Search

Purpose To assess the prognostic value of sex for non-muscle-invasive/muscle-invasive bladder urothelial carcinoma (NMIBC/MIBC) treated with radical surgery. Methods The PubMed, Web of Science, and Scopus databases were searched in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they involved the comparison of the overall, cancer-specific, progression, and recurrence-free survival of patients with NMIBC/MIBC. Formal sex-stratified meta-analyses of these outcomes were performed. Results Thirty-one studies, which included 32,525 patients with NMIBC, and 63 studies, which included 85,132 patients with MIBC, were eligible for review and meta-analysis. Female sex was associated with worse cancer-specific survival (pooled hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.11–1.31) and overall survival (pooled HR, 1.02; 95% CI, 1.00–1.05) in patients with MIBC. In contrast, however, sex was not associated with cancer-specific survival (pooled HR, 1.01; 95% CI, 0.70–1.46), progression-free survival (pooled HR, 1.04; 95% CI, 0.88–1.24), and recurrence-free survival (pooled HR, 1.06; 95% CI, 0.98–1.16) in patients with NMIBC. Conclusions Sex is associated with an increased risk of worse survival outcomes in patients with MIBC but not in those with NMIBC. Given the genetic and social differences between sexes, sex may represent a key factor in the clinical decision-making process.

Context: The European Association of Urology (EAU) has released an updated version of the guidelines on non-muscle-invasive bladder cancer (NMIBC). Objective: To present the 2021 EAU guidelines on NMIBC. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines since the 2020 version was performed. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1 and carcinoma in situ (CIS) are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of tissue obtained via transurethral resection of the bladder (TURB) for papillary tumours or via multiple bladder biopsies for CIS. For papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. In cases for which the initial resection is incomplete, there is no muscle in the specimen, or a T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risk of progression may be estimated for individual patients using the 2021 EAU scoring model. On the basis of their individual risk of progression, patients are stratified as having low, intermediate, high, or very high risk, which is pivotal to recommending adjuvant treatment. For patients with tumours presumed to be at low risk and for small papillary recurrences detected more than 1 yr after a previous TURB, one immediate chemotherapy instillation is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose intravesical bacillus Calmette-Guerin (BCG) immunotherapy or instillations of chemo therapy for a maximum of 1 yr. For patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. For patients at very high risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is also recommended for BCG-unresponsive tumours. The extended version of the guidelines is available on the EAU website at https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/. 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 the classification, risk factors, diagnosis, prognostic factors, and treatment of non- muscle-invasive bladder cancer. The recommendations are based on the literature up to 2020, with emphasis on the highest level of evidence. Classification of patients as having low, intermediate, or and high risk is essential in deciding on suitable treatment. Surgical removal of the bladder should be considered for tumours that do not respond to bacillus Calmette-Guerin (BCG) treatment and tumours with the highest risk of progression. (c) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Context: Active surveillance (AS) of biopsy-proven renal oncocytomas may reduce overtreatment. However, on biopsy, the risk of misdiagnosis owing principally to entities with peculiar hybrids and overlap morphology, and phenotypes argues for early intervention. Objective: To assess the benefit and harm of AS in biopsy-proven renal oncocytoma. Evidence acquisition: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We systematically searched PubMed, Scopus, and Web of Science databases from September 26 up to October 2021, for studies that analyzed the outcomes of AS in patients with biopsy-proven renal oncocytoma. Evidence synthesis: A total of ten studies with 633 patients met our inclusion criteria and were included for analysis. After a median follow-up of 34.5 mo (95% confidence interval [CI] 30.6-38.4), the overall definitive treatment rate from AS to definitive treatment was 17.3% (n = 75/433, six studies). The pooled pathological agreement between the initial renal mass biopsy and the surgical pathology report was 91.1%. The main indications for surgery during follow-up were rapid tumor growth and patient request. The pooled median growth rate was 1.55 mm/yr (95% CI 0.9-2.2). No metastasis or death related to renal oncocytoma was reported. Conclusions: Annual tumor growth of biopsy-proven renal oncocytoma is low. AS is oncologically safe, with favorable compliance of patients. Crossover to definitive treatment revealed a strong concordance between biopsy and final pathology. Further studies on the long-term outcomes of AS are needed. Patient summary: In this study, we examined the benefit and harm of active surveillance (AS) in biopsy-proven oncocytoma. Based on the available data, AS appears oncologically safe and may represent a promising alternative to immediate treatment. Patients should be included in AS decision discussions. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.Setting: Online Delphi survey and consensus conference.Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as >= 70% agreement and

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3-T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3-T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. Materials and Methods: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). Results: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75-0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32-0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58-1.35; p = 0.58). Conclusions: The administration of AC in patients with MIBC and pT3-T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.

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 1year 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.

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach. Patient summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Fragestellung und Ziel: Die lokale Kontrolle des nicht muskelinvasiven Harnblasenkarzinoms (NMIBC) umfasst eine transurethrale Resektion des Tumors (TUR-B) und je nach Stadium eine adjuvante Instillationstherapie, um das Rezidiv- und Progressrisiko zu verringern. Das Urokinase plasminogen activator [zum vollständigen Text gelangen Sie über die oben angegebene URL], 45. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Einleitung: Es gibt immer mehr Belege dafür, dass chronische Entzündungsprozesse im Körper das Krebsrisiko erhöhen. Die langfristigen Auswirkungen einer Tonsillektomie könnte die Produktion und Regulierung von Lymphozyten beeinflussen, was wiederum in einer beeinträchtigen[zum vollständigen Text gelangen Sie über die oben angegebene URL], 45. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Einleitung: Intravesikale Instillationen mit Bacillus Calmette Guérin (BCG) ist die effektivste Form der intravesikalen Therapie für highrisk NMIBC nach TUR/B. Hierfür sind unterschiedliche BCG Stämme erhältlich, die alle vom ursprünglichen Vakzin für Tuberkulose[zum vollständigen Text gelangen Sie über die oben angegebene URL], 45. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Einführung: Multidetector-computertomographische Urografie (MDCTU) wird vermehrt in der Diagnostik von Urothelkarzinomen des oberen Harntraktes (UTUC) eingesetzt. Dennoch ist die diagnostische Genauigkeit dieser Bildgebung nicht endgültig im klinischen Alltag etabliert. Wir führten eine[zum vollständigen Text gelangen Sie über die oben angegebene URL], 45. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Hintergrund: Ziel dieser Studie war die Bewertung der erforderlichen Zahl und örtlichen Verteilung der Stanzzylinder innerhalb einer Zielläsion (region of interest, ROI) in der mpMRT-geführten Fusionsbiopsie zur Detektion des Prostatakarzinoms. Material/Methoden: In diese[zum vollständigen Text gelangen Sie über die oben angegebene URL], 45. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Ziel: Ziel dieser retrospektiven Analyse von PatientInnen, die eine radikale Zystektomie und Lymphadenektomie zur Behandlung eines Urothelkarzinoms der Blase erhielten, ist es den Einfluss der Lymphadenektomie unterschiedlichen Ausmaßes auf perioperative Komplikationen und Rehospitalisierung aufzuzeigen.[zum vollständigen Text gelangen Sie über die oben angegebene URL], 45. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Context: This overview presents the updated European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS). Objective: To provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation and recommendations. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines has been performed annually since the last published version in 2017. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1, and/or CIS are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of the tissue obtained by transurethral resection (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a 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. Stratification of patients into low-, intermediate-, and high-risk groups is pivotal to the recommendation of adjuvant treatment. In patients with tumours presumed to be at a low risk and in those presumed to be at an intermediate risk with a low previous recurrence rate and an expected EORTC recurrence score of

