Molecular Analysis of Low Grade Prostate Cancer Using a Genomic Classifier of Metastatic Potential

Eric A. Klein, María Santiago-Jiménez, Kasra Yousefi, Bruce A. Robbins, Edward M. Schaeffer, Bruce J. Trock, Jeffrey Tosoian, Zaid Haddad, Seong Ra, Robert Jeffrey Karnes, Robert Brian Jenkins, John C. Cheville, Robert B. Den, Adam P. Dicker, Elai Davicioni, Stephen J. Freedland, Ashley E. Ross

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Purpose We determined how frequently histological Gleason 3 + 3 = 6 tumors have the molecular characteristics of disease with metastatic potential. Materials and Methods We analyzed prostatectomy tissue from 337 patients with Gleason 3 + 3 disease. All tissue was re-reviewed in blinded fashion by genitourinary pathologists using 2005 ISUP (International Society of Urological Pathology) Gleason grading criteria. A previously validated Decipher® metastasis signature was calculated in each case based on a locked model. To compare patient characteristics across pathological Gleason score categories we used the Fisher exact test or the ANOVA F test. The distribution of Decipher scores among different clinicopathological groups was compared with the Wilcoxon rank sum test. The association of Decipher score with adverse pathology features was examined using logistic regression models. The significance level of all statistical tests was 0.05. Results Of men with Gleason 3 + 3 = 6 disease only 269 (80%) had a low Decipher score with intermediate and high scores in 43 (13%) and 25 (7%), respectively. Decipher scores were significantly higher among pathological Gleason 3 + 3 = 6 specimens from cases with adverse pathological features such as extraprostatic extension, seminal vesicle involvement or positive margins (p <0.001). The median Decipher score in patients with margin negative pT2 disease was 0.23 (IQR 0.09–0.42) compared to 0.30 (IQR 0.17–0.42) in patients with pT3 disease or positive margins (p = 0.005). Conclusions Using a robust and validated prognostic signature we found that a small but not insignificant proportion of histological Gleason 6 tumors harbored molecular characteristics of aggressive cancer. Molecular profiling of such tumors at diagnosis may better select patients for active surveillance at diagnosis and trigger appropriate intervention during followup.

Original languageEnglish (US)
Pages (from-to)122-128
Number of pages7
JournalJournal of Urology
Volume197
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • genomics
  • neoplasm grading
  • neoplasm metastasis
  • prostatic neoplasms
  • watchful waiting

ASJC Scopus subject areas

  • Urology

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