title: A Biopsy-based 17-gene Genomic Prostate Score Predicts Recurrence After Radical Prostatectomy and Adverse Surgical Pathology in a Racially Diverse Population of Men with Clinically Low- and Intermediate-risk Prostate Cancer.
abstract: BACKGROUND
  Biomarkers that are validated in independent cohorts are needed to improve risk assessment for prostate cancer (PCa).
  
  
  OBJECTIVE
  A racially diverse cohort of men (20% African American [AA]) was used to evaluate the association of the clinically validated 17-gene Genomic Prostate Score (GPS) with recurrence after radical prostatectomy and adverse pathology (AP) at surgery.
  
  
  METHODS
  Biopsies from 431 men treated for National Comprehensive Cancer Network (NCCN) very low-, low-, or intermediate-risk PCa between 1990 and 2011 at two US military medical centers were tested to validate the association between GPS and biochemical recurrence (BCR) and to confirm the association with AP. Metastatic recurrence (MR) was also evaluated.
  
  
  METHODS
  Cox proportional hazards models were used for BCR and MR, and logistic regression was used for AP. Central pathology review was performed by one uropathologist. AP was defined as primary Gleason pattern 4 or any pattern 5 and/or pT3 disease.
  
  
  CONCLUSIONS
  GPS results (scale: 0-100) were obtained in 402 cases (93%); 62 men (15%) experienced BCR, 5 developed metastases, and 163 had AP. Median follow-up was 5.2 yr. GPS predicted time to BCR in univariable analysis (hazard ratio per 20 GPS units [HR/20 units]: 2.9; p<0.001) and after adjusting for NCCN risk group (HR/20 units: 2.7; p<0.001). GPS also predicted time to metastases (HR/20 units: 3.8; p=0.032), although the event rate was low (n=5). GPS was strongly associated with AP (odds ratio per 20 GPS units: 3.3; p<0.001), adjusted for NCCN risk group. In AA and Caucasian men, the median GPS was 30.3 for both, the distributions of GPS results were similar, and GPS was similarly predictive of outcome.
  
  
  CONCLUSIONS
  The association of GPS with near- and long-term clinical end points establishes the assay as a strong independent measure of PCa aggressiveness. Tumor aggressiveness, as measured by GPS, and outcomes were similar in AA and Caucasian men in this equal-access health care system.
  
  
  RESULTS
  Predicting outcomes in men with newly diagnosed prostate cancer is challenging. This study demonstrates that a new molecular test, the Genomic Prostate Score, which can be performed on a patient's original prostate needle biopsy, can predict the aggressiveness of the cancer and help men make decisions regarding the need for immediate treatment of their cancer.
authors.affiliation: Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Electronic address: jcullen@cpdr.org.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cullen
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: Inger L
authors.initials: IL
authors.lastname: Rosner
authors.affiliation: Madigan Army Medical Center, Tacoma, WA, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Brand
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Athanasios C
authors.initials: AC
authors.lastname: Tsiatis
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Moncur
authors.affiliation: Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Amina
authors.initials: A
authors.lastname: Ali
authors.affiliation: Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Dejan
authors.initials: D
authors.lastname: Knezevic
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Maddala
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: H Jeffrey
authors.initials: HJ
authors.lastname: Lawrence
authors.affiliation: Genomic Health, Inc., Redwood City, CA, USA.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Febbo
authors.affiliation: Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Shiv
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Joint Pathology Center, Silver Spring, MD, USA.
authors.forename: Isabell A
authors.initials: IA
authors.lastname: Sesterhenn
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: McLeod
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D062005:Biopsy, Large-Core Needle; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018570:Risk Assessment; D044465:White People / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor
keywords: Clinical validation; Gene expression; Molecular diagnostic testing; Neoplasm recurrence; Prostate neoplasms