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Alexander Haese

Publications and source records attributed to Alexander Haese.

At least 37 records · Page 2Linked to original sources
PubMed2006

Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation.

OBJECTIVE: To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. PATIENTS AND METHODS: The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from < or = 6 to > or = 7 or from 7 to > or = 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. RESULTS: Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. CONCLUSION: Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.

Adult↗
PubMed2005

Development and internal validation of a nomogram predicting the probability of prostate cancer Gleason sum upgrading between biopsy and radical prostatectomy pathology.

OBJECTIVE: Previous reports indicate that as many as 43% of men with low grade PCa at biopsy will be diagnosed with high-grade PCa at RP. We explored the rate of upgrading from biopsy to RP specimen in our contemporary cohort, and developed a model capable of predicting the probability of biopsy Gleason sum upgrading. MATERIALS AND METHODS: The study cohort consisted of 2982 men treated with RP, with available clinical stage, serum prostate specific antigen and biopsy Gleason scores. These clinical data were used as predictors in multivariate logistic regression models (LRM) addressing the rate of Gleason sum upgrading between biopsy and RP pathology. LRM regression coefficients were used to develop a nomogram predicting the probability of Gleason sum upgrading and was subjected to 200 bootstrap resamples for internal validation and to reduce overfit bias. RESULTS: Overall, 875 patients were upgraded (29.3%). In multivariate LRMs, all predictors were highly significant (all p values <0.0001). Bootstrap-corrected predictive accuracy of the nomogram predicting the probability of Gleason sum upgrading between biopsy and RP was 0.804. CONCLUSION: We developed a highly accurate clinical aid for treatment decision-making. It may prove useful when the possibility of a more aggressive Gleason variant may change the treatment options.

Biopsy↗
PubMed2005

Association of free-prostate specific antigen subfractions and human glandular kallikrein 2 with volume of benign and malignant prostatic tissue.

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.

Aged↗
PubMed2005

Reasonable delay of surgical treatment in men with localized prostate cancer--impact on prognosis?

PURPOSE: In many centers patients with clinically localized prostate cancer might be confronted with a delay in therapy due to not immediately available treatment capacity at that specific center. Furthermore, a growing amount of patients want to have a second or third opinion before they finally decide what therapeutic option to choose. We investigated whether a reasonable delay from diagnosis to definitive treatment impact recurrence free survival rates in men undergoing radical prostatectomy (RP) for localized prostate cancer. MATERIAL AND METHODS: Preoperative data of 795 men treated for localized prostate cancer by RP between 1/1992 and 6/2000 were evaluated including pretreatment PSA, clinical stage and biopsy Gleason score. In addition, time from biopsy to the date of RP was obtained and investigated as a potential prognostic factor. The influence of the time gap between biopsy and surgery was statistically evaluated by univariate Cox regression analyses and Kaplan-Meier analyses; a multivariate Cox Modell was performed including all preoperative parameters. Relapse following RP was defined as a postoperative PSA level >0.1 ng/ml. RESULTS: Mean followup of the patients was 33 months (1-116 months). Twenty-five percent of the patients failed during that time period. Mean time gap between diagnosis and treatment was 62 days (median 54 days) ranging from 5 to 518 days. Univariate Cox regression analysis showed no significant correlation (p=0.062) of waiting time with recurrence rate. Multivariate Cox regression documented a highly significant association of PSA (p<0.001), clinical stage (p=0.001) and biopsy Gleason grade (p<0.001) but not not for time to treatment (p=0.841). In patients with high-grade cancer again no significant impact of treatment delay was found. CONCLUSION: Treatment delay in the investigated time span of a few months did not adversely affect recurrence free survival rates. Patients can be reassured that they can evaluate treatment options without compromising efficacy due to a delay in treatment.

Biopsy↗
PubMed2005

Surgical management of prostate cancer: advances based on a rational approach to the data.

The management of localised prostate cancer has undergone important changes in the past two decades, with major improvements in surgical technique, a greater emphasis on structured assessment of quality of life, and a greater attempt to tailor treatment to biological risk. Disease diagnosis is predicated on identification of demographic risk factors, serum levels of prostate-specific antigen and its derivatives, and extended biopsy techniques. Surgical removal of the prostate may be accomplished by open or minimally invasive techniques and in experienced hands results in good functional outcomes a high rate of cure for those with organ confined disease. Radical prostatectomy is also appropriate in selected patients with locally advanced disease and after failed radiation therapy.

