title: Predictors of histological disease progression in untreated, localized prostate cancer.
abstract: OBJECTIVE
  Active surveillance for early prostate cancer is a policy of close monitoring with radical treatment targeted at cases with evidence of disease progression. There is no consensus on the need for or optimum timing of repeat biopsies as part of active surveillance.
  
  
  METHODS
  In a prospective cohort study of active surveillance 119 patients with untreated localized prostate cancer (T1/2a), prostate specific antigen less than 15 ng/ml, Gleason score 3 + 4 or less and 50% or less positive cores underwent repeat biopsy after 18 to 24 months. Histological disease progression was defined as primary Gleason grade 4 or greater, greater than 50% positive cores or a Gleason score increase from 6 or less to 7 or greater. The risk of histological disease progression was analyzed with respect to baseline clinical factors.
  
  
  RESULTS
  Median patient age was 66 years and median initial prostate specific antigen was 6.6 ng/ml. Histological disease progression was seen in 33 of 119 cases (28%). On multivariate analysis prostate specific antigen density (p = 0.002) and maximum percent involvement of any core (p = 0.04) were significant independent determinants of histological disease progression. Progression was seen in 22 of 40 cases (55%) with prostate specific antigen density 0.2 ng/ml/ml or greater and greater than 15% maximum involvement of any core. Progression was seen in 2 of 33 cases (6%) with prostate specific antigen density less than 0.2 ng/ml/ml and 15% or less maximum involvement of any core.
  
  
  CONCLUSIONS
  Repeat biopsy should be an integral part of active surveillance for untreated localized prostate cancer. Immediate repeat biopsy should be considered in patients who elect active surveillance but who have prostate specific antigen density greater than 0.2 ng/ml/ml. These findings must be validated in a cohort of patients with extended biopsies at diagnosis and followup.
authors.affiliation: Academic Unit of Radiotherapy and Oncology, Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust, Sutton, United Kingdom.
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Venkitaraman
authors.forename: Andrew
authors.initials: A
authors.lastname: Norman
authors.forename: Ruth
authors.initials: R
authors.lastname: Woode-Amissah
authors.forename: Cyril
authors.initials: C
authors.lastname: Fisher
authors.forename: David
authors.initials: D
authors.lastname: Dearnaley
authors.forename: Alan
authors.initials: A
authors.lastname: Horwich
authors.forename: Robert
authors.initials: R
authors.lastname: Huddart
authors.forename: Vincent
authors.initials: V
authors.lastname: Khoo
authors.forename: Alan
authors.initials: A
authors.lastname: Thompson
authors.forename: Chris
authors.initials: C
authors.lastname: Parker
mesh_terms: D000368:Aged; D001707:Biopsy, Needle; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy
chemical_list: D017430:Prostate-Specific Antigen