Longitudinal prostate-specific antigen reference ranges: Choosing the underlying model of age-related changes

Stat Methods Med Res. 2016 Oct;25(5):1875-1891. doi: 10.1177/0962280213503928. Epub 2013 Oct 9.


Serial measurements of prostate-specific antigen (PSA) are used as a biomarker for men diagnosed with prostate cancer following an active monitoring programme. Distinguishing pathological changes from natural age-related changes is not straightforward. Here, we compare four approaches to modelling age-related change in PSA with the aim of developing reference ranges for repeated measures of PSA. A suitable model for PSA reference ranges must satisfy two criteria. First, it must offer an accurate description of the trend of PSA on average and in individuals. Second, it must be able to make accurate predictions about new PSA observations for an individual and about the entire PSA trajectory for a new individual.

Keywords: fractional polynomials; functional principal components; linear mixed models; longitudinal data; prostate-specific antigen; regression splines.

MeSH terms

  • Aged
  • Aging / blood*
  • Humans
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / pathology
  • Reference Values


  • Prostate-Specific Antigen