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| 2. |
- Haese, A, et al.
(författare)
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The role of human glandular kallikrein 2 for prediction of pathologically organ confined prostate cancer
- 2003
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 54:3, s. 181-186
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. In recent studies serum levels of human glandular kallikrein 2 (hK2) demonstrated significant differences in pathologically organ-confined versus non-organ-confined prostate cancer (Pca). In this study we investigated whether hK2 adds independent information when considered together with traditionally used parameters to predict organ confined (pT2a/b) PCa. METHODS. Serum levels of hK2, total and free prostate-specific antigens (PSA) were obtained one day before radical prostatectomy in 245 consecutive men. These were included with clinical stage and biopsy Gleason grade into univariate analysis and multivariate logistic regression models. RESULTS. pT2a/b PCa was found in n = 148 patients. In univariate analysis all preoperative parameters demonstrated significant association with the presence of pT2a/b PCa. Using multivariate logistic regression model hK2 (P = 0.022), clinical stage (P < 0.0001), and Gleason grade (P < 0.0001) were independent predictors of pT2a/b PCa whereas PSA (P = 0.3) was not. In bootstrap corrected logistic regression based nomograms the addition of hK2 density marginally enhanced predictive accuracy when PSA, PSA density, clinical stage, and Gleason grade were considered (AUC = 0.879 without hK2 density and 0.883 with hK2 density). CONCLUSIONS. hK2 and hK2 density could independently predict pT2a/b PCa. However, improvement in predictive accuracy was marginal when nomograms based on traditional variables were complemented with this serum marker. (C) 2002 Wiley-Liss, Inc.
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| 6. |
- Steuber, T, et al.
(författare)
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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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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 63:1, s. 13-18
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Haese, A., et al.
(författare)
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A pre-specified model based on four kallikrein markers in blood improves predictions of adverse pathology and biochemical recurrence after radical prostatectomy
- 2020
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 123:4, s. 604-609
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Tidskriftsartikel (refereegranskat)abstract
- Background A pre-specified model based on four kallikrein markers in blood, commercially available as 4Kscore, predicts Gleason Grade (GG) 3 + 4 or higher prostate cancer on biopsy. However, sampling error and variation in pathology reporting may miss aggressive disease. Methods The 4Kscore was measured in cryopreserved blood from 2330 men obtained before prostatectomy at a single institution between 2002 and 2010. Adverse surgical pathology and biochemical recurrence (BCR) were pre-specified to be assessed in all men, biopsy GG 3 + 3, and 3 + 4. Results Adjusted for established clinical predictors, the 4Kscore was significantly associated with adverse pathology (OR 1.49; 95% CI 1.32, 1.67;p < 0.0001). Adding 4Kscore increased discrimination from (AUC) 0.672 to 0.718 and 0.644 to 0.659 within biopsy GG 3 + 3 and 3 + 4, respectively. Higher 4Kscore was associated with higher risk of BCR (HR 1.16, 95% CI 1.06, 1.26;p = 0.001). Adding 4Kscore improved the prediction of BCR (C-index 0.630-0.660) within GG 3 + 3, but not GG 3 + 4. Conclusions The 4Kscore can help guide the clinical decision whether additional risk assessment-such as confirmatory biopsy-is needed to decide between active surveillance versus curative therapy. Evidence that the panel could influence management in biopsy GG 3 + 4 is less strong and requires further investigation.
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| 13. |
- Haese, A, et al.
(författare)
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Human glandular kallikrein 2: a potential serum marker for predicting the organ confined versus non-organ confined growth of prostate cancer
- 2000
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Ingår i: Journal of Urology. - 1527-3792. ; 163:5, s. 1491-1497
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We measured serum levels of human glandular kallikrein 2 (hK2) in patients with prostate cancer treated with radical retropubic prostatectomy for clinically localized prostate cancer to determine whether preoperative hK2 levels discriminate stage pT2a/b from pathological stage T3a or greater cancer. This finding would help to predict preoperatively the organ confined versus non-organ confined growth of prostate cancer. MATERIALS AND METHODS: A total of 68 consecutive men underwent radical retropubic prostatectomy for clinically localized prostate cancer. Serum was obtained 1 day preoperatively before prostatic manipulation. hK2, and total and free prostate specific antigen (PSA) were measured using immunofluorometric assays. Mean, median and range of hK2, total and free PSA, and the ratio of free-to-total PSA (percent free PSA) were calculated. Each analyte or combination of analytes was evaluated to determine whether it significantly contributed to enhance the discrimination of organ confined from non-organ confined cancer. We calculated the statistical significance of observed differences using the Mann-Whitney U and Kruskal-Wallis tests. Sensitivity and specificity calculations were performed for hK2, total PSA and the algorithm, (hK2) x (total PSA/free PSA) in addition to receiver operating characteristics curves and the respective areas under the curves. Multivariate logistic regression analysis was done for hK2, and total and free PSA RESULTS: Disease was organ and non-organ (extraprostatic extension) confined in 38 and 30 men, respectively. In organ confined cancer mean hK2 was significantly lower than in non-organ confined cancer (0.09 ng./ml., range less than 0.03 to 0.23 versus 0.30, range 0.04 to 0.94, p <0.0001). In addition, there was significantly higher free and total but not percent free PSA in non-organ than in organ confined cases. There were also statistically significant differences in hK2, free PSA and total PSA at each pathological disease stage (p <0.001, <0.01 and <0.05, respectively). Sensitivity for detecting organ confined disease was 37% at 100% specificity (correct identification of all non-organ confined cancer) using hK2 measurements compared with a sensitivity of 14% for total PSA. At a specificity of 95%, sensitivity was 40% for hK2 versus 23% for total PSA, which was a statistically significant gain in sensitivity (p <0.05). Receiver operating characteristics curves demonstrated that hK2 had the largest area under the curve, followed by the algorithm, (hK2) x (total PSA/free PSA), and total PSA (0.76, 0.75 and 0.72, respectively). However, none of area under the curve differences was statistically significant. CONCLUSIONS: Compared with total and free PSA hK2 testing improved the preoperative evaluation of patients who underwent radical retropubic prostatectomy due to the superior discrimination of organ from non-organ confined cancer.
