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

BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.

• MeSH
• adjuvantní chemoterapie metody   MeSH
• antibiotika antitumorózní * terapeutické užití   aplikace a dávkování   MeSH
• aplikace intravezikální MeSH
• hodnocení rizik MeSH
• invazivní růst nádoru * MeSH
• lidé MeSH
• lokální recidiva nádoru prevence a kontrola   MeSH
• mitomycin * terapeutické užití   aplikace a dávkování   MeSH
• nádory močového měchýře neinvadující svalovinu MeSH
• nádory močového měchýře * farmakoterapie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

BACKGROUND: There is an urgent need to provide a risk-stratification tool for intermediate-risk non-muscle-invasive bladder cancer (NMIBC), especially at the time of bacillus Calmette-Guerin (BCG) shortage. OBJECTIVE: To assess whether patients with intermediate-risk NMIBC can be stratified into different risk groups, thereby providing a practical tool for the selection of the optimal adjuvant therapy, based on the individualized risk of disease progression. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of 636 patients with intermediate-risk NMIBC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariable Cox-regression model was built to evaluate the impact of each variable on recurrence and progression to muscle-invasive disease. A Cox-based nomogram to predict patient-specific probability of disease progression was performed, and the decision curve analysis (DCA) was used to evaluate its clinical benefit. RESULTS AND LIMITATIONS: Within a median follow-up of 92 mo (interquartile range 56-118), disease recurrence and progression occurred in 346 (54%) and 91 (14%) patients, respectively. On multivariable analysis, age, early recurrence (<12 mo), and tumor size≥3cm were found to be independent predictors of progression. The Harrell C-index of the model for the prediction of progression was 0.75 and exceeded that of the model proposed by the International Bladder Consultation Group. DCA showed superior net benefits for the nomogram compared with the strategies of treating all/none and previous predictive models. Limitations are inherent to the retrospective design. CONCLUSIONS: We provided a risk-stratification tool that helps identify individual risk of disease progression in patients with intermediate-risk NMIBC. This tool outperforms standard strategies in the threshold probability range of interest and could help select the optimal intravesical therapy regimen based on the individual risk of disease progression. PATIENT SUMMARY: In this study, we provided a practical tool for risk stratification in patients with intermediate-risk non-muscle-invasive bladder cancer. This tool may help select the most appropriate adjuvant therapy (either bacillus Calmette-Guerin [BCG] or chemotherapy) based on patient and tumor characteristics, thus making a step forward toward the era of personalized medicine.

• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• BCG vakcína * terapeutické užití   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   epidemiologie   MeSH
• nádory močového měchýře * farmakoterapie   patologie   MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články 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

This study aimed to assess both efficacy and safety outcomes of lowering the dose of BCG compared to intravesical chemotherapies in non-muscle-invasive bladder cancer (NMIBC) patients using a systematic review, meta-analysis, and network meta-analysis approach. A comprehensive literature search was performed through Pubmed®, Web of ScienceTM, and Scopus® in December 2022 to identify randomized controlled trials comparing the oncologic and/or safety outcomes of reduced dose intravesical BCG and/or intravesical chemotherapies according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. The outcomes of interest were risk of recurrence, progression, treatment-related adverse events, and discontinuation. Overall, 24 studies were eligible for quantitative synthesis. Among 22 studies that adopted induction followed by maintenance intravesical therapy, with reference to the lower-dose BCG, epirubicin was associated with a significantly higher risk of recurrence (Odds ratio [OR]: 2.82, 95% CI: 1.54-5.15), but not other intravesical chemotherapies. There were no significant differences in risk of progression among the intravesical therapies. On the other hand, standard-dose BCG was associated with a higher risk of any AEs (OR: 1.91, 95% CI: 1.07-3.41) but other intravesical chemotherapies had a comparable risk of AEs compared to lower-dose BCG. The discontinuation rate did not significantly differ between lower-dose and standard-dose BCG (OR: 1.40, 95% CI: 0.81-2.43) as well as other intravesical. According to the surface under the cumulative ranking curve, gemcitabine, and standard-dose BCG were preferable to lower-dose BCG in terms of recurrence risk; gemcitabine was also preferable to lower-dose BCG in terms of risk of AEs. In patients with NMIBC, lowering the dose of BCG decreases the risks of AEs and discontinuation rate compared to standard-dose BCG, but there is no difference in these endpoints compared to other intravesical chemotherapies. Standard-dose of BCG is preferred for all intermediate and high-risk NMIBC patients based on oncologic efficacy; however, lower-dose BCG and intravesical chemotherapies, especially gemcitabine, could be considered a reasonable alternative to BCG in selected patients who suffer from significant AEs or in case standard-dose BCG is not available.

• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• aplikace intravezikální MeSH
• BCG vakcína terapeutické užití   MeSH
• gemcitabin MeSH
• invazivní růst nádoru MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• nádory močového měchýře neinvadující svalovinu * MeSH
• nádory močového měchýře * farmakoterapie   MeSH
• síťová metaanalýza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

BACKGROUND AND OBJECTIVE: Therapeutic options for patients with non-muscle-invasive bladder cancer (NMIBC) have traditionally been limited to intravesical immunotherapy or chemotherapy. A considerable number of new options have been investigated in recent years. Our aim was to review the efficacy and toxicity of novel therapeutic options (results already reported or currently under investigation) for patients with NMIBC. METHODS: We assessed the efficacy of various novel therapeutic options by examining key endpoints in diverse settings, including recurrence, progression, overall survival, disease-specific survival, and complete response. We identified the principal advantages and limitations for each option. Safety was predominantly evaluated as the incidence of grade ≥3 adverse events. Our investigation focused on evidence from scientific articles and congress abstracts published in English within the past 5 yr. KEY FINDINGS AND LIMITATIONS: To date, pembrolizumab, nadofaragene firadenovec, and the combination of BCG with N-803 have received US Food and Drug administration approval for the treatment of BCG-unresponsive carcinoma in situ of the bladder (with or without papillary tumours). Five phase 3 trials are recruiting BCG-naïve patients with high-risk NMIBC. There is increasing interest in an ablative rather than an adjuvant approach for patients with intermediate-risk NMIBC. CONCLUSIONS AND CLINICAL IMPLICATIONS: Novel drugs and device-assisted drug delivery systems are on the verge of changing the treatment of NMIBC. Novel intravesical options seem to have the same efficacy with fewer adverse events in comparison to systemic therapies. PATIENT SUMMARY: We reviewed new therapy options for non-muscle-invasive bladder cancer. Two agents (pembrolizumab and nadofaragene firadenovec) have been approved to date. Ongoing trials are assessing direct delivery of drugs in solution into the bladder. This route seems to have similar efficacy and fewer side effects than intravenous immunotherapy.

• MeSH
• invazivní růst nádoru MeSH
• lidé MeSH
• nádory močového měchýře neinvadující svalovinu MeSH
• nádory močového měchýře * farmakoterapie   patologie   MeSH
• systémy cílené aplikace léků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Adjuvantní intravezikální léčba je podle současných doporučených postupů indikována u každého pacienta se svalovinu detruzoru neinfiltrujícím karcinomem močového měchýře. U pacientů s nízkým rizikem formou jednorázové bezprostřední instilace, v ostatních rizikových skupinách formou další následné instilační léčby ve smyslu intravezikální chemoterapie či intravezikální léčby vakcínou BCG. Indikace k intravezikální léčbě by měla vycházet z určení individuálního rizika recidivy a progrese nádoru. Jednorázová instilace cytostatika bezprostředně po transuretrální resekci tumoru by měla být podána u všech pacientů, kde předpokládáme nádor s nízkým a středním rizikem. U pacientů s nízce rizikovým tumorem Ta je tento způsob adjuvantní léčby dostatečný. U všech ostatních pacientů by měla navázat další následná intravezikální léčba - u nemocných se středně rizikovým nádorem adjuvantní instilační léčba vakcínou BCG v plné dávce a délce podávání 1 rok či adjuvantní intravezikální chemoterapie v délce trvání do 1 roku. Pacienti s vysokým rizikem by měli být léčeni intravezikální instilační léčbou vakcínou BCG v plné dávce a délce trvání 1-3 roky. U pacientů s vysokým rizikem progrese je možné uvážit neodkladnou radikální cystektomii jako alternativu k instilační léčbě. U pacientů refrakterních k léčbě vakcínou BCG by měla být provedena radikální cystektomie.

According to current guidelines, intravesical treatment should be offered to every patient with non-muscle invasive bladder cancer. The type of intravesical therapy should be based on the risk of recurrence and progression. In patients with low risk Ta tumours, a single intravesical instillation, immediately following resection, is recommended. A full course of intravesical chemotherapy or BCG instillation is recommended in all remaining risk groups. In patients with intermediate-risk tumours, one immediate post-resection administration of intravescial chemotherapy should be followed by one year of full course BCG treatment, or additional intravesical chemotherapy for a maximum of one year. In patients with high--risk tumours, full-dose intravesical BCG for 1-3 years should be administered. In tumours with a high risk of progression, immediate radical cystectomy should be considered. In BCG refractory tumours, a radical cystectomy should be performed as well.