ObjectivesWith the advent of novel genomic and transcriptomic technologies, new urinary biomarkers have been identified and tested for bladder cancer (BCa) surveillance. To summarize the current status of urinary biomarkers for the detection of recurrence and/or progression in the follow-up of non-muscle invasive BCa patients, and to assess the value of urinary biomarkers in predicting response to intravesical Bacillus Calmette-Guerin (BCG) therapy.Methods and materialsA medline/pubmed (c) literature search was performed. The performance of commercially available and investigational biomarkers has been reviewed. End points were cancer detection (recurrence), cancer progression, and response to BCG therapy.ResultsThe performance requirements for biomarkers are variable according to the clinical scenario. The clinical role of urinary biomarkers in the follow-up of non-muscle invasive BCa patients remains undefined. The FDA-approved tests provide unsatisfactory sensitivity and specificity levels and their use is limited. Fluorescence in situ hybridization (FISH) has been shown to be useful in specific scenarios, mostly as a reflex test and in the setting of equivocal urinary cytology. FISH and immunocytology could conceivably be used to assess BCG response. Recently developed biomarkers have shown promising results; upcoming large trials will test their utility in specific clinical scenarios in a manner similar to a phased drug development strategy.ConclusionsCurrent commercially available urinary biomarker-based tests are not sufficiently validated to be widely used in clinical practice. Several novel biomarkers are currently under investigation. Prospective multicenter analyses will be needed to establish their clinical relevance and value.

Background: Depression affects more than 300 million people of all ages worldwide. In patients with cancer the reported prevalence is up to 24%. Objective: To systematically review the literature to report the prevalence of depression and anxiety among patients with bladder cancer (BC). Methods: Web of Science, MEDLINE/PubMed, and The Cochrane Library were searched between January and March 2018 using the terms “bladder carcinoma OR bladder cancer AND depression OR anxiety”. Results: Thirteen studies encompassing 1659 patients with BC were included. Six studies assessed depression prior and after treatment at 1, 6 and 12 months. Three were conducted in the US, one each in Turkey, Sweden/Egypt and China. Four studies showed a reduction of depression after radical cystectomy (RC) at 1, 6 and 12 months, respectively. Contrary, two studies showed no significant difference in depression between baseline and follow-up. Four studies investigated anxiety; they reported a slight reduction in anxiety score compared to baseline. Seven additional studies reported the prevalence of depression and anxiety (five studies) among patients with BC at a specific time-point. Studies were conducted in Sweden (2), Italy, Greece, US, China and Spain. Pretreatment depression rates ranged from 5.7 to 23.1% and post-treatment from 4.7 to 78%. Post-treatment anxiety rates ranged from 12.5 to 71.3%. Conclusions: The prevalence of reported depression and anxiety among BC patients is high with large geographic heterogeneity. Gender and geriatric specific screening and management for anxiety and depression should be implemented to alleviate suffering.

Fragestellung: Eine der aktuell größten Herausforderungen beim Urothelkarzinom des oberen Harntraktes (UTUC) ist es Patienten zu identifizieren, welche für ein konservatives Vorgehen bzw. „kidney-sparing surgery“ (KSS) in Frage kommen. Die Leitlinien der europäischen[zum vollständigen Text gelangen Sie über die oben angegebene URL], 43. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Fragestellung: Ziel dieser Arbeit war es den prädiktiven und prognostischen Wert der präoperativen Thrombozytose (TC) hinsichtlich postoperativer histopathologischer Ergebnisse und Überleben nach radikaler Zystektomie und extendierter Lymphadenektomie bei invasivem oder rezidivierendem[zum vollständigen Text gelangen Sie über die oben angegebene URL], 43. Gemeinsame Tagung der Österreichischen Gesellschaft für Urologie und Andrologie und der Bayerischen Urologenvereinigung

Context: Tumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. Objective: To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. Evidence acquisition: A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. Evidence synthesis: Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. Conclusions: Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra-and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. Patient summary: This article summarises the utility of two different grading systems for non-muscle-invasive bladder cancer. Both systems predict progression and recurrence, although pathologists vary in their reporting; suggestions for further improvements are made. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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-Guerin (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. (C) 2016 Published by Elsevier B.V. on behalf of European Association of Urology.

Background: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. Patients: and methods We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201).Results: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type.Conclusions: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.

