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Introduction: The Albumin-Globulin Ratio (AGR; albumin/total protein - albumin) has been associated with oncological outcome in various malignancies. However, its role in urothelial carcinoma of the bladder (UCB) has not been clearly established. In this study, we assessed the association of preoperative AGR (pAGR) with survival in patients who underwent radical cystectomy (RC) for UCB., Material and Methods: We conducted a retrospective analysis of an established multicenter database of 4.335 patients who were treated with RC for UCB. The cohort was divided into 2 groups according to the pAGR status. Binominal logistic regression as well as uni- and multivariable Cox regression analyses were used. The predictive value of the models was assessed by calculating receiver operating characteristics curves and concordance-indices (C-Index). The additional clinical value was assessed using the decision curve analysis (DCA)., Results: Overall, 1.670 patients (38.5%) had a low pAGR. On multivariable logistic regression analyses, low pAGR was associated with an increased risk of ≥pT3 disease at RC (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.31, P= 0.04). On multivariable Cox regression analyses, low pAGR remained associated with worse recurrence-free survival (RFS, HR 1.24, 95% CI 1.1-1.37, P< 0.001), cancer-specific survival (CSS, HR 1.23, 95% CI 1.1-1.38, P< 0.001) and overall survival (OS, HR 1.17, 95% CI 1.07-1.28, P< 0.001). The addition of pAGR to multiple prognostic models that were respectively fitted for clinical and postoperative variables did not improve the predictive accuracy., Conclusion: pAGR status is an independent predictor of ≥pT3 disease, therefore it could help identify patients who have a higher likelihood to benefit from neoadjuvant systemic therapy. While pAGR was independently associated with RFS, CSS, and OS, it did not improve the predictive accuracy and clinical value beyond obtained by information already available. The predictive value of this biomarker in the age of immunotherapy needs further evaluation., Competing Interests: Conflicts of interest All authors have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Conflicting evidence exists on the complication rates after cystectomy following previous radiation (pRTC) with only a few available series. We aim to assess the complication rate of pRTC for abdominal-pelvic malignancies., Methods: Patients treated with radical cystectomy following any previous history of RT and with available information on complications for a minimum of 1 year were included. Univariable and multivariable logistic regression models were used to assess the relationship between the variable parameters and the risk of any complication., Results: 682 patients underwent pRTC after a previous RT (80.5% EBRT) for prostate, bladder (BC), gynecological or other cancers in 49.1%, 27.4%, 9.8% and 12.9%, respectively. Overall, 512 (75.1%) had at least one post-surgical complication, classified as Clavien ≥ 3 in 29.6% and Clavien V in 2.9%. At least one surgical complication occurred in 350 (51.3%), including bowel leakage in 6.2% and ureteric stricture in 9.4%. A medical complication was observed in 359 (52.6%) patients, with UTI/pyelonephritis being the most common (19%), followed by renal failure (12%). The majority of patients (86%) received an incontinent urinary diversion. In multivariable analysis adjusted for age, gender and type of RT, patients treated with RT for bladder cancer had a 1.7 times increased relative risk of experiencing any complication after RC compared to those with RT for prostate cancer (p = 0.023). The type of diversion (continent vs non-continent) did not influence the risk of complications., Conclusion: pRTC carries a high rate of major complications that dramatically exceeds the rates reported in RT-naïve RCs.

Objectives: To evaluate cancer-specific (CSS) and overall survival (OS) in a group of frail patients who were treated with RT without chemotherapy and to compare them with a matched cohort of patients treated with RC. Methods: This study identified 71 patients treated with RT only for high-risk bladder cancer. Patients with metastatic (cN + or cM+) or non-resectable tumors (cT4) and those who received any form of chemotherapy were excluded. Patients where matched 1:1 using propensity scores which adjusted for the effects of age, clinical stage and age-adjusted Charlson comorbidity index (CCI). OS and CSS were evaluated using the Cox proportional hazards regression model and the Fine and Gray competing risk model. Results: In the overall population, RT was associated with worse OS (HR = 1.78, 95% CI = 1.15-2.77, p  = 0.01) compared to RC, but not with CSS (HR 1.1, p  = 0.74). In the matched cohort, RT was neither associated with OS nor CSS ( p  > 0.05) compared to RC. In the competing risk analyses no statistically significant association of any of the treatments was observed in the total or in the matched data set ( p  > 0.05). Conclusion: The use of RT may be an alternative option in well selected patients with limited disease who are considered unfit for systemic chemotherapy and RC. Future research should focus on improving patient selection and assess the quality-of-life as well as the need for reintervention in patients treated with RT.

Purpose of Review: Transurethral resection of bladder cancer (TURB) is the critical step in the management of nonmuscle invasive bladder cancer (NMIBC). This review presents new improvements in the strategy and technique of TURB as well as in technological developments used for tumour visualization and removal., Recent Findings: The goal of TURB is to perform complete resection of NMIBC. Tumor visualization during procedure can be improved by enhanced optical technologies. Fluorescence-guided photodynamic diagnosis (PDD) and narrow-band imaging (NBI) used during TURB can improve tumour detection and potentially reduce recurrence rate, their influence on progression, however, remains controversial. TURB can be performed using monopolar or bipolar electrocautery without significant differences in results or safety. To overcome limitations of traditional TURB, the technique of en-bloc resection was introduced to improve the quality of tumour removal. In selected cases, an early re-resection (re-TURB) within 2-6 weeks after initial procedure is recommended., Summary: TURB is a fundamental step in diagnosis and treatment of NMIBC. Urologists should be aware of promising innovations including new imaging and surgical techniques and their potential benefits. Hopefully, new technologies and performance of TURB bring improved outcomes, which can alter the indication criteria for re-TURB.

Context: The European Association of Urology (EAU) panel on Non-muscle-invasive Bladder Cancer (NMIBC) released an updated version of the guidelines on Non-muscle-invasive Bladder Cancer., Objective: To present the 2016 EAU guidelines on NMIBC., Evidence Acquisition: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines published between April 1, 2014, and May 31, 2015, was performed. Databases covered by the search included Medline, Embase, and the Cochrane Libraries. Previous guidelines were updated, and levels of evidence and grades of recommendation were assigned., Evidence Synthesis: Tumours staged as TaT1 or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection of the bladder (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis. If the initial resection is incomplete, there is no muscle in the specimen, or a high-grade or T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour and intermediate-risk patients at a lower risk of recurrence, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy (RC) should be considered. RC is recommended in BCG-refractory tumours. The long version of the guidelines is available at the EAU Web site (www.uroweb.org/guidelines)., Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice., Patient Summary: The European Association of Urology has released updated guidelines on Non-muscle-invasive Bladder Cancer (NMIBC). Stratification of patients into low-, intermediate-, and high-risk groups is essential for decisions about adjuvant intravesical instillations. Risk tables can be used to estimate risks of recurrence and progression. Radical cystectomy should be considered only in case of failure of instillations or in NMIBC with the highest risk of progression., (Copyright © 2016. Published by Elsevier B.V.)

Objective: To externally validate the pT4a-specific risk model for cancer-specific survival (CSS) proposed by May et al. (Urol Oncol 2013; 31: 1141-1147) and to develop a new pT4a-specific nomogram predicting CSS in an international multicentre cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) PATIENTS AND METHODS: Data from 856 patients with pT4a UCB treated with RC at 21 centres in Europe and North-America were assessed. The risk model proposed by May et al., which includes female gender, presence of positive lymphovascular invasion (LVI) and lack of adjuvant chemotherapy administration as adverse predictors for CSS, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver-operating characteristic-derived area under the curve. A nomogram for predicting CSS in pT4a UCB after RC was developed after internal validation based on multivariable Cox proportional hazards regression analysis evaluating the impact of clinicopathological variables on CSS. Decision-curve analyses were applied to determine the net benefit derived from the two models., Results: The estimated 5-year-CSS after RC was 34% in our cohort. The risk model devised by May et al. predicted individual 5-year-CSS with an accuracy of 60.1%. In multivariable Cox proportional hazards regression analysis, female gender (hazard ratio [HR] 1.45), LVI (HR 1.37), lymph node metastases (HR 2.54), positive soft tissue surgical margins (HR 1.39), neoadjuvant (HR 2.24) and lack of adjuvant chemotherapy (HR 1.67, all P < 0.05) were independent predictors of an adverse CSS rate and formed the features of our nomogram with a predictive accuracy of 67.1%. Decision-curve analyses showed higher net benefits for the use of the newly developed nomogram in our cohort over all thresholds., Conclusions: The risk model devised by May et al. was validated with moderate discrimination and was outperformed by our newly developed pT4a-specific nomogram in the present study population. Our nomogram might be particularly suitable for postoperative patient counselling in the heterogeneous cohort of patients with pT4a UCB., (© 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.)

Purpose: En bloc resection of bladder tumors (ERBT) may improve staging quality and perioperative morbidity and influence tumor recurrence. This study was designed to evaluate the safety, efficacy, and recurrence rates of electrical versus laser en bloc resection of bladder tumors., Methods: This European multicenter study included 221 patients at six academic hospitals. Transurethral ERBT was performed with monopolar/bipolar current or holmium/thulium laser energy. Staging quality measured by detrusor muscle involvement, various perioperative parameters, and 12-month follow-up data was analyzed., Results: Electrical and laser ERBT were used to treat 156 and 65 patients, respectively. Median tumor size was 2.1 cm; largest tumor was 5 cm. Detrusor muscle was present in 97.3 %. A switch to conventional TURBT was significantly more frequent in the electrical ERBT group (26.3 vs. 1.5 %, p < 0.001). Median operation duration (25 min), postoperative irrigation (1 day), catheterization time (2 days), and hospitalization (3 days) were similar. Overall complication rate was low (Clavien ≥ 3, n = 6 [2.7 %]). Hemoglobin was significantly lower after electrical ERBT (p = 0.0013); however, overall hemoglobin loss was not clinically relevant (0.38 g/dl). Patients (n = 148) were followed for 12 months; 33 (22.3 %) had recurrences. In total, 63.6 % recurrences occurred outside the ERBT resection field. No difference was noted between ERBT groups., Conclusions: ERBT is safe and reliable regardless of the energy source and provides high-quality resections of tumors >1 cm. Recurrence rates did not differ between groups, and the majority of recurrences occurred outside the ERBT resection field.

Purpose of Review: Trimodal therapy (TMT) is considered the most effective bladder-sparing approach for muscle-invasive urothelial carcinoma of the bladder (MIBC) and an alternative to radical cystectomy. The purpose of this article was to review and summarize the current knowledge on the equivalence of TMT and radical cystectomy based on the recent literature., Recent Findings: TMT consists of a maximal transuretral resection of the bladder, followed by a concurrent radiotherapy and chemotherapy, limiting salvage radical cystectomy to nonresponder tumors or muscle-invasive recurrence. In large population studies, less than 6% of the patients with nonmetastatic MIBC receive a chemoradiation therapy and this rate is stable. A growing body of evidence exists that TMT provides good oncologic outcomes with low morbidity when compared with radical cystectomy. TMT requires, however, a close follow-up because of the high risk of local recurrence and salvage radical cystectomy in up to 30% of the patients. Salvage radical cystectomy can be performed with adequate results but does not offer the same opportunity of reconstruction and functional outcomes than primary radical cystectomy., Summary: Although radical cystectomy is still the treatment of reference for most of the patients with localized MIBC, TMT represents a reasonable alternative in highly selected patients. Any firm conclusion on the equivalence or superiority of one treatment to the other is still limited by the lack of randomized controlled trials and the heterogeneity of the available literature. Future studies and multidisciplinary approach are mandatory to optimize the patient selection and regimen of TMT.

Objectives: To evaluate risk factors for urethral recurrence (UR) in women with neobladder., Material and Methods: From 1994 to 2011, 297 women (median age = 54 y; interquartile range: 47-57) underwent radical cystectomy with ileal neobladder for bladder cancer in 4 centers. None of the patients had bladder neck involvement at preoperative assessment. Univariable and multivariable analyses were used to estimate recurrence-free survival and overall survival. The median follow-up was 64 months (interquartile range: 25-116)., Results: Of the 297 patients, 81 developed recurrence (27%). The 10- and 15-year recurrence-free survival rates were 66% and 66%, respectively. The 10- and 15-year overall survival rates were 57% and 55%, respectively. UR occurred in 2 patients (0.6%) with solitary urethral, 4 (1.2%) with concomitant urethral and distant recurrence, and 1 with concomitant urethral and local recurrence (0.3%). Bladder tumors were located at the trigone in 27 patients (9.1%). None of these patients developed UR. Lymph node tumor involvement was present in 60 patients (20.2%). On univariable and multivariable analyses, pathologic tumor and nodal stage were independent predictors for the overall risk of recurrence. UR was associated with a positive final urethral margin status (P<0.001) whereas no significant associations were found for carcinoma in situ, pathologic tumor and nodal stage, and bladder trigone involvement., Conclusions: In this series, only 0.6% of women developed solitary UR. A positive final urethral margin was associated with an increased risk of UR. Women with involvement of the bladder trigone were not at higher risk of UR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: ABO blood type is an inherited characteristic that has been associated with the prognosis of several malignancies, but there is little evidence in urothelial carcinoma of the bladder (UCB). The purpose of this study was to evaluate the effect of ABO blood type on mortality in patients with UCB treated with radical cystectomy (RC)., Methods: Multi-institutional data from 7,906 patients with UCB treated with RC between 1979 and 2012 were retrospectively analyzed. The effect of ABO blood type on UCB-related mortality was evaluated with univariable and multivariable competing-risks regression models., Results: ABO blood type was O in 3,728 (47%), A in 2,748 (35%), B in 888 (11%), and AB in 532 (7%) patients. Blood type B was associated with a greater likelihood of lymphovascular invasion (P = 0.010) and positive soft tissue margins (P = 0.008). The median follow-up was 41 months. The 5-year cumulative UCB-related mortality rates for blood type O, A, B, and AB were 29.5%, 30.5%, 33.2%, and 25.8%, respectively. In univariable competing-risks regression, patients with blood type B had worse UCB-related mortality than those with blood type O (P = 0.026) and AB (P = 0.020). In multivariable analysis, however, blood type lost its statistical significance., Conclusions: Among patients treated with RC, ABO blood type is associated with a statistically significant but clinically insignificant difference in UCB-related mortality. This association was not present in multivariable analysis. Our data therefore suggest no relevant association of ABO blood type with UCB-related prognosis., (© 2013 Published by Elsevier Inc.)

Context: The first European Association of Urology (EAU) guidelines on bladder cancer were published in 2002 [1]. Since then, the guidelines have been continuously updated., Objective: To present the 2013 EAU guidelines on non-muscle-invasive bladder cancer (NMIBC)., Evidence Acquisition: Literature published between 2010 and 2012 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the levels of evidence and grades of recommendation were assigned., Evidence Synthesis: Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the EORTC scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive one immediate instillation of chemotherapy followed by 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or by further instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-refractory tumours. The long version of the guidelines is available from the EAU Web site: http://www.uroweb.org/guidelines/., Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice., Patient Summary: The EAU Panel on Non-muscle Invasive Bladder Cancer released an updated version of their guidelines. Current clinical studies support patient selection into different risk groups; low, intermediate and high risk. These risk groups indicate the likelihood of the development of a new (recurrent) cancer after initial treatment (endoscopic resection) or progression to more aggressive (muscle-invasive) bladder cancer and are most important for the decision to provide chemo- or immunotherapy (bladder installations). Surgical removal of the bladder (radical cystectomy) should only be considered in patients who have failed chemo- or immunotherapy, or who are in the highest risk group for progression., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. 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: Cigarette smoking is the best-established risk factor for urothelial carcinoma (UC) development, but the impact on oncologic outcomes remains poorly understood., Objective: To analyse the effects of smoking status, cumulative exposure, and time from smoking cessation on the prognosis of patients with primary non-muscle-invasive bladder cancer (NMIBC)., Design, Setting, and Participants: We collected smoking data from 2043 patients with primary NMIBC. Smoking variables included smoking status, average number of cigarettes smoked per day (CPD), duration in years, and time since smoking cessation. Lifetime cumulative smoking exposure was categorised as light short term (≤ 19 CPD, ≤ 19.9 yr), light long term (≤ 19 CPD, ≥ 20 yr), heavy short term (≥ 20 CPD, ≤ 19.9 yr) and heavy long term (≥ 20 CPD, ≥ 20 yr). The median follow-up in this retrospective study was 49 mo., Interventions: Transurethral resection of the bladder with or without intravesical instillation therapy., Outcome Measurements and Statistical Analysis: Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on outcomes., Results and Limitations: There was no difference in clinicopathologic factors among never (24%), former (47%), and current smokers (29%). Smoking status was associated with the cumulative incidence of disease progression in multivariable analysis (p=0.003); current smokers had the highest cumulative incidences. Among current and former smokers, cumulative smoking exposure was associated with disease recurrence (p<0.001), progression (p<0.001), and overall survival (p<0.001) in multivariable analyses that adjusted for the effects of standard clinicopathologic factors and smoking status; 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 reduced the risk of disease recurrence (hazard ratio [HR]: 0.66; 95% confidence interval [CI], 0.52-0.84; p<0.001) and progression (HR: 0.42; 95% CI, 0.22-0.83; p=0.036) in multivariable analyses. The study is limited by its retrospective nature., Conclusions: Smoking status and a higher cumulative smoking exposure are associated with worse prognosis in patients with NMIBC. Smoking cessation >10 yr abrogates this detrimental effect. These findings underscore the need for integrated smoking cessation and prevention programmes in the management of NMIBC patients., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Our aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non-muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach., Objective: To critically review the recent data on the management of NMIBC to arrive at a general consensus., Evidence Acquisition: A detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched., Evidence Synthesis: The major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies., Conclusions: Urothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To identify clinicopathological factors that predict outcomes in patients with a single lymph node (LN) metastasis (pN1) treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). LN metastasis is an established predictor of clinical outcomes in patients. While most patients with large LN burden experience disease recurrence, lymphadenectomy can be curative in patients with pN1 disease., Patients and Methods: We analysed 381 patients with pN1 UCB from a multi-institutional cohort of 4335 patients with UCB treated with RC and lymphadenectomy without preoperative chemo- or radiotherapy. Subgroup analyses were performed for patients with ≥9 LNs removed and according to adjuvant chemotherapy administration (n = 215)., Results: The median (interquartile range, IQR) LN number was 15 (19) and the median (IQR) LN density was 6.7 (7.5)%. Within a median follow-up of 41 months, the mean (+/- SD) 2- and 5-year cancer-specific survival (CSS) rates were 55 (3)% and 46 (3)%, respectively. On multivariable analysis that adjusted for the effects of standard clinicopathological features, female gender (hazard ratio [HR] 1.48, P = 0.023), higher tumour stage (HR 1.68, P = 0.007), positive soft tissue surgical margin (STSM; HR 2.06, P = 0.004), higher LN density (HR 2.99, P = 0.025) and absence of adjuvant chemotherapy (HR 0.70, P = 0.026) were independently associated with CSS. In subgroup analyses of patients with ≥9 LNs removed, tumour stage and STSM status remained independent predictors for CSS (P = 0.009 and P < 0.001, respectively)., Conclusions: About half of the patients with pN1 UCB died from UCB within 5 years of RC. Pathological stage and STSM status are strong predictors for outcomes. Accurate prediction of the individual risk of CSS may help risk stratifying pN1 UCB in order to help improve clinical-decision making. Patients with pN1 UCB presenting with additional unfavourable risk factors need a closer follow-up scheduling and might receive adjuvant therapy., (© 2012 The Authors BJU International © 2012 BJU International.)

Purpose: To determine whether the number of lymph nodes (LNs) examined is associated with outcomes in patients without nodal metastasis after radical cystectomy (RC)., Patients and Methods: We retrospectively analyzed data from 4,188 patients treated at 12 centers with RC and pelvic lymphadenectomy without neo-adjuvant chemotherapy for urothelial carcinoma of the bladder (UCB). Outcomes of patients without LN metastasis (n = 3,088) were examined according to the LN yield analyzed as continuous variable, tertiles, and using the cutoffs of ≥ 9 and ≥ 20., Results: The median nodal yield was 18 (range 1-123; IQR:20). A total of 2591 (84 %) and 1445 (47 %) patients had a LN yield ≥ 9 and ≥ 20, respectively. Median follow-up was 47 months (IQR:70). In multivariable analyses that adjusted for the standard clinicopathologic factors, higher LN yield was associated with a decreased risk of disease recurrence (continuous: HR = 0.996, p = 0.05; 3rd vs 1st tertile: HR = 0.853, p = 0.048; cutoff ≥ 20: HR = 0.851, p = 0.032). In the subgroups of patients with muscle-invasive UCB or those with ≥ 9 LN removed, LN yield was not associated with outcomes (p values >0.05)., Conclusions: In this large multicenter cohort of patients with node-negative UCB, higher nodal yield improved recurrence-free survival when all patients were analyzed. Patients with a high LN yield (≥ 20 LN removed or 3rd tertile) had the largest benefit. The lack of prognostic significance of LN yield in patients with muscle-invasive UCB or those stratified by 9 LNs removed suggests that this effect is weak. Further prospective studies are needed to help identify preoperatively the optimal template for each patient.

Context: Follow-up of patients treated for bladder cancer (BCa) is of great importance for both non-muscle-invasive BCa (NMIBC) and muscle-invasive BCa (MIBC) because of the high incidence of recurrence and progression. The schedule and methods of follow-up should reflect the individual clinical situation., Objective: To evaluate the existing evidence for intensity and duration of follow-up recommendations in patients after surgical treatment of BCa., Evidence Acquisition: We searched the Medline, Embase, and Cochrane databases for published data on the follow-up of patients with NMIBC and MIBC after radical cystectomy (RC)., Evidence Synthesis: Follow-up in patients with NMIBC is necessary because of the high probability of tumour recurrence and the risk of progression. Cystoscopy plus cytology are the standard methods for follow-up. Cystoscopy should be done 3 mo after the transurethral resection in every patient, and the frequency after that depends on the individual recurrence/progression risk. Cytology should be used as an adjunctive method to cystoscopy in intermediate- and high-risk patients. None of the currently available urinary markers or imaging methods can substitute for cystoscopy-based follow-up. High-risk NMIBC patients require regular lifelong upper urinary tract monitoring. Follow-up in MIBC is based on the fact that early detection of recurrence after RC allows for timely treatment with the aim of improving outcomes. Patients with extravesical and lymph node-positive disease should have the most intensive follow-up because of the highest recurrence risk. Routine upper urinary tract imaging is advisable for all patients and should continue in the long term. Follow-up also allows for early detection of urinary diversion-related complications, the rate of which increases with time., Conclusions: Follow-up in BCa is necessary for diagnosing recurrence and progression, as well as for evaluating complications after radical treatment. Since randomised studies investigating the most appropriate follow-up schedule are lacking, most recommendations are based on only the retrospective experience. Nonetheless, reasonable recommendations can be made until further prospective randomised studies testing different follow-up schedules have been performed., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context and Objective: To present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC)., Evidence Acquisition: Literature published between 2004 and 2010 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the level of evidence (LE) and grade of recommendation (GR) were assigned., Evidence Synthesis: Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. In papillary tumours, the risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups-separately for recurrence and progression-is pivotal to recommending adjuvant treatment. For patients with a low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is recommended. Patients with an intermediate or high risk of recurrence and an intermediate risk of progression should receive one immediate instillation of chemotherapy followed by a minimum of 1 yr of bacillus Calmette-Guérin (BCG) intravesical immunotherapy or further instillations of chemotherapy. Papillary tumours with a high risk of progression and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to the highest risk patients, and it is at least recommended in BCG failure patients. The long version of the guidelines is available from the EAU Web site (www.uroweb.org)., Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Outcomes after disease recurrence in patients with urothelial carcinoma of the bladder treated with radical cystectomy are variable, but the majority of patients die from the disease within 2 years after disease recurrence. Knowledge about prognostic factors that may influence survival after disease recurrence is limited. We found that outcomes after disease recurrence in patients with urothelial carcinoma of the bladder are significantly affected by common clinicopathological factors. In addition, a shorter time from surgery to disease recurrence is significantly associated with poor outcomes. These factors should be considered when scheduling salvage chemotherapy protocols/clinical trials. OBJECTIVE To describe the natural history following disease recurrence after radical cystectomy (RC) and to identify prognostic factors that influence cancer-specific survival with special focus on time from RC to disease recurrence., METHODS We identified 1545 patients from 16 international institutions who experienced disease recurrence after RC and bilateral lymphadenectomy. None of the patients received preoperative chemotherapy; 549 patients received adjuvant chemotherapy., A multivariable Cox regression model addressed time to cancer-specific mortality after disease recurrence., RESULTS The median cancer-specific survival time after disease recurrence was 6.9 months (95% CI 6.3-7.4). Overall, 1254 of 1545 patients died from urothelial carcinoma of the bladder and 47 patients died from other causes. The actuarial cancer-specific survival estimate at 12 months after disease recurrence was 32%., On multivariable analysis, non-organ-confined tumour stages (hazard ratio [HR] 1.38, P= 0.002), lymph node metastasis (HR 1.25, P < 0.001), positive soft tissue surgical margin (HR 1.32, P= 0.002), female gender (HR 1.21, P= 0.003), advanced age (HR 1.16, P < 0.001) and a shorter interval from surgery to disease recurrence ( P < 0.001) were significantly associated with cancer-specific mortality., The adjusted risk of death from cancer within 1 year after disease recurrence for patients who recurred 6, 12 and 24 months after surgery was 70%, 64% and 60%, respectively., CONCLUSIONS Over two-thirds of patients who experience disease recurrence of urothelial carcinoma of the bladder after RC die within 12 months., Common clinicopathological factors are strongly associated with cancer-specific mortality. A shorter time from surgery to disease recurrence is significantly associated with poor outcomes., Accurate risk stratification could help in patient counselling and decision-making regarding salvage treatment. [ABSTRACT FROM AUTHOR]

Abstract: Context and objective: To present the updated version of 2008 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer. Evidence acquisition: A systematic review of the recent literature on the diagnosis and treatment of non-muscle-invasive bladder cancer was performed. The guidelines were updated and the level of evidence and grade of recommendation were assigned. Evidence synthesis: The diagnosis of bladder cancer depends on cystoscopy and histologic evaluation of the resected tissue. A complete and correct transurethral resection (TUR) is essential for the prognosis of the patient. When the initial resection is incomplete or when a high-grade or T1 tumour is detected, a second TUR within 2–6 wk should be performed. The short- and long-term risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients to low, intermediate, and high-risk groups—separately for recurrence and progression—represents the cornerstone for indication of adjuvant treatment. In patients at low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is strongly recommended. In those at an intermediate or high risk of recurrence and an intermediate risk of progression, one immediate instillation of chemotherapy should be followed by further instillations of chemotherapy or a minimum of 1 yr of bacillus Calmette-Guerin (BCG). In patients at high risk of tumour progression, after an immediate instillation of chemotherapy, intravesical BCG for at least 1 yr is indicated. Immediate cystectomy may be offered to the highest risk patients and in patients with BCG failure. The long version of the guidelines is available on www.uroweb.org. Conclusions: These EAU guidelines present the updated information about the diagnosis and treatment of non-muscle-invasive bladder cancer and offer the recent findings for the routine clinical application. [Copyright &y& Elsevier]