Biopsy↗
PubMed2005

Influence of nerve-sparing (NS) procedure during radical prostatectomy (RP) on margin status and biochemical failure.

PURPOSE: To evaluate whether nerve-sparing procedure itself is a risk factor for biochemical recurrence in carefully selected patients. MATERIAL AND METHODS: We compared patients of our historical series who in retrospect were candidates for nerve-sparing (NS) procedure with a contemporary cohort of patients. With respect to stage migration and selection bias between these two groups we performed a multivariate analysis adjusting for all explanatory variables in the model. NS was performed in n = 723 patients (bilateral n = 359, unilateral n = 364) in comparison to n = 620 patients undergoing non-NS RP, comprising n = 756 patients within the favorable pT2 category. We examined the association of clinical and histopathological parameters in relation to PSA recurrence in uni- and multivariate analyses including NS as a variable. Furthermore, for each prostate lobe separately we determined whether surgical procedure (nerve-sparing vs. non-nerve-sparing RP) resulted in a positive margin. RESULTS: In univariate analysis there was no difference in pT2 (log rank p = 0.091), pT3a (log rank p = 0.171) and pT3b (log rank p = 0.110) cancers between patients treated with NS compared to non-NS surgery. The 3- and 5-year recurrence free survival rate for patients with pT2, pT3a and pT3b cancers treated by NS vs. non-NS were 96.3/94.9 vs. 94.9/90.8, 75.0/61.8 vs. 73.4/55.0 and 46/30 vs. 38/23. Multivariate regression analysis showed no association with PSA failure (p = 0.798) for patients who underwent NS. Capsular penetration (p < 0.001), lymph-node status (p < 0.001), seminal vesicle invasion (p < 0.001), surgical margin status (p = 0.0130), Gleason score (p < 0.001) and preoperative PSA (p = 0.005) were significantly associated with risk of failure. The positive margin rate per each prostate lobe in pT2 cancers was 6.5% vs. 5.1% in NS and non-NS cases, 10.3% vs. 17.3% in patients with extracapsular extension and 15.0% vs. 25.1% in cases with seminal vesicle invasion respectively. CONCLUSION: NS RP is an oncologically safe procedure provided that appropriate preoperative selection of patients by means of a validated nomogram is performed. Moreover, evaluation of positive margins in patients undergoing NS and non-NS RP revealed no evidence that adequacy of tumor excision is compromised by NS procedure.

Aged↗
PubMed2005

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.

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.

Adult↗
PubMed2005

A multicenter clinical trial on the use of (-5, -7) pro prostate specific antigen.

PURPOSE: The determination of pro prostate specific antigen (proPSA) forms has been suggested to be promising in prostate cancer diagnosis. In this multicenter trial we evaluated the diagnostic usefulness of (-5, -7) proPSA. MATERIALS AND METHODS: A total of 2,055 white men, including 1,046 with and 1,009 without prostate cancer, with total PSA (tPSA) between 0.28 and 81 ng/ml were retrospectively analyzed. Of these men 2,026 and 1,727 had tPSA less than 20 and less than 10 ng/ml, respectively. All subjects were untreated for prostatic disease and underwent multisector needle biopsy of the prostate. An Elecsys 2010 analyzer was used to determine tPSA, free PSA (fPSA) and (-5, -7) proPSA in the 2,055 serum samples. ROC analyses were performed to discriminate men with biopsy positive and negative results in the entire and in select tPSA ranges. RESULTS: In the select tPSA range 2 to 4 ng/ml the area under the ROC curve for proPSA (0.53) and proPSA/fPSA (0.59) was not significantly larger than that for tPSA (0.60) or the fPSA/tPSA (f/tPSA) ratio (0.64). In the tPSA range 4 to 10 ng/ml the area under the curve for the ratio proPSA/fPSA (0.67) was larger than for tPSA (0.53) but not larger than for f/tPSA (0.69). The f/tPSA ratio demonstrated the best discriminatory power in this tPSA range of 4 to 10 ng/ml. CONCLUSIONS: In this multicenter study no improvement in diagnostic accuracy was shown when comparing (-5, -7) proPSA and the corresponding ratios with tPSA or f/tPSA. Further studies using other proPSA forms or tumor associated proteins should be done.