BACKGROUNDThere is few data on what constitutes the distribution of metastatic sites in prostate cancer (PCa). The aim of our study was to systematically describe the most common sites of metastases in a contemporary cohort of PCa patients. METHODSPatients with metastatic PCa were abstracted from the Nationwide Inpatient Sample (1998-2010). Most common metastatic sites within the entire population were described. Stratification was performed according to the presence of single or multiple (2 sites) metastases. Additionally, we evaluated the distribution of metastatic sites amongst patients with and without bone metastases. RESULTSOverall, 74,826 patients with metastatic PCa were identified. The most common metastatic sites were bone (84%), distant lymph nodes (10.6%), liver (10.2%), and thorax (9.1%). Overall, 18.4% of patients had multiple metastatic sites involved. When stratifying patients according to the site of metastases, only 19.4% of men with bone metastases had multiple sites involved. Conversely, among patients with lymph nodes, liver, thorax, brain, digestive system, retroperitoneum, and kidney and adrenal gland metastases the proportion of men with multiple sites involved was 43.4%, 76.0%, 76.7%, 73.0%, 52.2%, 60.9%, and 76.4%, respectively. When focusing exclusively on patients with bone metastases, the most common sites of secondary metastases were liver (39.1%), thorax (35.2%), distant lymph nodes (24.6%), and brain (12.4%). CONCLUSIONSAlthough the majority of patients with metastatic PCa experience bone location, the proportion of patients with atypical metastases is not negligible. These findings might be helpful when planning diagnostic imaging procedures in patients with advanced PCa. Prostate 74:210-216, 2014. (c) 2013 Wiley Periodicals, Inc.

Objective To examine whether percentage of tumour volume (%TV) and percentage of high-grade tumour volume (%HGTV) help to better identify men at higher risk of early biochemical recurrence (BCR) after radical prostatectomy (RP) for non-metastatic high-risk prostate cancer, as early BCR after RP might be associated with higher risk of metastases and cancer-specific mortality. Patients and Methods We examined the data of 595 men treated with RP for non-metastatic high-risk prostate cancer between 1992 and 2011 at two European tertiary care centres. Kaplan-Meier analyses were used to graphically depict 2-year BCR-free survival. Multivariable Cox regression models addressed early BCR. We tested whether addition of %TV and %HGTV to a multivariable Cox regression model helps to increase a model's predictive accuracy (PA) for prediction of early BCR. Results In all, 32 men (10%) with specimen-confined prostate cancer (pT2-pT3a, negative surgical margin, pN0) and 67 men (24%) with non-specimen-confined prostate cancer had early BCR. After stratification according to %HGTV (%HGTV threshold: ≤33.33 vs >33.33%), the 2-year BCR-free survival rates were respectively 93 vs 60% (log-rank P < 0.001). In multivariable Cox regression models %HGTV emerged as an independent predictor of early BCR (P < 0.001), whereas %TV did not (P > 0.05). However, adding %HGTV (regardless of its coding) to other covariates in multivariable Cox regression analysis did not increase the model's PA in a meaningful fashion compared with the use of the detailed Gleason grading system (6 vs 7a vs 7b vs 8 vs 9-10). Conclusions In a large cohort of patients with high-risk prostate cancer, %HGTV and %TV did not improve prediction of early BCR after RP substantially, although %HGTV was an independent predictor of early BCR. Therefore, sophisticated TV/HGTV measurements do not seem to have additional benefit for early BCR prediction relative to the use of Gleason grading. However, these results need to be confirmed in larger, prospective studies. © 2013 The Authors. BJU International © 2013 BJU International.

