title: Systematic Review and Meta-analysis of Factors Determining Change to Radical Treatment in Active Surveillance for Localized Prostate Cancer.
abstract: BACKGROUND
  Many men with clinically localized prostate cancer are being monitored as part of active surveillance (AS) programs, but little is known about reasons for receiving radical treatment.
  
  
  OBJECTIVE
  A systematic review of the evidence about AS was undertaken, with a meta-analysis to identify predictors of radical treatment.
  
  
  METHODS
  A comprehensive search of the Embase, MEDLINE and Web of Knowledge databases to March 2014 was performed. Studies reporting on men with localized prostate cancer followed by AS or monitoring were included. AS was defined where objective eligibility criteria, management strategies, and triggers for clinical review or radical treatment were reported.
  
  
  RESULTS
  The 26 AS cohorts included 7627 men, with a median follow-up of 3.5 yr (range of medians 1.5-7.5 yr). The cohorts had a wide range of inclusion criteria, monitoring protocols, and triggers for radical treatment. There were eight prostate cancer deaths and five cases of metastases in 24,981 person-years of follow-up. Each year, 8.8% of men (95% confidence interval 6.7-11.0%) received radical treatment, most commonly because of biopsy findings, prostate-specific antigen triggers, or patient choice driven by anxiety. Studies in which most men changed treatment were those including only low-risk Gleason score 6 disease and scheduled rebiopsies.
  
  
  CONCLUSIONS
  The wide variety of AS protocols and lack of robust evidence make firm conclusions difficult. Currently, patients and clinicians have to make judgments about the balance of risks and benefits in AS protocols. The publication of robust evidence from randomized trials and longer-term follow-up of cohorts is urgently required.
  
  
  RESULTS
  We reviewed 26 studies of men on active surveillance for prostate cancer. There was evidence that studies including men with the lowest risk disease and scheduled rebiopsy had higher rates of radical treatment.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK. Electronic address: andrew.simpkin@bristol.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Simpkin
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Tilling
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK; NIHR Bristol Nutrition Biomedical Research Unit, University of Bristol, Bristol, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: J Athene
authors.initials: JA
authors.lastname: Lane
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: Guy's Hospital, London, UK.
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.affiliation: Cancer Research UK, Cambridge Research Institute, Cambridge, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Metcalfe
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
mesh_terms: D001706:Biopsy; D018450:Disease Progression; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011467:Prostate / Q000473:pathology* / Q000601:surgery*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery* / Q000628:therapy; D012307:Risk Factors; D057832:Watchful Waiting
chemical_list: D017430:Prostate-Specific Antigen
keywords: Active monitoring; Active surveillance; Conservative management; Deferred treatment; Expectant management; Localized prostate cancer; Meta-analysis; Prostatic neoplasms; Systematic review; Watchful waiting