title: Active surveillance for prostate cancer: a systematic review of clinicopathologic variables and biomarkers for risk stratification.
abstract: BACKGROUND
  Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated.
  
  
  OBJECTIVE
  To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS.
  
  
  METHODS
  Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS.
  
  
  RESULTS
  Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up.
  
  
  CONCLUSIONS
  There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future.
  
  
  RESULTS
  Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way.
authors.affiliation: Department of Urology, New York University and the Manhattan Veterans Affairs Hospital, New York, NY, USA.
authors.forename: Stacy
authors.initials: S
authors.lastname: Loeb
authors.affiliation: Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Bruinsma
authors.affiliation: Health Sciences Library, New York University, New York, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Nicholson
authors.affiliation: Division of Oncology, Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: BC Cancer Agency Radiation Therapy Program, BC Cancer Agency, Vancouver Centre, Vancouver, Canada; University of British Columbia, Vancouver, BC, Canada.
authors.forename: Tom
authors.initials: T
authors.lastname: Pickles
authors.affiliation: Department of Urology, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kakehi
authors.affiliation: Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Sigrid V
authors.initials: SV
authors.lastname: Carlsson
authors.affiliation: Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands. Electronic address: m.roobol@erasmusmc.nl.
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood; D001706:Biopsy; D018450:Disease Progression; D006801:Humans; D008297:Male; D050596:Oncogene Fusion; D011159:Population Surveillance / Q000379:methods*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology* / Q000503:physiopathology; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000097:blood
chemical_list: D000951:Antigens, Neoplasm; C479341:prostate cancer antigen 3, human; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; D017430:Prostate-Specific Antigen
keywords: Active surveillance; Genetic markers; Nomogram; PSA; Prostate cancer; Risk stratification; Treatment