title: Risk stratification and validation of prostate specific antigen density as independent predictor of progression in men with low risk prostate cancer during active surveillance.
abstract: OBJECTIVE
  We assessed risk stratification in patients with low grade prostate cancer managed by active surveillance using a 20-core saturation biopsy technique.
  
  
  METHODS
  A total of 135 consecutive patients with low risk prostate cancer were prospectively entered in an active surveillance program in a 10-year period. The study entrance requirement and progression definition followed Epstein criteria using only pathological parameters, ie fewer than 3 positive cores, Gleason score 6 or less and 50% or less of any single core involved. All patients were monitored by restaging 20-core saturation biopsy every 12 to 18 months. A total of 120 patients with at least 1 rebiopsy form the basis of this report.
  
  
  RESULTS
  Of the cohort 30% progressed during a median of 2.4 years. Three multivariate analyses were performed. The first analysis used variables only at diagnosis biopsy and revealed that prostate specific antigen density greater than 0.08 ng/ml/cc and prostate cancer family history were significant predictors of progression. When combined in a 3-level risk factor score, they were significant (p = 0.003). The second multivariate analysis considered changes in characteristics between diagnosis biopsy and first rebiopsy. Prostate specific antigen velocity along with prostate specific antigen density and family history highly predicted progression according to a 4-level risk factor score (p <0.0001). The third multivariate analysis validated the previously reported prostate specific antigen density cutoff of 0.08 ng/ml/cc at first rebiopsy as a significant predictor of subsequent progression (HR 3.16, 95% CI 1.12, 8.93; p = 0.03).
  
  
  CONCLUSIONS
  Risk factor stratification can be used to significantly predict the outcome in patients on active surveillance. Prostate specific antigen density 0.08 ng/ml/cc at first rebiopsy was validated as a significant predictor of subsequent progression.
authors.affiliation: Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: San Francisco
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Marc B
authors.initials: MB
authors.lastname: Garnick
authors.forename: Glenn
authors.initials: G
authors.lastname: Bubley
authors.forename: William C
authors.initials: WC
authors.lastname: DeWolf
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood*; D001707:Biopsy, Needle; D016001:Confidence Intervals; D018450:Disease Progression; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D018570:Risk Assessment; D013997:Time Factors; D057832:Watchful Waiting / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen