title: Projecting Benefits and Harms of Novel Cancer Screening Biomarkers: A Study of PCA3 and Prostate Cancer.
abstract: BACKGROUND
  New biomarkers for early detection of cancer must pass through several phases of development. Early phases provide information on diagnostic properties but not on population benefits and harms. Prostate cancer antigen 3 (PCA3) is a promising prostate cancer biomarker still in early development. We use simulation modeling to project the impact of adding PCA3 to prostate-specific antigen (PSA) screening on prostate cancer detection and mortality in the United States.
  
  
  METHODS
  We used data from a recent study of PCA3 in men referred for prostate biopsy to extend an existing simulation model of PSA growth, disease progression, and survival. We specified several PSA-PCA3 strategies designed to improve specificity and reduce overdiagnosis. Using these strategies to screen a cohort of men biennially between ages 50 and 74, we projected true- and false-positive tests, overdiagnoses, and lives saved relative to a PSA-based strategy with a cutoff of 4.0 ng/mL for biopsy referral.
  
  
  RESULTS
  We identified several PSA-PCA3 strategies that substantially reduced false-positive tests and overdiagnoses while preserving the majority of lives saved. PCA3>35 for biopsy referral in men with PSA between 4.0 and 10.0 ng/mL retained 85% of lives saved while approximately halving false positives and reducing overdiagnoses by 25%.
  
  
  CONCLUSIONS
  Adding PCA3 to PSA screening can significantly reduce adverse screening outcomes. Strategies can be identified that preserve most of the lives saved relative to PSA-based screening.
  
  
  CONCLUSIONS
  Simulation modeling provides advance projections of population outcomes of new screening biomarkers and may help guide early detection research.
authors.affiliation: Department of Health Services, University of Washington, Seattle, Washington. kurian@uw.edu.
authors.forename: Jeanette K
authors.initials: JK
authors.lastname: Birnbaum
authors.affiliation: MD Anderson Cancer Center, Houston, Texas. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Roman
authors.initials: R
authors.lastname: Gulati
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Urology, UT Southwestern Medical Center at Dallas, Dallas, Texas.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, Michigan.
authors.forename: John T
authors.initials: JT
authors.lastname: Wei
authors.affiliation: Department of Health Services, University of Washington, Seattle, Washington. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Ruth
authors.initials: R
authors.lastname: Etzioni
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D003198:Computer Simulation; D055088:Early Detection of Cancer / Q000379:methods*; D005189:False Positive Reactions; D006801:Humans; D008297:Male; D000069342:Medical Overuse; D008875:Middle Aged; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality; D012680:Sensitivity and Specificity
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C479341:prostate cancer antigen 3, human