Objective: To define the reference range for the ratio of free to total prostate-specific antigen (fPSA%) in a population of healthy men with no clinically evident prostate cancer and to assess the influence of age on this tumour marker, thus determining the utility of fPSA% in enhancing the discriminatory power of PSA to differentiate healthy men and patients with benign prostatic hyperplasia from those with prostate cancer.
Subjects and methods: In a prospective cohort study between May and August 1996, 1160 white men aged 20-89 years (957 were 40-69 years old, 82% of all subjects) from nine European and eight non-European countries were assessed. None of the participants who had a history of prostate cancer had undergone prostatectomy. A standard clinical examination including a digital rectal examination was performed to exclude the presence of prostate cancer. Transrectal ultrasonography was not an inclusion criterion, as it was not available in every case. Total PSA (tPSA) and free PSA (fPSA) were determined in 61 laboratories using the appropriate Enzymun-Test for tPSA and fPSA (Boehringer Mannheim Diagnostics, Mannheim, Germany). Serum tPSA, fPSA and fPSA% were then assessed as a function of the subjects' age.
Results: The serum tPSA and fPSA were significantly different among age decades 2-8 (P < 0.001), with increasing median values, indicating that both variables depend on age. The recommended upper reference limit (95th percentile) for tPSA is 1.78 ng/mL for men aged 30-39 years, 1.75 ng/mL for 40-49 years, 2.27 ng/mL for 50-59 years, 3.48 ng/mL for 60-69 years and 4.26 ng/mL for 70-79 years. The fPSA% was not significantly different between decades 3-8 (P = 0.06). Those aged 20-29 years had a slightly higher median value (P = 0.03) than the other age groups. The recommended lower reference limit (fifth percentile) for fPSA% is 12.6%.
Conclusion: The fPSA% for clinically relevant age groups in healthy men was independent of age, which simplifies the use and interpretation of this relatively new tumour marker.