Match!

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

Published on Oct 1, 2019in BJUI4.52
· DOI :10.1111/bju.14811
Shea P. Connell6
Estimated H-index: 6
(UEA: University of East Anglia),
Marcelino Yazbek‐Hanna1
Estimated H-index: 1
(UEA: University of East Anglia)
+ 21 AuthorsJeremy Clark45
Estimated H-index: 45
(UEA: University of East Anglia)
View in Source
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.
  • References (34)
  • Citations (3)
References34
Newest
#1Richard M. Martin (UoB: University of Bristol)H-Index: 102
#2Jenny L Donovan (NIHR: National Institute for Health Research)H-Index: 82
Last.Freddie C. Hamdy (University of Oxford)H-Index: 71
view all 26 authors...
63 CitationsSource
#1Martin G. Sanda (American Urological Association)H-Index: 2
#2Jeffrey A. CadedduH-Index: 66
Last.Jonathan R. TreadwellH-Index: 3
view all 15 authors...
92 CitationsSource
#1Monty A. Aghazadeh (Hartford Hospital)H-Index: 1
#2Jason K Frankel (Hartford Hospital)H-Index: 1
Last.Joseph Wagner (Hartford Hospital)H-Index: 14
view all 7 authors...
6 CitationsSource
#2Dattatraya PatilH-Index: 7
Last.Martin G. SandaH-Index: 20
view all 10 authors...
5 CitationsSource
#1Jonathan S. Brajtbord (UCSF: University of California, San Francisco)H-Index: 9
#2Michael Leapman (UCSF: University of California, San Francisco)H-Index: 12
Last.Matthew R. Cooperberg (UCSF: University of California, San Francisco)H-Index: 55
view all 3 authors...
21 CitationsSource
#1Nicolas MottetH-Index: 31
#2Joaquim Bellmunt (Harvard University)H-Index: 69
Last.Philip CornfordH-Index: 15
view all 22 authors...
847 CitationsSource
#1Bogdan-Alexandru Luca (UEA: University of East Anglia)H-Index: 2
#2Daniel Brewer (UEA: University of East Anglia)H-Index: 25
Last.Colin S. Cooper (UEA: University of East Anglia)H-Index: 58
view all 22 authors...
7 CitationsSource
#1Hashim U. Ahmed (UCL: University College London)H-Index: 46
#2Ahmed El-Shater Bosaily (UCL: University College London)H-Index: 3
Last.Mark Emberton (UCL: University College London)H-Index: 64
view all 14 authors...
604 CitationsSource
#1Leander Van Neste (UM: Maastricht University)H-Index: 28
#2Rianne J. Hendriks (Radboud University Nijmegen)H-Index: 7
Last.Jack A. Schalken (Radboud University Nijmegen)H-Index: 62
view all 20 authors...
83 CitationsSource
#1Kathleen F. Kerr (UW: University of Washington)H-Index: 29
#2Marshall D. Brown (Fred Hutchinson Cancer Research Center)H-Index: 6
Last.Holly Janes (Fred Hutchinson Cancer Research Center)H-Index: 30
view all 4 authors...
40 CitationsSource
Cited By3
Newest
#1John W. Davis (University of Texas MD Anderson Cancer Center)H-Index: 33
Source
#1Robert BublakH-Index: 1
Source
#1Wei Feng (Nantong University)H-Index: 1
#2Ye Ding (Nantong University)
Last.Shaoqing Ju (Nantong University)H-Index: 15
view all 4 authors...
Source