1593 CLINICAL MANAGEMENT OF MUSCLE INVASIVE MICROPAPILLARY BLADDER CANCER

e644

THE JOURNAL OF UROLOGY姞

movement) recovery, hospital discharge order written, actual hospital discharge, opioid consumption, and overall postoperative ileus-related morbidity. Categorical and linear variables were compared using Fisher’s exact and Mann Whitney U tests, respectively. RESULTS: There was no significant differences in mean patient age, gender distribution, type of urinary diversion, or PCA usage between groups. There were no significant side effects reported in patients receiving alvimopan. Alvimopan significantly decreased time to return of bowel function (GI-2: 104⫾33hr vs. 142 ⫾ 53hr, p⬍0.01; GI-3: 102⫾34hr vs. 140⫾53hr, p⬍0.01). Hospital length of stay was significantly shorter in patients treated with alvimopan (5.8⫾1.3d vs. 7.5⫾2.9d, p⬍0.05). The 30-day readmission rate for vomiting, adynamic ileus, or partial small bowel obstruction in patients receiving alvimopan was 0% compared to 10.4% in the control group. CONCLUSIONS: Consistent with clinical trial data in general surgery series, alvimopan use following radical cystectomy shortened hospital length of stay and decreased time to return of bowel function by approximately 1.5 days. These results support the clinical benefit of alvimopan in patients undergoing radical cystectomy. Source of Funding: None

1591 AGE, COMORBIDITIES, AND RACE ARE PREDICTORS TO UNDERGO RADICAL CYSTECTOMY AT LOW VOLUME INSTITUTIONS Marco Bianchi*, Milan, Italy; Maxine Sun, Montreal, Canada; Jens Hansen, Hamburg, Germany; Nawar Hanna, Zhe Tian, Montreal, Canada; Alberto Briganti, Milan, Italy; Shahrokh Shariat, New York, NY; Paul Perrotte, Montreal, Canada; Francesco Montorsi, Milan, Italy; Pierre Karakiewicz, Montreal, Canada INTRODUCTION AND OBJECTIVES: We tested the hypothesis that old age, multiple comorbidities, and race may predict radical cystectomy at low volume institutions. METHODS: Overall, 10991 patients treated with radical cystectomy for bladder cancer were identified amongst 1052 hospitals originating from the Nationwide Inpatient Sample, between years 1998 and 2007. We examined patient age, baseline Charlson comorbidity index (CCI), gender, race, hospital teaching status, hospital region, and annual household income according to hospital volume, which was modeled in a continuously coded fashion. Finally, we examined the effect of hospital volume on patient age and CCI, using linear regression analyses. Adjustment was made for all the aforementioned covariates. RESULTS: The overall mean hospital volume was 8 cystectomies per year (median 4, interquartile range [IQR]: 2– 8). First, hospital volume decreased with increasing age (ⱕ59 years mean: 8.6 (median 4) vs. ⱖ80 years: 7.6 (median 4), P⬍0.001) and increasing CCI (0 mean: 8.6 (median 4) vs. ⱖ3: 6 (median 3), P⬍0.001). The effect of hospital volume also differed according to gender, hospital teaching status, and hospital region. Specifically, females, patients of black race, non-teaching hospitals, and hospitals located in the Midwest, were treated at institutions with the lowest hospital volume. In univariable linear regression analyses, decreasing age (beta: -0.038, P⬍0.001) and decreasing CCI (beta: -0.039, P⬍0.001) were inversely associated with increasing hospital volume. These findings were confirmed in multivariable analyses, where patients with increasing age (beta: -0.022, P⫽0.03) and higher CCI (beta: -0.028, P⫽0.005) were more likely to be operated at hospitals with a low hospital volume. CONCLUSIONS: Our data show that advanced age, multiple comorbidities, black race, and female gender are predictor of radical cystectomy at low volume institution. Clustering of patients with those characteristics at low volume institutions does not appear to be incidental and may predispose to worse outcomes Source of Funding: None

