Total and free PSA: a methodical and clinical evaluation of five assays

We studied the methodical and clinical relevance of five determination assays for free PSA (f-PSA) in addition to the corresponding total PSA antigen (t-PSA).

Both the total PSA- and free-PSA-values of frozen sera obtained pretherapeutically from 80 patients with carcinoma (PC) and 171 patients with benign hyperplasia of the prostate (BPH) were analysed by means of Enzymun-Test PSA/BM, PSA-RIACT/ CIS, CanAg PSA EIA/ Dia, Tandem-E PSA/Hyb, PSA IRMA/ IBL and Enzymun-Test PSA free/BM, F PSA-RIACT/CIS, CanAg Anti Free PSA/Dia, Tandem-R free PSA/Hyb, FREE PSA IRMA/IBL.

The coefficient of correlation between Hybritech PSA assay and the other assays was determined in patients with benign and malignant prostatic diseases. There was a strong overall correlation with all assays measuring total or free PSA, respectively. A satisfying correlation is also shown using a limited scale up to 50 ng/mL for total PSA and 5 ng/mL for free PSA. At 95% specificity sensitivities of total PSA between 40% and 50% of the ratio (Q) = free PSA/total PSA between 4% and 28% were calculated. In a second step only patients with total PSA values below the cutoff level of 16.5 [micrograms/l] (BM), 13.9 [micrograms/l] (CIS), 14.7 [micrograms/l] (Dia), 15.7 [micrograms/l] (Hyb) and 16.8 [micrograms/l] (IBL) were considered. Using the BM assays, of these patients 9 of 162 with BPH and 14 of 47 with PC [CIS: 14 of 162 with BPH and 4 of 48 with PC/Dia: 13 of 162 with BPH and 11 of 48 with PC/Hyb: 6 of 156 with BPH (missing values = 6) and 11 of 40 with PC/IBL: 11 of 160 with BPH (missing values = 1) and 13 of 33 with PC (missing values = 2)] were below the ratio Q = free PSA/total PSA. Considering both steps (total PSA and Q) using the BM assay 47 patlents with PC were detected correctly and 18 patients with BPH would have been biopsied unnecessarily (positive biopsy rate = pos. br.: 72%) [CIS: 38 patients with PC and 23 patients with BPH (pos. br.: 62%)/Dia: 43 patients with PC and 22 patients with BPH (pos. br.: 66%)/Hyb: 51 patients with PC and 15 patients with BPH (pos. br.: 77%)/IBL: 46 patients with PC and 20 patients with BPH (pos. br.: 70%)]

High total PSA levels of all assays are a very good indicator for the presence of prostate cancer. There is still concern to improve the differentiation between BPH and PC, when an intermediate or low value (< 95% specificity) is observed. The determination of Q is only useful in this range and it might be helpful for the clinicians decision to apply or avoid biopsy.