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Purpose: Radical cystectomy and urinary diversion may cause chronic metabolic acidosis, leading to long-term bone loss in patients with bladder cancer. However, the risk of fractures after radical cystectomy has not been defined. We assessed whether radical cystectomy and intestinal urinary diversion are associated with increased risk of fracture., Patients and Methods: Population-based study using SEER-Medicare-linked data from 2000 through 2007 for patients with stage 0-III bladder cancer. We evaluated the association between radical cystectomy and risk of fracture at any site, controlling for patient and disease characteristics., Results: The cohort included 50,520 patients, of whom 4,878 had cystectomy and urinary diversion. The incidence of fracture in the cystectomy group was 6.55 fractures per 100 person-years, compared with 6.39 fractures per 100 person-years in those without cystectomy. Cystectomy was associated with a 21% greater risk of fracture (adjusted hazard ratio, 1.21; 95% CI, 1.10 to 1.32) compared with no cystectomy, controlling for patient and disease characteristics. There was no evidence of an interaction between radical cystectomy and age, sex, comorbidity score, or cancer stage., Conclusion: Patients with bladder cancer who have radical cystectomy and urinary diversion are at increased risk of fracture., (© 2014 by American Society of Clinical Oncology.)

Objectives: Surveillance after radical cystectomy is recommended to detect tumor recurrence and treatment complications. We evaluated adherence to National Comprehensive Cancer Network (NCCN) guidelines using a large population-based database., Methods and Materials: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify patients aged ≥66 years diagnosed with nonmetastatic bladder cancer who had undergone radical cystectomy between 2000 and 2007. Medicare claims information identified recommended surveillance tests for 2 years after cystectomy as outlined in the NCCN guidelines. Adherence was defined as receipt of urine cytology and imaging of the chest, abdomen, and pelvis in each year. We evaluated the effect of patient and provider characteristics on adherence, controlling for demographic and disease characteristics., Results: Of 3,757 patients who had undergone radical cystectomy, 2,990 (80%) were alive after 2 years. Adherence to all recommended investigations was 17% for the first and the second years following surgery. Among patients surviving 2 years, only 9% had complete surveillance in both years. In either year, adherence was less likely in patients with advanced pathologic stage (III/IV) (adjusted odds ratio [AOR] = 0.74, 95% CI: 0.60-0.91) and unmarried patients (AOR = 0.82, 95% CI: 0.68-0.99). Adherence was more likely in patients treated by high-volume surgeons (AOR = 2.00, 95% CI: 1.70-2.36) and those who saw a medical oncologist (AOR = 1.52, 95% CI: 1.27-1.82). We also observed significant geographic variability in adherence., Conclusion: Patterns of surveillance after radical cystectomy deviate considerably from NCCN recommendations. Despite increased utilization of radiographic imaging investigations, the omission of urine cytology significantly contributed to the low rate of overall adherence to surveillance guidelines. Uniform adherence to surveillance guidelines was observed in patients treated by high-volume surgeons. This suggests an important opportunity for quality improvement in bladder cancer care., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Cigarette smoking is the best-established risk factor for urothelial carcinoma development., Objective: To elucidate the association of pretreatment smoking status, cumulative exposure, and time since smoking cessation on outcomes of patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC)., Design, Setting, and Participants: We retrospectively collected clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation, for 1506 patients treated with RC for UCB. Lifetime cumulative smoking exposure was categorized as light short-term (≤20 CPD for ≤20 yr), light long-term (≤20 CPD for >20 yr), heavy short-term (>20 CPD for ≤20 yr), and heavy long-term (>20 CPD for >20 yr)., Intervention: RC and bilateral lymph node (LN) dissection without neoadjuvant chemotherapy., Outcome Measurements and Statistical Analysis: Logistic regression and competing risk analyses assessed the association of smoking with disease recurrence, cancer-specific mortality, and overall mortality., Results and Limitations: There was no difference in clinicopathologic factors between patients who had never smoked (20%), former smokers (46%), and current smokers (34%). Smoking status was associated with the cumulative incidence of disease recurrence (p=0.004) and cancer-specific mortality (p=0.016) in univariable analyses and with disease recurrence in multivariable analysis (p=0.02); current smokers had the highest cumulative incidences. Among ever smokers, cumulative smoking exposure was associated with advanced tumor stages (p<0.001), LN metastasis (p=0.002), disease recurrence (p<0.001), cancer-specific mortality (p=0.001), and overall mortality (p=0.037) in multivariable analyses that adjusted for standard characteristics; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation ≥10 yr mitigated the risk of disease recurrence (hazard ratio [HR]: 0.44; p<0.001), cancer-specific mortality (HR: 0.42; p<0.001), and overall mortality (HR: 0.69; p=0.012) in multivariable analyses. The study is limited by its retrospective nature., Conclusions: Smoking is associated with worse prognosis after RC for UCB. This association seems to be dose-dependent, and its effects are mitigated by >10 yr smoking cessation. Health care practitioners should counsel smokers regarding the detrimental effects of smoking and the benefits of smoking cessation on UCB etiology and prognosis., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard of care for high-risk non-muscle-invasive and muscle-invasive bladder cancer (BCa)., Objective: To develop a model that allows quantification of the likelihood that a pathologically node-negative patient has, indeed, no positive nodes., Design, Setting, and Participants: We analyzed data from 4335 patients treated with RC and PLND without neoadjuvant chemotherapy at 12 international academic centers., Interventions: Patients underwent RC and PLND., Outcome Measurements and Statistical Analysis: We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative as a function of the number of examined nodes., Results and Limitations: Overall, the probability of missing a positive node decreases with the increasing number of nodes examined (52% if 3 nodes are examined, 40% if 5 are examined, and 26% if 10 are examined). The proportion of having a positive node increased proportionally with advancing pathologic T stage and lymphovascular invasion (LVI). Patients with LVI who had 25 examined nodes would have a pNSS of 80% (pT1), 88% (pT2), and 66% (pT3-T4), whereas 10 examined nodes were sufficient for pNSS exceeding 90% in patients without LVI and pT0-T2 tumors. This study is limited because of its retrospective design and multicenter nature., Conclusions: We developed a tool that estimates the likelihood of lymph node (LN) metastasis in BCa patients treated with RC by evaluating the number of examined nodes, the pathologic T stage, and LVI. The pNSS indicates the adequacy of nodal staging in LN-negative patients. This tool could help to refine clinical decision making regarding adjuvant chemotherapy, follow-up scheduling, and inclusion in clinical trials., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series., Patients and Methods: Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded. Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality. BMI was analysed as a continuous and categorical variable (<25 vs 25-29 vs ≥30 kg/m(2))., Results: Median BMI was 28.8 kg/m(2) (interquartile range 7.9); 25.3% had a BMI <25 kg/m(2), 32.5% had a BMI between 25 and 29.9 kg/m(2), and 42.2% had a BMI ≥30 kg/m(2). Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI. In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46-1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24-1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60-2.05, P < 0.001). Themain limitation is the retrospective design of the study., Conclusions: Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB. Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB., (© 2012 BJU International.)

Background: The extent of lymphadenectomy needed to optimize oncologic outcomes after radical cystectomy (RC) for patients with regionally advanced bladder cancer (BCa) is unclear., Objective: Evaluate the effect of the location of lymph node metastasis on recurrence-free survival (RFS) and cancer-specific survival (CSS) for patients undergoing RC with a mapping pelvic lymph node dissection (PLND)., Design, Setting, and Participants: A study of 591 patients undergoing RC with mapping PLND was completed between 2000 and 2010. Median follow-up was 30 mo., Intervention: RC with mapping PLND., Measurements: We evaluated the impact of lymph node involvement by location on disease outcomes using the 2010 TNM staging system. Survival estimates were described using Kaplan-Meier methods. Gender, age, pathologic stage, histology, number of positive nodes, location of positive nodes, node density, use of perioperative chemotherapy, and grade were evaluated as predictors of RFS and CSS using multivariate Cox proportional hazard regression., Results and Limitations: Overall, 114 patients (19%) had lymph node involvement, and 42 patients (7%) had pN3 disease. On multivariate analysis, the number of positive lymph nodes (one or two or more) was significantly associated with increased risk of cancer-specific death (hazard ratio [HR]: 1.9 [95% confidence interval (CI), 1.04-3.46], p=0.036; versus HR: 4.3 [95% CI, 2.25-8.34], p<0.0005). Positive lymph node location was not an independent predictor of RFS or CSS. Five-year RFS for pN3 patients undergoing RC with PLND was 25% (95% CI, 10-42). This finding was not statistically different from our pN1 and pN2 patients (38% [95% CI, 22-54] and 35% [95% CI, 11-60], respectively). This study is limited by the lack of prospective randomization and a control group., Conclusions: The outcome for patients with involved common iliac lymph nodes was similar to the outcome for patients with primary nodal basin disease. These data support inclusion of the common iliac lymph nodes (pN3) in the nodal staging system for BCa. Lymph node location was not an independent predictor of outcome, whereas the number of positive lymph nodes was an independent predictor of worse oncologic outcome (pN1, pN2). Further refinements of the TNM system to provide improved prognostication are warranted., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the standard of care for refractory non-muscle-invasive and muscle-invasive bladder cancer. Although consensus exists on the need for LND, its extent is still debated., Objective: To develop a model that allows preoperative determination of the minimum number of lymph nodes (LNs) needed to be removed at RC to ensure true nodal status., Design, Setting, and Participants: We analyzed data from 4335 patients treated with RC and pelvic LND without neoadjuvant chemotherapy at 12 academic centers located in the United States, Canada, and Europe., Measurements: We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed clinical (preoperative) nodal staging scores (cNSS), which represent the probability that a patient has LN metastasis as a function of the number of examined nodes., Results and Limitations: The probability of missing a positive LN decreased with an increasing number of nodes examined (52% if 3 nodes were examined, 40% if 5 were examined, and 26% if 10 were examined). A cNSS of 90% was achieved by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1 tumors, and 25 nodes for cT2 tumors. In contrast, examination of 25 nodes provided only 77% cNSS for cT3-T4 tumors. The study is limited due to its retrospective design, its multicenter nature, and a lack of preoperative staging parameters., Conclusions: Every patient treated with RC for bladder cancer needs an LND to ensure accurate nodal staging. The minimum number of examined LNs for adequate staging depends preoperatively on the clinical T stage. Predictive tools can give a preoperative estimation of the likelihood of nodal metastasis and thereby allow tailored decision-making regarding the extent of LND at RC., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We compared clinical outcomes, and identified predictors of cancer specific and overall survival after radical cystectomy in patients with urothelial carcinoma with squamous differentiation and those with pure squamous cell carcinoma., Materials and Methods: We reviewed data on 2,031 patients treated with radical cystectomy and pelvic lymph node dissection at a single high volume referral center. Of these patients 78 had squamous cell carcinoma and 67 had squamous differentiation. Survival estimates by histological subtype were described using Kaplan-Meier methods. Within histological subtypes pathological stage, nodal invasion, soft tissue margins, age and gender were evaluated as predictors of cancer specific survival and overall survival using univariate Cox regression., Results: Median followup was 44 months. Of 104 patient deaths 60 died of their disease. We did not find a statistically significant difference between survival curves of patients with squamous cell carcinoma and squamous differentiation (log rank overall survival p = 0.6, cancer specific survival p = 0.17). Positive soft tissue margins were associated with worse cancer specific survival (HR 6.92, 95% CI 2.98-16.10, p ≤0.0005) and overall survival (HR 3.68, 95% CI 1.84-7.35, p ≤0.0005) in patients with pure squamous cell carcinoma. Among patients with squamous differentiation, pelvic lymphadenopathy was associated with decreased overall survival (HR 2.52, 95% CI 1.33-4.77, p = 0.004) and cancer specific survival (HR 3.23, 95% CI 1.57-6.67, p = 0.002)., Conclusions: There appears to be no evidence of a difference in cancer specific survival or overall survival between patients with squamous cell carcinoma and those with squamous differentiation treated with radical cystectomy and pelvic lymph node dissection. Patients with squamous differentiation and tumor metastases to pelvic lymph nodes should be followed more closely, and adjuvant treatment should be considered to improve survival. Wide surgical resection is critical to achieve local tumor control and improve survival in patients with squamous cell carcinoma., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)