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

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.

Data and Resources

Additional Info

Field Value
Author Connell, Shea P.
Last Updated November 20, 2019, 16:52 (UTC)
Created November 4, 2019, 17:56 (UTC)
Article Host Type publisher
Article Is Open Access true
Article License Type cc-by-nc-nd
Article Version Type publishedVersion
Citation Report https://scite.ai/reports/10.1111/bju.14811
DOI 10.1111/bju.14811
Date Last Updated 2019-09-28T14:04:10.601334
Evidence open (via page says license)
Funder code(s) Masonic Charitable Foundation (); Movember Foundation GAP1 Urine Biomarker Project (); Bob Champion Cancer Trust (); King family (); Andy Ripley Memorial Fund (); Stephen Hargrave Trust ()
Journal Is Open Access false
Open Access Status hybrid
PDF URL https://onlinelibrary.wiley.com/doi/epdf/10.1111/bju.14811
Publisher URL https://doi.org/10.1111/bju.14811