Values for the Free to Total Prostate-Specific Antigen Ratio as a Function of Age: Necessity of Reference Range Validation

Abstract

Objective: To measure the levels of free prostate-specific antigen (PSA), total PSA, and free to total PSA ratio in a population of men with no known prostate pathology aged from 20 to 70 years. Patients and Methods: Serum total PSA and free PSA values were determined in 1,502 patients due for a systematic health examination. The digital rectal examination was only proposed for those over 50 years of age. The assays were determined on the AsXYM apparatus, from Abbott laboratories, by MEIA technology with monoclonal antibodies. Results: 1,274 men were available for study. The mean age was 43.6 ± 11 years (range 20–69 years). The total PSA level was stable up to 40 years. Beyond that, it increased with age. There was a linear regression between the age and the logarithm of the total PSA rate (r = 0.26, p < 0.0001) from 40 to 70 years. The upper limit of the normal value (95th percentile) increased from 1.07 for the 20- to 30-year age range to 2.82 for the 60- to 70-year range. The free PSA level was stable up to 50 years of age. It then significantly increased. The upper limit of the normal value was measured as 0.42 in the range of 20–30 years and as 0.53 in the range of 60–70 years with an annual average increase rate of roughly 0.5%. Overall there was a linear regression between age and the free PSA rate (r = 0.12, p < 0.0001). The upper limit of the free to total PSA ratio, measured as being 0.68 in the range of 20–29 years, dropped towards 60–69 years with an upper limit of the normal of 0.48. The average annual reduction rate was around 0.70%. There was a linear regression between the age and the free to total PSA ratio (r = 0.17, p < 0.0001). Conclusion: These total PSA levels are lower than the ones measured in other studies with other assay methods. These variations stress the importance of validating reference values of total PSA and free PSA as a function of the assay method and the population to which they are applied before using them as an aid in the diagnosis of prostate cancer.