title: Active surveillance for low-risk prostate cancer worldwide: the PRIAS study.
abstract: BACKGROUND
  Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa.
  
  
  OBJECTIVE
  To update our experience in the largest worldwide prospective AS cohort.
  
  
  METHODS
  Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤ 10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤ 6. PSA was measured every 3-6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification.
  
  
  METHODS
  Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy-free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time.
  
  
  CONCLUSIONS
  In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS.
  
  
  CONCLUSIONS
  Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized.
  
  
  BACKGROUND
  The current program is registered at the Dutch Trial Register with ID NTR1718 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718).
authors.affiliation: Department of Urology, Erasmus MC, Rotterdam, The Netherlands. m.bul@erasmusmc.nl
authors.forename: Meelan
authors.initials: M
authors.lastname: Bul
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Zhu
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdagni
authors.forename: Tom
authors.initials: T
authors.lastname: Pickles
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kakehi
authors.forename: Antti
authors.initials: A
authors.lastname: Rannikko
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.forename: Deric K
authors.initials: DK
authors.lastname: van der Schoot
authors.forename: Erik B
authors.initials: EB
authors.lastname: Cornel
authors.forename: Giario N
authors.initials: GN
authors.lastname: Conti
authors.forename: Egbert R
authors.initials: ER
authors.lastname: Boevé
authors.forename: Frédéric
authors.initials: F
authors.lastname: Staerman
authors.forename: Jenneke J
authors.initials: JJ
authors.lastname: Vis-Maters
authors.forename: Henk
authors.initials: H
authors.lastname: Vergunst
authors.forename: Joris J
authors.initials: JJ
authors.lastname: Jaspars
authors.forename: Petra
authors.initials: P
authors.lastname: Strölin
authors.forename: Erik
authors.initials: E
authors.lastname: van Muilekom
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Schröder
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D062665:Epidemiological Monitoring; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000628:therapy; D012306:Risk; D015996:Survival Rate