Ability of a Genomic Classifier to Predict Metastasis and Prostate Cancer-specific Mortality after Radiation or Surgery based on Needle Biopsy Specimens

Eur Urol. 2017 Nov;72(5):845-852. doi: 10.1016/j.eururo.2017.05.009. Epub 2017 May 19.

Abstract

Background: Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP).

Objective: To evaluate the ability of biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT).

Design, setting, and participants: Two hundred and thirty-five patients treated with either RP (n=105) or RT±androgen deprivation therapy (n=130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers. The highest-grade core was sampled and Decipher was calculated based on a locked random forest model.

Outcome measurements and statistical analysis: Metastasis and PCSM were the primary and secondary outcomes of the study, respectively. Cox analysis and c-index were used to evaluate the performance of Decipher.

Results and limitations: With a median follow-up of 6 yr among censored patients, 34 patients developed metastases and 11 died of prostate cancer. On multivariable analysis, biopsy Decipher remained a significant predictor of metastasis (hazard ratio: 1.37 per 10% increase in score, 95% confidence interval [CI]: 1.06-1.78, p=0.018) after adjusting for clinical variables. For predicting metastasis 5-yr post-biopsy, Cancer of the Prostate Risk Assessment score had a c-index of 0.60 (95% CI: 0.50-0.69), while Cancer of the Prostate Risk Assessment plus biopsy Decipher had a c-index of 0.71 (95% CI: 0.60-0.82). National Comprehensive Cancer Network risk group had a c-index of 0.66 (95% CI: 0.53-0.77), while National Comprehensive Cancer Network plus biopsy Decipher had a c-index of 0.74 (95% CI: 0.66-0.82). Biopsy Decipher was a significant predictor of PCSM (hazard ratio: 1.57 per 10% increase in score, 95% CI: 1.03-2.48, p=0.037), with a 5-yr PCSM rate of 0%, 0%, and 9.4% for Decipher low, intermediate, and high, respectively.

Conclusions: Biopsy Decipher predicted metastasis and PCSM from diagnostic biopsy specimens of primarily intermediate- and high-risk men treated with first-line RT or RP.

Patient summary: Biopsy Decipher predicted metastasis and prostate cancer-specific mortality risk from diagnostic biopsy specimens.

Keywords: Biopsy; Genomics; Metastasis; Prostate cancer-specific mortality.

Publication types

  • Evaluation Study
  • Multicenter Study

MeSH terms

  • Aged
  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Biopsy, Needle
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / genetics
  • Bone Neoplasms / secondary
  • Chemoradiotherapy* / adverse effects
  • Chemoradiotherapy* / mortality
  • Databases, Factual
  • Feasibility Studies
  • Gene Expression Profiling / methods*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phenotype
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prostatectomy* / adverse effects
  • Prostatectomy* / mortality
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Risk Factors
  • Tertiary Care Centers
  • Time Factors
  • Transcriptome
  • Treatment Outcome
  • United States

Substances

  • Androgen Antagonists
  • Biomarkers, Tumor