Adult↗
PubMed2005

Extraction and processing of high quality RNA from impalpable and macroscopically invisible prostate cancer for microarray gene expression analysis.

Molecular analyses of early-stage prostate cancers are necessary to assess their potential clinical significance based on established and/or novel biomarkers for tailored clinical management. A prerequisite for the application of RNA-based analyses of such, mostly macroscopically-undetectable, small prostate carcinomas is the recovery and preservation of sufficient RNA quantities and quality. Furthermore, in prostate cancer, heterogeneity is a common phenomenon that includes a juxtaposition of different tissue compositions and variable histological grades within the same tumor focus. To better understand the molecular mechanisms of prostate cancer, it is essential to correlate molecular data with a specific cell type. Here, we present a tissue collecting protocol which is aligned with the preoperative evaluation of tumor localization. In combination with the technique of laser microdissection and pressure catapulting, we are able to preserve RNA of high quality from homogeneous cell populations of macroscopically-undetectable small prostate carcinomas. To obtain the necessary RNA quantities for whole genome cDNA microarrays, the isolated total RNAs were amplified by T7-based RNA-polymerase in vitro transcription. The microarray analyses (Human Unigene Set RZPD3.1) resulted in 216 differentially expressed genes (191 down-regulated, 25 up-regulated). Among these were several known prostate cancer relevant genes, such as AMACR, TARP, LIM, GPR160 (all up-regulated), CAV1, NTN1, MT1X; CLU, TRIM29, SPARCL1 and HSPB8 (all down-regulated).

Down-Regulation↗
PubMed2004

Prostate-specific antigen and related isoforms in the diagnosis and management of prostate cancer.

Despite its unparalleled merits for prostate cancer detection and staging, prostate-specific antigen (PSA) is not a marker for prostate cancer only, but also is expressed in benign conditions. For early detection, limitations of PSA are obvious. Its widespread use has led to an extensive amount of expensive and often unnecessary diagnostic procedures associated with significant morbidity. Total PSA derivatives may enhance the accuracy of prostate cancer diagnosis. The ratio of free-to-total PSA improves specificity while maintaining a high sensitivity for prostate cancer detection for men with a total PSA of 2.5 to 10 ng/mL. Human glandular kallikrein also has the potential to be a valuable tool in combination with total and free PSA for early diagnosis of prostate cancer. Complex PSA seems to be a reliable tool to improve specificity at high sensitivity levels in men with suspected prostate cancer (mainly in PSA levels below 4 ng/mL). Newly discovered isoforms of free PSA also may impact early detection of prostate cancer with encouraging preliminary results that warrant further clinical investigation.

Humans↗
PubMed2004

Assessment of the enhancement in predictive accuracy provided by systematic biopsy in predicting outcome for clinically localized prostate cancer.

PURPOSE: Current localized prostate cancer treatment outcome nomograms rely on prostate specific antigen (PSA), tumor stage and grade. We investigated whether the addition of prostate biopsy features may enhance the accuracy of a nomogram predicting recurrence after radical prostatectomy (RP). MATERIALS AND METHODS: Clinical data from 1,152 patients who underwent RP were used and included PSA, clinical stage, biopsy Gleason grade and systematic biopsy information that quantified the amount of cancer and high grade cancer. Predictive accuracy for freedom from recurrence after RP was assessed with and without tumor quantification in the biopsy by the area under the receiver operating characteristics curve (AUC). RESULTS: Percentage and number of cores with cancer, and percentage and number of cores with high grade cancer were predictors of outcome when added to models that included PSA, Gleason grade and clinical stage (all p <0.0001). Nomogram accuracy with 3 traditional variables (AUC 0.790) was minimally enhanced with the addition of percentage or number of positive cores (AUC 0.804 and 0.800, respectively), or percentage or number of cores with high grade cancer (AUC 0.802 and 0.800, respectively). Maximum predictive accuracy of 0.811 was achieved after supplementing the traditional 3-variable nomogram with various combinations of additional pathological predictors. CONCLUSIONS: The information provided by systematic biopsies substantially improves the ability to predict outcome following RP. However, some incremental predictive accuracy was achieved by adding systematic biopsy features.

Adult↗
PubMed2003

Quantitative biopsy pathology for the prediction of pathologically organ-confined prostate carcinoma: a multiinstitutional validation study.

BACKGROUND: Quantitative biopsy pathology with prostate specific antigen significantly improves the prediction of pathologic stage in patients with clinically localized prostate carcinoma (PCa). The authors recently reported a computational model for predicting patient specific likelihood of organ confinement of PCa using biopsy pathology and clinical data. The current study validates the initial models and presents an new, improved tool for clinical decision making. METHODS: The authors assessed 10 biopsy pathologic parameters and 2 clinical parameters using data from two institutions. Of 1287 patients, 798 men had pathologically organ confined (OC) PCa, 282 men had nonorgan-confined disease with capsular penetration (NOC-CP) only, and 207 men showed seminal vesicle or lymph node invasion (NOC-AD) after undergoing pelvic lymphadenectomy and radical prostatectomy. Patient input data were evaluated by ordinal logistic (OLOGIT) and neural network (NN) models; and the likelihood of developing OC, NOC-CP, or NOC-AD disease was calculated for the combined and separate data sets and was compared with the results from original presentation. In addition, a new two-output model was constructed (OC/NOC-CP vs. NOC-AD). RESULTS: The three-output OLOGIT and NN models predicted OC disease with 95.0% and 98.6% accuracy, respectively, for the combined data set and with 93.0% and 98.6% accuracy, respectively, on subset analysis. The combined accuracy for predicting OC, NOC-CP, and NOC-AD disease in the entire validation set was 66.7% for OLOGIT model and 66.0% for the NN model. The two-output OLOGIT and NN models correctly predicted 94.9% and 100.0% of all OC/NOC-CP disease, respectively. CONCLUSIONS: Both computation models predicted OC PCa with an accuracy of 93.0-98.6% when they were validated with two different data sets. The OLOGIT and NN-based, two-output model permitted an appropriate treatment decision for 85.2-90.2% of patients. These data support the use of quantitative pathology and clinical data-based decision modeling to manage patients with clinically localized PCa.

Biopsy↗
PubMed2003

The role of human glandular kallikrein 2 for prediction of pathologically organ confined prostate cancer.

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.

Area Under Curve↗
PubMed2003

Can predictive models for prostate cancer patients derived in the United States of America be utilized in European patients? A validation study of the Partin tables.

OBJECTIVES: Prostate cancer patients in the US and Europe differ due to selection and treatment differences. Accuracy of predictive tools derived in the US might therefore suffer when applied to European patients. We tested the validity of the widely accepted Partin tables for their ability to predict pathologic stage in German patients. METHODS: Clinical and pathological characteristics were obtained from 1,298 consecutive men with clinically localized prostate cancer undergoing radical prostatectomy at the University Hospital Hamburg between January 1992 and February 2000. Receiver operating characteristic (ROC) curve analysis was performed to compare observed and predicted Partin rates for each pathologic stage. RESULTS: The rate for organ confinement was 56% in Hamburg patients compared to 48% in the Partin study. The rates of Hamburg patients for extracapsular extension without seminal vesicle or lymph node involvement were 25%, for seminal vesicle without lymph node involvement 14% and for lymph node metastases 5%. The corresponding rates of the Partin study were 40, 7 and 5%, respectively. The accuracy of Partin table derived probability was high with an area under the ROC curve of 0.817 (95% CI, 0.757-0.876) for organ confinement and 0.807 (95% CI, 0.781-0.833) for lymph node involvement. CONCLUSION: Our study demonstrated that predictive tools for prostate cancer developed in the US could be applied to European patients with comparable accuracy to that reported for validation studies performed with US patients.

Europe↗
PubMed2003

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.

