title: Utilization of biopsy-based genomic classifier to predict distant metastasis after definitive radiation and short-course ADT for intermediate and high-risk prostate cancer.
abstract: We examined the ability of a biopsy-based 22-marker genomic classifier (GC) to predict for distant metastases after radiation and a median of 6 months of androgen deprivation therapy (ADT).
  
  
  
  We studied 100 patients with intermediate-risk (55%) and high-risk (45%) prostate cancer who received definitive radiation plus a median of 6 months of ADT (range 3-39 months) from 2001-2013 at a single center and had available biopsy tissue. Six to ten 4 micron sections of the needle biopsy core with the highest Gleason score and percentage of tumor involvement were macrodissected for RNA extraction. GC scores (range, 0.04-0.92) were determined. The primary end point of the study was time to distant metastasis. Median follow-up was 5.1 years. There were 18 metastases during the study period.
  
  
  
  On univariable analysis (UVA), each 0.1 unit increase in GC score was significantly associated with time to distant metastasis (hazard ratio: 1.40 (1.10-1.84), P=0.006) and remained significant after adjusting for clinical variables on multivariable analysis (MVA) (adjusted hazard ratio: 1.36 (1.04-1.83), P=0.024). The c-index for 5-year distant metastasis was 0.45 (95% confidence interval: 0.27-0.64) for Cancer of the Prostate Risk Assessment score, 0.63 (0.40-0.78) for National Comprehensive Cancer Network (NCCN) risk groups, and 0.76 (0.57-0.89) for the GC score. Using pre-specified GC risk categories, the cumulative incidence of metastasis for GC>0.6 reached 20% at 5 years after radiation (P=0.02).
  
  
  
  We believe this is the first demonstration of the ability of the biopsy-based GC score to predict for distant metastases after definitive radiation and ADT for intermediate- and high-risk prostate cancer. Patients with the highest GC risk (GC>0.6) had high rates of metastasis despite multi-modal therapy suggesting that they could potentially be candidates for treatment intensification and/or enrollment in clinical trials of novel therapy.
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Nguyen
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA, USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Martin
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Choeurng
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Palmer-Aronsten
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Kolisnik
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Beard
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Orio
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Nezolosky
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Chen
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Shin
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: Department of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: F Y
authors.initials: FY
authors.lastname: Feng
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage; D000728:Androgens / Q000235:genetics; D001707:Biopsy, Needle; D003131:Combined Modality Therapy; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000726:Androgen Antagonists; D000728:Androgens