BACKGROUND: High-level evidence supporting the role of repeat transurethral resection (reTUR) in non-muscle-invasive bladder cancer (NMIBC) is lacking. A randomized controlled trial (RCT) assessing whether immediate reTUR has an impact on patient prognosis is essential. However, since such a RCT will require enrollment of a high number of patients, a preliminary feasibility study is appropriate. OBJECTIVE: To assess the feasibility of an RCT investigating the impact of immediate reTUR + adjuvant bacillus Calmette-Guérin (BCG) versus upfront induction BCG after initial TUR in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Eligible patients were randomly assigned to receive either reTUR + adjuvant BCG or upfront induction BCG after TUR. Patients with macroscopically completely resected high-grade T1 NMIBC, with or without concomitant carcinoma in situ, and with detrusor muscle (DM) present in the initial TUR specimen were considered eligible for inclusion. Exclusion criteria included lymphovascular invasion (LVI), histological subtypes, hydronephrosis, concomitant upper tract urothelial carcinoma (UTUC), or urothelial carcinoma within the prostatic urethra. The aim was to enroll 30 patients in this feasibility study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The patient recruitment rate was the primary outcome. Oncological outcomes (recurrence-free and progression-free survival) were secondary endpoints. RESULTS AND LIMITATIONS: Overall, 30 patients (15 per arm) were randomized over a period of 14 mo (August 2020-October 2021). Two eligible patients refused the randomization, resulting in a patient compliance rate of 93.3% for the study protocol. We excluded 49 ineligible patients before randomization because of histological subtypes (n = 16, 33%), LVI (n = 9, 18%), DM absence in the TUR specimen (n = 12, 24%), metastatic disease (n = 5, 10%), concomitant UTUC (n = 3, 6%), or hydronephrosis (n = 4, 8%). At reTUR, persistent disease was found in four patients (29%) and upstaging to muscle-invasive disease in one (7%). Over median follow-up of 17 mo, disease recurrence was detected in three patients (23%) in the reTUR arm and six patients (40%) in the upfront BCG arm. Progression to muscle-invasive disease was observed in one patient treated with upfront BCG. CONCLUSIONS: The feasibility of conducting an RCT comparing upfront BCG versus reTUR + BCG in high-grade T1 NMIBC has been demonstrated. Our results underline the need to screen a large number of patients owing to characteristics meeting the exclusion criteria in a high percentage of cases. PATIENT SUMMARY: We found that a clinical trial of the role of a repeat surgical procedure to remove bladder tumors through the urethra would be feasible among patients with high-grade non-muscle-invasive bladder cancer. These preliminary results may help in refining the role of this repeat procedure for patients in this category.

