513

JO - BJU International

JF - BJU International

SN - 1464-4096

ER -