title: The use of multiphase nonlinear mixed models to define and quantify long-term changes in serum prostate-specific antigen: data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
abstract: OBJECTIVE
  To test the hypothesis that the pattern of prostate-specific antigen (PSA) change in men diagnosed with high-risk prostate cancer (PrCA) differs from the pattern evident in men diagnosed with low-risk PrCA or those with no evidence of PrCA.
  
  
  METHODS
  A retrospective cohort study from which PSA measures were taken before PrCA diagnosis from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Data were fitted using a nonlinear regression model to estimate the adjusted absolute and relative (%) change of PSA.
  
  
  RESULTS
  Data on 20,888 men with an average age of 61.61 years were included in the analysis. Of these, the 324 (1.55%) diagnosed with high-risk PrCA had a steeper and earlier transition into an exponential pattern of PSA change than the 1368 men diagnosed with low-risk cancer. At 1 year before diagnosis and/or exit, the average absolute PSA rates were 0.05 ng/mL/year (0.05-0.05), 0.59 (0.52-0.66), and 2.60 (2.11-3.09) for men with no evidence of PrCA, men with low-risk PrCA and those with high-risk PrCA, respectively.
  
  
  CONCLUSIONS
  The pattern of PSA change with time was significantly different for men who develop high-risk PrCA from those diagnosed with low-risk PrCA. Further research is required to validate this method and its utilization in PrCA screening.
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia; Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia. Electronic address: shoaibi@email.sc.edu.
authors.forename: Azza
authors.initials: A
authors.lastname: Shoaibi
authors.affiliation: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia; Department of Family and Preventive Medicine, School of Medicine, University of South Carolina, Columbia.
authors.forename: Gowtham A
authors.initials: GA
authors.lastname: Rao
authors.affiliation: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia.
authors.forename: Bo
authors.initials: B
authors.lastname: Cai
authors.affiliation: Columbia Urological Associates, P.A., Columbia, SC.
authors.forename: John
authors.initials: J
authors.lastname: Rawl
authors.affiliation: South Carolina Statewide Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia; Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia. Electronic address: JHEBERT@mailbox.sc.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Hébert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D055088:Early Detection of Cancer; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012189:Retrospective Studies; D012306:Risk; D012680:Sensitivity and Specificity
chemical_list: D017430:Prostate-Specific Antigen
keywords: High-risk prostate cancer; Mixed-effect model; PSA change rate; PSA growth curves; PSA kinetics; PSA velocity; Prostate cancer detection