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125 Urinary-to-serum PSA ratio: Comparison with free-to-total serum PSA in improving detection of prostate cancer
125 URINARY-TO-SERUM TOTAL SERUM CANCER Irani’,
PSA
PSA RATIO: IN IMPROVING
COMPARISON DETECTION
Salomon L.*, SouliC M.3, Zlotta A.“, Millet
WITH OF
FREE-TOPROSTATE
C.’
‘CHU la MilCtrie, Department of Urology, Poitiers, France, 2CHU Mondor, Department of Urology, CrCteil, France, ‘Centre Hospital& Universitaire, Department of Urology, Toulouse, France, Ylniversity Hospital Erasme, Department of Urology, Bmxelles, Belgium INTRODUCTION & OBJECTIVES: Previous studies have reported that the ratio of urinary PSA and total serum PSA (U/S) improves the detection of men with prostate cancer. We tested this hypothesis by evaluating the clinical usefulness of this U/S PSA ratio and comparing it to the free-to-total (F/T) serum PSA ratio. MATERIAL & METHODS: One hundred and sixty five patients undergoing transrectal ultrasound-guided prostate biopsy were prospectively included in this multicentric study. PSA was measured preoperatively (Kryptor assay) in all patients from serum and 12.hour urine specimens in a centralized laboratory. RESULTS: Among the 165 patients, 83 (50.3%) had prostate cancer identified on their biopsy. Differences between patients without and with prostate cancer were statistically significant (p
U/S PSA ratioc6.8 U/S PSA ratio>=6.8
Cancer 13 2
(n= 15)
CONCLUSIONS: Our results confirm that U/S PSA ratio may be a useful test in prostate cancer detection when total serum PSA is between 4 and 10 ngiml. F/T serum PSA ratio and U/S PSA ratio are not correlated. This suggests that these 2 tests could complement each other particularly when F/T serum PSA ratio is in the grey zone.
126 IMPORTANCE PROSTATE
OF [-7]PROPSA CANCER WITHIN
FORM TOTAL
Kwiatkowski
M., Huber
F.
Kantonsspital
Aarau,
A., Reeker
Clinic
of Urology,
FOR EARLY DETECTION PSA RANGE 4-10 NG/ML
Aarau,
Savoca
R.2, Reeker
GLANDULAR PCA GRADE
KALLIKREIN ASSESSMENT
Kwiatkowski
M.‘,
‘Kantonsspital Aarau, Centre
Aarau, Clinic of Urology, Aarau, Switzerland, of Laboratory Medicine, Aarau, Switzerland
2 (HK2) WITHIN
F.’ *Kantonsspital
INTRODUCTION & OBJECTIVES: Recent studies have revealed that free prostate-specific antigen (PSA) is composed of several serum forms. One of these is proPSA, PSA precursor form containing a 7 amino acid pro-leader peptide. Another emerging tumour marker is human glandular kallikrein 2 (hK2), a new serum marker with 80% structure similarity to PSA. The aim of this study was to investigate the usefulness of [-7]proPSA and hK2 for identification of high grade (Gleason 7-10) prostate cancers (PCs) within total PSA (tPSA) range l-10 ngiml. MATERIAL & METHODS: Men participating in a prospective PSA-based screening study for PCs (1998-2002). 106 PCs cases (histologically confirmed by ultrasound guided sextant prostate biopsy) within total PSArange l-10 ngiml have been included in the study. 85 had Gleason <=6 (Group 1) and 21 had Gleason >=7 (Group 2). [-7]proPSA and hK2 were determined by using a research assay on Elecsys (electrochemiluminescence immunoassay; Roche Diagnostics GmbH, Germany). tPSA and free PSA (fPSA) were determined by Elecsys PSA and Elecsys free PSA (Roche Diagnostics GmbH, Germany). Various combinations of PSA total and free, [-7]proPSA form and hK2 were investigated by multivariate logistic regression analysis.
