1268 SIGNIFICANCE OF RANDOM BLADDER BIOPSIES IN PATIENTS UNDERGOING TRANSURETHRAL RESECTION OF NON-MUSCLE INVASIVE BLADDER CANCER

Vol. 187, No. 4S, Supplement, Monday, May 21, 2012

METHODS: Between 06/2008 and 02/2010 CEA and Ca19-9 were prospectively determined in 231 pat (173 m, 58 f, mean age 70 y) before undergoing TUR-B of a suspect bladder tumor. Additionally 11 pat (9 m, 2 f, median age 66 y) were presented initially with metastatic TCC. Immunhstochemical examinations (CEA and Ca19-9 staining) were performed in TUR-B specimens of 83 pat. RESULTS: No malignant bladder tumors were found in 71 pat. These pat. served as controls. 14 pat. with malignant bladder tumors but histological excluded TCC were excluded from analysis. In 146 pat histological examination showed TCC: 74% (n⫽108) with superficial, non-muscle invasive (NMIBC) and 26% (n⫽38) with muscle-invasive (MIBC) bladder cancer. Compared to controls pat. with TCC showed neither significant different CEA (p⫽0.234) nor Ca19-9 (p⫽0.061) levels. Pat. with MIBC (n⫽38) showed significant elevated CEA (p⫽0.008) and Ca19-9 serum levels (p⬎0.001) compared to NMIBC (n⫽108). In local advanced MIBC and/or presence of lymph node metastases (⬍pT3 ⫾ N⫹, n⫽19) only Ca19-9 was significantly elevated (p⫽0.04)compared to MIBC confined on the bladder muscle (pT2No, n⫽19). Concerning TCC-grading significant higher CEA (p⫽0.031) and Ca19-9 (p⫽0.001) serum levels were found with rising grading. Pat. with metastatic TCC showed compared to non-metastatic TCC the highest serum levels of Ca19-9 (p⫽0.003) but not for CEA (p⫽0.105). Immunhistochemical staining in 83 patients revealed a strong correlation between staining intensitiy and serum levels for Ca19-9 (p⫽0.004) but not for CEA (p⫽0.478). CONCLUSIONS: Our prospective data clearly show that neither CEA nor Ca19-9 serum levels are helpful tools in primary diagnosis of TCC. When during routine examination CEA and Ca19-9 levels are elevated and a gastrointestinal malignancy can be excluded you have to keep in mind existence of CEA/Ca-19-9 producing TCC and consecutively to check the urologic tract. Our date show a correlation of CEA and Ca19-9 serum levels with stage and grade of TCC confirmed by IHC. Ca19-9 is more promising as CEA. Source of Funding: None

1268 SIGNIFICANCE OF RANDOM BLADDER BIOPSIES IN PATIENTS UNDERGOING TRANSURETHRAL RESECTION OF NON-MUSCLE INVASIVE BLADDER CANCER Masafumi Kumano*, Hideaki Miyake, Masato Fujisawa, Kobe, Japan INTRODUCTION AND OBJECTIVES: Random bladder biopsies, taken from normal areas of urothelium, are widely performed to detect concomitant carcinoma in situ (CIS) in patients undergoing transurethral resection (TUR) of non-muscle invasive bladder cancer. However, there are few reports investigating the outcomes of random bladder biopsies based on the data from large series; thus, the significance of random biopsies remains controversial. The objective of this study was to retrospectively review the clinical outcomes of random bladder biopsies in patients with non-muscle invasive bladder cancer to identify predictive factors significantly associated with the findings of random biopsies. METHODS: This study included a total of 451 consecutive patients with histopathologically confirmed non-muscle invasive bladder cancer who underwent TUR and random bladder biopsies. The random biopsies were taken from the seven different sites of normalappearing urothelium, including right wall, left wall, trigone, dome, posterior wall, anterior wall and prostatic urethra. RESULTS: Random biopsies were positive in 72 patients (16.0%), of whom 66 (91.7%) and 6 (8.3%) were diagnosed as Tis and Ta, respectively. The incidence of positive random biopsies was significantly associated with past history of upper urinary tract cancer, urinary cytology before TUR, number of tumors, pathological stage, tumor grade and presence of concomitant CIS. Univariate analysis identified past history of upper urinary tract cancer, urinary cytology before TUR and number of tumors as significant predictors of positive random biopsies, among which only urinary cytology before TUR appeared to be independently associated with positive random bladder

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biopsies on multivariate analysis. Furthermore, consideration of the preoperative finding of urinary cytology could diagnose concomitant malignant disease by random biopsies with 59.4% sensitivity, 88.8% specificity, 50.0% positive predictive value and 92.0% negative predictive value. CONCLUSIONS: These findings suggest that the outcome of urinary cytology before TUR could be a useful predictor of positive biopsies in patients with non-muscle invasive bladder cancer. Accordingly, it would be important to further discuss the indication of random bladder biopsies in patients who were preoperatively diagnosed as negative in urinary cytology in order to avoid unnecessary biopsies. Source of Funding: None

1269 IMMUNOCYTOCHEMICAL DETECTION OF MINICHROMOSOME MAINTENANCE PROTEIN 2 (MCM-2) IN CELLS RETRIEVED FROM URINE CAN ACCURATELY DIAGNOSE UROTHELIAL CARCINOMA Kasra Saeb-Parsy*, Cambridge, United Kingdom; Wilson Alex, Aberdeen, United Kingdom; Marie Corcoran, Sian Chilcott, Cambridge, United Kingdom; Durgesh Rana, Nadira Narine, Manchester, United Kingdom; Bensita Bernard, Alessia Donnini, Aberdeen, United Kingdom; Nick Coleman, David Neal, Cambridge, United Kingdom INTRODUCTION AND OBJECTIVES: Cystoscopy and urine cytology are the primary investigations used in diagnosis and surveillance of patients with bladder cancer. In recent years there has been extensive research into identifying urinary markers which would improve diagnostic accuracy or even replace cystoscopy and cytology. Here we evaluate diagnostic accuracy of MCM-2 in diagnosis and surveillance of urothelial carcinoma. METHODS: Patients presenting with gross haematuria (GH) and those with known diagnosis of bladder cancer who are on cystoscopic surveillance (CS) were recruited into the study. A total 22 patient with gross haematuria and 55 patients on cystoscopic surveillance were included in the study. SurePath platform was used to process the urine and immunocytochemical analysis of MCM-2 in urine was performed for detection of urothelial cancer. MCM-2 threshold count of 50 in urine as a positive yield for presence of cancer in the GH group and an MCM-2 count of 200 for the CS group was used. Sensitivity, specificity and receiver-operator characteristics (ROC) curves were determined. RESULTS: Setting an MCM-2 count of 50 or more as positive for diagnosis of primary urothelial carcinoma in the GH group resulted in sensitivity 83.3% (95 %CI; 35.9-99.6) and specificty of 81.3% (95% CI, 54.4-96.0) with a negative predictive value of 92.9%. ROC curve analysis revealed the area under the curve of 0.943 (P⬍0.002). Additionally combination of MCM-2 and urine cytology increased the sensitivity to 100%. In the GH group, MCM-2 was able to identify 100% of the muscle invasive and Grade 3 tumors. Setting an MCM-2 count of 200 or more as positive for diagnosis of recurrent urothelial carcinoma in the CS group resulted in sensitivity of 90.9% (95% CI, 58.7-99.7) and specificity of 93.2% (95% CI, 81.4-98.6) with a negative predictive value of 97.6%. ROC curve analysis revealed the area under the curve of 0.973 (P⬍0.0005). In the CS group, MCM-2 identified 66.7% of G2 and 100% of G3 and CIS lesions. CONCLUSIONS: MCM-2 is a non-invasive test, which can be reliably used in diagnosis of primary and recurrent urothelial carcinoma. It is able to identify all life threatening and muscle invasive bladder cancers and as such further evaluation of its role in diagnosis and follow up of bladder cancer is warranted. Source of Funding: None