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A four-group urine risk classifier for predicting outcomes in patients with prostate cancer
- Source :
- Bju International, BJU International, 124, 4, pp. 609-620, BJU International, 124, 609-620
- Publication Year :
- 2019
-
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.
- Subjects :
- Oncology
medicine.medical_specialty
Urological Oncology
Urology
030232 urology & nephrology
#PCSM
03 medical and health sciences
Prostate cancer
0302 clinical medicine
All institutes and research themes of the Radboud University Medical Center
Interquartile range
Prostate
Internal medicine
Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15]
medicine
Liquid biopsy
cell free
medicine.diagnostic_test
liquid biopsy
business.industry
Hazard ratio
active surveillance
Rectal examination
Extracellular vesicle
medicine.disease
Confidence interval
urine
medicine.anatomical_structure
#ProstateCancer
030220 oncology & carcinogenesis
biomarker
business
Subjects
Details
- ISSN :
- 14644096
- Volume :
- 124
- Database :
- OpenAIRE
- Journal :
- BJU International
- Accession number :
- edsair.doi.dedup.....3e4af9de272d3452624635c2f52a4055