- Email: [email protected]
PSA-DENSITY RATIO
861
862
FINGER-PRICK PSA TESTING. DO PSA LEVELS IN CAPILLARY CORRELATE WITH PSA LEVELS IN VENOUS BLOOD? Vaidyanathan R.1, Sharma M.1, Partridge M.2, Cochrane D.2, Emberton M.3, Karim O.1, Walker I.4, Davidson I.2 1 Wexham Park Hospital, Urology, Slough, United Kingdom, 2Mediwatch PLC, Biochemistry, Rugby, United Kingdom, 3University College London, Institute of Urology, London, United Kingdom, 4Wexham Park Hospital, Biochemistry, Slough, United Kingdom INTRODUCTION & OBJECTIVES: PSA is routinely used as a serological marker for diagnosis and surveillance of prostatic disease. We present the first clinical evaluation and feasibility study on collecting small quantities of fingerprick (capillary) blood for analysis with a new quantitative PSA assay (PSAwatchTM) using a portable, point-of-care reader system (BioScanTM). In addition, we try to determine if PSA levels in capillary correlate with PSA levels in venous blood. MATERIAL & METHODS: Following ethical approval and appropriate consent, venous (BloodV) and capillary (BloodC) blood samples were taken from men (n=68) attending outpatient clinic. A finger-prick was performed using the Accu-Check® Softclix®Pro (Roche) and BloodC was collected into a Microvette® CB300 (Sarsted, Nümbrecht, Germany). BloodC and BloodV was evaluated using the PSAwatchTM - BioScanTM system - 35μL aliquots of heparinised blood and 15μL of buffer were placed in the PSAwatchTM cassette, comprising of a porous cellulose membrane impregnated with monoclonal anti-PSA antibodies and gold sol. Antibody-PSA complexes induced an immuno-chromatographic response which was measured by the BioScanTM reader. BloodV was, in addition, submitted for laboratory (DPC Immulite 2000 3rd generation) PSA measurement. RESULTS: Following finger-prick, it was possible to get an adequate amount of BloodC for analysis from 65 men. Venesection failed on one occasion, therefore, both BloodV and BloodC, was available for only 64 men. Correlation between BloodV and BloodC PSA levels was strong (R2=0.977) across the range tested (054.92μg/L). CONCLUSIONS: A finger-prick gives an adequate amount of blood for PSA analysis and correlates strongly with PSA levels in venous blood. This is the first report and comparison of venous and capillary PSA concentrations using PSAwatchTM and the BioScanTM reader system. Capillary blood sampling and assay with PSAwatchTM will simplify PSA screening or surveillance of patients with prostatic disease.
PSAWATCH™ - A 10-MINUTE, QUANTITATIVE PSA ASSAY ON STORED PLASMA Vaidyanathan R.1, Sharma M.1, Partridge M.2, Cochrane D.2, Emberton M.3, Karim O.1, Walker I.4, Davidson I.2 Wexham Park Hospital, Urology, Slough, United Kingdom, 2Mediwatch Plc, Biochemistry, Rugby, United Kingdom, 3University College London, Institute of Urology, London, United Kingdom, 4Wexham Park Hospital, Biochemistry, Slough, United Kingdom
1
INTRODUCTION & OBJECTIVES: PSA is routinely used as a serological marker for diagnosis and surveillance of prostatic disease. PSAwatch™ has been developed as a 10 minute point-ofcare PSA assay for whole blood, serum and plasma. We present the first clinical experience of the PSAwatch™ assay on stored plasma using a portable reader system (BioScan™). MATERIAL & METHODS: Following appropriate consent, two blood samples were taken from men attending our outpatient clinic. One sample was submitted for laboratory serum PSA testing using industry standard assays. Plasma from the second sample was stored at 4ºC for subsequent analysis using the BioScan™ system. After equilibrating to room temperature, 35μL aliquots of plasma were placed in the PSAwatch™ cassette, comprising of a porous cellulose membrane impregnated with monoclonal anti-PSA antibodies and gold sol. Antibody-PSA complexes induced an immuno-chromatographic response to PSA which was measured by the BioScan™ reader. Plasma from 33 female volunteers served as negative controls. RESULTS: 192 men (age 18 to 87 yrs) were recruited to the study. Laboratory PSA values ranged from 0.01 – 977μg/L. Correlation between the two methods was strong across the whole of the range tested (R2= 0.99). The PSAwatch™ assay precision was <8%, across the range and demonstrated a specificity of 99.5% with sensitivity to 0.25μg/L.
CONCLUSIONS: This is the first clinical experience of a quantitative, portable, point-of-care PSA reader system using plasma. This study demonstrates the versatility of the PSAwatch™ system, which, in addition, to being a 10 minute point-of-care assay, may be used to measure PSA on stored plasma, batched from busy clinics.
863
864
DETECTION OF PROSTATE CANCER USING (F/T)PSA/PSA-DENSITY RATIO
CALCULATING PSA VELOCITY – THE SECRET OF SUCCESS? REGRESS!
Müller M., Kapanadze G., Obaje A., Seifert H.H., Ackermann R. Heinrich-Heine-University, Urology, Düsseldorf, Germany INTRODUCTION & OBJECTIVES: Prostate-specific antigen (PSA) is the most widely used diagnostic tool for detection of prostate cancer. Due its low specificity, many patients with an elevated tPSA level undergo unnecessary transrectal biopsy. A ratio of (f/t) PSA/PSA-density has been reported to improve specificity as it takes prostate volume into account. Aim of the study was to validate this marker in a subset of patients with 4 to 10 ng/ml serum PSA. MATERIAL & METHODS: From January 2000 to May 2005, a consecutive series of 1.000 men were submitted to ultrasound-guided prostate biopsies that included 221 cases with tPSA between 4-10 ng/ml and an available f/tPSA ratio measured by enzyme immunoassay (Elecsys 2010, Roche). All patients underwent transrectal ultrasound-guided octant biopsy of the prostate. PSA density was calculated based upon the sonographically determined gland volume and the tPSA level.
Connolly D.1, Black A.2, Napolitano G.2, Murray L.J.2, Gavin A.2, Keane P.F.1 Belfast City Hospital, Urology, Belfast, United Kingdom, 2Queen’s University Belfast, Northern Ireland Cancer Registry, Belfast, United Kingdom
1
INTRODUCTION & OBJECTIVES: A PSA velocity (PSAV) of greater than 0.75ng/ml/ year is associated with an increased risk of prostate cancer. There are a number of methods of calculating PSA velocity which have the potential to produce differing results from the same PSA data. We compared PSAV values calculated using two different methods to assess if a simple equation is adequate for everyday clinical use. MATERIAL & METHODS: The Northern Ireland Cancer Registry (NICR) maintains an electronic register of all PSA tests performed in Northern Ireland, which is linked to the NICR database of incident cancers occurring within the region. Hospital discharge and histopathology data are used to identify men with benign histology. Men with cancer or benign histology and an initial PSA less than 10ng/ml were identified. Those with at least three PSA tests before diagnosis, which were carried out over a minimum of 18 months were included. PSAV was calculated as the rate of change of PSA using two methods – linear regression (LR) analysis or an arithmetic equation (AE) of the mean of PSA difference divided by time difference. LR and AE PSAV values were also dichotomised to above or below 0.75 ng/ml/yr to examine the validity of each method for cancer diagnosis.
RESULTS: Prostate cancer was found to be present in 65 (29.5%) cases, 13 pts. had high grade intraepithelial neoplasia and the remaining 143 cases showed benign prostatic hyperplasia. Mean tPSA, f/tPSA, and PSA-density were 6.89 ng/ ml (4.07-9.93 ng/ml), 0.17 (0.01-0.85), and 0.21 ng (0.05-0.94 ng), respectively. Mean (f/t) PSA/PSA-density ratio was 1.325 (0.05-14.16). AUC of f/tPSA was significantly lower than for (f/t)PSA/PSA-density ratio (0.653 vs. 0.714). Analysis of the obtained ROC curves showed a significant correlation to diagnosis of PCa for both values. Using an f/tPSA cut-off value of 0.165, sensitivity was 77% and specificity 45%, while with the suggested (f/t) PSA/PSA-density ratio cut-off of 1.5, sensitivity increased to 90.8%, but yielding a lower specificity of 37.2%. Best results were achieved with a 0.82 cut-off, yielding 70.8% sensitivity and 65.4% specificity.
RESULTS: 2215 men were included, with 718 (32.4%) having cancer and 1497 (67.6%) benign histology. The mean and median difference in PSAV values when using the two methods were 2.62 and 0.28 ng/ml/year respectively. Only 32.2% of values had a difference of less than 0.1 ng/ml/yr, with 38.6% having a difference of greater than 0.5 ng/ml/yr (see Table). The differences between the two methods decreased as the minimum time interval between PSA tests increased (Spearman’s r<0.0001). LR had a higher sensitivity (69.1% vs. 64.6%) and specificity (72.9% vs. 69.1%) compared to AE using a 0.75 ng/ml/yr cut-off, with fewer men misclassified using the LR method.
CONCLUSIONS: In accordance with results reported previously by others, a significant improvement in sensitivity and specificity by the (f/t) PSA/PSA-density ratio was determined in this study. However, the cut-off for this value has to be identified for each patient population.
CONCLUSIONS: Calculating PSAV using LR and AE produced markedly different results for the same PSA data. The difference in values was related to the minimum time interval between PSA tests, with results from the AE method being affected by short time intervals. LR demonstrated a greater validity than AE and should be the method of choice for calculating PSAV.
Eur Urol Suppl 2006;5(2):238
PSAV difference (ng/ml/yr)
0-0.09
0.1-0.19
0.2-0.29
0.3-0.39
0.4-0.49
≥0.5
Number of men
713
270
156
126
94
856
Proportion (%)
32.2
12.2
7.0
5.1
4.2
38.6
862
FINGER-PRICK PSA TESTING. DO PSA LEVELS IN CAPILLARY CORRELATE WITH PSA LEVELS IN VENOUS BLOOD? Vaidyanathan R.1, Sharma M.1, Partridge M.2, Cochrane D.2, Emberton M.3, Karim O.1, Walker I.4, Davidson I.2 1 Wexham Park Hospital, Urology, Slough, United Kingdom, 2Mediwatch PLC, Biochemistry, Rugby, United Kingdom, 3University College London, Institute of Urology, London, United Kingdom, 4Wexham Park Hospital, Biochemistry, Slough, United Kingdom INTRODUCTION & OBJECTIVES: PSA is routinely used as a serological marker for diagnosis and surveillance of prostatic disease. We present the first clinical evaluation and feasibility study on collecting small quantities of fingerprick (capillary) blood for analysis with a new quantitative PSA assay (PSAwatchTM) using a portable, point-of-care reader system (BioScanTM). In addition, we try to determine if PSA levels in capillary correlate with PSA levels in venous blood. MATERIAL & METHODS: Following ethical approval and appropriate consent, venous (BloodV) and capillary (BloodC) blood samples were taken from men (n=68) attending outpatient clinic. A finger-prick was performed using the Accu-Check® Softclix®Pro (Roche) and BloodC was collected into a Microvette® CB300 (Sarsted, Nümbrecht, Germany). BloodC and BloodV was evaluated using the PSAwatchTM - BioScanTM system - 35μL aliquots of heparinised blood and 15μL of buffer were placed in the PSAwatchTM cassette, comprising of a porous cellulose membrane impregnated with monoclonal anti-PSA antibodies and gold sol. Antibody-PSA complexes induced an immuno-chromatographic response which was measured by the BioScanTM reader. BloodV was, in addition, submitted for laboratory (DPC Immulite 2000 3rd generation) PSA measurement. RESULTS: Following finger-prick, it was possible to get an adequate amount of BloodC for analysis from 65 men. Venesection failed on one occasion, therefore, both BloodV and BloodC, was available for only 64 men. Correlation between BloodV and BloodC PSA levels was strong (R2=0.977) across the range tested (054.92μg/L). CONCLUSIONS: A finger-prick gives an adequate amount of blood for PSA analysis and correlates strongly with PSA levels in venous blood. This is the first report and comparison of venous and capillary PSA concentrations using PSAwatchTM and the BioScanTM reader system. Capillary blood sampling and assay with PSAwatchTM will simplify PSA screening or surveillance of patients with prostatic disease.
PSAWATCH™ - A 10-MINUTE, QUANTITATIVE PSA ASSAY ON STORED PLASMA Vaidyanathan R.1, Sharma M.1, Partridge M.2, Cochrane D.2, Emberton M.3, Karim O.1, Walker I.4, Davidson I.2 Wexham Park Hospital, Urology, Slough, United Kingdom, 2Mediwatch Plc, Biochemistry, Rugby, United Kingdom, 3University College London, Institute of Urology, London, United Kingdom, 4Wexham Park Hospital, Biochemistry, Slough, United Kingdom
1
INTRODUCTION & OBJECTIVES: PSA is routinely used as a serological marker for diagnosis and surveillance of prostatic disease. PSAwatch™ has been developed as a 10 minute point-ofcare PSA assay for whole blood, serum and plasma. We present the first clinical experience of the PSAwatch™ assay on stored plasma using a portable reader system (BioScan™). MATERIAL & METHODS: Following appropriate consent, two blood samples were taken from men attending our outpatient clinic. One sample was submitted for laboratory serum PSA testing using industry standard assays. Plasma from the second sample was stored at 4ºC for subsequent analysis using the BioScan™ system. After equilibrating to room temperature, 35μL aliquots of plasma were placed in the PSAwatch™ cassette, comprising of a porous cellulose membrane impregnated with monoclonal anti-PSA antibodies and gold sol. Antibody-PSA complexes induced an immuno-chromatographic response to PSA which was measured by the BioScan™ reader. Plasma from 33 female volunteers served as negative controls. RESULTS: 192 men (age 18 to 87 yrs) were recruited to the study. Laboratory PSA values ranged from 0.01 – 977μg/L. Correlation between the two methods was strong across the whole of the range tested (R2= 0.99). The PSAwatch™ assay precision was <8%, across the range and demonstrated a specificity of 99.5% with sensitivity to 0.25μg/L.
CONCLUSIONS: This is the first clinical experience of a quantitative, portable, point-of-care PSA reader system using plasma. This study demonstrates the versatility of the PSAwatch™ system, which, in addition, to being a 10 minute point-of-care assay, may be used to measure PSA on stored plasma, batched from busy clinics.
863
864
DETECTION OF PROSTATE CANCER USING (F/T)PSA/PSA-DENSITY RATIO
CALCULATING PSA VELOCITY – THE SECRET OF SUCCESS? REGRESS!
Müller M., Kapanadze G., Obaje A., Seifert H.H., Ackermann R. Heinrich-Heine-University, Urology, Düsseldorf, Germany INTRODUCTION & OBJECTIVES: Prostate-specific antigen (PSA) is the most widely used diagnostic tool for detection of prostate cancer. Due its low specificity, many patients with an elevated tPSA level undergo unnecessary transrectal biopsy. A ratio of (f/t) PSA/PSA-density has been reported to improve specificity as it takes prostate volume into account. Aim of the study was to validate this marker in a subset of patients with 4 to 10 ng/ml serum PSA. MATERIAL & METHODS: From January 2000 to May 2005, a consecutive series of 1.000 men were submitted to ultrasound-guided prostate biopsies that included 221 cases with tPSA between 4-10 ng/ml and an available f/tPSA ratio measured by enzyme immunoassay (Elecsys 2010, Roche). All patients underwent transrectal ultrasound-guided octant biopsy of the prostate. PSA density was calculated based upon the sonographically determined gland volume and the tPSA level.
