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1266 MOLECULAR BIOMARKER SIGNATURE FOR THE NON-INVASIVE DETECTION OF BLADDER CANCER
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THE JOURNAL OF UROLOGY姞
METHODS: A total of 362 NMIBC suspected patients were included in the trial based on positive urinary cytology and/or ultrasonographic suspicion of bladder tumors. The 181 cases of the study group underwent both WLC and HAL-BLC, while patients in the control group benefited from standard cystoscopy alone. A single postoperative mytomicin-C instillation was performed in all resection cases. No additional instillations were used in low risk patients, while adjuvant chemotherapy was applied in intermediate risk cases and BCG immunotherapy for high risk patients. The follow-up protocol consisted of abdominal ultrasound, urinary cytology and WLC, performed every 3 months for a period of 2 years and every 6 months in the third year. RESULTS: In the 142 NMIBC patients of the study group, HALBLC emphasized significantly improved CIS (95.2% versus 71.4%), pTa (95.3% versus 87.1%) and overall (95.8% versus 85.9%) cases’ detection rates. Additional tumors were found by HAL-BLC in a significantly higher proportion of cases (35.2% versus 14.1%). Consequently, the recurrence (16.2% versus 4.9%) and progression (21.1% versus 7%) risk categories of patients changed significantly due to HAL-BLC by comparison to WLC. As a result, the postoperative treatment was modified due to HAL-BLC for a significantly larger proportion of patients (19% versus 6.3%). A total of 115 and respectively 106 NMIBC cases of the two study arms completed the 36 months’ evaluation period. The 3 months’ recurrence rate was significantly lower in the HAL-BLC series (6.9% versus 15.1%) due to fewer other site recurrences (0.9% versus 6.6%). During the long term follow-up, the overall 1 (20.9% versus 31.1%), 2 (30.4% versus 44.3%) and 3 (35.6% versus 51.9%) years’ recurrence rates were significantly reduced in the HAL-BLC study arm. CONCLUSIONS: HAL-BLC emphasized superior NMIBC patients’ detection rates as well as a significant impact in terms of additional tumors’ cases, risk category changes and postoperative treatment modifications. Subsequently, the 3 months’, 1, 2 and 3 years’ recurrence rates were significantly improved in the HAL-BLC group. Source of Funding: None
1265 NUCLEAR MATRIX PROTEIN 22 (NMP22) AS URINE-BASED TUMOR MARKER FOR DETECTION OF PRIMARY AND RECURRENT BLADDER CANCER: COMPARISON OF THE POINT-OF-CARE VERSION (BLADDERCHEK®) AND THE ELISA Georgios Hatzichristodoulou*, Hubert Kuebler, Munich, Germany; Hartwig Schwaibold, Reutlingen, Germany; Stefan Wagenpfeil, Cornelia Eibauer, Christian Hofer, Juergen Gschwend, Uwe Treiber, Munich, Germany INTRODUCTION AND OBJECTIVES: To compare the diagnostic efficacy of the two available Nuclear Matrix Protein 22 (NMP22) assay formats, which are the NMP22 ELISA and the NMP22 BladderChek, as urine-based tumor markers for the detection of primary and recurrent bladder cancer (BC). METHODS: In this prospective study n⫽ 100 patients with pathohistological proven bladder cancer were included. A group of n⫽ 70 patients with benign urological diseases and a group of n⫽ 30 healthy volunteers served as controls. The urine of all patients was examined with the NMP22 ELISA and the NMP22 BladderChek (Alere, Scarborough, USA). Sensitivities and specificities were calculated for each test and compared against each other. Special focus was set in analysing subgroups of patients with primary and recurrent BC. RESULTS: From 100 patients with bladder cancer 71 had primary cancer and 29 recurrent carcinoma. Patients in all groups were comparable in terms of age and sex distribution. Sensitivities of the NMP22 BladderChek were calculated as 59%, 63% and 48% in the overall group, the patients with primary tumor and the group with recurrent cancer, respectively. Sensitivities of the NMP22 ELISA in these groups were 40%, 42% and 34%, respectively. The differences within each of the groups were not statistically significant. In the groups of overall tumor patients and patients with primary cancer sensitivities of the NMP22 BladderChek and the NMP22 ELISA significantly increased with advanced T-stage and grade.