• MeSH
• adjuvancia imunologická * terapeutické užití   MeSH
• BCG vakcína * terapeutické užití   aplikace a dávkování   MeSH
• cystektomie metody   MeSH
• invazivní růst nádoru * MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře neinvadující svalovinu MeSH
• nádory močového měchýře * chirurgie   patologie   farmakoterapie   MeSH
• reoperace MeSH
• senioři MeSH
• studie proveditelnosti * MeSH
• uretra MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND: Current European Association of Urology (EAU) guidelines support adjuvant intravesical Bacillus Calmette-Guérin (BCG) treatment after Transurethral Resection of Bladder Tumor (TURB) for intermediate- or high-risk Non-Muscle-Invasive Bladder Cancer (NMIBC) patients, aiming to reduce the risk of tumor recurrence. The quality of data, however, does not allow definitive conclusions on whether different strains and dosages of BCG have different efficacies on long-term survival outcomes. OBJECTIVE: To evaluate the long-term survival outcomes of different strains and dosages of BCG in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS: All NMIBC patients treated with intravesical BCG therapy from 2001 to 2020 were identified using a territory-wide database in Hong Kong. INTERVENTION: BCG strains and dosages (Connaught strain 81 mg, Connaught strain 27 mg, Tokyo strain 80 mg, and Danish strain 30 mg) were retrieved from medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. A multivariable Cox regression analysis was used to adjust potential confounding factors, and to estimate Hazard Ratio (HR) and 95% confidence interval (CI) of different BCG strains. A further subgroup analysis on adequate versus inadequate BCG treatment was performed. RESULTS AND LIMITATIONS: A total of 2602 NMIBC patients treated with intravesical BCG were identified. Among them, 1291 (49.6%) received Connaught strain 81 mg, 199 (7.6%) received Connaught strain 27 mg, 1014 (39.0%) received Tokyo strain, and 98 (3.8%) received Danish strain. The median follow-up was 11.0 years. No statistically significant differences in OS, CSS, RFS, and PFS were detected among the different groups. At the multivariable analysis, the Connaught strain 27 mg group was inferior to the Connaught strain 81 mg group in terms of OS (HR: 1.26, 95% CI: 1.05-1.51), CSS (HR: 1.69, 95% CI: 1.08-2.66), and PFS (HR: 1.86, 95% CI: 1.20-2.88). Adequate BCG treatment was associated with improved OS (HR: 0.82, 95% CI: 0.73-0.92), CSS (HR: 0.64, 95% CI: 0.47-0.86), RFS (HR: 0.80, 95% CI: 0.70-0.92), and PFS (HR: 0.52, 95% CI: 0.39-0.68). Among patients treated with adequate BCG, at the multivariable analysis the Connaught strain 27 mg group showed worse results than the Connaught strain 81 mg group in terms of CSS (HR: 1.93, 95% CI: 1.07-3.51). Compared with the Connaught strain 81 mg group, both Tokyo and Danish strains had similar survival outcomes in the whole cohort and the adequate BCG treatment subgroup. CONCLUSIONS: Our findings suggest that adequate BCG remains the most important factor in optimizing survival outcomes in patients with intermediate- and high-risk NMIBC. No significant differences in survival outcomes were observed between full-dose Connaught, Tokyo, and Danish strains. Reduced-dose Connaught strain was associated with the worst survival outcomes. PATIENT SUMMARY: We evaluated the efficacy of different strains and dosages of bacillus Calmette-Guérin (BCG) in patients with intermediate- or high-risk non-muscle-invasive bladder cancer in the past two decades in Hong Kong. We conclude no significant differences in long-term survival outcomes in terms of full-dose Connaught, Tokyo, and Danish strains, while reduced-dose Connaught strain was inferior to the full-dose group. Adequate BCG treatment benefits long-term survival.

• MeSH
• adjuvancia imunologická terapeutické užití   aplikace a dávkování   MeSH
• aplikace intravezikální MeSH
• BCG vakcína * terapeutické užití   aplikace a dávkování   MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory močového měchýře neinvadující svalovinu * mortalita   terapie   MeSH
• nádory močového měchýře * mortalita   terapie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Hongkong MeSH

• MeSH
• bakteriální lyzáty * farmakologie   klasifikace   terapeutické užití   MeSH
• BCG vakcína aplikace a dávkování   farmakologie   imunologie   terapeutické užití   MeSH
• glukany aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• imunologické faktory farmakologie   klasifikace   terapeutické užití   MeSH
• imunomodulační látky * aplikace a dávkování   farmakologie   klasifikace   terapeutické užití   MeSH
• mikrobiota fyziologie   imunologie   MeSH
• probiotika farmakologie   klasifikace   terapeutické užití   MeSH
• slizniční imunita imunologie   účinky léků   MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

• MeSH
• adjuvantní chemoterapie MeSH
• aplikace intravezikální MeSH
• BCG vakcína terapeutické užití   aplikace a dávkování   MeSH
• cystektomie metody   MeSH
• epirubicin aplikace a dávkování   MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitomycin aplikace a dávkování   terapeutické užití   MeSH
• nádory močového měchýře neinvadující svalovinu MeSH
• nádory močového měchýře * patologie   terapie   farmakoterapie   mortalita   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