Connolly D.1, Black A.2, Napolitano G.2, Murray L.J.2, Gavin A.2, Keane P.F.1 Belfast City Hospital, Urology, Belfast, United Kingdom, 2Queen’s University Belfast, Northern Ireland Cancer Registry, Belfast, United Kingdom
1
INTRODUCTION & OBJECTIVES: A PSA velocity (PSAV) of greater than 0.75ng/ml/ year is associated with an increased risk of prostate cancer. There are a number of methods of calculating PSA velocity which have the potential to produce differing results from the same PSA data. We compared PSAV values calculated using two different methods to assess if a simple equation is adequate for everyday clinical use. MATERIAL & METHODS: The Northern Ireland Cancer Registry (NICR) maintains an electronic register of all PSA tests performed in Northern Ireland, which is linked to the NICR database of incident cancers occurring within the region. Hospital discharge and histopathology data are used to identify men with benign histology. Men with cancer or benign histology and an initial PSA less than 10ng/ml were identified. Those with at least three PSA tests before diagnosis, which were carried out over a minimum of 18 months were included. PSAV was calculated as the rate of change of PSA using two methods – linear regression (LR) analysis or an arithmetic equation (AE) of the mean of PSA difference divided by time difference. LR and AE PSAV values were also dichotomised to above or below 0.75 ng/ml/yr to examine the validity of each method for cancer diagnosis.
RESULTS: Prostate cancer was found to be present in 65 (29.5%) cases, 13 pts. had high grade intraepithelial neoplasia and the remaining 143 cases showed benign prostatic hyperplasia. Mean tPSA, f/tPSA, and PSA-density were 6.89 ng/ ml (4.07-9.93 ng/ml), 0.17 (0.01-0.85), and 0.21 ng (0.05-0.94 ng), respectively. Mean (f/t) PSA/PSA-density ratio was 1.325 (0.05-14.16). AUC of f/tPSA was significantly lower than for (f/t)PSA/PSA-density ratio (0.653 vs. 0.714). Analysis of the obtained ROC curves showed a significant correlation to diagnosis of PCa for both values. Using an f/tPSA cut-off value of 0.165, sensitivity was 77% and specificity 45%, while with the suggested (f/t) PSA/PSA-density ratio cut-off of 1.5, sensitivity increased to 90.8%, but yielding a lower specificity of 37.2%. Best results were achieved with a 0.82 cut-off, yielding 70.8% sensitivity and 65.4% specificity.
RESULTS: 2215 men were included, with 718 (32.4%) having cancer and 1497 (67.6%) benign histology. The mean and median difference in PSAV values when using the two methods were 2.62 and 0.28 ng/ml/year respectively. Only 32.2% of values had a difference of less than 0.1 ng/ml/yr, with 38.6% having a difference of greater than 0.5 ng/ml/yr (see Table). The differences between the two methods decreased as the minimum time interval between PSA tests increased (Spearman’s r<0.0001). LR had a higher sensitivity (69.1% vs. 64.6%) and specificity (72.9% vs. 69.1%) compared to AE using a 0.75 ng/ml/yr cut-off, with fewer men misclassified using the LR method.
CONCLUSIONS: In accordance with results reported previously by others, a significant improvement in sensitivity and specificity by the (f/t) PSA/PSA-density ratio was determined in this study. However, the cut-off for this value has to be identified for each patient population.
CONCLUSIONS: Calculating PSAV using LR and AE produced markedly different results for the same PSA data. The difference in values was related to the minimum time interval between PSA tests, with results from the AE method being affected by short time intervals. LR demonstrated a greater validity than AE and should be the method of choice for calculating PSAV.
Eur Urol Suppl 2006;5(2):238
PSAV difference (ng/ml/yr)
0-0.09
0.1-0.19
0.2-0.29
0.3-0.39
0.4-0.49
≥0.5
Number of men
713
270
156
126
94
856
Proportion (%)
32.2
12.2
7.0
5.1
4.2
38.6