Vol. 187, No. 4S, Supplement, Tuesday, May 22, 2012

1592 IMPACT OF COMORBIDITIES ON PERIOPERATIVE COMPLICATIONS AFTER RADICAL CYSTECTOMY FOR BLADDER UROTHELIAL CARCINOMA: A TERTIARY SOUTH AMERICAN ONCOLOGY CENTER EXPERIENCE. Carlos H Watanabe, Renato F Ivanovic, Daher C Chade*, Claudio B Murta, Leonardo M de Souza, Polyne M de Souza, Mauricio D Cordeiro, Alexandre C Sant’Anna, Marcos F Dall’Oglio, Miguel Srougi, Sao Paulo, Brazil INTRODUCTION AND OBJECTIVES: Bladder cancer incidence is progressively increasing in Brazil due to an aging population. Previous studies, including data from our institution, suggest that the rate of postoperative complications is associated to preoperative clinical conditions. The objective of this study was to evaluate the association of comorbidities to postoperative complications, length of hospital stay and mortality. METHODS: We included 168 patients with urothelial bladder cancer who underwent radical cystectomy in our institution from June 2006 to July 2010. We used the Charlson Comorbidity Index (CCI). Postoperative complications were classified according to the modified Clavien system. Survival curves were derived from the estimated Kaplan-Meier method. Log-rank test was used to evaluate these survival functions. Univariate and multivariate analyses were performed to identify the risk factors in predicting postoperative death. RESULTS: Mean age was 65.4 years and mean hospital stay 13.6 days. Median follow-up was 24.4 months. The most frequent comorbidities were hypertension (49.1%), chronic renal failure (14.8%), diabetes (11.8%). 71% of patients had CCI 3-5 and 22.6% CCI ⬎ 5. 44% had postoperative complications (all grades) and 7.7% (n ⫽ 13) died within 3 months postoperatively. Overall, most frequent complications were ileus (8.9%), acute renal failure (6.5%), evisceration (6.5%), urinary tract infection (6%), deep venous trombosis (4.1%), urinary fistula (4.1%), myocardial infarction (3.6%) and enteric fistula (3.0%). In univariate regression, ICC⬎ 5 increased by 5.9 times the chance of death compared to ICC ⬍3 (p ⫽ 0.04). In multivariate analysis, age was the only predictor of mortality related to postoperative complications. CONCLUSIONS: The high rate of perioperative complications may be related to the increased incidence of comorbidities in our population. Better patient selection and treatment of clinical comorbidities prior to surgery may directly improve postoperative outcomes after bladder cancer treatment. Source of Funding: None

1593 CLINICAL MANAGEMENT OF MUSCLE INVASIVE MICROPAPILLARY BLADDER CANCER Joshua Meeks*, Jennifer Taylor, Harry Herr, S. Machele Donat, Bernard Bochner, Guido Dalbagni, New York, NY INTRODUCTION AND OBJECTIVES: High grade urothelial carcinoma may have divergent histologic variants, among the most aggressive is micropapillary (MP) type. So aggressive, that some advocate early cystectomy for muscle invasive (MI) MP forgoing the potential benefits of neoadjuvant chemotherapy. Our goal was to determine the response of MI MP bladder cancer to neoadjuvant chemotherapy. METHODS: Eighty-two patients were treated at Memorial Sloan-Kettering Cancer Center with MI bladder cancer with MP histology and were clinical stage T2 or greater. After exclusion for metastatic disease at presentation, MP first identified at radical cystectomy, and patients with significant medical comorbidities unfit for surgery, 49 patients were identified with MP diagnosed at TUR. MP histology was diagnosed at time of first presentation with T2 disease in 39 (80%) while 10 (20%) were initially diagnosed as T1 and later progressed to MI.

Vol. 187, No. 4S, Supplement, Tuesday, May 22, 2012

RESULTS: Of the 49 patients with MI MP, 88% were male, 72% were smokers, 90% were Caucasian with a median age of 73. MP was associated with CIS in 44% and vascular invasion was present in 30% of TURs. Neoadjuvant chemotherapy was initiated in 31 (62%) of patients. One patient had progression during neoadjuvant chemotherapy and was unable to undergo cystectomy. Radical cystectomy was performed in 43 (86%), while two were managed by TUR alone and two underwent partial cystectomy. Perineural invasion was present in 28%, CIS in 58%, lymphovascular invasion in 36%. Soft tissue margins were positive in 6%, urothelial margins in 4%. Final cystectomy pathology revealed 42% with ⬍pT2 (pT0/T1/Tis), pT2 in 16%, pT3 in 40% and pT4 in 2%. Lymph nodes were positive in 34%. After cystectomy, 34% recurred and 34% died of bladder cancer. Overall, the rate of recurrence was no different after neoadjuvant chemotherapy (42% vs. 27%, p⬍0.3) and there was no difference in cancer-specific survival (39% vs 27%, p⫽0.3) or the rate of nodal metastasis (35% vs. 31%, p⫽0.2). Down-staging occurred in 48% of those that underwent neoadjuvant chemotherapy to pT0, pT1 or pTis with 27% that were pT0. If downstaging occurred, recurrence after cystectomy (21% vs. 48%, p⬍0.07), and cancer-specific mortality (24% vs. 77%, p⬍0.1) were improved. CONCLUSIONS: Our retrospective data demonstrate that almost half of patients with MI MP do respond to neoadjuvant chemotherapy, with a downstaging rate similar to that reported in other studies. Progression on chemotherapy remains a risk and these patients may benefit from interim restaging. An opportunity is present for a trial comparing outcomes with or without neoadjuvant chemotherapy in this high-risk population. Source of Funding: This study was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers.

1594 OUTCOME OF UROTHELIAL BLADDER CANCER WITH HISTOLOGIC VARIANTS AFTER RADICAL CYSTECTOMY Ja Ku, Seoul, Korea, Republic of; Guiherme Godoy*, Gilad Amiel, Seth Lerner, Houston, TX INTRODUCTION AND OBJECTIVES: Pure forms of nonurothelial carcinomas are associated with more aggressive behavior and diminished patient survival. However, it is unclear whether this adverse prognsois extends to urothelial carcinoma with mixed histologic variants. In addition, because each differentiation pattern is characterized by its distinct biological behavior, the overall significance of urothelial carcinoma with histologic variants remains unclear. METHODS: We retrospectively reviewed the data of 340 patients (33.2 to 90.2 years of age; median age, 68.1; 292 men and 48 women) who underwent radical cystectomy with pelvic lymphadenectomy at our institution between 1998 and 2011. Histologic variants were noted in 43 patients. After squamous differentiation (n ⫽ 27), micropapillary (n ⫽ 9) and sarcomatoid (n ⫽ 4) variants were the most common histologic variants. Three patients with variants were excluded from the analysis due to the small number (lymphoepithelioma-like, n ⫽ 2 and plasmacytoid, n ⫽ 1). The median duration of follow-up was 26.1 months (range, 0.3 to148.0 months). RESULTS: The variant forms were found more frequently in female than in male patients (p ⫽ 0.010). Patients with variant forms had higher pT stage (p ⫽ 0.003) and higher tumor grade (p ⬍0.001) than those with pure form. Patients with pure form and squamous differentiation did not differ significantly in terms of cancer-specific and overall survival. However, statistical analysis of the survival curves of patients with pure form and micropapillary or sarcomatoid variants revealed a statistically significant difference (Figure). In our multivariate adjusted Cox regression model, variant form could predict cancerspecific survival after surgery (p ⫽ 0.010). CONCLUSIONS: Urothelial carcinoma with variant forms presents a higher stage and grade, compared with pure urothelial carcinoma. Prognosis is variable; it seems worse in micropapillary and sarcomatoid variants but it does not seem worse in squamous differ-

THE JOURNAL OF UROLOGY姞

e645

entiation after radical cystectomy when compared to pure urothelial carcinoma.

Source of Funding: None

1595 SQUAMOUS CELL CARCINOMA VS UROTHELIAL CARCINOMA VS UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION: DISEASE FREE SURVIVAL AFTER RADICAL CYSTECTOMY IN PATIENTS WITH HIGH GRADE DISEASE Giuseppe Simone*, Rome, Italy; Hassan Abol Enein, Mansoura, Egypt; Mariaconsiglia Ferriero, Rocco Papalia, Rome, Italy; Ahmed Mosbah, Mohamed Abdel-latif, Mona Abdelrahim, Mansoura, Egypt; Salvatore Guaglianone, Rome, Italy; Mohamed Ghoneim, Mansoura, Egypt; Michele Gallucci, Rome, Italy INTRODUCTION AND OBJECTIVES: To assess the prognostic role of histological subtypes of bladder cancer (non-bilharzial squamous cell carcinoma vs. urothelial carcinoma vs. urothelial carcinoma with squamous differentiation components) in a series of 1503 patients treated with radical cystectomy in two centres. METHODS: We retrospectively analyzed data of two prospectively-maintained institutional databases between 1999 and 2009. Out of 1503 patients, after excluding patients with low-grade disease, patients who received either neoadjuvant or adiuvant treatments and patients who underwent salvage cystectomy and did not receive PLND (pNx), 1159 patients with non-metastatic bladder cancer were selected for analysis. Univariable analysis was performed to test the effect of age, gender, pathological T (pT) and N (pN) stages, lymph-node count (LN-c), lymph-node density (LN-d), different histological subtypes, and tumour grade on disease-free survival. Significant variables (log-rank p⬍0.05) were entered in a multivariable Cox-regression model to identify independent prognostic factors. RESULTS: Cut-off points for continuous variables who reached the significance threshold at univariable analysis were identified with maximally-selected log-rank test in order to enter categorical variable into the Cox-regression model. ´ 3vs.¡U ¨ 2: Significant variables at univariable analysis were: pT (¡Y ¨ 27: p⫽0.001), LN-d (0%/1-11%/ p⬍0.001), pN (p⬍0.001), LN-c (¡Y´28vs.¡U 12-30%/31-100%: p⬍0.001), histological subtypes (UC/Mixed/SCC: p⬍0.001), and extent of PLND (extended vs standard: p⬍0.001). At multivariable analysis, independent prognostic factors were: ¨ 2: HR 2.49, 95% CI 1.95-3.19; p⬍0.001), LN-d pT stage (pT ¡Y´3vs.¡U (1-11% vs 0: HR 1.67, 95% CI 1.23-2.27; p⫽0.01. 12-30% vs 0: HR 3.17; 95% CI 2.34-4.29; p⬍0.001. 31-100% vs 0: HR 5.1, 95% CI 3.81-6.85; p⬍0.001), histological subtypes (Mixed vs UC: HR 1.44, 95% CI 1.014-2.05; p⫽0.041. SCC vs UC: HR 1.58, 95% CI 1.04-2.41; p⫽0.032) and extent of PLND (Extended vs Standard: HR 1.26, 95% CI 1.004-1.57; p⫽0.046). CONCLUSIONS: At RC, SCC and UC with squamous differentiation were independently associated with worse outcome than UC.