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| 14. |
- Haese, A, et al.
(författare)
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Total and Gleason grade 4/5 cancer volumes are major contributors of human kallikrein 2, whereas free prostate specific antigen is largely contributed by benign gland volume in serum from patients with prostate cancer or benign prostatic biopsies
- 2003
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 170:6, s. 2269-2273
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We measured concentrations of human glandular kallikrein 2 (hK2), total prostate specific antigen (tPSA), free PSA (fPSA) and percent fPSA to evaluate their relationship to total prostate gland volume, benign prostatic hyperplasia (BPH) volume, total prostate cancer (PCa) volume (CaVol) and the volume of Gleason grades 4/5 cancer (CaVolG14) in the serum of 256 patients with PCa undergoing radical retropubic prostatectomy and 185 with negative systematic sextant biopsies. Materials and Methods: Free and total PSA was measured using the Delfia Prostatus (Perkin-Elmer, Turku, Finland) total/free PSA assay and hK2 was measured using a research immunofluorometric assay. Transrectal ultrasound was used to determine total prostate and BPH volume. Total CaVol and CaVolG14/5 were calculated using a volumetric program in specimens from 158 men with pT2a/b and 98 with pT3a or greater PCa. The Pearson correlation was performed after logarithmic conversion of PSA and hK2 levels. Benign gland, and pT2a/b and pT3a or greater PCa cases were subdivided into small vs large prostate gland volumes (42 cc or less vs greater than 42 cc). Results: Total prostate and BPH volumes correlated closely with free PSA (r=0.64 to 0.65, p<0.0001) in 143 patients with negative biopsy and a prostate of greater than 42 cc. Correlations of hK2 and tPSA with total prostate and BPH volumes were weaker (r=0.35 to 0.36 and 0.45 to 0.46, respectively). In pT2a/b and pT3a or greater PCa cases hK2 most closely correlated with CaVol (range 0.31 to 0.62, p=0.0072 and <0.0001) and with CaVolG14/5 (range 0.26 to 0.56, p=0.021 and <0.0001, respectively). The tPSA level correlated significantly with CaVol and CaVolG14/5 except in glands 42 cc or greater harboring pT2a/b PCa (p=0.08). Free PSA correlated significantly with CaVolG14/5 only in pT3a or greater PCa (p<0.05), and with CaVol in pT3a or greater PCa and in small prostates harboring pT2a/b PCa. Conclusions: Large benign prostate gland volume affects fPSA more than tPSA in serum. In PCa hK2 more closely correlates with total cancer volume and high grade PCa volume compared with tPSA or fPSA.
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| 15. |
- Huland, H, et al.
(författare)
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Prediction of tumor heterogeneity in localized prostate cancer
- 2002
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Ingår i: Urologic Clinics of North America. - 0094-0143. ; 29:1, s. 213-213
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Tidskriftsartikel (refereegranskat)abstract
- The clinical T1-T2 prostatic carcinoma is a heterogeneous tumor in respect to pathologic stage and outcome. Tumor heterogeneity can be fairly good predicted by the use of classification and regression tree analysis with preoperative parameters, especially a quantitative analysis of Gleason grade 4-5 cancer in six systematic biopsies and a determination of preoperative prostate-specific antigen levels, to predict lymph node status, capsular penetration, and outcome.
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| 16. |
- Martin, Neil E, et al.
