1905 ADHERENCE TO SURVEILLANCE GUIDELINES AFTER RADICAL CYSTECTOMY: A POPULATION-BASED ANALYSIS

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THE JOURNAL OF UROLOGY姞

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

CONCLUSIONS: In this cohort with complete pathology rereview, we found that pathologic substaging added independent prognostic significance for patients with pT3N0 UC following RC, but not in those with pT2N0 disease. Additional studies are therefore needed to identify pathologic features that may further improve the prognostic ability of the AJCC staging system, especially for patients with pT2N0 disease. Source of Funding: None

1904 EXTRANODAL EXTENSION IS A POWERFUL PROGNOSTIC FACTOR IN BLADDER CANCER PATIENTS WITH LYMPH NODE METASTASIS Harun Fajkovic*, St.Poelten, Austria; Eugene Cha, New York, NY; Claudio Jeldres, Montreal, Canada; Brian Robinson, Michael Rink, New York, NY; Thomas Chromecki, Graz, Austria; Eckart Breinl, Gerhard Donner, St.Poelten, Austria; Robert Svatek, San Antonio, TX; Derya Tilki, Patrick Bastian, Munich, Germany; Pierre Karakiewicz, Montreal, Canada; Bjoern Volkmer, Kassel, Germany; Giacomo Novara, Padua, Italy; Christian Seitz, Vienna, Austria; Guru Sonpavde, Houston, TX; Siamak Daneshmand, Los Angeles, CA; Yair Lotan, Dallas, TX; Talia Faison, Douglas Scherr, Shahrokh Shariat, New York, NY INTRODUCTION AND OBJECTIVES: The prognosis of patients with invasive urothelial carcinoma of the bladder (UCB) treated with radical cystectomy is closely related to the pathologic stage of the primary tumor and the presence of lymph node metastasis (LNM). The aim of the current study was to assess the prognostic value of extranodal extension (ENE) and to test whether it improves the performance of predictive models constructed without ENE. METHODS: Retrospective analysis of 748 patients with LNM treated with radical cystectomy (RC) and lymphadenectomy for UCB without neoadjuvant therapy at 10 centers in Europe and North America. Microscopically, each LNM was evaluated for presence of ENE, defined as a clear-cut perforation of lymph node capsule by tumor. RESULTS: Overall, 375 patients (50.1%) had ENE. The median number of lymph nodes removed, number of positive lymph nodes, and lymph node density were 15, 2, and 15%, respectively. The rate of ENE increased with advancing pT stage (p⬍0.001). Within a median follow-up of 27 months (mean 39.8 ⫾ 41.8; IQR 44), disease recurrence occurred in 420 patients (56.1%), and 353 patients (47.2%) died of UCB. In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features, ENE was associated with disease recurrence (HR: 1.95, 95% CI: 1.59-2.40, p⬍0.001) and cancer-specific mortality (HR: 1.90, 95% CI: 1.52-2.37, p⬍0.001). Addition of ENE to multivariable predictive models improved predictive accuracies for recurrence-free and cancer-specific survival from 70.3% to 77.5% (p⫽0.015) and 71.8% to 80.2% (p⫽0.015), respectively. CONCLUSIONS: ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with clinical decisionmaking regarding follow-up.

Source of Funding: None

1905 ADHERENCE TO SURVEILLANCE GUIDELINES AFTER RADICAL CYSTECTOMY: A POPULATION-BASED ANALYSIS Behfar Ehdaie*, Coral Atoria, New York, NY; William Lowrance, Salt Lake City, UT; Andrew Feifer, Dean Bajorin, Bernard Bochner, S. Machele Donat, Guido Dalbagni, Elena Elkin, New York, NY INTRODUCTION AND OBJECTIVES: Surveillance after radical cystectomy is recommended to detect tumor recurrences and treatment complications. We evaluated the adherence of bladder cancer patients with the National Comprehensive Cancer Network (NCCN) guidelines for surveillance after radical cystectomy in a populationbased cohort of Medicare beneficiaries with bladder cancer. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)- Medicare linked database to identify patients aged 65 years or older diagnosed with non-metastatic bladder cancer who had radical cystectomy between 2000 and 2007. We used information from Medicare claims to examine the frequency of surveillance tests in the two years following surgery. The guidelines recommend urine cytology at least twice per year and annual imaging of the chest, abdomen and pelvis. We evaluated the impact of patient and provider characteristics on adherence with surveillance guidelines, controlling for demographic and clinical characteristics. RESULTS: Of 3,757 patients who had radical cystectomy, 2,990 (80%) were alive after two years. Adherence with all recommended investigations was 17% in the first year following surgery and 17% in the second year. Among those alive after 2 years, only 9% of patients had complete adherence with surveillance guidelines in both years. Patients with advanced pathologic stage (III/IV) and those who were unmarried were less likely to be adherent with surveillance guidelines in either year (adjusted odds ratio [AOR] for advanced stage 0.74, 95% CI 0.60-0.91; AOR for unmarried 0.82, 95% CI 0.68-0.99). Patients treated by high-volume surgeons and those who saw a medical oncologist were more likely to be adherent (AOR for high volume 2.00, 95% CI 1.70-2.36; AOR for medical oncology visit 1.52, 95% CI 1.27-1.82). We also observed significant geographic variability in adherence with surveillance guidelines. CONCLUSIONS: There is substantial deviation of clinical practice from the standards recommended by the NCCN for surveillance after radical cystectomy. Variation in adherence with clinical guidelines suggests important opportunities for quality improvement in bladder cancer care.

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

THE JOURNAL OF UROLOGY姞

Adherence with NCCN Postoperative Surveillance Guidelines Year 1 Year 2 Both Years (N ⫽ 3,757) (N ⫽ 2,990) (N ⫽ 2,990) Imaging of chest 2,808 (75%) 2,198 (74%) 1,791 (60%) Imaging of abdomen/pelvis

3,138 (84%)

2,320 (78%)

2,062 (69%)

Urine cytology

864 (23%)

679 (23%)

428 (14%)

All

650 (17%)

514 (17%)

264 (9%)

Source of Funding: This study was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers. Supported in part by funds from David H. Koch through the Prostate Cancer Foundation

1906 POSITIVE SURGICAL MARGINS CONTRIBUTE TO DELAYED FAILURES IN PATIENTS UNDERGOING RADICAL CYSTECTOMY FOR BLADDER CANCER Edwin Morales*, San Antonio, TX; Shahrokh Shariat, New York, NY; Pierre Karakiewicz, Montreal, Canada; Bjorn Volkmer, Kassel, Germany; Wassim Kassouf, Montreal, Canada; Yves Fradet, Quebec, Canada; Giacomo Novara, Padua, Italy; Hans-Martin Fritsche, Regensburg, Germany; Patrick Bastian, Munich, Germany; Jonathan Izawa, London, Canada; Christian Stief, Munich, Germany; Vicenzo Ficarra, Padua, Italy; Michael Rink, New York, NY; Seth Lerner, Houston, TX; Mark Schoenberg, Baltimore, MD; Colin Dinney, Houston, TX; Eila Skinner, Los Angeles, CA; Yair Lotan, Arthur Sagalowsky, Dallas, TX; Robert Svatek, San Antonio, TX INTRODUCTION AND OBJECTIVES: Disease recurrence (DR) following radical cystectomy (RC) for muscle-invasive bladder cancer usually occurs early after resection and for this reason 2-3 year survival correlates well with 5 year outcomes. Nevertheless, it is known that patients living beyond the initial “high-risk” period following surgery are still at risk for DR. We sought to characterize those unique patients experiencing late DR (⬎4 years after surgery) in order to elucidate possible mechanisms of delayed relapse and to help guide surveillance strategies. METHODS: An observational cohort study of 4338 patients from multiple centers treated with RC for bladder cancer was conducted. Clinical and pathologic features of patients with early (⬍4years from surgery) and late (⬎4 years from surgery) DR were compared. We sought to identify clinical and pathologic features that may be associated with late DR and disease-specific survival among patients experiencing 4 disease-free years after RC. RESULTS: A total of 1,443 (33.3%) were alive and without disease at 4 years following surgery. The median follow-up for these patients was 7.9 years (IQR 5.7-11.8 years). DR was observed in 1,460 (33.7%) of the entire cohort. Of those patients alive and without disease at 4 years, 100 (6.9%) were found to have disease recurrence and 74 (5.1%) died from bladder cancer. Pathologic stage of patients experiencing late DR include 34(36%) pT0-T1, 28(30%) pT2, and 33(35%) ⬎pT2. For patients with early DR, pathologic stage included 159(12%) pT0-T1, 275(20%) pT2, and 928(68%) ⬎pT2. Lymph node involvement was seen in 16% of patients with late DR; this differed from 48% involvement found with early DR. On univariable analysis, a positive surgical margin status was significantly associated with death from bladder cancer among patients with late DR (HR 3.99, 95%CI 1.73-9.20, P⫽0.001). After adjusting for competing variables, positive surgical margins retained statistical significance with cancer-specific mortality on multivariable analysis (HR 3.60, 95%CI 1.41-9.22, P⫽0.008). CONCLUSIONS: DR remains at a concerning 4-5% incidence per year even up to 10 years following RC for bladder cancer. Previous reports comment on surgical margins as an independently associated risk factor for DR of many different time frames, however, to our knowledge, this is the first to suggest that they are the only factor associated with an increased risk of late DR (⬎4y after RC). These findings suggest that late DR is largely related to technical error and operative technique and thus not necessarily intrinsic to tumor biology. Source of Funding: None

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1907 NEOADJUVANT CHEMOTHERAPY FOR UROTHELIAL BLADDER CANCER: TUMOR REGRESSION IS AN INDEPENDENT PREDICTOR OF SURVIVAL Roland Seiler*, Achim Fleischmann, Aurel Perren, George N. Thalmann, Bern, Switzerland INTRODUCTION AND OBJECTIVES: Tumor regression after chemotherapy in cancers of the rectum and oesophagus predicts survival superior to conventional staging systems (e.g.yTNM). In bladder cancer these studies are still missing. METHODS: A cohort of 59 patients with histopatholgically proven urothelial bladder cancer received neoadjuvant chemotherapy (median 4 cycles) before cystectomy and lymphadenectomy in a single centre institution. A tumor regression grade (TRG) was defined in analogy to the method proposed by Mandard et al. (Cancer 1994;71: 2680-6). TRG 1: complete regression without residual cancer and with extensive fibrosis of the tumor bed; TRG 2: presence of residual cancer cells scattered through the predominating fibrosis; TRG 3: residual cancer outgrowing fibrosis or absence of regression. Histopathological characteristics of the untreated tumors (growth patterns, histological subtypes, nuclear size, peri- and intratumoral inflammation, mitotic rate) were correlated with TRG and different parameters of the treated tumors were tested for overall survival (OS) stratification. RESULTS: In cystectomy specimens, ypT0, ypT1/2, ypT3 and ypT4 was found in 21 (36%), 15 (25%), 13 (22%) and 10 (17%) patients, respectively. TRG 1, TRG 2 and TRG 3 was determined in 18 (30%), 16 (27%) and 25 (43%) of patients. Increasing TRG grade was significantly (p⬍0.05) associated with unfavorable characteristics in surgical specimens (higher ypT, number of positive blocks, diameter of residual tumor and ypN). In univariate analysis, TRG, ypT, number of positive blocks, diameter of residual tumor and ypN stratified OS significantly. However, only TRG predicted OS independently (p⬍0.05) from all other tested risk factors in multivariate analysis. In the untreated cancers, the only parameter with significant (p⬍0.05) predictive value for therapy response was a high mitotic rate. CONCLUSIONS: The suggested tumor regression grade predicted survival independently, superior to the yTNM system and should be validated in other cystectomy series after neoadjuvant chemotherapy. The mitotic rate in TUR specimens was significantly associated with response rate. This parameter might help to identify patients which benefit from neoadjuvant chemotherapy. Source of Funding: None

1908 NUMBER OF LYMPH NODES REMOVED DOES NOT INFLUENCE SURVIVAL IN STAGE N0 BLADDER CANCER AFTER COMPLETE EXTENDED LYMPHADENECTOMY Matthew T Johnson*, Erinn M Hade, Amanda N Calhoun, Columbus, OH; Michael C Gong, Cleveland, OH; Debra L Zynger, Kamal S Pohar, Columbus, OH INTRODUCTION AND OBJECTIVES: Number of lymph nodes (LN) removed is accepted as a surrogate of the extent and quality of lymphadenectomy at radical cystectomy (RC). Removing more LN was reported to provide therapeutic benefit in node negative (pN0) patients. However, studies are limited by including patients with different anatomic extent of LN removal. The reported therapeutic benefit may in fact be a staging benefit (Will Rogers phenomenon) or a reflection of inadequate LN removal in a given template. An extended lymphadenectomy (ELN) when properly performed has been shown to correctly stage pN0 patients. The aim of our study was to determine if the number of LN removed influenced disease free survival (DFS) or overall survival (OS) in pN0 patients undergoing ELN by strict surgical standards. METHODS: The study included 100 patients with ⬎cT2 bladder cancer who underwent an ELN between 03/2006-12/2010. 21 patients had lesser extent of LN removal (history of pelvic radiation or aortic