Mean recurrence-free survival time is shorter with the AA genotype t

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Shachar Aharony*, Jack Baniel, Petah Tikva, Israel; Ofer. Yossepowitch, Ramat Hasharon, Israel. INTRODUCTION AND OBJECTIVES: Urine cytology is consid-.
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more likely with the AA genotype (Odds Ratio ⫽ 4.5, p ⫽ 0.038). Mean recurrence-free survival time is shorter with the AA genotype than AG genotype (80.9 ⫾ 6.03 versus 121 ⫾ 9.15 months, p ⫽ 0.036). There was no difference in time to progression and cancer-specific death between genotypes. CONCLUSIONS: The CTLA-4 -1661 AA genotype is associated with increased likelihood of recurrence and a shorter recurrencefree period. Our findings suggest that polymorphism in the CTLA-4 gene may correlate with response to BCG therapy in bladder cancer patients. They may serve as molecular markers to predict BCG failure and cancer recurrence. Source of Funding: NLAM, National University of Singapore

1351 CLINICALLY UNCONFIRMED POSITIVE URINE CYTOLOGY – ONCOLOGICAL IMPLICATIONS OVER LONG TERM FOLLOW-UP Shachar Aharony*, Jack Baniel, Petah Tikva, Israel; Ofer Yossepowitch, Ramat Hasharon, Israel INTRODUCTION AND OBJECTIVES: Urine cytology is considered a vital diagnostic tool in evaluating patients with suspected transitional cell carcinoma. It is often used in the context of hematuria and/or irritative voiding symptoms workup and as adjunct to cystoscopy in patients undergoing bladder cancer surveillance. While highly specific, an infrequent clinical finding is the presence of repeat positive urine cytology studies despite normal cystocsopy and upper tract imaging. We analyzed the clinical course in these unusual cases. METHODS: The medical records of all patients who underwent assessment for positive urine cytology in the absence of overt urinary tract tumor between 2000 and 2008 were reviewed. Urological workup was performed under anesthesia consisting of random bladder biopsies, lateral montanal prostate biopsies, bilateral retrograde pyelography and selective sampling of urine cytology from each ureter. Further evaluation was based on initial findings and conducted at the discretion of the treating physician. The Kaplan-Meier method was used to estimate the interval to final diagnosis and disease free probability. RESULTS: The cohort consisted of 48 patients at a median age of 59 years. Twenty seven patients (56%) had a prior history of bladder cancer and 21 patients (44%) were evaluated for irritative voiding symptoms or hematuria. At a median follow up time of 31 months (IQR 23, 52) the source of positive urine cytology was identified in 32 patients (67%): in 29 (60%) as bladder cancer, in 2 patients (4%) as a upper tract tumor and in 1 patient (2%) as transitional cell carcinoma of the prostate. Of the patients with clinically confirmed positive cytology, 29 (90%) had high grade disease and in 17 (53%) carcinoma in situ was diagnosed. The median interval from presentation to diagnosis was 19 months (IQR 8, 22). While there was no difference in cancer detection rates between patients with or without prior history of bladder cancer (p⬍0.53), the median time interval to diagnosis in the latter subgroup was significantly shorter (13 vs. 27 months, p ⬍ 0.07). The 4-year disease free survival with an intact bladder was 74% (95% CI 63, 85). CONCLUSIONS: Unconfirmed positive urine cytology often predates the subsequent development of high grade urothelial carcinoma. The bladder is most commonly involved. While the time interval from presentation to diagnosis is generally protracted (⬎1 year), the long term outcome of patients in this unique clinical setting appears to be favorable. Source of Funding: None

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1352 SYNERGISTIC EFFECT OF IMMEDIATE INTRAVESICAL CHEMOTHERAPY AND SUBSEQUENT INDUCTION COURSE OF BCG FOR NON-MUSCLE INVASIVE BLADDER CANCER Kazuhiro Matsumoto*, Hiroyuki Yamanaka, Masayuki Hagiwara, Akiharu Ninomiya, So Nakamura, Tokyo, Japan INTRODUCTION AND OBJECTIVES: BCG is currently the most effective intravesical agent at preventing the recurrence of nonmuscle invasive bladder cancer. However, some patients treated with BCG still unfortunately experience tumor recurrence. To date, multiple clinical trials have focused on the efficacy of single immediate instillation of chemotherapeutic agents. The aim of this study was to evaluate the synergistic effect of immediate intravesical chemotherapy and a subsequent induction course of BCG. METHODS: Between 1993 and 2007, 526 cases with diagnosed non-muscle invasive bladder cancer were treated with transurethral resection at our institution. Of these 526 cases, 115 low risk patients who had initially been diagnosed with a solitary Ta G1/2 tumor and 41 patients treated with induction courses of intravesical chemotherapy were excluded. The remaining 370 patients, consisting of 193 intermediate risk patients and 177 high risk patients, were the subjects in this retrospective study. The median follow-up interval was 3.1 years. RESULTS: No adjuvant intravesical therapy was performed in 115 patients (Group A). Only immediate epirubicin 40 mg instillation was performed in 56 patients (Group B), and 125 patients received only an induction course of 6 BCG instillations (Group C). The remaining 74 patients were treated with both immediate epirubicin instillation and a subsequent induction course of BCG (Group D). Initially there was no significant difference in the clinicopathological backgrounds of Group A and Group B, but the 3-year recurrence-free survival rate in Group A (31.9%) was less than in Group B (57.5%) (p⬍0.001), which proved the efficacy of immediate intravesical therapy using epirubicin. In Group C, the 3-year recurrence-free survival rate was 57.9%, which was almost the same as that in Group B (p⫽0.533), although statistically Group C included more high risk patients (72 of 125 patients) than Group B (17 of 56 patients) (p⬍0.001). Next, we compared Group C and Group D. No significant difference in their respective backgrounds was observed. However, the 3-year recurrence-free survival rate in Group D was significantly higher than that in Group C (75.5% vs 57.9%) (p⬍0.001), which suggested the combination therapy had a synergistic effect. CONCLUSIONS: For intermediate and high risk patients, our results indicate that the combination of immediate intravesical epirubicin instillation with a subsequent induction course of BCG exhibited a synergistic effect against potential tumor recurrence and is thus recommended. Source of Funding: None

1353 LOCATION OF TUMORS IN EARLY AND LATE RECURRENCES IN PATIENTS WITH T1G3 BLADDER CANCER TREATED WITH OR WITHOUT BCG: IS THERE ANY DIFFERENCE? Guillermo Urdaneta*, Juan Palou, Miriam Serrano, Rube´n Parada, Oscar Rodrı´guez, Lluis Gausa, Alberto Breda, Humberto Villavicencio, Barcelona, Spain INTRODUCTION AND OBJECTIVES: 10% of the patients with non muscle invasive bladder cancer (NMIBC) will present with T1G3 disease. These patients are often treated with transurethral resection (TUR) plus Re-TUR at one month, followed by BCG. Although BCG has decreased the recurrence rate of high grade disease, there is a debate around the real usefulness of Re-TUR. We present the recurrence rate and location of the recurrence in patients with T1G3 NMIBC treated with TUR, without Re-TUR, with or without BCG. METHODS: Patients with a final diagnosis of T1G3 were managed with no Re-TUR and further divided into 2 groups. Group 1 included patients who did not undergo BCG. Group 2 included patients treated with BCG (Connaught strain, 6 week induction course, without

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maintenance). Follow-up consisted of cystoscopy and cytology every 3 months for 2 years and 6 monthly thereafter. Early recurrence was defined as reappearance of NMIBC disease at first follow-up cystoscopy. Late recurrence was defined as NMIBC after first follow-up cystoscopy. Location of the recurrence was recorded for each case. RESULTS: 254 patients qualified for these criteria of whom 86.6% were males. 48.8% had concomitant CIS. Mean age was 67 years (25-87) and median follow-up was 87 months (4-258). Group 1 included 108 patients (control group) and group 2 included 146. The overall recurrence rate was 53.5% (n⫽136). When patients were treated without BCG the recurrence rate was 66.7 % and it was 43.8% with the BCG treatment (p⬍0.0001). Overall, 16.2% of the recurrences (n⫽22) were at the same location of the previous TUR. When looking at Group 1 and 2, 12.5% and 19.4% of the recurrences were at same location of the previous TUR (p⫽0.3). When sub-stratifying patients for early and late recurrence, 13% of the tumours recurred at 3 months and 40.5% at 6 months or later. Of the early recurrences, 38.2% happened to be at the same location of the previous TUR and the treatment with BCG diminished the recurrence among group 1 and 2 (23 and 48%; p⫽0.4). Of late recurrences, 8.8% were at the same location of the previous TUR and BCG treatment did not influence the recurrence rate nor the location significantly (11% vs 8%; p⫽1.0). CONCLUSIONS: There is a clear difference in recurrence between patients with primary T1G3 treated with or without BCG. When Re-TUR is not performed the overall recurrence rate at the same site of the previous TUR is low (8.6%). Early recurrence rate at the same site of the previous resection is higher (38.2%) than late recurrence rate (8.8%). BCG diminish the incidence of recurrence at the same site of the previous resection. Source of Funding: None

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CONCLUSIONS: Office TUR is associated with a higher risk of, and shorter interval to, recurrence when compared with hospital TUR in an at risk cohort of bladder cancer patients, despite comparable surveillance schedules. While this finding may reflect inadequacy of office resection, it may also reflect one of a variety of biases including tumor-specific, physician, and patient factors. Further analysis is needed to confirm the true impact of office TUR on disease recurrence.

Source of Funding: None

1355 PROSPECTIVE WITHIN-PATIENT MULTI-CENTRE PHASE III TRIAL TO COMPARE WHITE-LIGHT CYSTOSCOPY WITH NARROW BAND IMAGING IN THE DETECTION OF NON MUSCLE-INVASIVE BLADDER CANCER. Zhangqun YE*, Wuhan, China, People’s Republic of

1354 THE INFLUENCE OF OFFICE-BASED ENDOSCOPIC SURGERY FOR BLADDER CANCER ON RECURRENCE-FREE PROBABILITY Micah Hemani*, New York, NY; Danil Makarov, New Haven, CT; William Huang, Samir S. Taneja, New York, NY INTRODUCTION AND OBJECTIVES: We have previously observed that office management of bladder cancer experienced growth from 2002-2007 coinciding with an increase in reimbursement (Cancer 2010, in press). In the absence of clinical guidelines, we hypothesized that clinical outcomes may have been affected by the redistribution of TUR cases from the hospital to the office. We determined recurrencefree probability following TUR and identified factors that affected recurrence. METHODS: In a 10-physician faculty practice, we identified all TUR procedures performed between 2002-2007 in patients with a history of bladder cancer or CIS. We included all TURs resulting in pathology proven Ta, CIS or T1 bladder cancer, and cases of fulguration in which the operative report indicated the presence of a papillary lesion. The interval to recurrence was determined as the time from TUR to the development of a recurrent lesion on surveillance. We excluded cases of incomplete resection and TURs leading to cystectomy. Patients were followed into 2009 or censored at the last office visit. Analysis was performed using a cox proportional-hazards model and kaplan meier survival analysis. RESULTS: We identified 379 total TUR cases performed with 169 and 210 occurring in the hospital and the office, respectively. Office TUR was associated with a significantly higher likelihood of, and shorter interval to, recurrence when compared with hospital TUR, with HR 1.42 (1.09-1.85) and a median time to recurrence of 6 months in the office and 12.9 months in the hospital. The median time to surveillance was similar in both locations (3.5 months and 3.8 months). Grade, stage, date performed, use of perioperative mitomycin C, and subspecialty of the treating urologists did not significantly affect recurrence interval on multivariate analysis.

INTRODUCTION AND OBJECTIVES: Previous monocentric studies suggest that Narrow Band Imaging (NBI) improves the detection of Non-Muscle-Invasive Bladder Cancer (NMIBC) over conventional White Light (WL) cystoscopy. A possible limitation of the currently published studies is their monocentric nature and the possible observer-bias since WL and NBI were performed subsequently and observed by the same urologist. We investigated if the available data could be reproduced in a multi-centric setting with a randomized sequence of WL and NBI. METHODS: 103 consecutive patients with a suspicion of NMIBC underwent WL/NBI cystoscopy at 4 major academic centres. According to the randomization the bladder was initially mapped using the first imaging modality followed by the second. Thereafter biopsies were taken according to the mapping followed by one biopsy from an area appearing to be normal. All histological samples were examined by one local and one central reference pathologist who were both blinded to the imaging procedure. Primary end points were sensitivities and difference of sensitivities of WL and NBI to detect bladder cancer. Secondary end points include specificities, positive predictive values, and negative predictive values of WL and NBI cystoscopy. RESULTS: 87 patients had a confirmed bladder cancer with 167 tumours in total. In 29 (33.3%) of these patients, a total of 41 tumours (24.6%) (16pTa, 21pT1, 0pT2, 4pTis) were detected by NBI only, whereas 6 tumours (3.6%) (2pTa, 4pT1, 0pT2, 0pTis) within 4 patients (4.6%) were detected by WL only. The mean number of bladder cancers per patient detected by NBI was 1.85, versus 1.45 by WL. The detection rate of NBI was 96.4% versus 75.4% for WL (p⬍0.0001). The false-positive rate of NBI and WL was 39.1% and 41.4%, respectively. The positive predictive value for NBI and WL were respectively 75.6% and 69.6%. The negative predictive value for NBI and WL were respectively 93.1% and 65.5%. CONCLUSIONS: This study confirms in a multi-centric setting with randomized sequence of imaging modalities that NBI offers a superior overall detection rate of NMIBC if compared to WL cystoscopy. Source of Funding: None