Switzerland
INTRODUCTION & OBJECTIVES: Recent studies have revealed that free prostate-specific antigen (PSA) is composed of several serum forms. One of these is proPSA, PSA precursor form containing a 7 amino acid pro-leader peptide. The aim of this study was to investigate the usefulness of [-7]proPSA, to identify prostate cancer (PCs) within total PSA (tPSA) range 4-10 &ml. MATERIAL & METHODS: Men participating in a prospective randomised PSA-based screening study for PCs (1998-2002). 67 PCs and 224 BPH cases (all histologically confirmed by ultrasound guided sextant prostate biopsy) within total PSA range 4-10 ngiml have been included in the study. [-71 proPSA was determined by using a research assay on Elecsys (electrochemiluminescence immunoassay; Roche Diagnostics GmbH, Germany). tPSA and free PSA (fPSA) were determined by Elecsys PSA and Elecsys free PSA (Roche Diagnostics GmbH, Germany). Various combinations of PSA total and free and [-71 proPSA were investigated by multivariate logistic regression analysis. The overall diagnostic performance has been investigated by means of receiver operating characteristic (ROC) curves analysis. RESULTS: Median tPSA was 5.4 ngiml and 5.3 rig/ml (n.s.), free-to-total PSA ratio (F/T ratio) 0.130 and 0.159 (p
127 EVALUATION OF PSA, HUMAN AND [-7]PROPSA FORM FOR TOTAL PSA RANGE l-10 NG/ML
OF
128 SERUM CONCENTRATIONS OF HUMAN 2 (HK2) BUT NOT FREE PSA, TOTAL DISCRIMINATION OF PATHOLOGICALLY FROM NON-ORGAN CONFINED (NOC), STAGE TlC) PROSTATE CANCER
GLANDULAR KALLIKREIN PSA OR %FPSA PERMIT ORGAN-CONFINED (OC) NON-PALPABLE (CLINkAi
Haese’, Vaisanen Vz, Lilja H.‘, Pettersson I<.*, Sokoll L.“, Rittenhouse H.5, Huland H.‘, Ghan D.4, Partin A.6 ‘University Clinic Hamburg-Eppendorf, Department of Urology, Hamburg, Germany, 2University of Turku, Department of Biotechnology, Turku. Finland, ‘Memorial Sloan Kettering Cancer Centre, Department of Clinical Laboratories, Urology, and Medicine, New York, United States, 4The Johns Hopkins University Medical Institutions. Department of Pathology, Baltimore, United States, 5Hybritech Beckman Coulter Inc, Clinical Research, San Diego, United States, “The Johns Hopkms University Medxal Institutions, Department of Urology, Baltimore. United States INTRODUCTION & OBJECTIVES: Previously, human glandular kallikrein 2 (hK2) in sewn has been found to be useful for prediction of pathologically organ confined prostate cancer (PCs) in patients with climcally localized, palpable stage T2 disease. Here, we re-evaluated the utility of hK2, measured by two unmunoassays with distinctly different designs, to enhance discrimination of pathologically organ-confined non-palpable (clinical stage Tic) PCs. MATERIAL & METHODS: Swxn from 148 men v&h clinical stage T1 c PCs was analyzed for hK2 with two research assays. Total and free PSAwas measured with the Hybrltech Access Total and eee PSAassays. The ratlo of free to total PSA was calculated. We calculated a previously described algorithm, hK2*tPSA/tXA from data generated by each hK&xssay, and calculated means, medians and ranges for each analyte and computed-algorithms first in pT2aib vs. ?pT3a/b (including lymph node positive) PCs and subsequently m pTZa/b vs. pT3ah and pT2aib vs. pT3a hunours. Significance of difference was assessed using Mann-Whitney U analysis. Recewer-Operator Characteristics analyses were used to determine Areas under the Curve for each analyte and algorithm followed by evaluation of sensitivity and specificity Multivariate backward stepwise loglstlc regression analysis assessed the predictive performance of tPSA, each hK2 assay alone and computed hk7-algorithms.
