Ratio of Free or Complexed Prostate-specific Antigen (PSA) to Total PSA: Which Ratio Improves Differentiation between Benign Prostatic Hyperplasia and Prostate Cancer?

Abstract

Background: The aim of this study was to compare the diagnostic utility of a new assay that measures all forms of prostate-specific antigen complexed (cPSA) to serum proteins except α2-macroglobulin with the assay of free PSA (fPSA) and the corresponding ratios to total PSA (tPSA) to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Methods: Serum samples were collected from 91 men without prostate disease and with normal digital rectal examination (controls), 144 untreated patients with PCa, and 89 patients with BPH. tPSA and cPSA were measured using the Bayer Immuno 1 system; fPSA and the additional tPSA were measured with the Roche Elecsys system. Results: The median cPSA/tPSA, fPSA/tPSA, and fPSA/cPSA ratios were significantly different between patients with BPH and PCa (78.7% vs 90.7%, 25.5% vs 12.1%, and 36.8% vs 14.3%, respectively; P <0.001). No correlations of cPSA and its ratios to tumor stage and grade were found. ROC analysis showed that cPSA was not different from tPSA (areas under the curve, 0.632 vs 0.568), whereas the cPSA/tPSA ratio was similar to the fPSA/tPSA ratio in increasing discrimination between BPH and PCa patients with tPSA concentrations in the tPSA gray zone between 2 and 10 μg/L (areas under the curve, 0.851 vs 0.838). Conclusions: Compared with tPSA, the fPSA/tPSA and cPSA/tPSA ratios both improve the differentiation between BPH and PCa comparably and are similarly effective in reducing the rate of unnecessary biopsies, whereas cPSA alone does not have any effect.

Receiver‐operating characteristic as a tool for evaluating the diagnostic performance of prostate‐specific antigen and its molecular forms—What has to be considered?

“…The speci®city of fPSA% was superior to that of tPSA and cPSA for the cutoff values providing sensitivities between 80 and 90% [8]. We performed analogous measurements and came to similar conclusions [9]. These results are partly in contrast to those of Brawer et al [10,11] who described good results with cPSA measurements alone.…”

Effect of prostate manipulation on the serum levels of complexed prostate‐specific antigen and total prostate‐specific antigen

“…Although no study has been conclusive, some have shown promising results with an increased specificity over tPSA in the detection of prostate cancer while other studies have shown an equivalence to the f/t PSA. [15][16][17][18][19][20] There also is a cost advantage in using cPSA. In comparison to the measurement of the f/t PSA, which requires two assays, the measurement of cPSA requires only one assay.…”

Predictors of prostate cancer on repeat prostatic biopsy in men with serum total prostate‐specific antigen between 4.1 and 10 ng/mL

“…Several investigators have shown that fPSA/tPSA or tPSA/cPSA ratios improve specificity in the detection of prostate cancer. [12][13][14][15][16][17] Our previous study also demonstrated that fPSA/tPSA and tPSA/cPSA ratios are superior to tPSA in detecting prostate cancer. [18][19][20] In the present study, we determine whether the different molecular forms of prostate-specific antigen and other PSA variables can predict prostate cancer in men undergoing repeat prostate needle biopsy.…”

“…Moreover, serum from patients with prostate cancer contains a higher proportion of PSA complexed with a 1-antichymotrypsin than does serum from patients with BPH. [12][13][14][15][16][17] Complexed PSA assay (cPSA) thus seems a fruitful approach to diagnosing prostate cancer. Several investigators have shown that fPSA/tPSA or tPSA/cPSA ratios improve specificity in the detection of prostate cancer.…”