Objective To assess the prognostic role of extranodal extension (ENE) and the size of the largest lymph node (LN) metastasis in predicting early biochemical relapse (eBCR) in patients with LN metastasis after radical prostatectomy (RP). Patients and Methods We evaluated BCR-free survival in men with LN metastases after RP and pelvic LN dissection performed in six high-volume centres. Multivariable Cox regression tested the role of ENE and diameter of largest LN metastasis in predicting eBCR after adjusting for clinicopathological variables. We compared the discrimination of multivariable models including ENE, the size of largest LN metastasis and the number of positive LNs. Results Overall, 484 patients were included. The median (interquartile range, IQR) follow-up was 16.1 (6-27.5) months. The median (IQR) number of removed LNs was 10 (4-14), and the median (IQR) number of positive LNs was 1 (1-2). ENE was present in 280 (58%) patients, and 211 (44%) had their largest metastasis >10 mm. Patients with ENE and/or largest metastasis of >10 mm had significantly worse eBCR-free survival (all P < 0.01). On multivariable analysis, number of positive LNs (≤2 vs >2) and the diameter of LN metastasis (≤10 vs >10 mm), but not ENE, were significant predictors of eBCR (all P < 0.003). ENE and diameter of LN metastasis increased the area under the curve of a baseline multivariable model (0.663) by 0.016 points. Conclusions The diameter of the largest LN metastasis and the number of positive LNs are independent predictors of eBCR. Considered together, ENE and the diameter of the largest LN metastasis have less discrimination than the number of positive LNs.

A recent population-based analysis suggested a potential survival benefit with respect to performing lymph node dissection at nephrectomy in node-positive patients with RCC. The findings of the present study failed to corroborate the association of a survival benefit with the performance of lymph node dissection at nephrectomy. Objective Previous studies showed no survival benefit with respect to performing lymph node dissection (LND) at nephrectomy, whereas a recent population-based analysis suggested otherwise, although the latter relied on imputation. To reconcile the findings of that study by critically evaluating the handling of missing data. Patients and Methods Study participants comprised patients diagnosed with non-metastatic renal cell carcinoma (RCC) of all stages who underwent LND at nephrectomy (n = 10596). Multivariable Cox regression models were performed to predict cancer-specific mortality (CSM), where the primary variable of interest was the extent of LND. To examine differences in approaches with respect to handling missing data, separate analyses were performed: (i) imputed population; (ii) exclusion of patients with missing data; and (iii) inclusion of patients with missing data as a sub-category. Results Overall, 2916 (28%) patients had missing tumour grade. In multivariable analyses, our findings showed that increasing the extent of LND was associated with a significant protective effect on CSM in patients with pN1 after imputation (hazard ratio [HR], 0.82; P = 0.04). By contrast, the extent of LND was no longer significantly associated with a lower risk of CSM after excluding patients with a missing tumour grade (HR, 0.83; P = 0.1) or when including patients with missing tumour grade as a sub-category (HR, 0.82; P = 0.05). Conclusions The findings of the present study failed to corroborate the association of a survival benefit with increasing extent of LND at nephrectomy. The different methodologies employed to account for missing data may introduce important biases. Such considerations are non-negligible with respect to the interpretation of results for investigators who rely on administrative cohorts.

Fragestellung: Arbeiten zur prognostischen Qualität des UICC Tumor-Node-Metastasis Staging Systems (TNM) beim Nierenzellkarzinom (RCC) werden entscheidend vom klarzelligen Subtyp dominiert. Die wenigen Studien mit isolierter Analyse von Patienten mit papillärem RCC (papRCC) liefern widersprüchliche[zum vollständigen Text gelangen Sie über die oben angegebene URL], 42. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

Fragestellung: Das papilläre Nierenzellkarzinom (papRCC) ist mit ca. 10-15% der Fälle der zweithäufigste RCC-Subtyp. Obwohl Männer einer deutlich höhere Inzidenz für diesen Subtyp aufweisen, wurden bisher weder geschlechtsspezifische Unterschiede bezüglich klinischer[zum vollständigen Text gelangen Sie über die oben angegebene URL], 42. Gemeinsame Tagung der Bayerischen Urologenvereinigung und der Österreichischen Gesellschaft für Urologie und Andrologie

