Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease

Abstract

Objective: To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease.

Design: Case-control study of men with and without prostate disease who were participants in a prospective aging study.

Setting: Gerontology Research Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging.

Patients: Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer.

Outcome measures: Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease.

Results: Changes in androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer greater than BPH greater than control; P less than .01). At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75 micrograms/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively.

Conclusions: The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.

Fig 1

Observed data on prostate-specific antigen (PSA) levels μg/L) plotted as a function of age for each individual in the three diagnostic groups (solid lines). The broken horizontal line marks the single PSA criterion of 4.0 μg/L The PSA values at visit closest to diagnosis are indicated for individuals who progress beyond a PSA value of 14 μg/L.

Fig 2

Observed data on prostate-specific antigen (PSA) levels μg/L) plotted as a function of years before diagnosis for each individual subject with cancer (local or regional and metastatic). The PSA values at visit closest to diagnosis are indicated for individuals who progress beyond a PSA value of 14 μg/L

Fig 3

Average curves (±95% confidence intervals) of prostate-specific antigen levels μg/L) as a function of years before diagnosis for three diagnostic groups estimated from a mixed-effects model assuming an age of diagnosis of 75 years.