SERUM PROSTATE-SPECIFIC ANTIGEN IN A COMMUNITY-BASED POPULATION OF HEALTHY-MEN - ESTABLISHMENT OF AGE-SPECIFIC REFERENCE RANGES

Objective.-To define the characteristics of serum prostate-specific an tigen (PSA) in a population of healthy men without clinically evident prostate cancer, but who are at risk for developing the malignancy. Th e influence of patient age and prostatic size on the serum PSA concent ration was assessed in order to use PSA more appropriately to detect c linically significant prostate cancer at an early, potentially curable stage. Design.-Prospective, community-based study. Participants.-Betw een December 1989 and March 1991, 2119 healthy men aged 40 to 79 years from Olmsted County, Minnesota, were entered into a prospective study to assess the natural history of benign prostatic hyperplasia. Of the se, 537 (25%) were randomly chosen to participate in a detailed clinic al examination that included a serum PSA determination (Tandem-R PSA a ssay), digital rectal examination, and transrectal ultrasonography. Fo ur hundred seventy-one (88%) completed the prostatic evaluation and ha d no evidence of prostate cancer by any of these three diagnostic test s; these men formed the study population on which all analyses were pe rformed. Main Outcome Measure.-Serum PSA concentration, prostatic volu me, and PSA density (serum PSA level/prostatic volume) as a function o f patient age. Results.-The serum PSA concentration is correlated with patient age (r=.43; P<.0001) and prostatic volume (r=.55; P<.0001). P rostatic volume, in turn, is directly correlated with patient age (r=. 43; P<.0001), whereas the PSA density value is only weakly correlated with patient age (r=.25; P<.001). For a healthy 60-year-old man with n o evidence of prostate cancer, the serum PSA concentration increases b y approximately 3.2% per year (0.04 ng/mL per year). The recommended r eference range for serum PSA (95th percentile) for men aged 40 to 49 y ears is 0.0 to 2.5 ng/mL; for 50 to 59 years, 0.0 to 3.5 ng/mL; 60 to 69 years, 0.0 to 4.5 ng/mL; and 70 to 79 years, 0.0 to 6.5 ng/mL. Conc lusions.-The serum PSA concentration is directly correlated with patie nt age and prostatic volume, the latter of which also is directly rela ted to age. Thus, rather than rely on a single reference range for men of all age groups, it is more appropriate to have age-specific refere nce ranges. These age-specific reference ranges have the potential to make serum PSA a more discriminating tumor marker for detecting clinic ally significant cancers in older men (increasing specificity) and to find more potentially curable cancers in younger men (increasing sensi tivity).