Context: There is uncertainty regarding the oncologic effectiveness of kidney-sparing surgery (KSS) compared with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Objective: To systematically review the current literature comparing oncologic outcomes of KSS versus RNU for UTUC. Evidence acquisition: A computerised bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of KSS versus RNU. Approaches considered for KSS were segmental ureterectomy (SU) and ureteroscopic (URS) or percutaneous (PC) management. Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we identified 22 nonrandomised comparative retrospective studies published between 1999 and 2015 that were eligible for inclusion in this systematic review. A narrative review and risk-of-bias (RoB) assessment were performed using cancer-specific survival (CSS) as the primary end point. Evidence synthesis: Seven studies compared KSS overall (n = 547) versus RNU (n = 1376). Information on the comparison of SU (n = 586) versus RNU (n = 3692), URS (n = 162) versus RNU (n = 367), and PC (n = 66) versus RNU (n = 114) was available in 10, 5, and 2 studies, respectively. No significant difference was found between SU and RNU in terms of CSS or any other oncologic outcomes. Only patients with low-grade and noninvasive tumours experienced similar CSS after URS or PC when compared with RNU, despite an increased risk of local recurrence following endoscopic management of UTUC. The RoB assessment revealed, however, that the analyses were subject to a selection bias favouring KSS. Conclusions: Our systematic review suggests similar survival after KSS versus RNU only for low-grade and noninvasive UTUC when using URS or PC. However, selected patients with high-grade and invasive UTUC could safely benefit from SU when feasible. These results should be interpreted with caution due to the risk of selection bias. Patient summary: We reviewed the studies that compared kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma. We found similar oncologic outcomes for favourable tumours when using ureteroscopic or percutaneous management, whereas indications for segmental ureterectomy could be extended to selected cases of aggressive tumours. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Maxine Sun1, Firas Abdollah2, Jan Schmitges1, Claudio Jeldres1, Shahrokh F Shariat3, Paul Perrotte4, Pierre I Karakiewicz1,4 1Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; 2Department of Urology, Vita Salute San Raffaele University, Milan, Italy; 3Department of Urology, Weill Medical College of Cornell University, New York, NY, USA; 4Department of Urology, University of Montreal Health Center, Montreal, CanadaAbstract: The efficacy of sequential everolimus, an orally administered inhibitor of mammalian target of rapamycin (mTOR), was proven in a placebo-controlled phase III study, where median progression-free survival was 4.9 vs 1.9 months for placebo (hazard ratio: 0.33, P < 0.001). Placebo crossovers (80%) contaminated overall survival data. Adverse event discontinuation rate was of only 10% and health-adjusted quality-of-life was sustained. These data represent the first placebo-controlled evidence of efficacy for a seque ntially used targeted agent. Everolimus resulted in the strongest hazard ratio ever recorded for progression-free survival, despite it being tested in a population with the most aggressive natural history ever recorded in all available phase III metastatic renal cell carcinoma trials. Everolimus use after exclusively one prior antivascular endothelial growth factor f ailure resulted in an even longer progression-free survival time (5.4 months) than in the entire population (4.9 months). These benefits should also be considered in the light of sustained and unimpaired health-related quality of life. Use in first line other than second or subsequent lines remains to be validated.Keywords: everolimus, metastatic renal cell carcinoma, targeted therapy, sequential therapy, mTOR

Introduction and Objectives: The impact of prognostic factors in T1G3 patients (pts) is critical for proper treatment decision making, however most available data are from small series of pts. The aim of the current study is to assess prognostic factors in a large group of pts who received BCG as initial treatment of T1G3 tumours and identify a subgroup of high risk pts who should be considered for early cystectomy. Patients and Methods: Individual pt data were collected for 1743 ptsfrom 20 centers who received induction or maintenance BCG between 1990 and 2008. Using Cox regression analysis, the prognostic importance of the following variables were assessed for time to recurrence, progression to muscle invasive disease and overall survival:age (70yrs), gender, primary T1G3 vs. recurrent T1G3 after previous non T1G3 tumour, tumour size (3 cm), multiplicity (single vs. multiple), concomitant CIS (no/yes), and maintenance BCG (no/yes). Results: Median age was 68yrs, 84% were male, 89% were primary T1G3, 50% had multifocal disease, 67% had tumours less than 3 cm, 24% had concomitant CIS, 30% had a restaging TUR, 52% received some sort of maintenance BCG. With a follow up out to 15 years, 801 pts (46%) recurred, 326 (19%) progressed, 291 underwent cystectomy (17%) and 409 (23%) died, 151 (9%) due to bladder cancer. In multivariate analyses, the most important prognostic factors (p70, size >3 cm and presence of CIS. Progression free rates at 10 yrs were 84%, 75%, 66% and 28% for patients with 0, 1, 2 and 3 bad factors while the corresponding overall survival rates were 78%, 56%, 45% and 6%, respectively. Conclusion: T1G3 patients treated with BCG have a heterogeneous prognosis, with overall survival at 10 yrs ranging from 78% to 6%. Although maintenance BCG improves outcome as compared to induction alone, fit pts over 70 yrs of age with tumours greater than 3 cm and concomitant CIS should be considered for an early cystectomy.