RESULTS: Median tPSAwas 4.0 ngiml and 5.0 rig/ml (n.s.) and free-to-total PSA ratio (F/T ratio) 0.135 and 0.132 (ns.) in group 1 and 2, respectively. %proPSA calculated as ratio [-7]proPSA to fPSA was 0.682 in group 1 and 0.597 in group 2 (p
RESULTS: HK2 concentrations alone, measured by each assay, and hK2-based algorithms were significantly different (p=O.O34-0.0001) for pT2aib vs. ZpT3a PCs, compared to no significant difference in levels of tPSA (p=O.O6), free PSA (p=O.90) or %fPSA (0.059). Tins difference was maintained after elimination of pT3b and lymph-node positive patients. Likewise, hK2 gave higher AUC than any form of PSA. At 95% sensitwity for organ-confined cancer the tPSA gave 1.8% specificity compared to 12 to 21% specificity for hK2 as a single analyte or the hK2*tPSA/iPSA+.lgorithm. By multivaiate logistic regression analysis. hK2 alone or as NU*tPSAifPSA-algorithm (measured by each assay) were independent predictors of pTZ-stage whereas %fPSA and tPSA were not. Comparison of present results to earlier studies consistently demonstrated the AUC of hK2 to be greater than the AUC for PSA for both hK2 assays.
CONCLUSIONS: In total PSA range l-10 rig/ml, %proPSA was significantly lower and hK2 was significantly higher in PCs with Gleason 7-10 grade as compared to Gleason 6 or less. The PCs evaluation with several markers may be a promising approach for more precise identification of aggressive disease. Because of small number of cases within wide range of total PSA, this study should be considered preliminary.
CONCLUSIONS: The current and previously reported results find AUC’s for hK2 measured by each research assay to be higher than AUC’s for any forms of PSA in the discrimination of pT2alb from ?pT3a. For the first time, it is shown that hK2 alone or hKZZ*tPSA/fPSA, measured by two assays with distinctly different analytical designs, sigmficantly enhances preoperative discrimination of men with pT2aib vs. those with ?pT3a -PCs compared to tPSA, fPSA or %IPSA in a third, demographically and geographically different set of men with Tic PCs. Hence, inclusion of IX2 in the preoperahve biochemical evaluation of PCs may prowde significant improvement in the selection ofpatIents with PCs, which may receive optimal benefit from radical prostatectomy.
European
Urology
Supplements
3 (2004)
No. 2, pp. 34
PSA
PSA RATIO: IN IMPROVING
COMPARISON DETECTION
Salomon L.*, SouliC M.3, Zlotta A.“, Millet
WITH OF
FREE-TOPROSTATE
C.’
‘CHU la MilCtrie, Department of Urology, Poitiers, France, 2CHU Mondor, Department of Urology, CrCteil, France, ‘Centre Hospital& Universitaire, Department of Urology, Toulouse, France, Ylniversity Hospital Erasme, Department of Urology, Bmxelles, Belgium INTRODUCTION & OBJECTIVES: Previous studies have reported that the ratio of urinary PSA and total serum PSA (U/S) improves the detection of men with prostate cancer. We tested this hypothesis by evaluating the clinical usefulness of this U/S PSA ratio and comparing it to the free-to-total (F/T) serum PSA ratio. MATERIAL & METHODS: One hundred and sixty five patients undergoing transrectal ultrasound-guided prostate biopsy were prospectively included in this multicentric study. PSA was measured preoperatively (Kryptor assay) in all patients from serum and 12.hour urine specimens in a centralized laboratory. RESULTS: Among the 165 patients, 83 (50.3%) had prostate cancer identified on their biopsy. Differences between patients without and with prostate cancer were statistically significant (p
U/S PSA ratioc6.8 U/S PSA ratio>=6.8
Cancer 13 2
(n= 15)
CONCLUSIONS: Our results confirm that U/S PSA ratio may be a useful test in prostate cancer detection when total serum PSA is between 4 and 10 ngiml. F/T serum PSA ratio and U/S PSA ratio are not correlated. This suggests that these 2 tests could complement each other particularly when F/T serum PSA ratio is in the grey zone.
126 IMPORTANCE PROSTATE
OF [-7]PROPSA CANCER WITHIN
FORM TOTAL
Kwiatkowski
M., Huber
F.
