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Purpose: Urothelial carcinoma of the bladder is the 4th most common malignancy in men and the 8th most common cause of male cancer death in the United States. Conversely, upper tract urothelial carcinoma accounts for only 5% to 10% of all urothelial carcinoma. Due to the relative preponderance of urothelial carcinoma of the bladder, much of the clinical decision making regarding upper tract urothelial carcinoma is extrapolated from evidence that is based on urothelial carcinoma of the bladder cohorts. In fact, only 1 major urological organization has treatment guidelines specific for upper tract urothelial carcinoma. While significant similarities exist between these 2 diseases, ignoring the important differences may be preventing us from optimizing therapy in patients with upper tract urothelial carcinoma. Therefore, we explored these dissimilarities, including the differential importance of gender, anatomy, staging, intracavitary therapy, surgical lymphadenectomy and perioperative systemic chemotherapy on the behavior of urothelial carcinoma of the bladder and upper tract urothelial carcinoma. Materials and Methods: A nonsystematic literature search using the MEDLINE/PubMed® database was conducted to identify original articles, review articles and editorials. Searches were limited to the English language and studies in humans and in adults, and used the key words urothelial carcinoma, upper tract urothelial carcinoma or transitional cell carcinoma combined with several different sets of key words to identify appropriate publications for each section of the manuscript. The key words, broken down by section, were 1) epidemiology, sex, gender; 2) location, tumor location; 3) staging, stage; 4) intracavitary, intravesical, topical therapy; 5) lymphadenectomy, lymph node, lymph node dissection and 6) adjuvant, neoadjuvant, chemotherapy. Results: Women who present with urothelial carcinoma of the bladder do so with less favorable tumor characteristics and have worse survival than men. However, gender does not appear to be associated with survival outcomes in upper tract urothelial carcinoma. The prognostic effect that urothelial carcinoma tumor location has on outcomes prediction is a matter of debate, and the influence of tumor location may reflect our technical ability to accurately stage and treat the disease more than the actual tumor biology. Moreover, technical limitations of upper tract urothelial carcinoma sampling compared to transurethral resection for urothelial carcinoma of the bladder are the most important source of staging differences between the 2 diseases. Intravesical chemotherapy and immunotherapy are essential components of standard of care for most nonmuscle invasive bladder cancer, while adjuvant intracavitary therapy for patients with upper tract urothelial carcinoma treated endoscopically or percutaneously has been sparsely used and without any clear guidelines. The widespread adoption of the use of intracavitary therapy in the upper tract will likely not only require additional data to support its efficacy, but will also require a less cumbersome means of administration. Lymphadenectomy at the time of radical cystectomy is widely accepted while lymphadenectomy at the time of radical nephroureterectomy is performed largely at the discretion of the surgeon. Among other reasons, this may be due in part to the variable lymphatic drainage along the course of the ureter compared to the relatively confined lymphatic landing sites for the bladder. Level I evidence has demonstrated a clear survival benefit for systemic chemotherapy before radical surgery or radiation in patients with clinical T2-4N0M0 urothelial carcinoma of the bladder. Such data are not available in the population with upper tract urothelial carcinoma. However, the use of neoadjuvant chemotherapy may be even more important in upper tract urothelial carcinoma than in urothelial carcinoma of the bladder because of the obligatory kidney function loss that occurs at radical nephroureterectomy. Conclusions: While urothelial carcinoma of the bladder and upper tract urothelial carcinoma share many characteristics, they represent 2 distinct diseases. There are practical, anatomical, biological and molecular differences that warrant consideration when risk stratifying and treating patients with these disparate twin diseases. To overcome the challenges that impede progress toward evidence-based medicine in upper tract urothelial carcinoma, we believe that focused collaborative efforts will best augment our understanding of this rare disease and ultimately improve the care we deliver to our patients. [Copyright &y& Elsevier]

Purpose: We assessed the impact of hexaminolevulinate fluorescence cystoscopic detection of papillary, nonmuscle invasive bladder cancer on the long-term recurrence rate., Materials and Methods: Long-term followup was assessed in 551 participants enrolled in a prospective, randomized study of fluorescence cystoscopy for Ta or T1 urothelial bladder cancer. In the original study 280 patients in the white light cystoscopy group and 271 in the fluorescence cystoscopy group were followed with cystoscopy for 3, 6 and 9 months after initial resection or until recurrence. A study extension protocol was done for long-term followup of these patients., Results: Followup information was obtained for 261 of the 280 patients (93%) in the white light group and 255 of the 271 (94%) in the fluorescence group. Median followup in the white light and fluorescence groups was 53.0 and 55.1 months, and 83 (31.8%) and 97 patients (38%) remained tumor free, respectively. Median time to recurrence was 9.4 months in the white light group and 16.4 months in the fluorescence group (p = 0.04). The intravesical therapy rate was similar in the 2 groups (46% and 45%, respectively). Cystectomy was done in 22 of 280 cases (7.9%) in the white light group and in 13 of the 271 (4.8%) in the fluorescence group (p = 0.16)., Conclusions: Hexaminolevulinate fluorescence cystoscopy significantly improves long-term bladder cancer time to recurrence with a trend toward improved bladder preservation., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: • To determine whether there is a difference in survival in patients with node-negative pT2a vs pT2b urothelial carcinoma of the bladder (UBC), as recent studies suggest that the new American Joint Committee on Cancer substratification may not have prognostic significance., Patients and Methods: • Of 252 patients undergoing radical cystectomy (RC) and extended bilateral pelvic lymphadenectomy (ePLND) between 1999 and 2009, 72 (28.6%), with a mean (range) age of 66 (44-83) years (50 men, 22 women), had pathologically confirmed pT2 UCB. • Fisher's exact test and Cox regression analysis were used for uni- and multivariate analysis of risk factors of recurrence at a median (range) follow-up of 28 (2.2-115.7) months. • Kaplan-Meier plots were used to estimate the impact of pT2 substratification in lymph node (LN)-negative disease on recurrence-free (RFS) and cancer-specific (CSS) survival using log-rank test., Results: • Of the 72 patients, 39 had pT2a (54.2%) and 33 pT2b UCB (45.8%) on definitive histological examination. The median (range) number of LNs removed was 19 (6-38) in pT2a and 22 (4-36) in pT2b (P = 0.31) UCB. • At RC, there was LN-positive disease in one patient with pT2a UCB, whereas seven patients with pT2b UCB had LN-positive disease (P = 0.02). • The median (range) number of LNs removed in LN-positive disease was 18 (11-30) and in LN-negative disease was 20 (4-38) (P = 0.52). • In LN-negative disease, actuarial 5-year RFS was 85.9% in patients with pT2a UCB vs 37.5% in those with pT2b UCB (P < 0.001). Actuarial 5-year CSS was 84.8% in patients with LN-negative pT2a UCB vs 59.6% in patients with LN-negative pT2b UCB (P = 0.01). • In Cox regression analysis, pT2 substratification was the only independent risk factor of recurrence and cancer-specific death (P < 0.001 and P = 0.008)., Conclusions: • In this contemporary series of patients undergoing RC with ePLND, there was a significant difference in RFS and CSS between LN-negative pT2a and pT2b UCB, and pT2 substratification was the only risk factor of recurrence and cancer-specific death. • These data are supportive of the current concept of substratification in LN-negative pT2 UCB., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)