BACKGROUND: Adverse events induced by intravesical bacillus Calmette-Guérin (BCG) to treat high-grade non-muscle-invasive bladder cancer (NMIBC) often lead to treatment discontinuation. The EAU-RF NIMBUS trial found a reduced number of standard-dose BCG instillations to be inferior with the standard regimen. Nonetheless, it remains important to evaluate whether patients in the reduced BCG treatment arm had better quality of life (QoL) due to a possible reduction in toxicity or burden. OBJECTIVE: To evaluate whether patients in the EAU-RF NIMBUS trial experienced better QoL after a reduced BCG instillation frequency. DESIGN SETTING AND PARTICIPANTS: A total of 359 patients from 51 European sites were randomized to one of two treatment arms between December 2013 and July 2019. The standard frequency arm (n = 182) was 6 weeks of BCG induction followed by 3 weeks of maintenance at months 3, 6, and 12. The reduced frequency arm (n = 177) was BCG induction at weeks 1, 2, and 6, followed by maintenance instillations at weeks 1 and 3 of months 3, 6, and 12. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Analyses were performed using an intention-to-treat analysis and a per-protocol analysis. QoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 version 3.0 (QLQ-C30 v.03) prior to the first and last instillations of each BCG cycle. Group differences were determined using linear regression corrected for QoL at baseline. Differences in QoL over time were tested for significance using a linear mixed model. Side effects were recorded by the treating physician using a standardized form. Chi-square tests were used to compare the side-effect frequency between the arms. RESULTS AND LIMITATIONS: There were no significant differences in the means of each QoL scale between the two arms. There were also no significant changes over time in all QoL domains for both arms. However, differences in the incidence of general malaise at T1 (before the last induction instillation), frequency, urgency, and dysuria at T7 (before the last maintenance instillation) were detected in favor of the reduced frequency arm. CONCLUSIONS: Reducing the BCG instillation frequency does not improve the QoL in NMIBC patients despite lower storage symptoms. PATIENT SUMMARY: In this study, we evaluated whether a reduction in the number of received bacillus Calmette-Guérin instillations led to better quality of life in patients with high-grade non-muscle-invasive bladder cancer. We found no difference in the quality of life between the standard and the reduced bacillus Calmette-Guérin instillation frequency. We conclude that reducing the number of instillations does not lead to better quality of life in patients with high-grade non-muscle-invasive bladder cancer.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Intravesical instillation of bacillus Calmette-Guérin (BCG) is an accepted strategy to prevent recurrence of non-muscle-invasive bladder cancer (NMIBC) but associated with significant toxicity. OBJECTIVE: NIMBUS assessed whether a reduced number of standard-dose BCG instillations are noninferior to the standard number and dose in patients with high-grade NMIBC. DESIGN, SETTING, AND PARTICIPANTS: A total of 345 patients from 51 sites were randomised between December 2013 and July 2019. We report results after a data review and safety analysis by the Independent Data Monitoring Committee based on the cut-off date of July 1, 2019. INTERVENTION: The standard BCG schedule was 6 wk of induction followed by 3 wk of maintenance at 3, 6, and 12 mo (15 instillations). The reduced frequency BCG schedule was induction at wks 1, 2, and 6 followed by 2 wk (wks 1 and 3) of maintenance at 3, 6, and 12 mo (nine instillations). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was time to first recurrence. Secondary endpoints included progression to ≥ T2 and toxicity. RESULTS AND LIMITATIONS: In total, 170 patients were randomised to reduced frequency and 175 to standard BCG. Prognostic factors at initial resection were as follows: Ta/T1: 46/54%; primary/recurrent: 92/8%; single/multiple: 57/43%; and concomitant carcinoma in situ: 27%. After 12 mo of median follow-up, the intention-to-treat analysis showed a safety-relevant difference in recurrences between treatment arms: 46/170 (reduced frequency) versus 21/175 patients (standard). Additional safety analyses showed a hazard ratio of 0.40 with the upper part of the one-sided 97.5% confidence interval of 0.68, meeting a predefined stopping criterion for inferiority. CONCLUSIONS: The reduced frequency schedule was inferior to the standard schedule regarding the time to first recurrence. Further recruitment of patients was stopped immediately to avoid harm in the reduced frequency BCG arm. PATIENT SUMMARY: After surgical removal of the tumour, patients with high-grade non-muscle-invasive bladder cancer are treated with bacillus Calmette-Guérin to prevent recurrence and progression. This is associated with significant side effects. We report the results of a clinical trial showing a reduction in the number of instillations (from 15 to nine in total) being inferior to the standard protocol. From today's perspective, complete tumour resection and a standard number of instillations remain the standard of care.