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 (CaVolGl4) 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 CaVolGl4/5 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 CaVolGl4/5 (range 0.26 to 0.56, p = 0.021 and <0.0001, respectively). The tPSA level correlated significantly with CaVol and CaVolGl4/5 except in glands 42 cc or greater harboring pT2a/b PCa (p = 0.08). Free PSA correlated significantly with CaVolGl4/5 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.

Fluoroimmunoassay↗
PubMed2003

Standardization of two immunoassays for human glandular kallikrein 2.

BACKGROUND: Measurement of human kallikrein 2 (hK2) has improved early detection and staging of prostate cancer. However, reported concentrations of hK2 among currently used assays have not been standardized in any way. We compared two hK2 assays and five different recombinant hK2 variants (rhK2) and suggest a common calibrator as an important step and putative reference substance in hK2 assay standardization. METHODS: We measured 146 sera by two hK2 assays, using assay-specific calibrators to assess the difference between the two assays. Serial dilutions of five rhK2 preparations were measured repeatedly, with one preparation assigned as calibrator and the others as unknowns to define which variant provided the closest match between the two assays. This rhK2 variant was used to recalibrate both assays. We measured hK2 concentrations in the same 146 patients to evaluate the change in the difference. RESULTS: Use of assay-specific calibrators for comparison of the two assays yielded a Deming regression equation of: y = 0.789 (95% confidence interval, 0.674-0.922)x + 0.014 (0.004-0.025) micro g/L; R(2) = 0.667. Analysis of five rhK2 variants revealed that the enterokinase (ek)-rhK2 form provided the best match between both assays. Using the ek-rhK2 as a common calibrator, we observed a change in the slope of the regression curve to: y = 1.106 (0.872-1.340)x + 0.006 (-0.002 to 0.016) micro g/L; R(2) = 0.648, suggesting an increase in the mean estimate of agreement between the two assays. CONCLUSION: Calibration with a common calibrator substantially increased agreement between the assays. The ek-rhK2 variant provided the best performance of all tested rhK2 variants and should undergo mass spectrometry and amino acid analysis for exact mass determination and value assignment to evaluate its potential as a reference material for immunoassays for hK2.

Biomarkers, Tumor↗
PubMed2002

Validation of a biopsy-based pathologic algorithm for predicting lymph node metastases in patients with clinically localized prostate carcinoma.

BACKGROUND: The authors validated an algorithm for the preoperative prediction of lymph node (LN) metastases in patients with clinically localized prostate carcinoma. The algorithm was applied to sextant biopsy material and radical retropubic prostatectomy (RRP) stage obtained from a cohort of men who were treated at the authors' institution. METHODS: Four hundred forty-three patients underwent systematic sextant biopsy and RRP with staging lymphadenectomy. The original algorithm was based on systematic sextant biopsy data and classified patients into three risk groups for LN metastases based on the biopsy result. If > or = 4 of 6 biopsies contained any Gleason Pattern 4 disease, then the patient was at high risk for LN metastases (45%). Patients with > or = 1 of 6 biopsies with dominant Gleason Pattern 4 disease (excluding high-risk patients) had an intermediate predicted risk (19%) of LN metastases. All other patients had a low predicted risk of LN metastases (2.2%). The authors assed the percentage of patients who were positive and negative for LN metastases and calculated the specificity and negative predictive value in the series when patients were classified according to the original algorithm. RESULTS: Twenty of 443 patients had intraoperative LN metastases. When applied to the current data, the Hamburg algorithm classified 404 patients in the low-risk group, 30 patients in the intermediate-risk group, and 9 patients in the high risk group. The incidence of LN metastases was 2.47% in the low-risk group, 20% in the intermediate-risk group, and 44.4% in the high-risk group. The negative predictive value for the low-risk group was 97.52%, and the specificity was 94.14%. CONCLUSIONS: The Hamburg algorithm proved a valid tool for the prediction of lymphatic spread in this validation study on data from the authors' institution. The algorithm may serve as a tool to select patients who do not need to undergo pelvic lymphadenectomy at the time they undergo RRP, hence reducing morbidity and expense. More importantly, with the increasing numbers of men undergoing treatment options in whom LN dissection is not performed, this validated algorithm provides an important selection basis regarding the appropriateness of a therapy that does not routinely include LN staging.

Algorithms↗