Objectives To examine cancer-specific mortality in patients with nodal metastases relative to patients without nodal involvement at nephrectomy for non-metastatic renal cell carcinoma in a population-based cohort. Methods A total of 11374 non-metastatic renal cell carcinoma patients who underwent a lymph node dissection at nephrectomy were identified using the Surveillance, Epidemiology and End Results database (19882008). The 5-year cancer-specific mortality-free survival rates were examined according to the presence or absence of nodal involvement within the entire cohort, and stratified according to pathological tumor stage (pT1vspT2vspT3vspT4) and Fuhrman grade (IvsIIvsIIIvsIV). Cox regression analyses for prediction of cancer-specific mortality were modeled to assess the effect of nodal metastases versus no nodal involvement in the entire population. Finally, separate Cox regression models were fitted within each pathological stage and grade. Results Overall, 1260 (11%) patients had nodal metastases at nephrectomy. The overall 5-year cancer-specific mortality-free survival rates were 38.4 versus 83.8% in patients with nodal metastases and without nodal metastases, respectively. In multivariable analyses, amongst pT1, pT2, pT3 and pT4, patients with nodal metastases were 6.0-, 3.6-, 3.2- and 2.0-fold, respectively, more likely to die after nephrectomy (all P

Objective To quantify the effect of partial nephrectomy (PN) vs radical nephrectomy (RN) on other-cause mortality (OCM) in elderly patients with localized renal cell carcinoma (RCC) and/or multiple comorbidities. Methods Using the Surveillance, Epidemiology, and End Results Medicare-linked database, patients with T1 RCC, aged >= 75 years, or who had >= 2 comorbidities, were identified (1988-2005). To adjust for inherent differences between treatment types, propensity-based matched analyses were performed. Competing-risks regression analyses for prediction of OCM were assessed according to treatment type. The effect of PN and RN on OCM was examined in three sub-groups: patients aged >= 75 years; patients with >= 2 comorbidities; and patients aged >= 75 years with >= 2 comorbidities. Results After propensity-based matched analyses and adjustment for all covariates, PN was found to exert a protective effect relative to RN with respect to OCM in all patients (hazard ratio [HR]: 0.84, P = 0.048). In subanalyses, no difference was recorded between PN and RN in patients who were aged >= 75 years (HR: 0.83, P = 0.2), with >= 2 baseline comorbidities at diagnosis (HR: 0.83, P = 0.1), or in patients who were aged >= 75 years and who had >= 2 baseline comorbidities (HR: 0.77, P = 0.2). Conclusions Some elderly patients and/or those with multiple comorbidities at diagnosis may not benefit from PN with respect to OCM. After rigorous patient selection, alternative treatment options could be considered.

Objective To examine the impact of length of survival on future survival probability, otherwise known as the effect of conditional survival (CS), after nephrectomy (NT) in patients diagnosed with renal cell carcinoma (RCC). Patients and Methods Overall, 42090 patients with RCC who underwent NT were abstracted from the Surveillance, Epidemiology, and End Results database (1988-2008). Based on cumulative survival estimates, CS rates were derived according to patient and disease characteristics. Separate multivariable Cox regression analyses were performed for the prediction of cancer-specific mortality (CSM), according to 1-, 2-, 3-, 4- and 5-year survival postoperatively. Results Immediately after surgery, the 5-year cancer-specific survival rate was 83.5%. Amongst patients who survived 1, 2, 3, 4, and 5 years after NT, the probability rates for surviving an additional 5 years were 87.0, 89.6, 90.9, 92.0 and 92.3%, respectively. Provided that patients survived 1 and 2 years after NT, the probability of being CSM-free for another 5 years increased by +4.1 and 4.3% for stage III and +12.9 and 10.3% for stage IV disease, respectively. Similar observations were recorded for patient age, grade, nodal stage and tumour size, and were confirmed upon multivariable analyses. Conclusion Survival probabilities vary according to length of survival after NT. Specifically, even amongst patients with more advanced disease at surgery, a more favourable prognosis can be achieved after surviving for 1-2 years.

