title: Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population.
abstract: OBJECTIVE
  Patients with locally advanced prostate cancer after radical prostatectomy are candidates for secondary therapy. However, this higher risk population is heterogeneous. Many cases do not metastasize even when conservatively managed. Given the limited specificity of pathological features to predict metastasis, newer risk prediction models are needed. We report a validation study of a genomic classifier that predicts metastasis after radical prostatectomy in a high risk population.
  
  
  METHODS
  A case-cohort design was used to sample 1,010 patients after radical prostatectomy at high risk for recurrence who were treated from 2000 to 2006. Patients had preoperative prostate specific antigen greater than 20 ng/ml, Gleason 8 or greater, pT3b or a Mayo Clinic nomogram score of 10 or greater. Patients with metastasis at diagnosis or any prior treatment for prostate cancer were excluded from analysis. A 20% random sampling created a subcohort that included all patients with metastasis. We generated 22-marker genomic classifier scores for 219 patients with available genomic data. ROC and decision curves, competing risk and weighted regression models were used to assess genomic classifier performance.
  
  
  RESULTS
  The genomic classifier AUC was 0.79 for predicting 5-year metastasis after radical prostatectomy. Decision curves showed that the genomic classifier net benefit exceeded that of clinical only models. The genomic classifier was the predominant predictor of metastasis on multivariable analysis. The cumulative incidence of metastasis 5 years after radical prostatectomy was 2.4%, 6.0% and 22.5% in patients with low (60%), intermediate (21%) and high (19%) genomic classifier scores, respectively (p<0.001).
  
  
  CONCLUSIONS
  Results indicate that genomic information from the primary tumor can identify patients with adverse pathological features who are most at risk for metastasis and potentially lethal prostate cancer.
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota. Electronic address: karnes.r@mayo.edu.
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Bergstralh
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
authors.forename: Mercedeh
authors.initials: M
authors.lastname: Ghadessi
authors.forename: Christine
authors.initials: C
authors.lastname: Buerki
authors.forename: Anirban P
authors.initials: AP
authors.lastname: Mitra
authors.forename: Anamaria
authors.initials: A
authors.lastname: Crisan
authors.forename: Nicholas
authors.initials: N
authors.lastname: Erho
authors.forename: Ismael A
authors.initials: IA
authors.lastname: Vergara
authors.forename: Lucia L
authors.initials: LL
authors.lastname: Lam
authors.forename: Rachel
authors.initials: R
authors.lastname: Carlson
authors.forename: Darby J S
authors.initials: DJ
authors.lastname: Thompson
authors.forename: Zaid
authors.initials: Z
authors.lastname: Haddad
authors.forename: Benedikt
authors.initials: B
authors.lastname: Zimmermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Sierocinski
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Triche
authors.forename: Thomas
authors.initials: T
authors.lastname: Kollmeyer
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.forename: Peter C
authors.initials: PC
authors.lastname: Black
authors.forename: George G
authors.initials: GG
authors.lastname: Klee
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
mesh_terms: D015331:Cohort Studies; D023281:Genomics; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology* / Q000601:surgery
keywords: AUC; BCR; CC; ECE; GC; GPSM; GS; Gleason score; Gleason score, preoperative PSA, SVI, SM; MVA; N+; PSA; RP; SM+; SVI; area under ROC curve; biochemical recurrence; clinical only classifier; extracapsular extension; genomic classifier; lymph node involvement; multivariable analysis; ncRNA; neoplasm metastasis; noncoding RNA; positive surgical margin; prognosis; prostate; prostate specific antigen; prostatic neoplasms; radical prostatectomy; seminal vesicle invasion; transcriptome