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1171 COMBINATION OF URINE-BASED TUMOR MARKERS AND URINE CYTOLOGY IN THE DETECTION OF TRANSITIONAL CARCINOMA
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THE JOURNAL OF UROLOGY姞
tumor cells. These manipulated urothelial cells provoke false positive results due to secondary molecular changes in the UroVysion and the uCyt⫹ tests. The enormous false negative rate for patients with regular voided specimens underlines the association of mechanical manipulation with molecular changes. These observations stress the outstanding relevance of urinary sampling for the appropriate interpretation of urinary test for the early detection of TCC. Source of Funding: None
1171 COMBINATION OF URINE-BASED TUMOR MARKERS AND URINE CYTOLOGY IN THE DETECTION OF TRANSITIONAL CARCINOMA Christian Schwentner*, Joerg Hennenlotter, Ursula Kuehs, Henriette Sleiman, Daniela Colleselli, Severine Huber, David Schilling, KarlDietrich Sievert, Arnulf Stenzl, Tuebingen, Germany INTRODUCTION AND OBJECTIVES: The number of noninvasive diagnostic tests for transitional cell carcinoma (TCC) has increased tremendously over the last years with a large number of experimental and commercial tests being available. However, their relevance in the diagnostic regimen remains to be discussed. These tests are usually combined with plain urinary cytology (Cyt). Still there are no recommendations on the preferred combinations. Herein, we evaluate whether addition of one of the urine based tumor markers uCyt⫹ (DiagnoCure), UroVysion (Vysis) or NMP22 ELISA (Matritech) to routine cytology Cyt increases the predictive value of urine-based tests for TCC. METHODS: Urine Cyt and urine tests uCyt⫹ (DiagnoCure), UroVysion (Vysis) and NMP22 ELISA (Matritech) were performed in 723 patients without any history of TCC prior to cystoscopy with or without transurethral resection. Sensitivity, specificity and accuracy were determined for every single marker as well as for all possible combinations of Cyt with any of the aforementioned tests. Combinations were considered positive if at least one marker was positive and all tests regarding the respective combination were performed. Results were compared descriptively and interpreted for clinical use. RESULTS: Histological evidence for TCC was found in 92 (12.7%) patients. The tumor stages were as follows: Ta 56.4%, T1 17.0%, ⱖT2 24.1%. Of those, 34.2% were low-grade TCCs and 65.8% were high-grade TCCs. Overall sensitivity was 80.8%, 68.5%, 82.1% and 72.6% for Cyt, UroVsion, uCyt⫹ and NMP22, respectively. Specificity was 89.0%, 88.0%, 82.6% and 42.6%. Accuracy was 87.5%, 85.6%, 82.6% and 46.8%, respectively. If Cyt was combined with UroVysion, uCyt⫹ and NMP22 test sensitivities were 81.5%, 85.5% and 90.4%, respectively. Specifities were 84.6%, 76.7% and 39.2% while accuracy was 84.2%, 78.0% and 46.4%, respectively. CONCLUSIONS: Within the evaluated cohort, sensitivity of the uCyt⫹ test was superior to the values of the remaining tests whereas cytology offers the best specifity as well as the highest accuracy. Every additional urine based marker increases the sensitivity of plain Cyt with NMP22 being most sensitive. However, especially in this combination specificity decreases dramatically. Given our data, the combination of Cyt and UroVysion is the most efficient combination with sensitivity, specificity and accuracy above 81%. Nevertheless, it is important to keep in mind that any adjunct to routine Cyt will decrease test specificity. Hence, individual decision-making is required to avoid unnecessary urinary tract instrumentation. Source of Funding: None
Vol. 183, No. 4, Supplement, Monday, May 31, 2010
1172 HEMATURIA: HELPFUL OR MISLEADING FOR THE EARLY DETECTION OF TRANSITIONAL CELL CARCINOMA– RESULTS FROM A COHORT OF 2008 PATIENTS Christian Schwentner*, Joerg Hennenlotter, Ursula Kuehs, Veronika Tews, Daniela Colleselli, Severine Huber, David Schilling, Karl-Dietrich Sievert, Arnulf Stenzl, Tuebingen, Germany INTRODUCTION AND OBJECTIVES: Several non-invasive urine tests are currently available in the diagnosis of transitional cell carcinoma (TCC). However, their accuracy remains limited. Hematuria (HU), a widespread phenomenon in diagnosing TCC, may influence the results. Herein, we evaluate the impact of HU on urine cytology, the UroVysion FISH test (VysisR), the NPM22 ELISA (Matritech) and the uCyt⫹-test (DiagnoCure). METHODS: A cohort of 2008 consecutive patients suspected to have TCC underwent multimarker testing of the 4 mentioned tests followed by cystoscopy and -in case of suspicious findings- transurethral resection. HU was determined by Combur 10 evaluation and urine microscopy, whereby every sign of blood was deemed to be HU. The test results were compared to the HU status by contingency analysis and Chi-square tests separated for patients without evidence of TCC and with