Objectives The 2004 National Comprehensive Cancer Network practice guidelines recommend pelvic lymph node dissection at radical prostatectomy. We sought to examine the adherence to the 2004 National Comprehensive Cancer Network guidelines and to test the their accuracy, as well as the accuracy of the most contemporary National Comprehensive Cancer Network, American Urological Association, and European Association of Urology guidelines to predict lymph node metastases. Methods A total of 33037 radical prostatectomy patients were identified, between 2004 and 2006. Adherence to the 2004 National Comprehensive Cancer Network guidelines was calculated using three clinically plausible cut-offs: 2, 5 and 10%. The accuracy was tested using the area under the curve. Results Overall, 63% of patients underwent pelvic lymph node dissection. Of those, 61, 49 and 45% were managed according to the 2004 National Comprehensive Cancer Network guideline cut-off of 2, 5 and 10%, respectively. The accuracy of all the examined guidelines ranged from 61% to 71%. The highest accuracy was recorded for the European Association of Urology and the 2004 National Comprehensive Cancer Network cut-off 5% guidelines. The lowest accuracy was recorded for the most contemporary National Comprehensive Cancer Network guideline. Conclusions Adherence to the 2004 National Comprehensive Cancer Network guidelines was suboptimal. The accuracy of all the examined guidelines ranged from 61% to 71%. None of the examined guidelines can be regarded as an ideal indication for pelvic lymph node dissection.

Objective To examine the discriminant properties of the most contemporary version of the Tumour-Node-Metastasis (TNM) staging for renal cell carcinoma (RCC) sub-classification of T2 lesions according to a threshold size of 10cm. Other thresholds were also assessed. Patients and Methods Between 1988 and 2006, within the Surveillance, Epidemiology, and End Results database, patients with T2 N0-2 M0-1 RCC treated with a nephrectomy were abstracted. Tumour size was evaluated according to several thresholds: 8, 9, 10, 11, and 12cm. Kaplan-Meier and life tables for cancer-specific mortality (CSM) were computed. Several Cox regression modes were fitted for prediction of CSM, using different thresholds. The predictive accuracy of various thresholds was compared using the area under the curve and methods of calibration. Results In all, 4963 patients were identified. Kaplan-Meier analyses showed statistically significant CSM-free survival differences between all examined thresholds. In multivariable Cox-regression models, all tested tumour size thresholds emerged as independent predictors of CSM. Of all thresholds, the values of 9 (0.55) and 11cm (0.55) achieved the highest discrimination in univariable analysis, followed by 10 (0.539), 12 (0.539), and 8cm (0.531). When the thresholds were combined with all other variables, the 11cm (0.688) achieved the highest discrimination. Conclusion The discriminant properties of all examined thresholds showed very similar discriminant properties, which brings into questioning whether a dichotomization of pT2 tumours is really necessary.

Background: Approximately 10-20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence). Objective: To determine features associated with late recurrence. Design, setting, and participants: A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78-135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78-134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93-149]). Interventions: Patients underwent radical nephrectomy or nephron-sparing surgery. Outcome measurements and statistical analysis: Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM). Results and limitations: Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p < 0.001), Fuhrman grade 3-4 (OR: 1.60; p = 0.001), and pT stage >pT1 (OR: 2.28; p < 0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3-4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: Late recurrence risk 3.1%; 1-3 points: 8.4%; 4-5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67-73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p < 0.001), pT stage (HR: 1.24; p < 0.001), Fuhrman grade (HR: 2.40; p < 0.001), age (HR: 1.01; p < 0.001), and gender (HR: 0.71; p = 0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design. Conclusions: LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design. © 2012 European Association of Urology.