title: The role of treatment modality on the utility of predictive tissue biomarkers in clinical prostate cancer: a systematic review.
abstract: BACKGROUND
  Tissue biomarkers could pivotally improve clinical outcome prediction following prostate cancer therapy. Clinically, prostate cancer is managed by diverse treatment modalities whose individual influence on a biomarker's predictive ability is not well understood and poorly investigated in the literature.
  
  
  OBJECTIVE
  We conducted a systematic review to assess the predictive value of biomarkers in different treatment contexts in prostate cancer.
  
  
  METHODS
  A literature search was performed using the MeSH headings "prostate neoplasms" and "biological markers". Rigorous selection criteria identified studies correlating expression with clinical outcomes from primary androgen deprivation therapy (ADT), radical prostatectomy and radiotherapy (± neoadjuvant ADT).
  
  
  RESULTS
  Of 10,668 studies identified, 481 papers matched initial inclusion criteria. Following rescreening, 384 studies identified 236 individual tissue biomarkers, of which 29 were predictive on multivariate analysis in at least 2 independent cohorts. The majority were only tested in surgical cohorts. Only 8 predictive biomarkers were tested across all 3 treatments with Ki67 identified as universal predictive marker. p16 showed potential for treatment stratification between surgery and radiotherapy but needs further validation in independent studies.
  
  
  CONCLUSIONS
  Despite years of research, very few tissue biomarkers retain predictive value in independent validation across therapy context. Currently, none have conclusive ability to help treatment selection. Future biomarker research should consider the therapy context and use uniform methodology and evaluation criteria.
authors.affiliation: Translational Prostate Cancer Group, Hutchison MRC Research Centre, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK.
authors.forename: Naveen
authors.initials: N
authors.lastname: Kachroo
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Gnanapragasam
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D042501:Angiogenic Proteins / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D017024:Chemotherapy, Adjuvant; D019941:Cyclin-Dependent Kinase Inhibitor p16; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000379:methods; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D018714:Radiotherapy, Adjuvant; D058028:Research Report / Q000592:standards*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D042501:Angiogenic Proteins; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D014157:Transcription Factors