title: ProPSA and diagnostic biopsy tissue DNA content combination improves accuracy to predict need for prostate cancer treatment among men enrolled in an active surveillance program.
abstract: OBJECTIVE
  To assess a novel application of the Prostate Health Index (phi) and biopsy tissue DNA content in benign-adjacent and cancer areas to predict which patients would eventually require treatment of prostate cancer in the Proactive Surveillance cohort.
  
  
  METHODS
  We identified 71 men who had had serum and biopsy tissue from their diagnosis banked and available for the present study. Of the 71 patients, 39 had developed unfavorable biopsy findings and 32 had maintained favorable biopsy status during surveillance. The serum total prostate-specific antigen (tPSA), free PSA (fPSA) and [-2]proPSA were measured using the Beckman Coulter immunoassay. The DNA content measurements of Feulgen-stained biopsy sections were performed using the AutoCyte imaging system.
  
  
  RESULTS
  The ratio of phi was significantly greater (37.23 ± 15.76 vs 30.60 ± 12.28; P = .03) in men who ultimately had unfavorable biopsy findings. The serum phi ratio (P = .003), [-2]proPSA/%fPSA (P = .004), biopsy tissue DNA content (ie, benign-adjacent excess of optical density, P = .019; and cancer area standard deviation of optical density, P = .002) were significant predictors of unfavorable biopsy conversion on Cox regression analysis. However, phi and [-2]proPSA/%fPSA showed a highly significant correlation (rho = 0.927, P < .0001) and no difference in accuracy (c-index, 0.6247 vs 0.6158; P = .704) for unfavorable biopsy conversion prediction. Furthermore, phi and [-2]proPSA/%fPSA remained significant (P = .047 and P = .036, respectively) in the multivariate models and, combined with the biopsy tissue DNA content, showed improvement in the predictive accuracy (c-index, 0.6908 and 0.6884, respectively) for unfavorable biopsy conversion.
  
  
  CONCLUSIONS
  The Prostate Health Index to proPSA/%fPSA, combined with biopsy tissue DNA content, improved the accuracy to about 70% to predict unfavorable biopsy conversion at the annual surveillance biopsy examination among men enrolled in an Active Surveillance program.
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Isharwal
authors.forename: Danil V
authors.initials: DV
authors.lastname: Makarov
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Sokoll
authors.forename: Patricia
authors.initials: P
authors.lastname: Landis
authors.forename: Cameron
authors.initials: C
authors.lastname: Marlow
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: H Ballentine
authors.initials: HB
authors.lastname: Carter
authors.forename: Robert W
authors.initials: RW
authors.lastname: Veltri
mesh_terms: D000368:Aged; D001707:Biopsy, Needle; D004273:DNA, Neoplasm / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D020033:Protein Isoforms / Q000097:blood; D057832:Watchful Waiting
chemical_list: D004273:DNA, Neoplasm; D020033:Protein Isoforms; D017430:Prostate-Specific Antigen