| 1. |
- Haese, A, et al.
(author)
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Comparison of predictive accuracy for pathologically organ confined clinical stage T1c prostate cancer using human glandular kallikrein 2 and prostate specific antigen combined with clinical stage and Gleason grade
- 2005
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In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 173:3, s. 752-756
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Journal article (peer-reviewed)abstract
- Purpose: Previously human glandular kallikrein 2 (hK2) has been implicated to predict pathologically organ confined prostate cancer (PCa) in patients with stage T2 disease. Now we evaluated the usefulness of hK2, as measured by 2 entirely different immunoassay designs, to enhance the discrimination of pathologically organ from nonorgan confined clinical stage T1c PCa. Materials and Methods: A consecutive series of pretreatment serum from 148 men with clinical stage T1c PCa was used in 2 equally sensitive and specific methods to measure total hK2 with independent reagents and entirely different assay designs. Total prostate specific antigen (tPSA) and free PSA (fPSA) were measured and percent fPSA was calculated. We determined the algorithm, hK2*tPSA/fPSA, from data generated by each hK2 assay, calculated means, medians and ranges for each analyte and algorithm, and calculated the significance of differences on univariate analysis. Using pretreatment PSA, clinical stage and biopsy Gleason grade we then developed a multivariate logistic regression base model to predict organ confined cancer and we compared predictions of the base model supplemented by the different hK2 measurements. Results: hK2 and hK2 based algorithms obtained by each hK2 assay were significantly different for pT2a/b vs pT3a or greater PCa (p = 0.034 to 0.0001) compared to tPSA (p = 0.06), fPSA (p = 0.90) or percent fPSA (p = 0.059). However, AUC (0.67 to 0.70) calculated by ROC analysis of the 4 models containing hK2 derived information was not significantly larger than that of the base model (AUC = 0.64, p = 0.52). Conclusions: The current data confirm that hK2 alone or hK2*tPSA/fPSA measured by 2 immunoassays is significantly lower in men with pT2a/b vs pT3a or greater PCa compared to tPSA, fPSA or percent fPSA on univariate analysis of a validation set of clinical stage T1c prostate cancer treated at an American center of excellence for prostate cancer surgery. However, the incorporation of preoperative hK2 into multiparameter predictive models for pT2 cancers did not increase predictive accuracy in this cohort of men.
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| 2. |
- Steuber, T, et al.
(author)
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Association of free-prostate specific antigen subfractions and human glandular kallikrein 2 with volume of benign and malignant prostatic tissue
- 2005
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In: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 63:1, s. 13-18
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Journal article (peer-reviewed)abstract
- BACKGROUND. We investigated the association of different subfractions of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), such as total PSA (tPSA), complexed PSA (cPSA), free PSA (fPSA), "single-chain Intact fPSA" (fPSA-I), "multi-chain nicked fPSA" (fPSA-N), and total hK2 with volumes of total prostate gland, transition zone (tz), and prostate cancer (PCa) tissue in patients with benign and malignant prostatic disease. METHODS. Serum samples were collected from men with negative biopsy (n = 164) and PCa (n = 252). Total and fPSA were measured using a commercially immunoassay. We measured hK2 and fPSA-I by previously reported in-house research assays specific for hK2 and single-chain, non-cleaved fPSA, respectively. Levels of fPSA-N (=fPSA-fPSA-I) and cPSA (=tPSA-fPSA) were calculated. Total prostate and tz volume were measured using transrectal ultrasound (TRUS); PCa volume was calculated using a computer assisted volumetric program. Association with tz and cancer volumes (CaVols) was performed by linear regression analysis. RESULTS. All PSA subfractions and hK2 were associated with tz volume in multivariable linear regression analysis. Only hK2, fPSA, and fPSA-N were significantly associated with CaVol in multivariable analysis, fPSA-I seemed to be cancer related. CONCLUSIONS. The multi-chain fPSA-N subfractions of fPSA may be a valuable predictor of both benign prostate hyperplasia (BPH) and CaVol that is likely to be more useful in predicting tz volumes than CaVols. fPSA-I may provide information on cancer without being influenced by the presence of BPH.
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| 3. |
- Bostwick, DG, et al.
(author)
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Epidemiology and statistical methods in prediction of patient outcome.
