- Email: [email protected]
URINARY - BASED TUMOUR MARKERS EVALUATED EITHER BY WHITE LIGHT OR PHOTODYNAMIC TRANSURETHRAL RESECTION IN BLADDER CANCER. IS THERE ANY DIFFERENCE?
THE JOURNAL OF UROLOGY®
Vol. 181, No. 4, Supplement, Monday, April 27, 2009
imaging revealed histologic distinctions between normal and neoplastic urothelium comparable to standard H&E analysis. Pending further technologic development and clinical validation, confocal endomicroscopy may emerge as a valuable adjunct to cystoscopy for minimally invasive diagnosis of bladder neoplasms.
Source of Funding: Stanford Cancer Center Developmental Cancer Research Award
1163 NARROW BAND IMAGING FLEXIBLE CYSTOSCOPY: AN UPDATE AND A NEW USER’S EXPERIENCE Richard T Bryan*, Birmingham, United Kingdom; Z H Shah, Reading, United Kingdom; Stuart I Collins, D. Michael A Wallace, Birmingham, United Kingdom INTRODUCTION AND OBJECTIVES: We have previously demonstrated a significantly improved detection rate for bladder cancer recurrences with narrow band imaging (NBI) flexible cystoscopy when compared with conventional white-light imgaing (WLI) flexible cystoscopy. We investigated whether a “new user” of NBI flexible cystoscopy, previously unfamiliar with this technique, could reproduce our results. METHODS: The same protocol from our initial study was continued into this second study at The Queen Elizabeth Hospital, Birmingham, UK, but with a “new user” (ZHS): between September 2007 and May 2008 NBI flexible cystoscopy was performed on 23 patients with known recurrences of urothelial cancer (UC) of the bladder following initial conventional WLI flexible cystoscopy with the same switchable Olympus Lucera sequential RGB instrument. RESULTS: In our first series (published), NBI detected a total of 15 additional UCs in 12 of 29 patients (41%), as compared with WLI: a mean difference of 0.52 UCs per patient (standard deviation 0.74; Wilcoxon paired signed-rank test p-value 0.0005). In this second series, NBI detected 15 additional UCs in 8 of the 23 patients (35%): six of these patients had one additional UC, one had four additional UCs, and one had five additional UCs when compared with WLI, with a mean of 0.65 additional UCs per patient (SD1.30; Wilcoxon p=0.01). When the second series with the “new user” is compared with the first series, there is no statistical evidence that the excess number of UCs detected by NBI is different (Wilcoxon (unpaired) signed-rank test p=0.74), suggesting that there is no difference between a new user and an experienced user in the application of NBI. When the two series are combined, NBI detected 30 additional UCs in 20 of 52 patients (38%): 16 patients had one additional UC, and one each had two, three, four and five additional UCs, with a mean of 0.58 additional UCs per patient overall (SD 1.02; Wilcoxon paired signed-rank test p<0.001). CONCLUSIONS: A new user can obtain the same significant benefits with NBI as an experienced user in improving the detection rate of bladder UC recurrences. We continue to demonstrate a significant benefit of NBI flexible cystoscopy in the follow-up of patients with bladder cancer. Source of Funding: KeyMed Olympus (UK) and Olympus (Japan) provided the authors with the flexible cystoscopy equipment required to carryout this study.
415
1164 MAIN PREDICTORS OF FALSE POSITIVES IN PHOTODYNAMIC DIAGNOSIS OF TRANSITIONAL CELL CARCINOMA OF THE BLADDER Ronald O.P. Draga*, Matthijs C.M. Grimbergen, Esther T. Kok, Trudy Jonges, Ruud Bosch, Utrecht, Netherlands INTRODUCTION AND OBJECTIVES: Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violet-blue light. The specificity is approximately 50%. The aim of the study is to identify the main predictors of false positives in multivariate analysis. The second objective is to determine the optimal waiting period after transurethral resection of bladder tumors (TURBT) and intravesical therapy (IVT) to minimize the number of false positives in PDD. METHODS: Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Age, gender, recent TURBT, previous IVT, urinary tract infections (UTIs) and tumor classification were examined for association with the false-positive rates in fluorescence cystoscopy. RESULTS: The sensitivity and specificity of white light endoscopy (WLE) and PDD are 71% and 76%, 96% and 43%, respectively. Significant univariate associations are found between false positives and female gender (p=0.007, OR=2.01), IVT instillations (p=0.02, OR=1.85), Bacille Calmette-Guérin instillations (BCG; p=0.03, OR=2.16) and TURBT in the past 90 days (p=0.01, OR=2.23). In multivariate analysis female gender (p=0.001, OR=2.68) and TURBT within 90 days before PDD (p=0.01, OR=2.27) are the only significant independent predictors of false positives. In a second multivariate model the dichotomous variable ‘>1 BCG instillation in the past 90 days’ is the only predictor for falsepositive findings in PDD (p=0.002, OR=4.67). Tangential illumination of the bladder wall does not seem to result in additional false positives. The false-positive rate decreases during the first 12 weeks after the latest TURBT and the latest BCG instillation. CONCLUSIONS: Female gender, previous TURBT and recent BCG instillations are important predictors of false positives in PDD. The false-positive rate decreases during the first 12 weeks after the latest TURBT and the latest BCG instillation. We recommend to perform a fluorescence guided TURBT 9-12 weeks after an incomplete first resection of low or intermediate risk non-muscle invasive tumors and 9-12 weeks after the latest BCG instillation. Source of Funding: The Dutch Cancer Society, grant-number UU 2007-3922
1165 URINARY - BASED TUMOUR MARKERS EVALUATED EITHER BY WHITE LIGHT OR PHOTODYNAMIC TRANSURETHRAL RESECTION IN BLADDER CANCER. IS THERE ANY DIFFERENCE? Marcus Horstmann*, Tuebingen, Germany; Oliver Patschan, Malmoe, Sweden; Joerg Hennenlotter, Daniela Colleselli, Gerhard Feil, Arnulf Stenzl, Tuebingen, Germany INTRODUCTION AND OBJECTIVES: Photodynamic diagnostic (PDD) improves the detection of transitional cell carcinoma of the bladder (TCC). Still sensitivity and specificity of urinary-based tumour markers and cytology have been validated only by white light cystoscopy or resection (WL). Aim of this study was to evaluate how the sensitivity and specificity of urinary-based tumor markers changes if either WL TUR or photodynamic TUR were used. METHODS: Cytology, FISH, U-Cyt+, and NMP22 were evaluated prior to transurethral resection in 335 serial patients with the suspicion of primary TCC (n=163) or TCC recurrence (n=172) of the bladder. In each case histopathological results served as a control. PDD was used in 112 patients during resection. BCa was found in 128 (57%) out of 223 (100%) patients in WL and in 70 (62%) out of 112 (100) patients in PDD.
THE JOURNAL OF UROLOGY®
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Vol. 181, No. 4, Supplement, Monday, April 27, 2009
Tumours found in WL were n=74 pTa (58%), n=15 pT1 (12%), n=21 q pT2 (16%), and 17 pCis (13%) and in PDD n=45 pTa (64%), n=7 pT1 (10%), n=6 q pT2 (9%), and n=12 pCis (17%). RESULTS: Sensitivity, specificity, and accuracy of the markers for both groups were as follows: Sensitifity Sensitivity % Specifity Accuracy Specifity % PDD % % PDD WL (n=223) (n=112) WL WL
Marker
Accuracy % PDD
clinical impact of CK-20 as an indicator of lymph node micrometastases and prognosticator for disease progression in combination with an extended pelvic lymphadenectomy. Source of Funding: Gruber Stiftung Munich
1167
Cytology
79
84
74
49
77
70
NESTED UROTHELIAL CARCINOMA: A CLINICOPATHOLOGIC AND IMMUNOHISTOCHEMICAL ANALYSIS OF 33 CASES
FISH
66
81
75
49
75
69
Matthew Wasco, Deborah Bradley, Rajal B Shah*, Ann Arbor, MI
NMP22
69
73
48
30
60
57
U-Cyt+
77
75
69
48
73
65
INTRODUCTION AND OBJECTIVES: Urothelial carcinoma (UC) with nested growth pattern is a rare and less studied variant of UC, characterized by deceptively bland morphology resembling small von Brunn s nests, yet aggressive biology. METHODS: We analyzed a series of 33 patients with nested UC who underwent definitive treatment to better understand its clinicopathological spectrum, immunophenotype and clinical outcome. Tumors demonstrating either pure or mixed nested morphology with variable component of conventional UC were included. RESULTS: Patients age ranged from 41 to 81 years (avg 65) with a male: female ratio of 2.7:1. Pure nested UCs accounted for 33% of cases. When seen along with conventional UC, the nested component ranged from 30% to 90%. Of the 22 cases associated with conventional UC, 29% had an additional component of divergent differentiation. Muscle invasion at TURBT and extravesical disease ( T3) at cystectomy were observed in 82% and 83% of cases respectively (p <0.0001 compared to non-nested highgrade UC). Angiolymphatic invasion was common (73%). In comparison to pure conventional high grade UC, nested UCs were associated with metastatic disease, in the form of lymph node and/or distant metastases (16% vs 72% p <0.0001). Behavior was similarly aggressive whether tumor was pure nested or mixed nested. Despite overall bland morphology, nested component demonstrated random high grade atypia, specifically in the deeper invasive component. Growth patterns of nested component ranged from haphazard small isolated nests to areas with confluent nested growth with minimal desmoplasia. When associated with conventional UC, the nested component was part of the deeply invasive tumor. Nested UCs demonstrated immunophenotype similar to conventional UC (94% CK7+, 68% CK20+, 93% K903+, and 93% p63+). Follow-up was available on 31 patients, and ranged from 1 to 31 months (average 12). 18% of patients died of disease, and 36% of patients were alive with disease at last followup. 16/33 patients (48%) received neoadjuvant chemotherapy, only two had response to therapy. 24 patients were treated with cystectomy, 1 with nephroureterectomy, another 3 were treated with TURBT only, and 5 received radiation. Seven (21%) patients received adjuvant chemotherapy. CONCLUSIONS: UC demonstrating pure or variable component of nested morphology is an aggressive tumor with uniformly bad outcome. Increased awareness of the spectrum of this tumor and its early recognition is important due to its subtle and heterogeneous morphology.
Results showed as indicated above a better sensitivity for all markers in the PDD group and a worse specificity and also accuracy. CONCLUSIONS: PDD improved the sensitivity but not the specificity and accuracy of the tumour markers in this group of patients. As there is strong evidence that PDD is currently the best diagnostic tool for BCa PDD and not WL should be used for the validation of urinarybased tumour markers. Source of Funding: None
1166 MOLECULAR STAGING OF LYMPH NODES FROM MUSCLEINVASIVE BLADDER CANCER PATIENTS BY RT-PCR COMPARED TO PATHOLOGIC FINDINGS - ARE THERE DIFFERENCES IN LOCALIZATION AND DETECTION RATES? Michael Autenrieth*, Roman Nawroth, Saskia Semmlack, Gregor Weirich, Juergen E Gschwend, Margitta Retz, Munich, Germany INTRODUCTION AND OBJECTIVES: Detection of lymph nodes metastases is an important prognosticator for progression-free survival after radical cystectomy. Currently, a large German multicenter study (LEA, AUO AB 25/02) is active for patients undergoing radical cystectomy with pelvic lymphadenectomy. Patients are randomized to receive either a conventional or extended lymphadenectomy (complete pelvic lymph nodes up to the inferior mesenteric artery) . The aim of this study was to investigate molecular staging and detection of lymph node metastases that are not identified with classical histopathological methods along with the LEA clinical study. METHODS: For detection of occult disseminated bladder tumor cells we established a RT-PCR protocol. As a marker for micrometastases in lymph nodes we analyzed the expression of cytokeratin-20 (CK-20) which is expressed in urothelial bladder cancer cells but not in blood and lymph nodes. In total 758 out of 1499 lymph nodes were suitable for molecular analysis by RT-PCR. Lymph nodes were cartographically localized according to the LEA study. Each lymph node was divided in two halves. One half was examined by a pathologists applying conventional histology. The second half was assessed by frozen section histopathology as well as prepared for RNA extraction followed by a CK20 nested RT-PCR. RESULTS: Histopathological examination revealed 19 out of 758 lymph nodes (2.5%) as positive. All of them were confirmed to be CK-20 positive. By CK-20 RT-PCR 103 (13.6%) out of 739 histopathologically negative lymph nodes were CK-20 positive. Depending on the mode of lymphadenectomy 51 lymph node micrometastases were found in the extended lymphadenectomy group, whereas 52 lymph node micrometastases were detected in the standard lymphadenectomy group. Nearly one third (16/51; 31.4%) of CK-20 positive nodes were located outside the standard lymphadenectomy field. More than 13% (7/51) of CK-20 positive lymph nodes were located in the paraaortic and paracaval field. Skip metastasis were neither detected by conventional pathology nor by CK-20 RT-PCR. CONCLUSIONS: CK-20 RT-PCR is a specific and sensitive method for the detection of occult tumor cells in lymph nodes from bladder cancer patients. Long-term observation will be necessary to evaluate the
Source of Funding: None
1168 DOES SCREENING FOR BLADDER CANCER PRODUCE A STAGE MIGRATION TOWARDS NON-MUSCLE INVASIVE CANCERS? Alexandre R Zlotta, Toronto, ONCanada; Thierry Roumeguere, Brussels, Belgium; Sultan S. Alkhateeb*, Toronto, ONCanada; Sandrine Rorive, Anne Lemy, Isabelle Salmon, Martin Wissing, Daniel Abramowicz, Claude Schulman, Brussels, Belgium; Neil E. Fleshner, Michael A s Jewett, Toronto, ONCanada; Joelle Nortier, Brussels, Belgium INTRODUCTION AND OBJECTIVES: In the last 3 decades, sadly, the presentation of bladder cancer has not changed much where 25% of new cases are still muscle-invasive at first diagnosis. Although intuitively it should, it is unproven whether screening for bladder cancer could detect more bladder tumors at a non-muscle invasive stage. The goal of this study is to evaluate the potential benefits of bladder
Vol. 181, No. 4, Supplement, Monday, April 27, 2009
imaging revealed histologic distinctions between normal and neoplastic urothelium comparable to standard H&E analysis. Pending further technologic development and clinical validation, confocal endomicroscopy may emerge as a valuable adjunct to cystoscopy for minimally invasive diagnosis of bladder neoplasms.
Source of Funding: Stanford Cancer Center Developmental Cancer Research Award
1163 NARROW BAND IMAGING FLEXIBLE CYSTOSCOPY: AN UPDATE AND A NEW USER’S EXPERIENCE Richard T Bryan*, Birmingham, United Kingdom; Z H Shah, Reading, United Kingdom; Stuart I Collins, D. Michael A Wallace, Birmingham, United Kingdom INTRODUCTION AND OBJECTIVES: We have previously demonstrated a significantly improved detection rate for bladder cancer recurrences with narrow band imaging (NBI) flexible cystoscopy when compared with conventional white-light imgaing (WLI) flexible cystoscopy. We investigated whether a “new user” of NBI flexible cystoscopy, previously unfamiliar with this technique, could reproduce our results. METHODS: The same protocol from our initial study was continued into this second study at The Queen Elizabeth Hospital, Birmingham, UK, but with a “new user” (ZHS): between September 2007 and May 2008 NBI flexible cystoscopy was performed on 23 patients with known recurrences of urothelial cancer (UC) of the bladder following initial conventional WLI flexible cystoscopy with the same switchable Olympus Lucera sequential RGB instrument. RESULTS: In our first series (published), NBI detected a total of 15 additional UCs in 12 of 29 patients (41%), as compared with WLI: a mean difference of 0.52 UCs per patient (standard deviation 0.74; Wilcoxon paired signed-rank test p-value 0.0005). In this second series, NBI detected 15 additional UCs in 8 of the 23 patients (35%): six of these patients had one additional UC, one had four additional UCs, and one had five additional UCs when compared with WLI, with a mean of 0.65 additional UCs per patient (SD1.30; Wilcoxon p=0.01). When the second series with the “new user” is compared with the first series, there is no statistical evidence that the excess number of UCs detected by NBI is different (Wilcoxon (unpaired) signed-rank test p=0.74), suggesting that there is no difference between a new user and an experienced user in the application of NBI. When the two series are combined, NBI detected 30 additional UCs in 20 of 52 patients (38%): 16 patients had one additional UC, and one each had two, three, four and five additional UCs, with a mean of 0.58 additional UCs per patient overall (SD 1.02; Wilcoxon paired signed-rank test p<0.001). CONCLUSIONS: A new user can obtain the same significant benefits with NBI as an experienced user in improving the detection rate of bladder UC recurrences. We continue to demonstrate a significant benefit of NBI flexible cystoscopy in the follow-up of patients with bladder cancer. Source of Funding: KeyMed Olympus (UK) and Olympus (Japan) provided the authors with the flexible cystoscopy equipment required to carryout this study.
415
1164 MAIN PREDICTORS OF FALSE POSITIVES IN PHOTODYNAMIC DIAGNOSIS OF TRANSITIONAL CELL CARCINOMA OF THE BLADDER Ronald O.P. Draga*, Matthijs C.M. Grimbergen, Esther T. Kok, Trudy Jonges, Ruud Bosch, Utrecht, Netherlands INTRODUCTION AND OBJECTIVES: Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violet-blue light. The specificity is approximately 50%. The aim of the study is to identify the main predictors of false positives in multivariate analysis. The second objective is to determine the optimal waiting period after transurethral resection of bladder tumors (TURBT) and intravesical therapy (IVT) to minimize the number of false positives in PDD. METHODS: Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Age, gender, recent TURBT, previous IVT, urinary tract infections (UTIs) and tumor classification were examined for association with the false-positive rates in fluorescence cystoscopy. RESULTS: The sensitivity and specificity of white light endoscopy (WLE) and PDD are 71% and 76%, 96% and 43%, respectively. Significant univariate associations are found between false positives and female gender (p=0.007, OR=2.01), IVT instillations (p=0.02, OR=1.85), Bacille Calmette-Guérin instillations (BCG; p=0.03, OR=2.16) and TURBT in the past 90 days (p=0.01, OR=2.23). In multivariate analysis female gender (p=0.001, OR=2.68) and TURBT within 90 days before PDD (p=0.01, OR=2.27) are the only significant independent predictors of false positives. In a second multivariate model the dichotomous variable ‘>1 BCG instillation in the past 90 days’ is the only predictor for falsepositive findings in PDD (p=0.002, OR=4.67). Tangential illumination of the bladder wall does not seem to result in additional false positives. The false-positive rate decreases during the first 12 weeks after the latest TURBT and the latest BCG instillation. CONCLUSIONS: Female gender, previous TURBT and recent BCG instillations are important predictors of false positives in PDD. The false-positive rate decreases during the first 12 weeks after the latest TURBT and the latest BCG instillation. We recommend to perform a fluorescence guided TURBT 9-12 weeks after an incomplete first resection of low or intermediate risk non-muscle invasive tumors and 9-12 weeks after the latest BCG instillation. Source of Funding: The Dutch Cancer Society, grant-number UU 2007-3922
1165 URINARY - BASED TUMOUR MARKERS EVALUATED EITHER BY WHITE LIGHT OR PHOTODYNAMIC TRANSURETHRAL RESECTION IN BLADDER CANCER. IS THERE ANY DIFFERENCE? Marcus Horstmann*, Tuebingen, Germany; Oliver Patschan, Malmoe, Sweden; Joerg Hennenlotter, Daniela Colleselli, Gerhard Feil, Arnulf Stenzl, Tuebingen, Germany INTRODUCTION AND OBJECTIVES: Photodynamic diagnostic (PDD) improves the detection of transitional cell carcinoma of the bladder (TCC). Still sensitivity and specificity of urinary-based tumour markers and cytology have been validated only by white light cystoscopy or resection (WL). Aim of this study was to evaluate how the sensitivity and specificity of urinary-based tumor markers changes if either WL TUR or photodynamic TUR were used. METHODS: Cytology, FISH, U-Cyt+, and NMP22 were evaluated prior to transurethral resection in 335 serial patients with the suspicion of primary TCC (n=163) or TCC recurrence (n=172) of the bladder. In each case histopathological results served as a control. PDD was used in 112 patients during resection. BCa was found in 128 (57%) out of 223 (100%) patients in WL and in 70 (62%) out of 112 (100) patients in PDD.
THE JOURNAL OF UROLOGY®
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Vol. 181, No. 4, Supplement, Monday, April 27, 2009
Tumours found in WL were n=74 pTa (58%), n=15 pT1 (12%), n=21 q pT2 (16%), and 17 pCis (13%) and in PDD n=45 pTa (64%), n=7 pT1 (10%), n=6 q pT2 (9%), and n=12 pCis (17%). RESULTS: Sensitivity, specificity, and accuracy of the markers for both groups were as follows: Sensitifity Sensitivity % Specifity Accuracy Specifity % PDD % % PDD WL (n=223) (n=112) WL WL
Marker
Accuracy % PDD
clinical impact of CK-20 as an indicator of lymph node micrometastases and prognosticator for disease progression in combination with an extended pelvic lymphadenectomy. Source of Funding: Gruber Stiftung Munich
1167
Cytology
79
84
74
49
77
70
NESTED UROTHELIAL CARCINOMA: A CLINICOPATHOLOGIC AND IMMUNOHISTOCHEMICAL ANALYSIS OF 33 CASES
FISH
66
81
75
49
75
69
Matthew Wasco, Deborah Bradley, Rajal B Shah*, Ann Arbor, MI
NMP22
69
73
48
30
60
57
U-Cyt+
77
75
69
48
73
65
INTRODUCTION AND OBJECTIVES: Urothelial carcinoma (UC) with nested growth pattern is a rare and less studied variant of UC, characterized by deceptively bland morphology resembling small von Brunn s nests, yet aggressive biology. METHODS: We analyzed a series of 33 patients with nested UC who underwent definitive treatment to better understand its clinicopathological spectrum, immunophenotype and clinical outcome. Tumors demonstrating either pure or mixed nested morphology with variable component of conventional UC were included. RESULTS: Patients age ranged from 41 to 81 years (avg 65) with a male: female ratio of 2.7:1. Pure nested UCs accounted for 33% of cases. When seen along with conventional UC, the nested component ranged from 30% to 90%. Of the 22 cases associated with conventional UC, 29% had an additional component of divergent differentiation. Muscle invasion at TURBT and extravesical disease ( T3) at cystectomy were observed in 82% and 83% of cases respectively (p <0.0001 compared to non-nested highgrade UC). Angiolymphatic invasion was common (73%). In comparison to pure conventional high grade UC, nested UCs were associated with metastatic disease, in the form of lymph node and/or distant metastases (16% vs 72% p <0.0001). Behavior was similarly aggressive whether tumor was pure nested or mixed nested. Despite overall bland morphology, nested component demonstrated random high grade atypia, specifically in the deeper invasive component. Growth patterns of nested component ranged from haphazard small isolated nests to areas with confluent nested growth with minimal desmoplasia. When associated with conventional UC, the nested component was part of the deeply invasive tumor. Nested UCs demonstrated immunophenotype similar to conventional UC (94% CK7+, 68% CK20+, 93% K903+, and 93% p63+). Follow-up was available on 31 patients, and ranged from 1 to 31 months (average 12). 18% of patients died of disease, and 36% of patients were alive with disease at last followup. 16/33 patients (48%) received neoadjuvant chemotherapy, only two had response to therapy. 24 patients were treated with cystectomy, 1 with nephroureterectomy, another 3 were treated with TURBT only, and 5 received radiation. Seven (21%) patients received adjuvant chemotherapy. CONCLUSIONS: UC demonstrating pure or variable component of nested morphology is an aggressive tumor with uniformly bad outcome. Increased awareness of the spectrum of this tumor and its early recognition is important due to its subtle and heterogeneous morphology.
Results showed as indicated above a better sensitivity for all markers in the PDD group and a worse specificity and also accuracy. CONCLUSIONS: PDD improved the sensitivity but not the specificity and accuracy of the tumour markers in this group of patients. As there is strong evidence that PDD is currently the best diagnostic tool for BCa PDD and not WL should be used for the validation of urinarybased tumour markers. Source of Funding: None
1166 MOLECULAR STAGING OF LYMPH NODES FROM MUSCLEINVASIVE BLADDER CANCER PATIENTS BY RT-PCR COMPARED TO PATHOLOGIC FINDINGS - ARE THERE DIFFERENCES IN LOCALIZATION AND DETECTION RATES? Michael Autenrieth*, Roman Nawroth, Saskia Semmlack, Gregor Weirich, Juergen E Gschwend, Margitta Retz, Munich, Germany INTRODUCTION AND OBJECTIVES: Detection of lymph nodes metastases is an important prognosticator for progression-free survival after radical cystectomy. Currently, a large German multicenter study (LEA, AUO AB 25/02) is active for patients undergoing radical cystectomy with pelvic lymphadenectomy. Patients are randomized to receive either a conventional or extended lymphadenectomy (complete pelvic lymph nodes up to the inferior mesenteric artery) . The aim of this study was to investigate molecular staging and detection of lymph node metastases that are not identified with classical histopathological methods along with the LEA clinical study. METHODS: For detection of occult disseminated bladder tumor cells we established a RT-PCR protocol. As a marker for micrometastases in lymph nodes we analyzed the expression of cytokeratin-20 (CK-20) which is expressed in urothelial bladder cancer cells but not in blood and lymph nodes. In total 758 out of 1499 lymph nodes were suitable for molecular analysis by RT-PCR. Lymph nodes were cartographically localized according to the LEA study. Each lymph node was divided in two halves. One half was examined by a pathologists applying conventional histology. The second half was assessed by frozen section histopathology as well as prepared for RNA extraction followed by a CK20 nested RT-PCR. RESULTS: Histopathological examination revealed 19 out of 758 lymph nodes (2.5%) as positive. All of them were confirmed to be CK-20 positive. By CK-20 RT-PCR 103 (13.6%) out of 739 histopathologically negative lymph nodes were CK-20 positive. Depending on the mode of lymphadenectomy 51 lymph node micrometastases were found in the extended lymphadenectomy group, whereas 52 lymph node micrometastases were detected in the standard lymphadenectomy group. Nearly one third (16/51; 31.4%) of CK-20 positive nodes were located outside the standard lymphadenectomy field. More than 13% (7/51) of CK-20 positive lymph nodes were located in the paraaortic and paracaval field. Skip metastasis were neither detected by conventional pathology nor by CK-20 RT-PCR. CONCLUSIONS: CK-20 RT-PCR is a specific and sensitive method for the detection of occult tumor cells in lymph nodes from bladder cancer patients. Long-term observation will be necessary to evaluate the
Source of Funding: None
1168 DOES SCREENING FOR BLADDER CANCER PRODUCE A STAGE MIGRATION TOWARDS NON-MUSCLE INVASIVE CANCERS? Alexandre R Zlotta, Toronto, ONCanada; Thierry Roumeguere, Brussels, Belgium; Sultan S. Alkhateeb*, Toronto, ONCanada; Sandrine Rorive, Anne Lemy, Isabelle Salmon, Martin Wissing, Daniel Abramowicz, Claude Schulman, Brussels, Belgium; Neil E. Fleshner, Michael A s Jewett, Toronto, ONCanada; Joelle Nortier, Brussels, Belgium INTRODUCTION AND OBJECTIVES: In the last 3 decades, sadly, the presentation of bladder cancer has not changed much where 25% of new cases are still muscle-invasive at first diagnosis. Although intuitively it should, it is unproven whether screening for bladder cancer could detect more bladder tumors at a non-muscle invasive stage. The goal of this study is to evaluate the potential benefits of bladder