• MeSH
• adjuvancia imunologická aplikace a dávkování   MeSH
• aplikace intravezikální MeSH
• BCG vakcína aplikace a dávkování   MeSH
• invazivní růst nádoru MeSH
• lidé MeSH
• nádory močového měchýře farmakoterapie   patologie   MeSH
• prospektivní studie MeSH
• referenční standardy MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

Kontext: Tato guidelines byla vytvořena pod záštitou Evropské urologické asociace (EAU) s cílem pomoci urologům při léčbě poranění močové trubice. Cíl: Stanovit nejvhodnější diagnostické postupy a tera peutické modality pro léčbu poranění močové trubice na základě hodnocení přehledu mezinárodních publikací. Sběr údajů: Byla vytvořena skupina odborníků na léčbu urologických traumat, jejíž členové měli za úkol zrecenzovat dostupnou literaturu zaměřenou na diagnostiku a léčbu poranění močopohlavních cest (včetně poranění močové trubice). Guidelines pro léčbu urologických traumat byla vytvořena na základě údajů získaných z on-line průzkumu databáze MEDLINE a dalších dokumentů publikovaných před rokem 2009. Členové skupiny byli požádáni o kritické posouzení materiálu bez formálního hodnocení údajů. K této problematice je k dispozici pouze malé množství kvalitních, randomizovaných, kontrolovaných studií, velké množství údajů tedy bylo nashromážděno z retrospektivních studií. Členové pracovní skupiny jsou si tohoto nedostatku vědomi. Syntéza údajů: Kompletní text guidelines je k dispozici přímo v Central Office EAU a na webové stránce EAU (www.uroweb.org). Tento článek představuje zkrácenou verzi jedné ze sekcí guidelines pro léčbu urologických traumat. Závěr: Předkládáme aktualizovanou verzi guidelines pro léčbu poranění močové trubice. Cílem těchto guidelines je poskytnout pomoc praktickým urologům vzhledem k tomu, že uretrální traumata jsou spojena s významnou morbiditou. Vzhledem k rozmanitosti poranění močové trubice, sdružených poranění, načasování a dostupnosti terapeutických modalit a poměrně vzácnému výskytu tohoto typu traumatu je léčba poranění močové trubice mnohdy kontroverzní.

Context: These guidelines were prepared on behalf of the European Association of Urology (EAU) to assist urologists in the management of traumatic urethral injuries. Objective: To determine the optimal evaluation and management of urethral injuries by review of the world's literature on the subject. Evidence acquisition: A working group of experts on Urological Trauma was convened to review and summarize the literature concerning the diagnosis and treatment of genitourinary trauma, including urethral trauma. The Urological Trauma guidelines have been based on a review of the literature identified using on-line searches of MEDLINE and other source documents published before 2009. A critical assessment of the findings was made, not involving a formal appraisal of the data. There were few high-powered, randomized, controlled trials in this area and considerable available data was provided by retrospective studies. The Working Group recognizes this limitation. Evidence synthesis: The full text of these guidelines is available through the EAU Central Office and the EAU website (www.uroweb.org). This article comprises the abridged version of a section of the Urological Trauma guidelines. Conclusions: Updated and critically reviewed Guidelines on Urethral Trauma are presented. The aim of these guidelines is to provide support to the practicing uro - logist since urethral injuries carry substantial morbidity. The diversity of urethral injuries, associated injuries, the timing and availability of treatment options as well as their relative rarity contribute to the controversies in the management of urethral trauma.

• Klíčová slova
• uretrální trauma, hodnocení, operační léčba, odložená léčba,
• MeSH
• algoritmy MeSH
• diagnóza MeSH
• diferenciální diagnóza MeSH
• iatrogenní nemoci prevence a kontrola   MeSH
• klasifikace MeSH
• lidé MeSH
• rány a poranění diagnóza   chirurgie   klasifikace   MeSH
• striktura uretry chirurgie   MeSH
• terapie metody   využití   MeSH
• uretra zranění   MeSH
• urologické chirurgické výkony u mužů metody   využití   MeSH
• urologické chirurgické výkony metody   využití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• směrnice pro lékařskou praxi MeSH