(författare)
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Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer
- 2015
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 67:3, s. 460-467
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment.OBJECTIVE: To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value.DESIGN, SETTING, AND PARTICIPANTS: We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set.RESULTS AND LIMITATIONS: We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons.CONCLUSIONS: We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care.PATIENT SUMMARY: Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.
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| 21. |
- Sooriakumaran, P., et al.
(författare)
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Survival Among Men at High Risk of Disseminated Prostate Cancer Receiving Initial Locally Directed Radical Treatment or Initial Androgen Deprivation Therapy
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:3, s. 345-351
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is increasing low-quality evidence rationalizing the use of radical therapy for men at high risk of disseminated prostate cancer. Objective: To investigate, using high-quality epidemiologic data, whether initial radical therapy in men at high risk of disseminated prostate cancer improves survival. Design, setting, and participants: An observational population-based Swedish study from 1996 to 2010 of men at high risk of disseminated prostate cancer (prostate-specific antigen [PSA] > 50) initially treated by radical therapy (radiation therapy [n = 630] or radical prostatectomy [n = 120]) or androgen deprivation therapy (n = 17 602), and followed for up to 15 yr. Outcome measurements and statistical analysis: Prostate-cancer and other-cause mortality was estimated for the treatment groups. We also matched the two cohorts for grade, T stage, M stage, Charlson score, year of diagnosis, age, and PSA, and found androgen deprivation therapy patient matches for 575 of the radical therapy patients, and then repeated comparative effectiveness analyses. Results and limitation: Prostate-cancer mortality was substantially greater in the androgen deprivation therapy group compared with the radically treated one, in unmatched (9062/17 602 vs 86/750) and matched (177/575 vs 71/575) cohorts. Among matched cohorts, initial androgen deprivation therapy was associated with nearly three-fold higher hazard of prostate-cancer death compared with initial radical therapy (2.87; 95% confidence interval 2.16-3.82). Multiple sensitivity analyses suggested that the findings were robust, although the general limitations of nonrandomized studies remain. Further, the study cohort may have included men with both systemic and nonsystemic disease, as a sole eligibility criterion of PSA > 50 was used. Conclusions: This large and comprehensive population-based study suggests that initial radical therapy in men at high risk of disseminated prostate cancer improves survival. Patient summary: This large Swedish study suggests that men with prostate cancer that has spread beyond the prostate benefit from treating the prostate itself with radiation therapy or surgery rather than treating the disease with hormones alone. (C) 2017 European Association of Urology.
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| 22. |
- Steuber, T, et al.
(författare)
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Discrimination of benign from malignant prostatic disease by selective measurements of single chain, intact free prostate specific antigen
- 2002
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Ingår i: Journal of Urology. - 1527-3792. ; 168:5, s. 1917-1922
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Free prostate specific antigen (PSA) in serum consists of heterogeneous molecular subforms. Recently we developed an immunoassay for selective measurement of a subfraction of free PSA called intact PSA, which has been shown to be closely associated with prostate cancer. We assessed the ability of serum intact PSA to discriminate between benign and malignant prostatic disease. Materials and Methods: In serum of 178 men with benign disease and 255 men with prostate cancer we measured total PSA and free PSA using a commercially available immunoassay. Intact PSA levels were analyzed by a newly developed assay specific for noncleaved, that is single chain forms of free PSA. Internally cleaved "nicked" PSA was calculated by subtracting intact from free PSA. We also calculated ratios of intact PSA-to-free PSA (intact-to-free PSA) and nicked PSA-to-total PSA (nicked-to-total PSA). We compared means, medians and ranges of all analytes and ratios in patients with and without cancer for the entire total PSA range and in a subset with total PSA ranging from 2 to 10 ng/ml. Furthermore, various combinations of PSA forms were tested for their predictive ability. For statistical comparison we used the Mann-Whitney U test and ROC analysis. Results: The ratio intact-to-free PSA was significantly higher in cancer (median 48.5%) compared to noncancer cases (median 41.8%, p <0.0001). Conversely, the ratio nicked-to-total PSA was significantly higher in men without compared to those with prostate cancer (median 11.0% and 6.0%, respectively, p <0.0001). Highest discriminative ability was observed for a combination of intact, total and free PSA (log [intact, free, total], AUC = 0.773) followed by nicked-to-total PSA (AUC 0.755). In the subgroup of patients with total PSA levels from 2 to 10 ng/ml. only the AUC of log intact, free, total (AUC 0.706, p = 0.0017) and nicked-to-total PSA (AUC 0.704, p = 0.0019) were significantly larger compared to the AUC of total PSA (AUC 0.602). Conclusions: By contrast to measuring crude free PSA concentration, selective determination of specific free PSA subforms, intact PSA and nicked PSA proved to be useful to discriminate men with benign from malignant prostatic disease. These markers may serve to generate specific serum profiles of PSA for improved specificity and early detection of prostate cancer. To translate the encouraging statistical advantage shown in this study into a clinically applicable tool warrants further investigation.
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