title: Multicenter evaluation of an investigational prostate cancer methylation assay.
abstract: OBJECTIVE
  Prostate specific antigen tests have low specificity, which frequently results in unnecessary biopsy and typically limits screening to patients with prostate specific antigen greater than 4.0 ng/ml. We evaluated an investigational prostate cancer methylation specific polymerase chain reaction assay that detects aberrant methylation in 3 markers (GSTP1, RARbeta2 and APC) that indicate the presence of prostate cancer.
  
  
  METHODS
  The assay was evaluated in 337 post-digital rectal examination urine samples (178 cancer and 159 noncancer) collected prospectively at a total of 9 clinical sites. Samples were processed wholly or after division into equal portions. Subject prostate specific antigen was 2.0 to 10.0 ng/ml. All subjects underwent transrectal ultrasound guided needle biopsy with 6 or greater cores sampled. Detection of 1 or greater markers indicated positivity.
  
  
  RESULTS
  Methylation specific polymerase chain reaction assay performance was better in whole than in divided urine cohorts (p = 0.035). Assay AUC was 0.72 in the whole urine cohort and 0.67 in the combined population. These values were higher than those of prostate specific antigen alone using 4.0 ng/ml as the cutoff (p = 0.00 and 0.01, respectively). Moreover, the assay together with the Prostate Cancer Prevention Trial risk calculator or a standard nomogram significantly improved AUC in the whole urine cohort and the combined population vs predictive algorithms alone (p <0.05). Assay positive predictive value was 54% in whole urine cohort with prostate specific antigen 2.0 to 4.0 ng/ml and negative predictive value was 87% with prostate specific antigen 4.1 to 10.0 ng/ml. Assay positive predictive value was higher in subjects with all 3 methylation markers positive.
  
  
  CONCLUSIONS
  These data demonstrate that this investigational assay used in conjunction with current screening algorithms may potentially add value to the biopsy decision making process.
authors.affiliation: Veridex, LLC, Raritan, New Jersey, USA. jbaden@its.jnj.com
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baden
authors.forename: George
authors.initials: G
authors.lastname: Green
authors.forename: Jennifer
authors.initials: J
authors.lastname: Painter
authors.forename: Katy
authors.initials: K
authors.lastname: Curtin
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Markiewicz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jones
authors.forename: Tara
authors.initials: T
authors.lastname: Astacio
authors.forename: Susan
authors.initials: S
authors.lastname: Canning
authors.forename: Jedidiah
authors.initials: J
authors.lastname: Quijano
authors.forename: Wilson
authors.initials: W
authors.lastname: Guinto
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Leibovich
authors.forename: Joel B
authors.initials: JB
authors.lastname: Nelson
authors.forename: Janet
authors.initials: J
authors.lastname: Vargo
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.forename: Cao
authors.initials: C
authors.lastname: Wuxiong
mesh_terms: D000328:Adult; D000368:Aged; D001681:Biological Assay; D051517:Digital Rectal Examination; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000175:diagnosis*