Measurements of free and total PSA, tissue polypeptide-specific antigen (TPS), and CYFRA 21-1 in prostate cancer patients under intermittent androgensuppression therapy

BACKGROUND. The present study evaluated monthly measurements of free and to tal prostate-specific antigen (PSA), and the tumor proliferation markers ti ssue polypeptide-specific antigen (TPS) and cytokeratin fragment 21-1 (CYFR A 21-1) in patients with advanced prostate cancer receiving intermittant an drogen suppression therapy (IAS). METHODS. Thirty-four men received alternating cycles of 8 month androgen su ppression and treatment cessation (mean duration, 10.3 months) until PSA in creased to >20 mu g/l. Measurements of testosterone, percentage of free PSA , TPS, and CYFRA 21-1 were performed using ELISA and RIA assays. RESULTS. Periods of androgen suppression resulted in reversible reductions of testosterone (from 6 +/- 0.8 to <0.58 ng/ml), PSA (from 31.2 +/- 4.5 to <1.7 mu g/l), and prostatic volume (mean reduction, 22.2 +/- 4.6%), indicat ing apoptotic regression of the tumors. Upon treatment cessation, testoster one increased to 6.1 +/- 0.56 ng/ml within 2 months, followed by an increas e of PSA to 5.8 +/- 0.8 mu g/l. The mean percentage of free PSA (15.1 +/- 2 .6%) exhibited no significant change during the whole LAS cycle. TPS showed a decrease of 50% after 3 months, and CYFRA 21-1 a 25% decrease after 7 mo nths of androgen suppression treatment. During treatment cessation, TPS exc eeded the normal cutoff value of 90 U/l late in tumor regrowth (9-11 months ), whereas CYFRA 21-1 remained below the normal cutoff value of 3.3 ng/ml. CONCLUSIONS. PSA is the best and most sensitive marker of prostate cancer r egression and regrowth during IAS cycles of the markers tested in this stud y. Free PSA constitutes approximately 15% of total PSA (range, 5-32%), and its percentage showed no significant change during IAS cycles. The TPS and CYFRA 21-1 proliferation marker changes in LAS seem to be related mainly to effects on normal androgen-dependent tissues. (C) 1999 Wiley-Liss, Inc.