EPS Biomarkers Improve Stratification of NCCN Active Surveillance Candidates: Performance of Secretion Capacity and TMPRSS2:ERG Models

Purpose—Active surveillance (AS) is a viable patient option for prostate cancer where a clinical determination of low-risk and presumably organ-confined disease can be made. In an effort to standardize risk stratification schemes, the National Comprehensive Cancer Network (NCCN) has provided guidelines for the AS option. Our purpose was to determine the effectiveness of expressed prostatic secretion (EPS) biomarkers in detecting occult risk factors in NCCN AS candidates. Materials and Methods—EPS specimens were obtained prior to Robot-Assisted Radical Prostatectomy (RARP). Secretion capacity biomarkers: total RNA and EPS specimen volume were measured by standard techniques. RNA expression biomarkers: TXNRD1-mRNA, PSAmRNA, TMPRSS2:ERG fusion mRNA and PCA3-mRNAs were measured by quantitative reverse-transcription PCR. Results—Of the 528 patients from whom EPS was collected, 216 were eligible for AS under NCCN guidelines. Variable Selection in logistic regression identified two models, one featuring Type III and Type VI TMPRSS2:ERG variants, and one featuring two secretion capacity biomarkers. Of the two high performing models, the secretion capacity model was the most effective in detecting patients within this group that were upstaged or both upstaged and upgraded. It reduced the risk of upstaging in patients with a negative test by nearly 8 fold, and reduced the risk of being both upstaged and upgraded by about 5 fold, while doubling the prevalence upstaging in the positive test group. Conclusions—Non-invasive EPS testing may improve patient acceptance of AS by dramatically reducing the presence of occult risk factors among patients eligible for AS under NCCN guidelines. © 2013 American Urological Association. Published by Elsevier Inc. All rights reserved. Corresponding Author: Steven S. Smith, Ph.D., City of Hope, Familian Science Bldg, Room 1100, 1500 E. Duarte Road, Duarte CA, USA, Phone: (626) 301-8316, Fax: (626) 256-8774, ssmith@coh.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript J Urol. Author manuscript; available in PMC 2015 January 01. Published in final edited form as: J Urol. 2014 January ; 191(1): 220–226. doi:10.1016/j.juro.2013.05.019. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript