title: Longitudinal screening algorithm that incorporates change over time in CA125 levels identifies ovarian cancer earlier than a single-threshold rule.
abstract: OBJECTIVE
  Longitudinal algorithms incorporate change over time in biomarker levels to individualize screening decision rules. Compared with a single-threshold (ST) rule, smaller deviations from baseline biomarker levels are required to signal disease. We demonstrated improvement in ovarian cancer early detection by using a longitudinal algorithm to monitor annual CA125 levels.
  
  
  METHODS
  We retrospectively evaluated serial preclinical serum CA125 values measured annually in 44 incident ovarian cancer cases identified from participants in the PLCO (Prostate Lung Colorectal and Ovarian) Cancer Screening Trial to determine how frequently and to what extent the parametric empirical Bayes (PEB) longitudinal screening algorithm identifies ovarian cancer earlier than an ST rule.
  
  
  RESULTS
  The PEB algorithm detected ovarian cancer earlier than an ST rule in a substantial proportion of cases. At 99% specificity, which corresponded to the ST-rule CA125 cutoff ≥ 35 U/mL that was used in the PLCO trial, 20% of cases were identified earlier by using the PEB algorithm. Among these cases, the PEB signaled abnormal CA125 values, on average, 10 months earlier and at a CA125 concentration 42% lower (20 U/mL) than the ST-rule cutoff. The proportion of cases detected earlier by the PEB algorithm and the earliness of detection increased as the specificity of the screening rule was reduced.
  
  
  CONCLUSIONS
  The PEB longitudinal algorithm identifies ovarian cancer earlier and at lower biomarker concentrations than an ST screening algorithm adjusted to the same specificity. Longitudinal biomarker assessment by using the PEB algorithm may have application for screening other solid tumors in which biomarkers are available.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M2-B230, Seattle, WA 98104, USA. cdresche@fhcrc.org
authors.forename: Charles W
authors.initials: CW
authors.lastname: Drescher
authors.forename: Chirag
authors.initials: C
authors.lastname: Shah
authors.forename: Jason
authors.initials: J
authors.lastname: Thorpe
authors.forename: Kathy
authors.initials: K
authors.lastname: O'Briant
authors.forename: Garnet L
authors.initials: GL
authors.lastname: Anderson
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.forename: Nicole
authors.initials: N
authors.lastname: Urban
authors.forename: Martin W
authors.initials: MW
authors.lastname: McIntosh
mesh_terms: D000368:Aged; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D018394:CA-125 Antigen / Q000032:analysis* / Q000097:blood; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008565:Membrane Proteins / Q000032:analysis* / Q000097:blood; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins