1770 CLINICAL OUTCOME IN PATIENTS WITH T1 MICROPAPILLARY UROTHELIAL CARCINOMA OF THE BLADDER

Vol. , No. , Supplement, Tuesday, May 7, 2013

1768 IMPACT OF MICROPAPILLARY UROTHELIAL CARCINOMA VARIANT HISTOLOGY ON SURVIVAL AFTER RADICAL CYSTECTOMY: A MULTI-INSTITUTIONAL ANALYSIS Adrian Fairey*, Los Angeles, CA; Eila Skinner, Stanford, CA; Stephen Boorjian, Jeffrey Wang, Igor Frank, Rochester, MN; Mark Schoenberg, Eric Hyndman, Adam Reese, Baltimore, MD; Gary Steinberg, Michael Large, Chicago, IL; Christina Hulsbergen-vandeKaa, Max Bruins, Radboud, Netherlands; Jie Cai, Siamak Daneshmand, Los Angeles, CA INTRODUCTION AND OBJECTIVES: The role of micropapillary urothelial carcinoma (MUC) variant histology as an independent prognostic factor for survival after radical cystectomy (RC) is controversial. We report the first multi-institutional analysis to examine the impact of MUC on survival outcomes. METHODS: Institutional bladder cancer databases containing detailed information on patients treated with RC between 1980 and 2011 were obtained from 5 academic centers. Data were collected on 1,497 patients and combined into a relational database formatted with patient characteristics, pathologic characteristics, and survival status. All surgical specimens underwent institutional pathologic review by genitourinary pathologists. Histologic type was categorized as urothelial carcinoma (UC; N⫽1,346) or MUC (N⫽151). Patients were classified as MUC if they had any component of MUC in the pathologic specimen. The Kaplan-Meier method and Cox proportional regression models were used to analyze overall survival (OS) and recurrence-free survival (RFS). RESULTS: Median follow-up was 10.0 years for the UC group and 7.8 years for the MUC group (P⫽0.01). Median age (67 years vs 67 years, P⫽0.81), sex (male: 80% vs 83%, P⫽0.39), neoadjuvant chemotherapy use (7% vs 5%, P⫽0.37), adjuvant chemotherapy use (21% vs 27%, P⫽0.10), and clinical TNM stage (ⱕcT2N0M0: 91% vs 89%; ⱖcT3N0M0: 7% vs 7%; cTanyN1-3M0: 2% vs 4%, P⫽0.35) did not differ between the UC and MUC groups. Notably, MUC was associated with advanced pathologic TNM stage (ⱕpT2N0M0: 27% vs 60%; ⱖpT3N0M0: 23% vs 18%; pTanyN1-3M0: 50% vs 22%, P⬍0.01) and a higher rate of lymphovascular invasion (LVI) (58% vs 29%, P⬍0.01). Moreover, compared to patients with UC, patients with MUC were noted on unadjusted analysis to have poorer OS (5-year: 38% vs 61%, P⬍0.01) and RFS (5-year: 44% vs 70%, P⬍0.01). However, in multivariable analysis controlling for age, sex, pathologic TNM stage, LVI, and perioperative chemotherapy use, histologic type was not independently associated with OS (HR 1.19, 95% CI 0.96-1.49, P⫽0.12) or RFS (HR 1.16, 95% CI 0.89-1.53, P⫽0.27). CONCLUSIONS: This multi-institutional analysis showed that, while MUC was associated with locally advanced disease at RC, survival outcomes are similar to those for UC when controlling for clinicopathologic tumor features.

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location were defined as multiple-site tumor. Pattern of LNM, overall survival (OS), and recurrence free survival (RFS) was compared among five locations and between single-site and multiple-site tumors. RESULTS: Out of 1964 patients, we identified 1777 patients (1400 males) with the mean age of 67 yrs (range, 23 - 93) who had complete information on tumor location. Median follow-up was 12.9 yrs (range, 0 - 36.6). 408/1777 (22.9%) patients had single-site tumor. There was no significant difference either among five locations or between single- and multiple-site tumors with regards to percentage of LN positive disease (P⫽0.4), number of positive LNs (P⫽0.3), and LN density (P⫽0.3). Regarding the level of LNM one PLND template, trigone tumors were less likely to involve LNs above aortic bifurcation (LN-AAB) when compared to other locations (2/13 (15%) vs. 10/24 (41.6%); P⫽0.02) but there was no difference between single-site and multiple-site tumors (12/47 (34%) vs. 15/83 (38%); P⫽0.5).Posterior wall tumors had worse OS compared to other locations (HR⫽1.7; P⫽0.03) but there was no difference in OS between single- and multiple-site tumors (P⫽0.9). There was no difference in RFS either among five locations (P⫽0.1) or between single- and multiple-site tumors (P⫽0.2). (Figure 1). CONCLUSIONS: There does not appear to be much difference in rate of LNM and RFS among different tumor locations. However, LNM in trigone tumors tend to be confined to area below aortic bifurcation and posterior wall tumors have worse OS.

Source of Funding: None

Bladder Cancer: Superficial (II)

Source of Funding: None

Moderated Poster Session 65 Tuesday, May 7, 2013

1:00 PM-3:00 PM

1769 INTRAVESICAL LOCATION OF THE TUMOR: HOW DOES IT AFFECT THE PATTERN OF LYMPH NODE METASTASIS AND ONCOLOGICAL OUTCOME IN UROTHELIAL CANCER OF BLADDER? Hamed Ahmadi*, Gus Miranda, Jie Cai, Siamak Daneshmand, Los Angeles, CA INTRODUCTION AND OBJECTIVES: To evaluate the effect of tumor location on the pattern of lymph node metastasis (LNM) and oncological outcome in patients with bladder cancer (BC). METHODS: Based on pathology reports of radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND) performed at USC Institute of Urology between 1971 and 2008, five discrete anatomical locations were defined as anterior wall, posterior wall, lateral wall, dome, and trigone (including uretrovesical junction and bladder neck). Single-site tumor was considered when tumor was located exclusively in one anatomical location and tumors that involved more than one anatomical

1770 CLINICAL OUTCOME IN PATIENTS WITH T1 MICROPAPILLARY UROTHELIAL CARCINOMA OF THE BLADDER Massimiliano Spaliviero*, Guido Dalbagni, Bernard H. Bochner, Bing Ying Poon, Timothy F. Donahue, Hikmat A. Al-Ahmadie, Jennifer M. Taylor, Joshua J. Meeks, Hongying Huang, Daniel D. Sjoberg, S. Machele Donat, Harry W. Herr, New York, NY INTRODUCTION AND OBJECTIVES: Micropapillary carcinoma of the bladder is a rare and aggressive variant of urothelial carcinoma (UC). Management of non-muscle-invasive micropapillary UC papillary features is controversial, although early radical cystectomy has been advocated. We report the overall survival in patients with non-muscle-invasive micropapillary UC who underwent restaging transurethral resection of bladder tumor (TURBT).

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METHODS: Following Institutional Review Board approval, the records of 42 patients restaged within 3 months of initial ⱕT1 disease diagnosis were reviewed. Early cystectomy or conservative management was offered according to disease features at restaging TURBT (residual tumor volume, multifocality, presence of carcinoma in situ, lymphovascular invasion), or patient’s preference. We defined early cystectomy as cystectomy performed within a 3-month landmark after restaging TURBT. Other management (intravesical bacillus CalmetteGuerin, surveillance, or cystectomy after the landmark) was considered conservative. Overall and differences in survival probabilities were estimated using Kaplan-Meier methods and log rank test, respectively, starting at the landmark time. Confidence intervals (CI) for survival differences were estimated using bootstrap resampling. RESULTS: Median patient age was 68 years (range 40-93). Male to female ratio was 3.7:1. At restaging TURBT, stage distribution was 14 T0 (33%), 2 high-grade Ta (5%), 9 Tis (21%), and 17 highgrade T1 (41%). Eighteen (43%) patients underwent early cystectomy; 24 (57%) were managed conservatively. Rates of T0 stage upon restaging TURBT were similar (33% vs. 33%, p ⫽ 1) in both groups. Median follow-up time from landmark was 3.2 years for survivors. Kaplan-Meier estimate of 5-year survival probability (Figure 1) was 72% in the early cystectomy group (dashed line) and 69% in the conservative treatment group (solid line), with an absolute difference of 3% (95% CI: -21%, 14%). No significant differences in survival probabilities between the two groups was found throughout follow-up using the log rank test (p ⫽ 1). CONCLUSIONS: In our cohort of patients with T1 non-muscleinvasive micropapillary UC there was no significant difference in survival among patients treated conservatively or undergoing early cystectomy.

Vol. 189, No. 4S, Supplement, Tuesday, May 7, 2013

number of tumours detected using white (WL) and fluorescent (FL) light and their pathological features were recorded and compared between the two arms. RESULTS: One hundred and thirty-three men and 18 women (11.9%) aged 74 ⫾ 14 years had a first TURB, including 72 (47.7%) with HAL. The number of tumours visualised in WL and FL in patients with HAL was 2.66 ⫾ 2.26 and 3.04 ⫾ 2.54 respectively. In the 79 patients without HAL, 2.42 ⫾ 1.72 tumours were seen in WL. Twentytwo patients and 6 patients who had a cystectomy, respectively, for a muscle-invasive tumour or a T1G3 ⫹ CIS tumour diagnosed by the first TURB, 5 patients T0, 15 patients refusing the 2nd TURB (including 5 for Ta tumours of low grade and 5 due to worsening of their general condition), 2 intercurrent deaths from cardiac causes and 8 patients lost to follow-up have not had a 2nd TURB. Ninety-three patients (62%) had a 2nd REV. The number of tumours visualised in WL and FL in 43 patients who underwent the first TURB with HAL was 2.02 ⫾ 1.66 and 2.56 ⫾ 2.10 respectively. For the 50 patients who had the first TURB without HAL, the number of tumours visualised in WL and FL was 1.90 ⫾ 2.29 and 2.06 ⫾ 2.45 respectively. CONCLUSIONS: TURB with HAL fluorescence in patients with high grade urine cytology provides a gain in the number of tumours diagnosed compared to WL alone. This gain was observed during the first and 2nd with TURB with HAL. However, the differences observed in this prospective randomised study were not significant. With HAL when 1st TURB 74 ⫾ 14 years

Age % women

Without HAL when 1st TURB 74 ⫾ 14 years

p⫽ 0.93

11.1%

12.7%

0.77

Tumours (WL) 1st TURB

2.66 ⫾ 2.26

2.42 ⫾ 1.72

0.65

n (%) T2 diagnosed by 1st TURB

10 (14.3%)

15 (19.2%)

0.69

n (%) T2 diagnosed by 2nd TURB

1 (2.3%)

2 (4.0%)

0.54

n (%) cis diagnosed by 1st TURB

15 (21.7%)

13 (16.9%)

0.84

n (%) cis diagnosed by 2nd TURB

9 (20.9%)

14 (29.8%)

0.47

1,97 ⫾ 1,79

2,20 ⫾ 2,26

0.63

n (%) T0 diagnosed by 1st TURB

3 (4.6%)

5 (6.8%)

0.72

n (%) T0 diagnosed by 2nd TURB

23 (53.5%)

25 (48.0%)

0.25

Tumours (WL) 2nd TURB

Source of Funding: None

1772 REFLEX FLUORESCENCE IN-SITU HYBRIDIZATION (FISH) ASSAY FOR ATYPICAL URINARY CYTOLOGY IN BLADDER CANCER PATIENTS UNDERGOING SURVEILLANCE CYSTOSCOPY Source of Funding: None

1771 RANDOMISED PROSPECTIVE EVALUATION OF FLUORESCENCE FOR TRANSURETHRAL RESECTION OF THE BLADDER: WHAT IS THE REAL GAIN FOR DIAGNOSIS? Yann NEUZILLET*, Charlotte METHORST, Suresnes, France; Marc SCHNEIDER, Colmar, France; Mathieu ROUANNE, Thierry LEBRET, Henry BOTTO, Suresnes, France INTRODUCTION AND OBJECTIVES: To evaluate the gain provided by fluorescence for diagnostic cystoscopy during transurethral resection of bladder (TURB) in patients with at least one bladder tumor diagnosed by endoscopy, a priori non-muscle invasive, and high grade urine cytology. METHODS: Randomised prospective study. From November 2009 to September 2012, 151 patients were randomised in two centres for the first TURB with or without fluorescence using Hexaminolevulinate (HAL) instilled at least 1 hour before TURB. A second TURB with fluorescence was systematically programmed 6 weeks afterwards. The

Philip H. Kim*, Ranjit Sukhu, Billy H. Cordon, John P. Sfakianos, Daniel D. Sjoberg, Oscar Lin, Guido Dalbagni, Harry W. Herr, New York, NY INTRODUCTION AND OBJECTIVES: Chromosomal changes in normal appearing urothelium may precede visual evidence of recurrence or progression in patients on surveillance for non-muscle invasive bladder cancer (NMIBC). We report the results of reflex UroVysion FISH testing in NMIBC patients with atypical cytology but negative cystoscopy. METHODS: Patients on surveillance for NMIBC were followed with office flexible cystoscopy and urinary cytology every three to six months. Between March 2007 and February 2012, all surveillance patients with atypical cytology underwent reflexive FISH analysis. FISH was deemed uninformative if the submitted specimen did not have enough cells for analysis. All relevant clinical and pathologic data were reviewed. Recurrence-free (RFS) and progression-free survival (PFS) were estimated using Kaplan Meier analysis. Predictors for recurrence and progression were evaluated using univariate and multivariate Cox regression analyses. RESULTS: Of 500 patients who had FISH ordered reflexively for atypical cytology results during surveillance for NMIBC, 243 also