title: Comparative effectiveness review: prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer.
abstract: OBJECTIVE
  We compared the effectiveness of PCA3 (prostate cancer antigen 3) and select comparators for improving initial or repeat biopsy decision making in men at risk for prostate cancer, or treatment choices in men with prostate cancer.
  
  
  METHODS
  MEDLINE®, EMBASE®, Cochrane Database and gray literature were searched from January 1990 through May 2012. Included studies were matched, and measured PCA3 and comparator(s) within a cohort. No matched analyses were possible. Differences in independent performance estimates between PCA3 and comparators were computed within studies. Studies were assessed for quality using QUADAS (Quality Assessment of Diagnostic Accuracy Studies) and for strength of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.
  
  
  RESULTS
  Among 1,556 publications identified, 34 observational studies were analyzed (24 addressed diagnostic accuracy and 13 addressed treatment decisions). Most studies were conducted in opportunistic cohorts of men referred for procedures and were not designed to answer key questions. Two study biases (partial verification and sampling) were addressed by analyses, allowing some conclusions to be drawn. PCA3 was more discriminatory than total prostate specific antigen increases (eg at an observed 50% specificity, summary sensitivities were 77% and 57%, respectively). Analyses indicated that this finding holds for initial and repeat biopsies, and that the markers were independent predictors. For all other biopsy decision making comparisons and associated health outcomes, strength of evidence was insufficient. For treatment decision making, strength of evidence was insufficient for all outcomes and comparators.
  
  
  CONCLUSIONS
  PCA3 had a higher diagnostic accuracy than total prostate specific antigen increases, but strength of evidence was low (limited confidence in effect estimates). Strength of evidence was insufficient to conclude that PCA3 testing leads to improved health outcomes. For all other outcomes and comparators, strength of evidence was insufficient.
authors.affiliation: Department of Pathology and Laboratory Medicine, Women & Infants Hospital/Alpert Medical School of Brown University, Providence, Rhode Island, USA. lbradley@ipmms.org
authors.forename: Linda A
authors.initials: LA
authors.lastname: Bradley
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
authors.forename: Steven
authors.initials: S
authors.lastname: Gutman
authors.forename: David
authors.initials: D
authors.lastname: Samson
authors.forename: Naomi
authors.initials: N
authors.lastname: Aronson
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C479341:prostate cancer antigen 3, human
keywords: CER; EVN; FPR; KQ; PCA3; PSA; PSAD; SOE; TEP; Technical Expert Panel; biopsy; cPSA; comparative effectiveness research; comparative effectiveness review; complexed prostate specific antigen; externally validated nomogram; fPSA; false-positive rate; free prostate specific antigen; key question; predictive value of tests; prostate cancer antigen 3; prostate cancer antigen 3, human; prostate specific antigen; prostate specific antigen density; prostatic neoplasms; strength of evidence; tPSA; total prostate specific antigen