histologically proven TCC. RESULTS: For the UroVysion test, false positive results occurred in 17.4 and 20.7% of patients without and with HU, respectively (p⫽0.135). False negative results were seen in 40.0 and 26.9% of patients without and with HU (p⫽0.104). For the NMP22 test, false positive results occurred in 35.8 and 66.2% of patients without and with HU, respectively (p⬍0.001). False negative results were noted in 54.1 and 20.7% of patients without and with HU (p⬍0.001). For the uCyt⫹ test, false positive results occurred in 11.1 and 25.0% of patients without and with HU, respectively (p⫽0.0002). False negative results were detected in 55.0 and 20.8% of patients without and with HU (p⫽0.0027). For cytology, false positive results occurred in 12.9 and 17.8% of patients without and with HU, respectively (p⫽0.012). False negative results appeared in 37.2 and 17.9% of patients without and with HU (p⫽0.0002). CONCLUSIONS: HU did not influence the diagnostic properties of the UroVysion test. In contrast to that, the results of NMP22 and the uCyt⫹ test were directly dependent on the HU-status. Therefore, both, false positivity in the absence of TCC, as well as false negativity in the presence of significant TCC may occur. Moreover, urine cytology was found to be similarly influenced by HU. Persistent HU itself may alter the cytological status leading to further invasive measures. These results underline the relevance of the HU-status for the appropriate interpretation of urine tests. Source of Funding: None
1173 EARLY DETECTION OF TRANSITIONAL CELL CARCINOMA – PREDICTIVE POWER OF URINE-BASED TUMOR MARKERS WITH REGARD TO TUMOR GRADE AND STAGE Christian Schwentner*, Joerg Hennenlotter, Ursula Kuehs, Henriette Sleiman, Daniela Colleselli, Severine Huber, David Schilling, KarlDietrich Sievert, Arnulf Stenzl, Tuebingen, Germany INTRODUCTION AND OBJECTIVES: The number of noninvasive diagnostic tests for transitional cell carcinoma (TCC) has increased tremendously over the last years with a large number of experimental and commercial tests being available. However, their relevance in the diagnostic regimen remains controversial. Routine cytology (Cyt) is nowadays frequently combined with molecular tests. The aim of this study was to comparatively evaluate the predictive value of urine Cyt, the UroVysion FISH test (Vysis), the NPM22 ELISA (Matritech) and the uCyt⫹ test (DiagnoCure) regarding tumor grade and stage. METHODS: Urine Cyt and urine tests uCyt⫹ (DiagnoCure), UroVysion (Vysis) and NMP22 ELISA (Matritech) were performed in
THE JOURNAL OF UROLOGY姞
tumor cells. These manipulated urothelial cells provoke false positive results due to secondary molecular changes in the UroVysion and the uCyt⫹ tests. The enormous false negative rate for patients with regular voided specimens underlines the association of mechanical manipulation with molecular changes. These observations stress the outstanding relevance of urinary sampling for the appropriate interpretation of urinary test for the early detection of TCC. Source of Funding: None
1171 COMBINATION OF URINE-BASED TUMOR MARKERS AND URINE CYTOLOGY IN THE DETECTION OF TRANSITIONAL CARCINOMA Christian Schwentner*, Joerg Hennenlotter, Ursula Kuehs, Henriette Sleiman, Daniela Colleselli, Severine Huber, David Schilling, KarlDietrich Sievert, Arnulf Stenzl, Tuebingen, Germany INTRODUCTION AND OBJECTIVES: The number of noninvasive diagnostic tests for transitional cell carcinoma (TCC) has increased tremendously over the last years with a large number of experimental and commercial tests being available. However, their relevance in the diagnostic regimen remains to be discussed. These tests are usually combined with plain urinary cytology (Cyt). Still there are no recommendations on the preferred combinations. Herein, we evaluate whether addition of one of the urine based tumor markers uCyt⫹ (DiagnoCure), UroVysion (Vysis) or NMP22 ELISA (Matritech) to routine cytology Cyt increases the predictive value of urine-based tests for TCC. METHODS: Urine Cyt and urine tests uCyt⫹ (DiagnoCure), UroVysion (Vysis) and NMP22 ELISA (Matritech) were performed in 723 patients without any history of TCC prior to cystoscopy with or without transurethral resection. Sensitivity, specificity and accuracy were determined for every single marker as well as for all possible combinations of Cyt with any of the aforementioned tests. Combinations were considered positive if at least one marker was positive and all tests regarding the respective combination were performed. Results were compared descriptively and interpreted for clinical use. RESULTS: Histological evidence for TCC was found in 92 (12.7%) patients. The tumor stages were as follows: Ta 56.4%, T1 17.0%, ⱖT2 24.1%. Of those, 34.2% were low-grade TCCs and 65.8% were high-grade TCCs. Overall sensitivity was 80.8%, 68.5%, 82.1% and 72.6% for Cyt, UroVsion, uCyt⫹ and NMP22, respectively. Specificity was 89.0%, 88.0%, 82.6% and 42.6%. Accuracy was 87.5%, 85.6%, 82.6% and 46.8%, respectively. If Cyt was combined with UroVysion, uCyt⫹ and NMP22 test sensitivities were 81.5%, 85.5% and 90.4%, respectively. Specifities were 84.6%, 76.7% and 39.2% while accuracy was 84.2%, 78.0% and 46.4%, respectively. CONCLUSIONS: Within the evaluated cohort, sensitivity of the uCyt⫹ test was superior to the values of the remaining tests whereas cytology offers the best specifity as well as the highest accuracy. Every additional urine based marker increases the sensitivity of plain Cyt with NMP22 being most sensitive. However, especially in this combination specificity decreases dramatically. Given our data, the combination of Cyt and UroVysion is the most efficient combination with sensitivity, specificity and accuracy above 81%. Nevertheless, it is important to keep in mind that any adjunct to routine Cyt will decrease test specificity. Hence, individual decision-making is required to avoid unnecessary urinary tract instrumentation. Source of Funding: None
Vol. 183, No. 4, Supplement, Monday, May 31, 2010
1172 HEMATURIA: HELPFUL OR MISLEADING FOR THE EARLY DETECTION OF TRANSITIONAL CELL CARCINOMA– RESULTS FROM A COHORT OF 2008 PATIENTS Christian Schwentner*, Joerg Hennenlotter, Ursula Kuehs, Veronika Tews, Daniela Colleselli, Severine Huber, David Schilling, Karl-Dietrich Sievert, Arnulf Stenzl, Tuebingen, Germany INTRODUCTION AND OBJECTIVES: Several non-invasive urine tests are currently available in the diagnosis of transitional cell carcinoma (TCC). However, their accuracy remains limited. Hematuria (HU), a widespread phenomenon in diagnosing TCC, may influence the results. Herein, we evaluate the impact of HU on urine cytology, the UroVysion FISH test (VysisR), the NPM22 ELISA (Matritech) and the uCyt⫹-test (DiagnoCure). METHODS: A cohort of 2008 consecutive patients suspected to have TCC underwent multimarker testing of the 4 mentioned tests followed by cystoscopy and -in case of suspicious findings- transurethral resection. HU was determined by Combur 10 evaluation and urine microscopy, whereby every sign of blood was deemed to be HU. The test results were compared to the HU status by contingency analysis and Chi-square tests separated for patients without evidence of TCC and with histologically proven TCC. RESULTS: For the UroVysion test, false positive results occurred in 17.4 and 20.7% of patients without and with HU, respectively (p⫽0.135). False negative results were seen in 40.0 and 26.9% of patients without and with HU (p⫽0.104). For the NMP22 test, false positive results occurred in 35.8 and 66.2% of patients without and with HU, respectively (p⬍0.001). False negative results were noted in 54.1 and 20.7% of patients without and with HU (p⬍0.001). For the uCyt⫹ test, false positive results occurred in 11.1 and 25.0% of patients without and with HU, respectively (p⫽0.0002). False negative results were detected in 55.0 and 20.8% of patients without and with HU (p⫽0.0027). For cytology, false positive results occurred in 12.9 and 17.8% of patients without and with HU, respectively (p⫽0.012). False negative results appeared in 37.2 and 17.9% of patients without and with HU (p⫽0.0002). CONCLUSIONS: HU did not influence the diagnostic properties of the UroVysion test. In contrast to that, the results of NMP22 and the uCyt⫹ test were directly dependent on the HU-status. Therefore, both, false positivity in the absence of TCC, as well as false negativity in the presence of significant TCC may occur. Moreover, urine cytology was found to be similarly influenced by HU. Persistent HU itself may alter the cytological status leading to further invasive measures. These results underline the relevance of the HU-status for the appropriate interpretation of urine tests. Source of Funding: None
1173 EARLY DETECTION OF TRANSITIONAL CELL CARCINOMA – PREDICTIVE POWER OF URINE-BASED TUMOR MARKERS WITH REGARD TO TUMOR GRADE AND STAGE Christian Schwentner*, Joerg Hennenlotter, Ursula Kuehs, Henriette Sleiman, Daniela Colleselli, Severine Huber, David Schilling, KarlDietrich Sievert, Arnulf Stenzl, Tuebingen, Germany INTRODUCTION AND OBJECTIVES: The number of noninvasive diagnostic tests for transitional cell carcinoma (TCC) has increased tremendously over the last years with a large number of experimental and commercial tests being available. However, their relevance in the diagnostic regimen remains controversial. Routine cytology (Cyt) is nowadays frequently combined with molecular tests. The aim of this study was to comparatively evaluate the predictive value of urine Cyt, the UroVysion FISH test (Vysis), the NPM22 ELISA (Matritech) and the uCyt⫹ test (DiagnoCure) regarding tumor grade and stage. METHODS: Urine Cyt and urine tests uCyt⫹ (DiagnoCure), UroVysion (Vysis) and NMP22 ELISA (Matritech) were performed in