Kantonsspital
Aarau,
A., Reeker
Clinic
of Urology,
FOR EARLY DETECTION PSA RANGE 4-10 NG/ML
Aarau,
Savoca
R.2, Reeker
GLANDULAR PCA GRADE
KALLIKREIN ASSESSMENT
Kwiatkowski
M.‘,
‘Kantonsspital Aarau, Centre
Aarau, Clinic of Urology, Aarau, Switzerland, of Laboratory Medicine, Aarau, Switzerland
2 (HK2) WITHIN
F.’ *Kantonsspital
INTRODUCTION & OBJECTIVES: Recent studies have revealed that free prostate-specific antigen (PSA) is composed of several serum forms. One of these is proPSA, PSA precursor form containing a 7 amino acid pro-leader peptide. Another emerging tumour marker is human glandular kallikrein 2 (hK2), a new serum marker with 80% structure similarity to PSA. The aim of this study was to investigate the usefulness of [-7]proPSA and hK2 for identification of high grade (Gleason 7-10) prostate cancers (PCs) within total PSA (tPSA) range l-10 ngiml. MATERIAL & METHODS: Men participating in a prospective PSA-based screening study for PCs (1998-2002). 106 PCs cases (histologically confirmed by ultrasound guided sextant prostate biopsy) within total PSArange l-10 ngiml have been included in the study. 85 had Gleason <=6 (Group 1) and 21 had Gleason >=7 (Group 2). [-7]proPSA and hK2 were determined by using a research assay on Elecsys (electrochemiluminescence immunoassay; Roche Diagnostics GmbH, Germany). tPSA and free PSA (fPSA) were determined by Elecsys PSA and Elecsys free PSA (Roche Diagnostics GmbH, Germany). Various combinations of PSA total and free, [-7]proPSA form and hK2 were investigated by multivariate logistic regression analysis.
Switzerland
INTRODUCTION & OBJECTIVES: Recent studies have revealed that free prostate-specific antigen (PSA) is composed of several serum forms. One of these is proPSA, PSA precursor form containing a 7 amino acid pro-leader peptide. The aim of this study was to investigate the usefulness of [-7]proPSA, to identify prostate cancer (PCs) within total PSA (tPSA) range 4-10 &ml. MATERIAL & METHODS: Men participating in a prospective randomised PSA-based screening study for PCs (1998-2002). 67 PCs and 224 BPH cases (all histologically confirmed by ultrasound guided sextant prostate biopsy) within total PSA range 4-10 ngiml have been included in the study. [-71 proPSA was determined by using a research assay on Elecsys (electrochemiluminescence immunoassay; Roche Diagnostics GmbH, Germany). tPSA and free PSA (fPSA) were determined by Elecsys PSA and Elecsys free PSA (Roche Diagnostics GmbH, Germany). Various combinations of PSA total and free and [-71 proPSA were investigated by multivariate logistic regression analysis. The overall diagnostic performance has been investigated by means of receiver operating characteristic (ROC) curves analysis. RESULTS: Median tPSA was 5.4 ngiml and 5.3 rig/ml (n.s.), free-to-total PSA ratio (F/T ratio) 0.130 and 0.159 (p
127 EVALUATION OF PSA, HUMAN AND [-7]PROPSA FORM FOR TOTAL PSA RANGE l-10 NG/ML
OF
128 SERUM CONCENTRATIONS OF HUMAN 2 (HK2) BUT NOT FREE PSA, TOTAL DISCRIMINATION OF PATHOLOGICALLY FROM NON-ORGAN CONFINED (NOC), STAGE TlC) PROSTATE CANCER
GLANDULAR KALLIKREIN PSA OR %FPSA PERMIT ORGAN-CONFINED (OC) NON-PALPABLE (CLINkAi
Haese’, Vaisanen Vz, Lilja H.‘, Pettersson I<.*, Sokoll L.“, Rittenhouse H.5, Huland H.