title: Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy after Radical Prostatectomy.
abstract: Despite salvage radiation therapy (SRT) for recurrent prostate cancer (PCa) after radical prostatectomy (RP), some patients still progress to metastases. Identifying these men would allow them to undergo systemic therapy including testing novel therapies to reduce metastases risk.
  
  
  
  To test whether the genomic classifier (GC) predicts development of metastatic disease.
  
  
  
  Retrospective multi-center and multi-ethnic cohort study from two academic centers and one Veterans Affairs Medical Center in the United States involving 170 men receiving SRT for recurrent PCa post-RP.
  
  
  
  Time from SRT to development of metastatic disease tested using Cox regression, survival c-index, and decision curve analysis. Performance of GC was compared to the Cancer of the Prostate Risk Assessment Score and Briganti risk models based on these metrics.
  
  
  
  With a median 5.7 yr follow-up after SRT, 20 patients (12%) developed metastases. On multivariable analysis, for each 0.1 unit increase in GC (scaled from 0 to 1), the hazard ratio for metastasis was 1.58 (95% confidence interval 1.16-2.17; p=0.002). Adjusting for androgen deprivation therapy did not materially change the results. The c-index for GC was 0.85 (95% confidence interval 0.73-0.88) versus 0.63-0.65 for published clinico-pathologic risk models. The 5-yr cumulative incidence of metastasis post-SRT in patients with low, intermediate, and high GC scores was 2.7%, 8.4%, and 33.1%, respectively (p<0.001).
  
  
  
  While validation in larger, prospectively collected cohorts is required, these data suggest GC is a strong predictor of metastases among men receiving SRT for recurrent PCa post-RP, accurately identifying men who are excellent candidates for systemic therapy due to their very high-risk of metastases.
  
  
  
  Genomic classifier and two clinico-pathologic risk models were evaluated on their ability to predict metastases among men receiving salvage radiation therapy for recurrent prostate cancer. Genomic classifier was able to identify candidates for further therapies due to their very high-risk of metastases.
authors.affiliation: Department of Surgery, Division of Urology, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Surgery Section, Durham Veteran Affairs Medical Center, Durham, NC, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
authors.affiliation: GenomeDx Biosciences Inc., Vancouver, BC, Canada.
authors.forename: Voleak
authors.initials: V
authors.lastname: Choeurng
authors.affiliation: Surgery Section, Durham Veteran Affairs Medical Center, Durham, NC, USA; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Howard
authors.affiliation: Surgery Section, Durham Veteran Affairs Medical Center, Durham, NC, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: De Hoedt
authors.affiliation: GenomeDx Biosciences Inc., Vancouver, BC, Canada.
authors.forename: Marguerite
authors.initials: M
authors.lastname: du Plessis
authors.affiliation: GenomeDx Biosciences Inc., Vancouver, BC, Canada.
authors.forename: Kasra
authors.initials: K
authors.lastname: Yousefi
authors.affiliation: GenomeDx Biosciences Inc., Vancouver, BC, Canada.
authors.forename: Lucia L
authors.initials: LL
authors.lastname: Lam
authors.affiliation: GenomeDx Biosciences Inc., Vancouver, BC, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Buerki
authors.affiliation: San Diego Pathologists Medical Group, San Diego, CA, USA.
authors.forename: Seong
authors.initials: S
authors.lastname: Ra
authors.affiliation: San Diego Pathologists Medical Group, San Diego, CA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Robbins
authors.affiliation: Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Edouard J
authors.initials: EJ
authors.lastname: Trabulsi
authors.affiliation: GenomeDx Biosciences Inc., Vancouver, BC, Canada.
authors.forename: Nikhil L
authors.initials: NL
authors.lastname: Shah
authors.affiliation: Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Firas
authors.initials: F
authors.lastname: Abdollah
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: GenomeDx Biosciences Inc., Vancouver, BC, Canada.
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: Robert.Den@jeffersonhospital.org.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Den
mesh_terms: D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D011379:Prognosis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D016879:Salvage Therapy; D059467:Transcriptome
chemical_list: D000726:Androgen Antagonists
keywords: Genomic classifier; Metastasis; Prognosis; Prostate cancer; Salvage radiation therapy