Free and total serum PSA values in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer and BPH. Is F/T PSA a potential probe for dormant and manifest cancer?

Free and total PSA serum concentrations were retrospectively measured in 106 subjects: 45 patients with intraepithelial prostatic neoplasia (PIN), 30 subjects with benign prostatic hypertrophy (BPH) and 31 subjects with untreated prostatic carcinoma. The (F/T) x 100 PSA value is recorded in subjects with the elevated total PSA level (> 4 ng/ml). PIN patients were divided into two groups: a low grade PIN (PIN 1) and high grade PIN (PIN II-III) patients. The mean (F/T) x 100 PSA value in low grade PIN patients was 27.9 +/- 16.2 (range 17.1-41.2, median 25.1) and has been numerically similar to the respective value in BPH subjects (29.1 +/- 13.2, 15.8-48.0, 27.7). These parameters differed markedly (P < 0.01) from the mean (F/T) x 100 PSA value in high grade PIN patients (16.9 +/- 9.0, range 9.9-24.9, median 16.5). The later values were in turn comparable (P > > 0.05) with the respective value measured in untreated prostate cancer patients (14.4 +/- 10.8, 6.6-21.4, 12.6). Hence, values derived from the measurement of free and total serum PSA level may distinguish low grade PIN that prevailingly remains latent disease from high grade PIN that is in most cases not only early prostatic carcinoma but that is often a precursor of an aggressive neoplasm. The published literature is incoherent regarding the influence of tumor spread on F/T PSA level. The cutoff point that divides BPH from cancer may depend on tumor stage. We have not investigated F/T PSA values related to different stages and grades of prostate cancer. The cutoff point of (F/T) x 100 PSA in our study that divides malignant from benign prostate, or latent from manifest cancer, was tentatively assigned as 18 with a specificity of 91% and selectivity of 69%. Our data are based on the application of the CIS assay that, according to the literature, gives higher F-PSA % compared to other respective kits.