The rise and fall of PSA: clinical implications of prostate specific antigen kinetics.
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Humans↗
Biomedical subjects
Axel Semjonow
Publications and source records attributed to Axel Semjonow.
Combining free and total prostate specific antigen assays from different manufacturers: the pitfalls.
OBJECTIVES: We investigated the impact of interchanging free prostate specific antigen (f-PSA) concentrations from 10 different assays over a reference total PSA (t-PSA) on predicting prostate histology with free-to-total PSA ratios (f/t-PSA). METHODS: Archival sera from 80 t-PSA- and age-matched pairs of histologically confirmed prostate cancer (PCA) and benign prostatic hyperplasia (BPH) patients with t-PSA levels between 2 and 25 microg/l were investigated. Serum aliquots were analyzed for t- and f-PSA using a reference method (Access, Beckmann-Coulter Hybritech) and 10 commercially available f-PSA assays. Passing Bablok and linear regression were performed to investigate the interassay agreement between f-PSA assays. To compare diagnostic performance, ROC curves for PCA detection were calculated for the 10 f/t-PSA combinations using the reference t-PSA as denominator. Sensitivities, specificities and f/t-PSA cut-offs were calculated for varying points of the ROC curve. RESULTS: Despite good correlation of all 10 f-PSA assays with the reference method 4 showed significantly lower mean f-PSA levels. For f/t-PSA as a predictor of prostate histology, areas under the ROC curve (AUC) varied between 0.65 and 0.71 and, if compared to the reference method (AUC=0.70), were significantly lower in three cases. Ensuring 80% specificity, sensitivities ranged between 34% and 54% (reference method: 53%) and f/t-PSA cutpoints differed considerably depending on the f-PSA assay used (range: 0.15-0.24; reference: 0.15). Similar variations were noted at 95% specificity and 80% and 95% sensitivity. CONCLUSIONS: Arbitrary combinations of f- and t-PSA assays should not be used to calculate f/t-PSA ratios unless adequate studies have validated the diagnostic performance and cut-offs of that particular assay choice.
Aged↗
Multicenter evaluation of an artificial neural network to increase the prostate cancer detection rate and reduce unnecessary biopsies.
BACKGROUND: The percentage of free prostate-specific antigen (%fPSA) has been shown to improve specificity for the diagnosis of prostate cancer (PCa) over total PSA (tPSA). A multicenter study was performed to evaluate the diagnostic value of a %fPSA-based artificial neural network (ANN) in men with tPSA concentrations between 2 and 20 microg/L for detecting patients with increased risk of a positive prostate biopsy for cancer. METHODS: We enrolled 1188 men from six different hospitals with PCa or benign prostates between 1996 and 2001. We used a newly developed ANN with input data of tPSA, %fPSA, patient age, prostate volume, and digital rectal examination (DRE) status to calculate the risk for the presence of PCa within different tPSA ranges (2-4, 4.1-10, 2-10, 10.1-20, and 2-20 microg/L) at the 90% and 95% specificity or sensitivity cutoffs, depending on the tPSA concentration. ROC analysis and cutoff calculations were used to estimate the diagnostic improvement of the ANN compared with %fPSA alone. RESULTS: In the low tPSA range (2-4 microg/L), the ANN detected 72% and 65% of cancers at specificities of 90% or 95%, respectively. At 4-10 microg/L tPSA, the ANN detected 90% and 95% of cancers with specificities of 62% and 41%, respectively. Use of the ANN with 2-10 microg/L tPSA enhanced the specificity of %fPSA by 20-22%, thus reducing the number of unnecessary biopsies. CONCLUSIONS: Enhanced accuracy of PCa detection over that obtained using %fPSA alone can be achieved with a %fPSA-based ANN that also includes clinical information from DRE and prostate volume measurements.
Adult↗
Antiprostasome antibodies: possible serum markers for prostate cancer metastasizing liability.
Prostasomes are secretory granules synthesized, stored, and secreted by normal and neoplastic human prostate epithelial cells. In prostate cancer, they are anticipated to be released into the blood circulation where they may be immunogenic. The aim of our study was to examine whether prostasome antibody presence in serum bears any prognostic significance for men with prostate cancer. We developed a sensitive and specific immunoassay (enzyme-linked immunosorbent assay) to establish the presence of antiprostasome antibodies in serum. The antiprostasome antibody titer in serum, sampled before any kind of therapy for prostate cancer, was examined together with clinicopathologic variables and outcome over a median follow-up of 350 days in 218 patients with verified prostate cancer. We detected these antibodies in 191 (88%) of these patients. This antibody titer did not correlate to serum values of prostate-specific antigen. Significant, inverse relationships were registered for antiprostasome antibody titer, and metastases to bone and/or lymph nodes (P = 0.035) and pT (P = 0.025). These results indicate that the antiprostasome antibody titer in serum may be a novel marker for prostate cancer liability to metastasize.
Adult↗