• MeSH
• BCG vakcína aplikace a dávkování   MeSH
• dítě MeSH
• infekce epidemiologie   MeSH
• lidé MeSH
• očkovací schéma MeSH
• uprchlíci * MeSH
• vakcína proti spalničkám, příušnicím a zarděnkám aplikace a dávkování   MeSH
• vakcinace * normy   MeSH
• vakcíny klasifikace   terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVE: To investigate the predictive value of tumour-infiltrating immune cells (TIICs) on oncological outcomes and response to BCG treatment in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A systematic review and meta-analysis was performed using PubMed, Scopus and the Cochrane Library in July 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The pooled recurrence-free survival (RFS) rate was calculated using a fixed-effect model. RESULTS: We retrieved 15 studies (including 791 patients) evaluating the effect of TIICs on oncological outcomes in patients with NMIBC treated with intravesical BCG. TIICs were reported to be a significant predictor of oncological outcomes and response to BCG treatment in 10 studies. Tumour-associated macrophages were associated with worse RFS (pooled hazard ratio 2.30, 95% confidence interval 1.64-3.22). CONCLUSIONS: Based on these data, TIICs are significant predictors of RFS and response to BCG treatment in patients with NMIBC; therefore, incorporation of TIICs into risk stratification models may help patients and physicians in the clinical decision-making process in order to achieve the maximum possible benefit from BCG treatment.

• MeSH
• adjuvancia imunologická aplikace a dávkování   MeSH
• aplikace intravezikální MeSH
• BCG vakcína aplikace a dávkování   MeSH
• lidé MeSH
• nádory močového měchýře farmakoterapie   imunologie   patologie   MeSH
• tumor infiltrující lymfocyty * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

• MeSH
• adjuvancia imunologická aplikace a dávkování   MeSH
• aplikace intravezikální MeSH
• BCG vakcína aplikace a dávkování   MeSH
• COVID-19 * MeSH
• lidé MeSH
• nádory močového měchýře farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH

PURPOSE: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC). MATERIALS AND METHODS: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression. RESULTS: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55). CONCLUSION: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.

• MeSH
• adjuvancia imunologická aplikace a dávkování   MeSH
• aplikace intravezikální MeSH
• BCG vakcína aplikace a dávkování   MeSH
• imunoterapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře farmakoterapie   patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sexuální faktory MeSH
• stupeň nádoru MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

PURPOSE: This systematic review assessed compliance to guidelines for the management of nonmuscle-invasive bladder carcinoma (NMIBC). METHODS: The PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in November 2019 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement. RESULTS: Fifteen studies incorporating a collective total of 10,575 NMIBC patients were eligible for inclusion in this systematic review. We found that the rates of compliance were 53.0% with a single immediate intravesical instillation in patients with presumed low or intermediate risk, 37.1% with intravesical bacillus Calmette-Guerin or chemotherapy in those with intermediate risk, 43.4% with performance of a second transurethral resection in high-risk patients, 32.5% with administration of adjuvant intravesical bacillus Calmette-Guerin in high-risk patients, 36.1% with radical cystectomy in highest-risk patients, and 82.2% with cystoscopy for follow-up. CONCLUSIONS: Compliance with NMIBC guidelines remains low. Better guideline education and understanding holds the key to achieving high compliance. Strategies to improve guideline compliance at the physician level are urgently required.

• MeSH
• adjuvancia imunologická aplikace a dávkování   MeSH
• adjuvantní chemoterapie metody   normy   statistika a číselné údaje   MeSH
• antitumorózní látky aplikace a dávkování   MeSH
• aplikace intravezikální MeSH
• BCG vakcína aplikace a dávkování   MeSH
• cystektomie normy   statistika a číselné údaje   MeSH
• cystoskopie normy   statistika a číselné údaje   MeSH
• dodržování směrnic statistika a číselné údaje   MeSH
• hladké svalstvo diagnostické zobrazování   patologie   chirurgie   MeSH
• invazivní růst nádoru MeSH
• karcinom z přechodných buněk diagnóza   patologie   terapie   MeSH
• lékařská onkologie normy   statistika a číselné údaje   MeSH
• lidé MeSH
• močový měchýř diagnostické zobrazování   patologie   chirurgie   MeSH
• nádory močového měchýře diagnóza   patologie   terapie   MeSH
• následná péče normy   statistika a číselné údaje   MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• urologie normy   statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled 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