- 2005
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In: Scand J Urol Nephrol Suppl. - : Informa UK Limited. ; 39:216, s. 94-110
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Journal article (peer-reviewed)abstract
- Substantial gaps exist in the data of the assessment of risk and prognosis that limit our understanding of the complex mechanisms that contribute to the greatest cancer epidemic, prostate cancer, of our time. This report was prepared by an international multidisciplinary committee of the World Health Organization to address contemporary issues of epidemiology and statistical methods in prostate cancer, including a summary of current risk assessment methods and prognostic factors. Emphasis was placed on the relative merits of each of the statistical methods available. We concluded that: An international committee should be created to guide the assessment and validation of molecular biomarkers. The goal is to achieve more precise identification of those who would benefit from treatment. Prostate cancer is a predictable disease despite its biologic heterogeneity. However, the accuracy of predicting it must be improved. We expect that more precise statistical methods will supplant the current staging system. The simplicity and intuitive ease of using the current staging system must be balanced against the serious compromise in accuracy for the individual patient. The most useful new statistical approaches will integrate molecular biomarkers with existing prognostic factors to predict conditional life expectancy (i.e. the expected remaining years of a patient's life) and take into account all-cause mortality.
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| 4. |
- Phronen, T, et al.
(author)
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Enhanced discrimination of benign from malignant prostatic disease by selective measurements of cleaved forms of urokinase receptor in serum
- 2006
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 52:5, s. 838-844
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Journal article (peer-reviewed)abstract
- Background: Early detection of prostate cancer (PCa) centers on measurements of prostate-specific antigen (PSA), but current testing practices suffer from lack of specificity and generate many unnecessary prostate biopsies. Soluble urokinase plasminogen activator receptor (uPAR) is present in blood in both intact and cleaved forms. Increased uPAR in blood is correlated with poor prognosis in various cancers, but uPAR has not been shown to be useful in PCa diagnostics. We assessed the ability of immunoassays for specific uPAR forms to discriminate PCa from benign conditions. Methods: We measured total PSA (tPSA), free PSA (fPSA), intact uPAR [uPAR(I-III)], intact uPAR + cleaved uPAR domains II+III [uPAR(I-III) + uPAR(II-III)], and cleaved uPAR domain I [uPAR(I)] in sera from 224 men with and 166 men without PCa. We assessed differences in serum concentrations between the PCa and noncancer groups within the entire cohort and in men with tPSA concentrations of 2-10 mu g/L. The diagnostic accuracy of individual analytes and analyte combinations was explored by logistic regression and ROC analyses and evaluations of sensitivity and specificity pairs. Results: Serum uPAR(I) and uPAR(II-III) were higher in PCa than in benign disease. In men with tPSA between 2 and 10 mu g/L, the combination of %fPSA with the ratio uPAR(I)/uPAR(I-III) had a greater area under the ROC curve (0.73) than did %fPSA (0.68). Conclusions: Specific measurements of different uPAR forms in serum improve the specificity of PCa detection. The uPAR forms may therefore be complementary to PSA for PCa detection, most importantly in men with moderately increased PSA. (c) 2006 American Association for Clinical Chemistry.
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| 5. |
- Steuber, T, et al.
(author)
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Risk assessment for biochemical recurrence prior to radical prostatectomy: significant enhancement contributed by human glandular kallikrein 2 (hk2) and free prostate specific antigen (PSA) in men with moderate PSA-elevation in serum
- 2006
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In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 118:5, s. 1234-1240
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Journal article (peer-reviewed)abstract
- Most models to predict biochemical recurrence (BCR) of prostate cancer use pretreatment serum prostate-specific antigen (PSA), clinical stage and prostate biopsy Gleason grade. We investigated whether human glandular kallikrein 2 (hK2) and free prostate-specific antigen (fPSA) measured in pretreatment serum enhance prediction. We retrospectively measured total PSA (tPSA), fPSA and hK2 in preoperative serum samples from 461 men with localized prostate cancer treated with radical prostatectomy between 1999 and 2001. We developed a regression model to predict BCR using preoperative tPSA, clinical stage and biopsy Gleason grade. We then compared the predictive accuracy of this "base" model with a model with fPSA and hK2 as additional predictors. BCR was observed in 90 patients (20%), including 48 patients with a pretreatment tPSA <= 14 ng/ml (13%), and 28 patients (10%) With a pretreatment tPSA <= 10 ng/ml. Overall, the predictive accuracy of the base model (bootstrap-corrected concordance index of 0.813) was not improved after the addition of fPSA or hK2 (0.818). However, for men with moderate tPSA-elevation (tPSA <= 10 ng/ml), addition of fPSA and hK2 data increased predictive accuracy (from a base model concordance index of 0.756-0.815, p = 0.005). The improvement in accuracy was not sensitive to the threshold for "moderately elevated" PSA. For patients with a moderate tPSA-elevation (tPSA <= 10 ng/ml), which closely corresponds to concurrent disease demographics, BCR-prediction was enhanced when fPSA and hK2 were added to the conventional model. Measurements of fPSA and hK2 improve on our ability to counsel patients prior to treatment as to their risk of BCR. (c) 2005 Wiley-Liss, Inc.
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