‘, Ghan D.4, Partin A.6 ‘University Clinic Hamburg-Eppendorf, Department of Urology, Hamburg, Germany, 2University of Turku, Department of Biotechnology, Turku. Finland, ‘Memorial Sloan Kettering Cancer Centre, Department of Clinical Laboratories, Urology, and Medicine, New York, United States, 4The Johns Hopkins University Medical Institutions. Department of Pathology, Baltimore, United States, 5Hybritech Beckman Coulter Inc, Clinical Research, San Diego, United States, “The Johns Hopkms University Medxal Institutions, Department of Urology, Baltimore. United States INTRODUCTION & OBJECTIVES: Previously, human glandular kallikrein 2 (hK2) in sewn has been found to be useful for prediction of pathologically organ confined prostate cancer (PCs) in patients with climcally localized, palpable stage T2 disease. Here, we re-evaluated the utility of hK2, measured by two unmunoassays with distinctly different designs, to enhance discrimination of pathologically organ-confined non-palpable (clinical stage Tic) PCs. MATERIAL & METHODS: Swxn from 148 men v&h clinical stage T1 c PCs was analyzed for hK2 with two research assays. Total and free PSAwas measured with the Hybrltech Access Total and eee PSAassays. The ratlo of free to total PSA was calculated. We calculated a previously described algorithm, hK2*tPSA/tXA from data generated by each hK&xssay, and calculated means, medians and ranges for each analyte and computed-algorithms first in pT2aib vs. ?pT3a/b (including lymph node positive) PCs and subsequently m pTZa/b vs. pT3ah and pT2aib vs. pT3a hunours. Significance of difference was assessed using Mann-Whitney U analysis. Recewer-Operator Characteristics analyses were used to determine Areas under the Curve for each analyte and algorithm followed by evaluation of sensitivity and specificity Multivariate backward stepwise loglstlc regression analysis assessed the predictive performance of tPSA, each hK2 assay alone and computed hk7-algorithms.
RESULTS: Median tPSAwas 4.0 ngiml and 5.0 rig/ml (n.s.) and free-to-total PSA ratio (F/T ratio) 0.135 and 0.132 (ns.) in group 1 and 2, respectively. %proPSA calculated as ratio [-7]proPSA to fPSA was 0.682 in group 1 and 0.597 in group 2 (p
RESULTS: HK2 concentrations alone, measured by each assay, and hK2-based algorithms were significantly different (p=O.O34-0.0001) for pT2aib vs. ZpT3a PCs, compared to no significant difference in levels of tPSA (p=O.O6), free PSA (p=O.90) or %fPSA (0.059). Tins difference was maintained after elimination of pT3b and lymph-node positive patients. Likewise, hK2 gave higher AUC than any form of PSA. At 95% sensitwity for organ-confined cancer the tPSA gave 1.8% specificity compared to 12 to 21% specificity for hK2 as a single analyte or the hK2*tPSA/iPSA+.lgorithm. By multivaiate logistic regression analysis. hK2 alone or as NU*tPSAifPSA-algorithm (measured by each assay) were independent predictors of pTZ-stage whereas %fPSA and tPSA were not. Comparison of present results to earlier studies consistently demonstrated the AUC of hK2 to be greater than the AUC for PSA for both hK2 assays.
CONCLUSIONS: In total PSA range l-10 rig/ml, %proPSA was significantly lower and hK2 was significantly higher in PCs with Gleason 7-10 grade as compared to Gleason 6 or less. The PCs evaluation with several markers may be a promising approach for more precise identification of aggressive disease. Because of small number of cases within wide range of total PSA, this study should be considered preliminary.
CONCLUSIONS: The current and previously reported results find AUC’s for hK2 measured by each research assay to be higher than AUC’s for any forms of PSA in the discrimination of pT2alb from ?pT3a. For the first time, it is shown that hK2 alone or hKZZ*tPSA/fPSA, measured by two assays with distinctly different analytical designs, sigmficantly enhances preoperative discrimination of men with pT2aib vs. those with ?pT3a -PCs compared to tPSA, fPSA or %IPSA in a third, demographically and geographically different set of men with Tic PCs. Hence, inclusion of IX2 in the preoperahve biochemical evaluation of PCs may prowde significant improvement in the selection ofpatIents with PCs, which may receive optimal benefit from radical prostatectomy.
European
Urology
Supplements
3 (2004)
No. 2, pp. 34