Vol. 187, No. 4S, Supplement, Monday, May 21, 2012
Specificities of both test versions were 100% each in healthy individuals. Furthermore, in patients with benign urological diseases specificities of both assay formats were as high as in healthy individuals and showed no significant difference (BladderChek: 93% vs. ELISA: 99%). CONCLUSIONS: Direct comparison of the two assay formats of NMP22 showed no significant superiority of one of them, although the BladderChek yielded higher values for sensitivities. The BladderChek offers some advantages like on-site processing, immediate availability of results, easy performance and cost effectiveness and is therefore prefered. Due to the aforementioned sensitivities, NMP22 is not able to replace cystoscopy in the diagnosis and follow-up of BC patients. Source of Funding: None
1266 MOLECULAR BIOMARKER SIGNATURE FOR THE NON-INVASIVE DETECTION OF BLADDER CANCER Virginia Urquidi, Steve Goodison, Orlando, FL; Yunpeng Cai, Yijun Sun, Gainesville, FL; Charles Rosser*, Orlando, FL INTRODUCTION AND OBJECTIVES: Bladder cancer (BCa) is among the five most common malignancies world-wide, and due to high rates of recurrence, one of the most prevalent. Improvements in non-invasive urine-based assays to detect BCa would benefit both patients and healthcare systems. In this study, we applied genomewide expression profiling to exfoliated urothelia to obtain a diagnostic signature of BCa in urine samples. METHODS: We prospectively analyzed the urine specimens from 92 subjects (52 BCa and 40 non-BCa). Fifty milliliters of urine was obtained by urinary bladder barbotage. Urine samples were centrifuged, total RNA was extracted and prepared for hybridization to Affymetrix Human Genome arrays (U133A). Next, fifty milliliters of voided urine was obtained from an independent cohort comprised of 81 subjects (44 BCa and 37 non-BCa). Urine samples were centrifuged and total RNA was extracted. A panel of targets from the microarray data were validated in voided urine samples from using quantitative PCR. Statistical analyses of data identified 14 cancer-associated genes (p ⬍ 0.001). RESULTS: Using sophisticated bio-informatics and selection algorithm an accurate BCa diagnostic signature comprised of 44 genes was identified from the microarray assay. Through PCR analysis of 44 targets in an independent urine sample set, we derived an optimal diagnostic signature. A 14-gene molecular classifier was able to discriminate subjects with and without BCa, achieving a specificity of 100% at 90% sensitivity. CONCLUSIONS: We are the first group to report genomic analysis of urine samples to identify a BCa diagnostic signature. A robust BCa diagnostic signature was discovered and validated. Further refinement of a multi-gene urothelial cell signature will facilitate the accurate non-invasive detection and surveillance of BCa. Source of Funding: NIH/NCI, Department of Health James and Esther King Foundation, FAMRI
1267 IS THERE A VALUE OF CEA AND CA19-9 IN TRANSITIONAL CELL CARCINOMA OF THE BLADDER ? SEROLOGICAL AND IMMUNHISTOLOGICAL FINDINGS Verena Mecklenburg, Marburg, Germany; Zoltan Varga, Sigmaringen, Germany; Peter Olbert, Rainer Hofmann, Axel Hegele*, Marburg, Germany INTRODUCTION AND OBJECTIVES: Since reliable markers predicting presence, muscle invasiveness or metastatic TCC have not been established up to now, cystoscopy, causing discomfort to the pat, represents still the goldstandard in diagnosis of TCC. The aim of the present study was to evaluate the clinical value of CEA and Ca19-9 as a tumor marker in the diagnosis of TCC and to determine the relationship between the marker levels and the histopathological results.
THE JOURNAL OF UROLOGY姞
METHODS: A total of 362 NMIBC suspected patients were included in the trial based on positive urinary cytology and/or ultrasonographic suspicion of bladder tumors. The 181 cases of the study group underwent both WLC and HAL-BLC, while patients in the control group benefited from standard cystoscopy alone. A single postoperative mytomicin-C instillation was performed in all resection cases. No additional instillations were used in low risk patients, while adjuvant chemotherapy was applied in intermediate risk cases and BCG immunotherapy for high risk patients. The follow-up protocol consisted of abdominal ultrasound, urinary cytology and WLC, performed every 3 months for a period of 2 years and every 6 months in the third year. RESULTS: In the 142 NMIBC patients of the study group, HALBLC emphasized significantly improved CIS (95.2% versus 71.4%), pTa (95.3% versus 87.1%) and overall (95.8% versus 85.9%) cases’ detection rates. Additional tumors were found by HAL-BLC in a significantly higher proportion of cases (35.2% versus 14.1%). Consequently, the recurrence (16.2% versus 4.9%) and progression (21.1% versus 7%) risk categories of patients changed significantly due to HAL-BLC by comparison to WLC. As a result, the postoperative treatment was modified due to HAL-BLC for a significantly larger proportion of patients (19% versus 6.3%). A total of 115 and respectively 106 NMIBC cases of the two study arms completed the 36 months’ evaluation period. The 3 months’ recurrence rate was significantly lower in the HAL-BLC series (6.9% versus 15.1%) due to fewer other site recurrences (0.9% versus 6.6%). During the long term follow-up, the overall 1 (20.9% versus 31.1%), 2 (30.4% versus 44.3%) and 3 (35.6% versus 51.9%) years’ recurrence rates were significantly reduced in the HAL-BLC study arm. CONCLUSIONS: HAL-BLC emphasized superior NMIBC patients’ detection rates as well as a significant impact in terms of additional tumors’ cases, risk category changes and postoperative treatment modifications. Subsequently, the 3 months’, 1, 2 and 3 years’ recurrence rates were significantly improved in the HAL-BLC group. Source of Funding: None
1265 NUCLEAR MATRIX PROTEIN 22 (NMP22) AS URINE-BASED TUMOR MARKER FOR DETECTION OF PRIMARY AND RECURRENT BLADDER CANCER: COMPARISON OF THE POINT-OF-CARE VERSION (BLADDERCHEK®) AND THE ELISA Georgios Hatzichristodoulou*, Hubert Kuebler, Munich, Germany; Hartwig Schwaibold, Reutlingen, Germany; Stefan Wagenpfeil, Cornelia Eibauer, Christian Hofer, Juergen Gschwend, Uwe Treiber, Munich, Germany INTRODUCTION AND OBJECTIVES: To compare the diagnostic efficacy of the two available Nuclear Matrix Protein 22 (NMP22) assay formats, which are the NMP22 ELISA and the NMP22 BladderChek, as urine-based tumor markers for the detection of primary and recurrent bladder cancer (BC). METHODS: In this prospective study n⫽ 100 patients with pathohistological proven bladder cancer were included. A group of n⫽ 70 patients with benign urological diseases and a group of n⫽ 30 healthy volunteers served as controls. The urine of all patients was examined with the NMP22 ELISA and the NMP22 BladderChek (Alere, Scarborough, USA). Sensitivities and specificities were calculated for each test and compared against each other. Special focus was set in analysing subgroups of patients with primary and recurrent BC. RESULTS: From 100 patients with bladder cancer 71 had primary cancer and 29 recurrent carcinoma. Patients in all groups were comparable in terms of age and sex distribution. Sensitivities of the NMP22 BladderChek were calculated as 59%, 63% and 48% in the overall group, the patients with primary tumor and the group with recurrent cancer, respectively. Sensitivities of the NMP22 ELISA in these groups were 40%, 42% and 34%, respectively. The differences within each of the groups were not statistically significant. In the groups of overall tumor patients and patients with primary cancer sensitivities of the NMP22 BladderChek and the NMP22 ELISA significantly increased with advanced T-stage and grade.
Vol. 187, No. 4S, Supplement, Monday, May 21, 2012
Specificities of both test versions were 100% each in healthy individuals. Furthermore, in patients with benign urological diseases specificities of both assay formats were as high as in healthy individuals and showed no significant difference (BladderChek: 93% vs. ELISA: 99%). CONCLUSIONS: Direct comparison of the two assay formats of NMP22 showed no significant superiority of one of them, although the BladderChek yielded higher values for sensitivities. The BladderChek offers some advantages like on-site processing, immediate availability of results, easy performance and cost effectiveness and is therefore prefered. Due to the aforementioned sensitivities, NMP22 is not able to replace cystoscopy in the diagnosis and follow-up of BC patients. Source of Funding: None
1266 MOLECULAR BIOMARKER SIGNATURE FOR THE NON-INVASIVE DETECTION OF BLADDER CANCER Virginia Urquidi, Steve Goodison, Orlando, FL; Yunpeng Cai, Yijun Sun, Gainesville, FL; Charles Rosser*, Orlando, FL INTRODUCTION AND OBJECTIVES: Bladder cancer (BCa) is among the five most common malignancies world-wide, and due to high rates of recurrence, one of the most prevalent. Improvements in non-invasive urine-based assays to detect BCa would benefit both patients and healthcare systems. In this study, we applied genomewide expression profiling to exfoliated urothelia to obtain a diagnostic signature of BCa in urine samples. METHODS: We prospectively analyzed the urine specimens from 92 subjects (52 BCa and 40 non-BCa). Fifty milliliters of urine was obtained by urinary bladder barbotage. Urine samples were centrifuged, total RNA was extracted and prepared for hybridization to Affymetrix Human Genome arrays (U133A). Next, fifty milliliters of voided urine was obtained from an independent cohort comprised of 81 subjects (44 BCa and 37 non-BCa). Urine samples were centrifuged and total RNA was extracted. A panel of targets from the microarray data were validated in voided urine samples from using quantitative PCR. Statistical analyses of data identified 14 cancer-associated genes (p ⬍ 0.001). RESULTS: Using sophisticated bio-informatics and selection algorithm an accurate BCa diagnostic signature comprised of 44 genes was identified from the microarray assay. Through PCR analysis of 44 targets in an independent urine sample set, we derived an optimal diagnostic signature. A 14-gene molecular classifier was able to discriminate subjects with and without BCa, achieving a specificity of 100% at 90% sensitivity. CONCLUSIONS: We are the first group to report genomic analysis of urine samples to identify a BCa diagnostic signature. A robust BCa diagnostic signature was discovered and validated. Further refinement of a multi-gene urothelial cell signature will facilitate the accurate non-invasive detection and surveillance of BCa. Source of Funding: NIH/NCI, Department of Health James and Esther King Foundation, FAMRI
1267 IS THERE A VALUE OF CEA AND CA19-9 IN TRANSITIONAL CELL CARCINOMA OF THE BLADDER ? SEROLOGICAL AND IMMUNHISTOLOGICAL FINDINGS Verena Mecklenburg, Marburg, Germany; Zoltan Varga, Sigmaringen, Germany; Peter Olbert, Rainer Hofmann, Axel Hegele*, Marburg, Germany INTRODUCTION AND OBJECTIVES: Since reliable markers predicting presence, muscle invasiveness or metastatic TCC have not been established up to now, cystoscopy, causing discomfort to the pat, represents still the goldstandard in diagnosis of TCC. The aim of the present study was to evaluate the clinical value of CEA and Ca19-9 as a tumor marker in the diagnosis of TCC and to determine the relationship between the marker levels and the histopathological results.