The value of (-7, -5)pro-prostate-specific antigen and human kallikrein-2 as serum markers for grading prostate cancer.

OBJECTIVE: To assess the value of the precursor form (-7,5pro) of prostate-specific antigen (PSA) and human kallikrein-2 (hK2) for detecting and grading prostate cancer, as better serum markers with improved specificity are needed in men with lower ranges of total (t)PSA. PATIENTS AND METHODS: tPSA, free PSA (fPSA), the precursor (-7,5)proPSA and hK2 were measured in a subset of participants of the European Randomised Study of Screening of Prostate Cancer. In a pilot study, sera from 143 men biopsied but with no prostate cancer, 142 with BPH, and 146 with prostate cancer were analysed to determine the relative value of serum markers for differentiating between the groups. Then, in 141 men with prostate cancer who had a radical prostatectomy, these serum markers were related to the pathological grading to analyse their value as prognostic variables. RESULTS: Levels of (-7,5)proPSA, hK2 and fPSA could be used to distinguish between BPH and cancer, but proPSA and hK2, alone or combined, did not improve the specificity of fPSA for discriminating BPH and cancer. There was also no correlation between these serum markers and pathological tumour grade. CONCLUSION: The clinical effect of using (-7,5)proPSA or hK2 for detecting and grading prostate cancer remains limited.

Different PSA assays lead to detection of prostate cancers with identical histological features.

OBJECTIVE: Because different PSA assays still show a wide inter-assay variation, we wondered what influence these discrepancies could have on the individual tumour characteristics of the cancers that each of these assays detect in a critical low PSA range. We analysed five different PSA assays in a biopsy simulation with PSA cut-offs of 3.0 and 4.0 ng/ml. MATERIALS AND METHODS: Randomly taken samples of 360 men with prostate cancer and 96 with benign prostatic disease from a screened population with PSA range of 1.0-6.0 ng/ml (Tandem-E) were investigated. In all cases the diagnosis was confirmed by sextant biopsies. One hundred and thirty-seven men (38%) underwent radical prostatectomy. Variability amongst assays was illustrated in terms of missed cancers and unnecessary biopsies, and in terms of pathologic features of detected cancers at both PSA cut-offs. RESULTS: Compared to Tandem-E, all assays, except Access, showed significant differences in PSA measurements. Furthermore, none of the assays discriminated significantly between benign and malignant prostatic disease (p>0.05). Tandem-E and Elecsys lead significantly more frequently to the detection of cancers at the cost of more unnecessary biopsies compared to the other assays. Yet, at both PSA cut-offs the proportion of cancers with a certain pathologic grade or stage that were detected by each assay were approximately the same. CONCLUSIONS: Our study shows that the use of different PSA assays only have consequences for the number, and not for the tumour characteristics of the prostate cancers that are detected. Thus, different PSA assays detect prostate cancers with the same tumour features.

Discordant performance of assays for free and total prostate-specific antigen in relation to the early detection of prostate cancer.

OBJECTIVE: To assess the value of applying rigid threshold values in interpreting prostate specific antigen (PSA) results, by selecting and comparing five current methods for measuring free and total PSA. MATERIALS AND METHODS: Samples taken from an ongoing screening study for prostate cancer (total PSA by Tandem-E assay, 17 334 participants; biopsy criterion a PSA of 3.0 microg/L, 4 464 men) from men with a total PSA of 1.0-6.0 microg/L were measured for free and total PSA using the Access, Immulite, Elecsys and Prostatus analysis kits, in two patient groups, i.e. with prostate cancer or no evidence of disease. RESULTS: Both patient groups had equal means for total PSA but not for free PSA. In all, 360 samples from men with cancer and 96 from men with no evidence of disease were analysed. All methods applied to both groups deviated statistically significantly from the Tandem-E result for total PSA, except for the Access kit. There was a close correlation among all the methods (correlation coefficients of 0.89-0.97). There were very discordant results for the combination of the Tandem-E vs Prostatus (8% difference), representing 315 participants at a threshold of 3.0 microg/L. For free PSA (free/total PSA) the situation was worse, with extreme differences of 32% and 36% for both patient groups (Elecsys vs Access). CONCLUSIONS: Depending on the threshold value applied as an indication for biopsy, when using the total PSA alone or combined with the free/total PSA, care is needed in interpreting patient groups because of the discordance among PSA assays.