• MeSH
• adjuvantní chemoterapie * metody   MeSH
• aplikace intravezikální * MeSH
• BCG vakcína * aplikace a dávkování   terapeutické užití   MeSH
• cytostatické látky aplikace a dávkování   MeSH
• hodnocení rizik MeSH
• imunoterapie metody   MeSH
• karcinom in situ MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• nádory močového měchýře * terapie   MeSH
• pooperační péče metody   MeSH
• postup MeSH
• prognóza MeSH
• recidiva MeSH
• sekundární prevence MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

CONTEXT: The first European Association of Urology (EAU) guidelines on bladder cancer were published in 2002 [1]. Since then, the guidelines have been continuously updated. OBJECTIVE: To present the 2013 EAU guidelines on non-muscle-invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION: Literature published between 2010 and 2012 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the levels of evidence and grades of recommendation were assigned. EVIDENCE SYNTHESIS: Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the EORTC scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive one immediate instillation of chemotherapy followed by 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or by further instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-refractory tumours. The long version of the guidelines is available from the EAU Web site: http://www.uroweb.org/guidelines/. CONCLUSIONS: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. PATIENT SUMMARY: The EAU Panel on Non-muscle Invasive Bladder Cancer released an updated version of their guidelines. Current clinical studies support patient selection into different risk groups; low, intermediate and high risk. These risk groups indicate the likelihood of the development of a new (recurrent) cancer after initial treatment (endoscopic resection) or progression to more aggressive (muscle-invasive) bladder cancer and are most important for the decision to provide chemo- or immunotherapy (bladder installations). Surgical removal of the bladder (radical cystectomy) should only be considered in patients who have failed chemo- or immunotherapy, or who are in the highest risk group for progression.

• MeSH
• adjuvantní chemoterapie MeSH
• antitumorózní látky aplikace a dávkování   MeSH
• aplikace intravezikální MeSH
• BCG vakcína aplikace a dávkování   MeSH
• biopsie normy   MeSH
• cystektomie normy   MeSH
• cystoskopie normy   MeSH
• diagnostické techniky urologické normy   MeSH
• invazivní růst nádoru MeSH
• karcinom diagnóza   patologie   chirurgie   MeSH
• lidé MeSH
• medicína založená na důkazech normy   MeSH
• nádory močového měchýře diagnóza   patologie   chirurgie   MeSH
• prediktivní hodnota testů MeSH
• progrese nemoci MeSH
• společnosti lékařské normy   MeSH
• staging nádorů MeSH
• stupeň nádoru MeSH
• urologie normy   MeSH
• urotel patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Evropa MeSH

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

• MeSH
• adjuvantní chemoterapie MeSH
• antitumorózní látky aplikace a dávkování   škodlivé účinky   MeSH
• aplikace intravezikální MeSH
• BCG vakcína aplikace a dávkování   škodlivé účinky   MeSH
• časové faktory MeSH
• cystektomie škodlivé účinky   MeSH
• hodnocení rizik MeSH
• invazivní růst nádoru MeSH
• karcinom diagnóza   epidemiologie   sekundární   terapie   MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• medicína založená na důkazech MeSH
• nádory močového měchýře diagnóza   epidemiologie   patologie   terapie   MeSH
• rizikové faktory MeSH
• rozvrh dávkování léků MeSH
• staging nádorů MeSH
• urotel patologie   MeSH
• výběr pacientů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• směrnice pro lékařskou praxi MeSH

BACKGROUND: Bacillus Calmette-Guérin (BCG) immunotherapy, the standard adjuvant intravesical therapy for some intermediate and most high-risk non-muscle invasive bladder cancers (NMIBCs), suffers from a heterogenous response rate. Molecular markers to help guide responses are scarce and currently not used in the clinical setting. METHODS: To identify novel biomarkers and pathways involved in response to BCG immunotherapy, we performed a genome-wide DNA methylation analysis of NMIBCs before BCG therapy. Genome-wide DNA methylation profiles of DNA isolated from tumors of 26 BCG responders and 27 failures were obtained using the Infinium MethylationEPIC BeadChip. RESULTS: Distinct DNA methylation patterns were found by genome-wide analysis in the two groups. Differentially methylated CpG sites were predominantly located in gene promoters and gene bodies associated with bacterial invasion of epithelial cells, chemokine signaling, endocytosis, and focal adhesion. In total, 40 genomic regions with a significant difference in methylation between responders and failures were detected. The differential methylation state of six of these regions, localized in the promoters of the genes GPR158, KLF8, C12orf42, WDR44, FLT1, and CHST11, were internally validated by bisulfite-sequencing. GPR158 promoter hypermethylation was the best predictor of BCG failure with an AUC of 0.809 (p-value < 0.001). CONCLUSIONS: Tumors from BCG responders and BCG failures harbor distinct DNA methylation profiles. Differentially methylated DNA regions were detected in genes related to pathways involved in bacterial invasion of cells or focal adhesion. We identified candidate DNA methylation biomarkers that may help to predict patient prognosis after external validation in larger, well-designed cohorts.

• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• BCG vakcína terapeutické užití   MeSH
• celogenomová asociační studie MeSH
• CpG ostrůvky MeSH
• heterochromatin MeSH
• imunoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA * MeSH
• nádorové biomarkery genetika   MeSH
• nádory močového měchýře farmakoterapie   genetika   patologie   MeSH
• promotorové oblasti (genetika) MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH