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Context: Non-muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence risk, partly because of the persistence of lesions following transurethral resection of bladder tumour (TURBT) due to the presence of multiple lesions and the difficulty in identifying the exact extent and location of tumours using standard white-light cystoscopy (WLC). Hexaminolevulinate (HAL) is an optical-imaging agent used with blue-light cystoscopy (BLC) in NMIBC diagnosis. Increasing evidence from long-term follow-up confirms the benefits of BLC over WLC in terms of increased detection and reduced recurrence rates., Objective: To provide updated expert guidance on the optimal use of HAL-guided cystoscopy in clinical practice to improve management of patients with NMIBC, based on a review of the most recent data on clinical and cost effectiveness and expert input., Evidence Acquisition: PubMed and conference searches, supplemented by personal experience., Evidence Synthesis: Based on published data, it is recommended that BLC be used for all patients at initial TURBT to increase lesion detection and improve resection quality, thereby reducing recurrence and improving outcomes for patients. BLC is particularly useful in patients with abnormal urine cytology but no evidence of lesions on WLC, as it can detect carcinoma in situ that is difficult to visualise on WLC. In addition, personal experience of the authors indicates that HAL-guided BLC can be used as part of routine inpatient cystoscopic assessment following initial TURBT to confirm the efficacy of treatment and to identify any previously missed or recurrent tumours. Health economic modelling indicates that the use of HAL to assist primary TURBT is no more expensive than WLC alone and will result in improved quality-adjusted life-years and reduced costs over time., Conclusions: HAL-guided BLC is a clinically effective and cost-effective tool for improving NMIBC detection and management, thereby reducing the burden of disease for patients and the health care system., Patient Summary: Blue-light cystoscopy (BLC) helps the urologist identify bladder tumours that may be difficult to see using standard white-light cystoscopy (WLC). As a result, the amount of tumour that is surgically removed is increased, and the risk of tumour recurrence is reduced. Although use of BLC means that the initial operation costs more than it would if only WLC were used, over time the total costs of managing bladder cancer are reduced because patients do not need as many additional operations for recurrent tumours., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Live surgery is an important part of surgical education, with an increase in the number of live surgery events (LSEs) at meetings despite controversy about their real educational value, risks to patient safety, and conflicts of interest., Objective: To provide a European Association of Urology (EAU) policy on LSEs to regulate their organisation during urologic meetings., Evidence Acquisition: The project was carried out in phases: a systematic literature review generating key questions, surveys sent to Live Surgery Panel members, and Internet- and panel-based consensus finding using the Delphi process to agree on and formulate a policy., Evidence Synthesis: The EAU will endorse LSEs, provided that the EAU Code of Conduct for live surgery and all organisational requirements are followed. Outcome data must be submitted to an EAU Web-based registry and complications reported using the revised Martin criteria. Regular audits will take place to evaluate compliance as well as the educational role of live surgery., Conclusions: This policy represents the consensus view of an expert panel established to advise the EAU. The EAU recognises the educational role of live surgery and endorses live case demonstration at urologic meetings that are conducted within a clearly defined regulatory framework. The overriding principle is that patient safety must take priority over all other considerations in the conduct of live surgery., Patient Summary: Controversy exists regarding the true educational value of live surgical demonstrations on patients at surgical meetings. An EAU committee of experts developed a policy on how best to conduct live surgery at urologic meetings. The key principle is to ensure safety for every patient, including a code of conduct and checklist for live surgery, specific rules for how the surgery is organised and performed, and how each patient's results are reported to the EAU. For detailed information, please visit www.uroweb.org., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Kidney cancer is among the 10 most frequently occurring cancers in Western communities. Globally, about 270 000 cases of kidney cancer are diagnosed yearly and 116 000 people die from the disease. Approximately 90% of all kidney cancers are renal cell carcinomas (RCC)., Objective: The causes of RCC are not completely known. We have reviewed known aetiologic factors., Evidence Acquisition: The data provided in the current review are based on a thorough review of available original and review articles on RCC epidemiology with a systemic literature search using Medline., Evidence Synthesis: Smoking, overweight and obesity, and germline mutations in specific genes are established risk factors for RCC. Hypertension and advanced kidney disease, which makes dialysis necessary, also increase RCC risk. Specific dietary habits and occupational exposure to specific carcinogens are suspected risk factors, but results in the literature are inconclusive. Alcohol consumption seems to have a protective effect for reasons yet unknown. Hardly any information is available for some factors that may have a high a priori role in the causation of RCC, such as salt consumption., Conclusions: Large collaborative studies with uniform data collection seem to be necessary to elucidate a complete list of established risk factors of RCC. This is necessary to make successful prevention possible for a disease that is diagnosed frequently in a stage where curative treatment is not possible anymore., (Copyright © 2011. Published by Elsevier B.V.)

Context: The clinical benefit of photodynamic diagnosis (PDD) with 5-aminolevulinic acid or hexaminolevulinate in addition to white-light cystoscopy (WLC) in bladder cancer has been discussed controversially., Objective: To assess in a systematic review the effect of PDD in addition to WLC on (1) the diagnosis and (2) the therapeutic outcome of primary or recurrent non-muscle-invasive bladder cancer investigated by cystoscopy or transurethral resection., Evidence Acquisition: An electronic database search of Medline, Embase, the Cochrane Library, and CancerLit was undertaken, plus hand searching of relevant congress abstracts and urologic journals. Trials were included if they prospectively compared WLC with PDD in bladder cancer. The review process followed the guidelines of the Cochrane Collaboration. Two reviewers evaluated independently both trial eligibility and methodological quality and data extraction., Evidence Synthesis: The primary end point of diagnostic accuracy was additional detection rate. The primary end points of therapeutic outcome were residual tumour at second resection and recurrence-free survival (RFS). Seventeen trials were identified. Twelve diagnostic trials used WLC and PDD with the same patients. Seven reported results for the subgroup of patients with carcinoma in situ (CIS). Five randomised trials studied therapeutic outcome. The results were combined in random effects meta-analyses if end points, designs, and populations were comparable. Twenty percent (95% confidence interval [CI], 8-35) more tumour-positive patients were detected with PDD in all patients with non-muscle-invasive tumours and 39% (CI, 23-57) more when only CIS was analysed. Heterogeneity was present among diagnostic studies even when the subgroup of patients with CIS was investigated. Residual tumour was significantly less often found after PDD (odds ratio: 0.28; 95% CI, 0.15-0.52; p<0.0001). RFS was higher at 12 and 24 mo in the PDD groups than in the WLC-only groups. The combined p value of log-rank tests of RFS was statistically significant (0.00002)., Conclusions: PDD detects more bladder tumour-positive patients, especially more with CIS, than WLC. More patients have a complete resection and a longer RFS when diagnosed with PDD., (Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Compared with standard white-light cystoscopy, photodynamic diagnosis with blue light and the photosensitiser hexaminolevulinate has been shown to improve the visualisation of bladder tumours, reduce residual tumour rates by at least 20%, and improve recurrence-free survival. There is currently no overall European consensus outlining specifically where hexaminolevulinate is or is not indicated., Objective: Our aim was to define specific indications for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC)., Evidence Acquisition: A European expert panel was convened to review the evidence for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of NMIBC (identified through a PubMed MESH search) and available guidelines from across Europe. On the basis of this information and drawing on the extensive clinical experience of the panel, specific indications for the technique were then identified through discussion., Evidence Synthesis: The panel recommends that hexaminolevulinate-guided fluorescence cystoscopy be used to aid diagnosis at initial transurethral resection following suspicion of bladder cancer and in patients with positive urine cytology but negative white-light cystoscopy for the assessment of tumour recurrences in patients not previously assessed with hexaminolevulinate, in the initial follow-up of patients with carcinoma in situ (CIS) or multifocal tumours, and as a teaching tool. The panel does not currently recommend the use of hexaminolevulinate-guided fluorescence cystoscopy in patients for whom cystectomy is indicated or for use in the outpatient setting with flexible cystoscopy., Conclusions: Evidence is available to support the use of hexaminolevulinate-guided fluorescence cystoscopy in a range of indications, as endorsed by an expert panel., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: The gained expertise in the surgical technique of partial nephrectomy (PN) with excellent oncologic outcome and reduced morbidity has contributed to more frequent use of PN in many centres of reference, and the recent evidence favouring PN over radical nephrectomy (RN) in the prevention of chronic kidney disease and possibly linking it to a better overall survival (OS) will constitute a strong argument for wider use of PN., Objective: To objectively analyse the advantages of PN over RN and to evaluate the risk-benefit ratio of expanding the indications of PN T1b renal cortical tumours., Evidence Acquisition: Literature searches on English-language publications were performed using the National Library of Medicine database. The queries included the keywords partial nephrectomy and nephron sparing surgery. Eight hundred four references were scrutinised, and 175 publications were identified and reviewed. Sixty-nine articles were selected for this review. These references formed the basis for this analysis and were selected based on their relevance and the importance of their content., Evidence Synthesis: The use of PN has been steadily increasing, particularly in tertiary care centres. This trend is now strengthened by evidence supporting the role of PN in reducing the risk of chronic kidney disease in patients with renal masses < or =4 cm. A wider use of PN for larger tumours, granted technical feasibility, is supported by the preliminary evidence, suggesting an OS advantage favouring PN over RN. However, the potential for selection bias and residual confounding factors may contribute to the observed difference. In the carefully selected patients with tumours >4 cm, PN obtained equivalent oncologic outcome to that achieved after RN. Although higher morbidity rates were seen after PN, the complication type and severity were not prohibitive., Conclusions: The available evidence supports elective PN as the standard surgical treatment for renal cortical tumours < or =4 cm. For larger tumours, PN has demonstrated feasibility and oncologic safety in the carefully selected patient population studied., (Copyright 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess cancer-specific survival of partial nephrectomy (PN) patients with >or= 7-cm lesions or unfavorable pathology (stage T3a or Fuhrman grades III-IV)., Material and Methods: At 13 participation centers, 4072 partial or radical nephrectomies (RN) were performed for RCC between 1984 and 2001. Of all procedures, 925 (22.7%) were for tumors > 7 cm, 973 (23.9%) had Fuhrman grades III or IV, and 861 (21.1%) had stage pT3a. None had nodal or distant metastases. Matched (age, gender, tumor size, T stage, histologic subtype, and Fuhrman grade [FG]) survival analyses addressed the effect of nephrectomy type (partial vs radical) on cancer-specific mortality., Results: Partial nephrectomy for tumors > 7 cm was associated with higher mortality than RN (HR = 5.3; P = .025). No significant cancer-specific survival differences were recorded after PN for FG III-IV (HR = 0.7, P = .5) or for pT3a lesions (HR = 2.5, P = .9)., Conclusions: Partial nephrectomy may undermine cancer control in patients with tumors > 7 cm. Conversely, after PN, the same cancer control rates as after RN may be expected in patients with Fuhrman grades III-IV or with pT3a histology.

Background: The prognostic significance of venous tumor thrombus extension in patients with renal cell carcinoma (RCC) is a matter of many controversies in the current literature., Objective: To evaluate the prognostic role of inferior vena cava (IVC) involvement in a large series of pT3b and pT3c RCCs., Design, Setting, and Participants: A total of 1192 patients from 13 European institutions underwent a radical nephrectomy for pT3b and pT3c RCC between 1982 and 2003. The patients were evaluated in a retrospective manner. Age, gender, clinical symptoms, Eastern Cooperative Oncology Group (ECOG) performance status, TNM stage, tumor size, adrenal invasion, perinephric fat invasion, histological type, and Fuhrman grade were reviewed. The log-rank and Cox uni- and multivariate regression analyses were used to evaluate prognostic factors for overall survival., Measurements: Overall survival and prognostic factors for overall survival in patients with RCC extending to the renal vein (RV) or to the IVC., Results and Limitations: The median follow-up was 61.4 mo (56.3-66.5 mo). The mean age was 63.2 yr. The mean tumor size was 8.9 cm. Group 1 (Gr 1) included 933 patients with a renal vein tumor thrombus (78.3%), Group 2 (Gr 2) included 196 patients with a subdiaphragmatic IVC tumor thrombus (16.4%), and Group 3 (Gr 3) included 63 patients with a supradiaphragmatic IVC tumor thrombus (5.3%). Median survival was 52 mo for Gr 1, 25.8 mo for Gr 2, and 18 mo for Gr 3. In univariate analysis, Gr 1 had a significantly better overall survival than Gr 2 (p<0.001) and Gr 3 (p

Background: Until now the therapeutic value of lymphadenectomy for renal-cell carcinoma has remained controversial. Several studies attempting to solve this controversy have been published, but none of them were set up as prospective randomized trials., Objective: To assess whether a complete lymph-node dissection in conjunction with a radical nephrectomy for renal-cell cancer is more effective than a radical nephrectomy alone., Design, Setting, and Participants: In 1988, the European Organization for Research and Treatment of Cancer (EORTC) Genitourinary Group started a randomized phase 3 trial comparing radical nephrectomy with a complete lymphadenectomy to radical nephrectomy alone. After the renal-cell carcinoma was judged to be N0M0 and resectable, patients were randomly selected prior to surgery to undergo either a radical nephrectomy with a complete lymph-node dissection or to undergo a radical nephrectomy alone. Postoperatively all patients were followed for progression of disease and mortality., Intervention: All patients underwent a radical nephrectomy with or without a complete lymph-node dissection., Measurements: All patients were postoperatively evaluated for time-to-progression, overall survival, and progression-free survival. Time-to-event curves were estimated based on the Kaplan-Meier method and compared using a two-sided log-rank test., Results and Limitations: Of the 772 patients selected for randomization, 40 were not eligible for the study. 383 patients were randomly selected to receive a complete lymph-node dissection together with a radical nephrectomy, and 389 patients were randomly selected to undergo a radical nephrectomy alone. The complication rate did not differ significantly between the two groups. Complete lymph-node dissections in 346 patients revealed an absence of lymph-node metastases in 332 patients. The study revealed no significant differences in overall survival, time to progression of disease, or progression-free survival between the two study groups., Conclusions: This study shows that, after proper preoperative staging, the incidence of unsuspected lymph-node metastases is low (4.0%) and that, notwithstanding a possible relationship to this low incidence rate, no survival advantage of a complete lymph-node dissection in conjunction with a radical nephrectomy could be demonstrated.

Objectives: Collecting duct renal cell carcinoma (CDRCC) is a rare but reportedly aggressive histologic subtype. We assessed the stage and histologic features of patients with CDRCC and compared cancer-specific mortality in CDRCC and matched patients with clear-cell renal cell carcinoma (CRCC)., Methods: Forty-one (0.6%) patients with CDRCC and 5246 CRCC patients were identified within a cohort of 6608 patients treated with either radical or partial nephrectomy for renal cancer. Within the 5246 CRCC cases, 105 were matched with CDRCC cases for grade, tumour size, and T, N, and M stages. Kaplan-Meier and life table analyses addressed RCC-specific survival., Results: Of all CDRCC patients, 76% had pT3 disease at nephrectomy versus 37% for those with CRCC. The predominant Fuhrman grades were III (56%) and IV (22%) in CDRCC versus II (42%) and III (28%) for CRCC. Moreover, 49% of CDRCC patients were pN1-2 versus 8% for CRCC. Of CDRCC patients 19% had distant metastases at nephrectomy versus 14% for CRCC. Finally, 73% of CDRCC patients had either local or systemic symptoms versus 56% for CRCC. After matching, the RCC-specific mortality of CDRCC patients was no different from that for CRCC patients (RR=1.1; p=0.8). One- and 5-yr CDRCC-specific survival rates were 86% and 48%, respectively, versus 86% and 57% for matched CRCC controls., Conclusions: CDRCC patients present with more advanced stage and with more aggressive disease compared with CRCC patients. After nephrectomy, when CDRCC cases were matched with CRCC, the same cause-specific survival was seen.

Objectives: To analyse the influence of age at diagnosis on tumour characteristics and cancer-specific survival in renal cell carcinoma (RCC)., Methods: Data on age, tumour characteristics, and survival for 4774 patients from 12 European RCC databases were recorded. Patients were divided into four groups according to age at diagnosis: < or =40, >40 and <60, > or =60 and <80, and > or =80 yr. The following variables were analysed: TNM stage, Fuhrman grade, tumour size, symptoms at diagnosis, ECOG performance status (PS), and cancer-specific survival. The groups were compared for usual clinical and pathologic variables, and cancer-specific survival., Results: The four groups accounted for 288 (6%), 1839 (38.5%), 2499 (52.3%), and 148 cases (3.2%), respectively. Differences were found among groups for tumour stage, symptoms at diagnosis, ECOG PS, Fuhrman grade (p<0.001), tumour size, M stage, and histologic subtype (p: 0.02). Patients < or =40 yr were more likely to have papillary or chromophobe RCCs and less likely to have clear-cell RCCs. No significant difference was found among groups for N stage (p: 0.15). The 5-yr cancer-specific survival rates for the four age categories were 85%, 74%, 70%, and 69%, respectively. In multivariate analysis age category remained an independent prognostic parameter (p<0.001)., Conclusions: Renal tumours diagnosed in younger age are characterized by lower tumour stages and grades as well as favourable histologic patterns compared with tumours in older patients. Basic research is required for explaining such a relationship between age, tumour aggressiveness, and therefore tumour biology.

Objective: To assess the prognostic value of microscopic venous invasion (MVI) in a long-term follow-up series., Patients and Method: 255 patients had a radical nephrectomy between 1980 and 1990 for pT1 to pT3b N0 M0 renal cell carcinoma. We reviewed the disease free, specific and overall survival after 183 months of median follow-up. Survival analyses using Kaplan-Meier and Log-rank models for univariate comparisons and Cox proportional hazards model for multivariate analyses were performed. The studied variables were: age, size, side, extracapsular invasion, renal vein invasion, local stage, Fuhrman's grade and MVI., Results: MVI was found in 74 cases (29%). The MVI was strongly correlated to metastases appearance and survival (p < 0.0001). Multivariate analysis of disease free survival showed the following independent variables: size (p < 0.0001) and Fuhrman's grade (p < 0.0001). For cancer specific survival, the analysis found size (p < 0.0001), age (p = 0.0005), Fuhrman's grade (p = 0.0035) and MVI (p = 0.016) with a relative risk of cancer related death of 2.16. Independent prognostic factors of overall survival were age (p < 0.0001), size (p < 0.0001), MVI (p = 0.015) and Fuhrman's grade (p = 0.045). The relative risk of cancer related death for MVI is 1.82., Conclusion: It seems that MVI is an independent prognostic factor of survival for patients with pT1 to pT3b N0 M0 renal cell carcinoma.

Objective: Incidence of multifocality in Renal Cell Carcinoma (RCC) is estimated at between 5 and 25%. Multifocality has been largely studied because of the growing interest in conservative surgery which is a risk of local recurrence. The aim of this study is to evaluate the relationship between multifocality and other prognostic parameters and whether it is an independent prognostic factor., Material and Methods: From 1980 to 1990, 255 patients (median age: 60.9 years) were treated by radical nephrectomy for pT1 to pT3b N0M0 RCC. The median follow-up time was 183 months. Multifocality was defined as the existence of at least one other tumoral localization, macroscopically and microscopically diagnosed as renal cell carcinoma, in the same kidney. Studied parameters were: age, sex, side, size, stage, Fuhrman's grade, capsular invasion, renal vein involvement and microvascular invasion. Survival was assessed with Kaplan-Meier and Cox models., Results: 37 cases of multifocal RCC were diagnosed (14.5%). There was only a significant correlation with stage (p=0.002) and with capsular invasion (p=0.002). No other factor was correlated with multifocality. It had no influence on the risk of metastatic progression, overall or specific survival., Conclusion: There is a significant correlation between capsular invasion and multifocality that has to be considered before proposing conservative surgery for a localized RCC. Multifocality has no influence on survival or metastatic progression in case of radical nephrectomy.