1897 OUTCOMES AND CLINICOPATHOLOGIC PREDICTORS ASSOCIATED WITH LATE RECURRENCE AFTER RADICAL CYSTECTOMY

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

pre-operative and at least one post-operative questionnaire and were included in this analysis. The Wilcoxon Signed Rank Test was used to compare scores in each domain across all time points with a P value of 0.05 representing significance. RESULTS: CARE scores were decreased in multiple domains at the 2 week post-operative time point. This is illustrated by a 16.61 point decrease in the overall summary score at the 2 week time point when compared to pre-operative scores (p⬍0.01). The pain, gastrointestinal, and activity domains demonstrate significant difference from pre-operative function 2 weeks post-operatively with mean decreases of 8.17 (p⬍0.01), 17.45 (p⬍0.01), and 39.83 (p⬍0.01) points respectively. This deficit from baseline scores persists at the 4 week time point with mean decreases of 4.50 (p⫽0.03), 8.12 (p⬍0.01), and 21.70 (p⬍0.01) points. Significant difference from pre-operative scores is not noted at the 6 week post-operative time point in the summary, pain, or gastrointestinal domains (p⬎0.05). There is continued impairment in the activity domain at the 6 week post-operative time point with a 14.61 point decrease from pre-operative score (p⬍0.01). CONCLUSIONS: Significant impairment from baseline was seen in multiple domains 2 weeks post-operatively but only the activity domain demonstrated continued impairment at 6 weeks. Recovery is suggested in the summary, pain, and gastrointestinal domains between the 4 and 6 week time points. This information would be useful when counseling prospective patients regarding the timeline of recovery following cystectomy with urinary diversion. Source of Funding: None

1896 CYCLIN D1 EXPRESSION INDEPENDENTLY PREDICTS SURVIVAL AND RESPONSE TO CHEMOTHERAPY IN LYMPH NODE POSITIVE BLADDER CANCER Roland Seiler*, Achim Fleischmann, Diana Rotzer, George N. Thalmann, Bern, Switzerland INTRODUCTION AND OBJECTIVES: Cyclin D1 (CD1) expression predicts survival and also response to chemotherapy in different cancers. The prognostic impact of CD1 expression in lymph node positive bladder cancer and its potential to predict chemosensibility has never been determined. METHODS: Hundred and fifty two lymph node positive patients with urothelial bladder cancer underwent cystectomy and pelvic lymphadenectomy. A tissue microarray was constructed with two samples from the primary tumor and two from lymph node metastasis per patient. In each spot, percentage of stained cancer cells was determined. Expression data were correlated with tumor features and cancer-specific survival (CSS). RESULTS: Nuclear and cytoplasmic CD1 expression were significantly (p⬍0.05) up-regulated in metastases (median nuclear/ cytoplasmic expression: 50%/15%) compared to primary tumors (median nuclear/cytoplasmic expression: 30%/0%). CD1 expression was not correlated with tumor features (TNM stage; number, total diameter and extranodal extension of metastases). High nuclear CD1 expression in metastases predicted early death significantly (p⫽0.001) and independently (p⫽0.01) from other risk factors. Subgroup analyses showed that survival stratification was best in patients without any chemotherapy, all patients with high nuclear Cyclin D1 expression died during the first 2.5 years. Importantly, survival of this high risk subgroup increased dramatically when any chemotherapy (5-year CSS: 22%) and particularly platin-based chemotherapy (5-year CSS: 37%) was applied while the low risk group did not profit substantially. CD1 in all other tumor cell compartments failed to stratify survival. CONCLUSIONS: Nuclear CD1 expression in lymph node metastases of bladder cancer predicts cancer related death independently and is a strong predictor of favorable response to chemotherapy. This prognostic and predictive information may help to identify high-risk patients and personalize adjuvant therapies, thus improving patient management. Source of Funding: None

THE JOURNAL OF UROLOGY姞

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1897 OUTCOMES AND CLINICOPATHOLOGIC PREDICTORS ASSOCIATED WITH LATE RECURRENCE AFTER RADICAL CYSTECTOMY Igor Frank*, John Cheville, Prabin Thapa, Robert Tarrell, Stephen Boorjian, Rochester, MN INTRODUCTION AND OBJECTIVES: While the initial natural history following radical cystectomy (RC) for bladder cancer has been well-characterized, outcomes in patients who experience late recurrence (LR) have not been well-defined. Herein, we report the incidence and the pattern of LR, evaluate predictors, and compare oncologic outcome between patients with early (⬍5 years after RC) and late (⬎5 years after RC) recurrence. METHODS: We reviewed 1738 patients who underwent RC at our institution for TanyNanyM0 urothelial carcinoma from 1980-2003. Median follow-up was 17.6 years (range 8.5-27.6). A total of 57 (3.3%) patients experienced their first recurrence of disease ⬎5 years after RC. Recurrences were categorized by site as non-urothelial (pelvic ⫹ distant) and urothelial (upper tract ⫹ urethra). Associations of pathologic and clinical features with LR were analyzed using Cox proportional hazard regression models. Cancer-specific survival (CSS) in patients with LR was estimated using the Kaplan-Meier method and compared using the log rank test to the outcomes from 635 (36.5%) patients in our dataset found to have early disease recurrence. RESULTS: LR was diagnosed at a median of 7.7 years (range 5.0-21.6) after RC. A total of 42 (74%) of these patients experienced LR at a non-urothelial site, while 15 (26%) demonstrated LR in the remnant urothelium. Interestingly, the majority of LRs occurred in patients with pathologic non-muscle invasive disease at RC (80% in the urothelial group; 67% in non-urothelial cohort). However, in a multivariate analysis, no pathologic feature was significantly associated with the risk of LR. CSS at 5 years after LR was 54%, 71%, and 48% for patients with any LR, urothelial LR, and non-urothelial LR, respectively. We found no difference in the 5-year CSS between patients with early versus late urothelial recurrences (71% vs 64%; p⫽0.17). However, among nonurothelial recurrences, LR was associated with a significantly better 5-year CSS compared to early recurrence (48% vs 15%; p⫽0.0001). CONCLUSIONS: While late recurrence is uncommon after RC, patients continue to be at risk even after being disease-free for 5 years. Patients with non-urothelial LR have a significantly better outcome than patients with early recurrence. Continued investigation is needed to identify potential risk factors for LR, and to develop evidence-based surveillance protocols. Source of Funding: None

1898 COMPARISON OF THE AMERICAN JOINT COMMITTEE ON CANCER SUBSTRATIFICATION IN LYMPH-NODE NEGATIVE PT3 BLADDER CANCER: ANALYSIS OF PATIENT OUTCOMES IN A CONTEMPORARY SERIES Mohamed F. Abdelhafez*, Tilman Todenhöfer, Markus Renninger, Arnulf Stenzl, Georgios Gakis, Tuebingen, Germany INTRODUCTION AND OBJECTIVES: To determine whether there is a difference in survival in patients with lymph-node negative pT3a vs. pT3b bladder cancer as some recent single-center studies suggest that the American Joint Committee on Cancer substratification in pT3 disease may not have any prognostic significance. METHODS: Of 307 consecutive patients undergoing radical cystectomy with bilateral pelvic lymphadenectomy between 1999 and 2011, 97 (30.9%) had pT3cM0 bladder cancer. Fisher Exact Test and Cox-proportional hazard assumption were used for uni- and multivariate analysis of risk factors. Kaplan Meier plots were used to estimate the impact of pT3 substaging in lymph-node negative disease on recurrence-free (RFS) survival using log-rank test. Median follow-up was 27 months (6-116) in the total cohort.