PURPOSE OF REVIEW: Bladder cancer (BC) is a highly heterogenous disease comprising tumours of various molecular subtypes and histologic variants. This heterogeneity represents a major challenge for the development of novel therapeutics. Preclinical models that closely mimic in vivo tumours and reflect their diverse biology are indispensable for the identification of therapies with specific activity in various BC subtypes. In this review, we summarize efforts and progress made in this context during the last 24 months. RECENT FINDINGS: In recent years, one main focus was laid on the development of patient-derived BC models. Patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) were demonstrated to widely recapitulate the molecular and histopathological characteristics, as well as the drug response profiles of the corresponding tumours of origin. These models, thus, represent promising tools for drug development and personalized medicine. Besides PDXs, syngenic in vivo models are of growing importance. Since these models are generated using immunocompetent hosts, they can, amongst others, be used to develop novel immunotherapeutics and to evaluate the impact of the immune system on drug response and resistance. SUMMARY: In the past two years, various in vivo and in vitro models closely recapitulating the biology and heterogeneity of human bladder tumours were developed.

• MeSH
• individualizovaná medicína metody   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• nádory močového měchýře * terapie   patologie   farmakoterapie   genetika   imunologie   MeSH
• organoidy MeSH
• protinádorové látky terapeutické užití   farmakologie   MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protinádorové látky MeSH

PURPOSE: Data about optimal management of plasmacytoid (PCV) bladder cancer patients are extremely scarce and limited by sample size. We focused on PCV bladder cancer patients to explore the effect of radical cystectomy (RC) and chemotherapy in non-metastatic (T 2-4N0-3M0), as well as in metastatic (TanyNanyM1) subgroups. METHODS: Using the Surveillance, Epidemiology and End Results database (2000-2016), we identified 332 PCV patients with muscle-invasive disease or higher (≥ T2N0M0). Kaplan-Meier plots and Cox regression models addressed cancer-specific mortality (CSM). RESULTS: In 332 PCV patients, median age was 68 years (Interquartile range [IQR]:58-76). Of those, 252 were non-metastatic patients (76%) vs 80 were metastatic patients (24%), at presentation. Of non-metastatic patients, 142 (56%) underwent RC and 131 (52%) underwent chemotherapy. Chemotherapy did not improve CSM in non-metastatic PCV. Conversely, RC was associated with lower CSM (hazard ratio [HR]: 0.51, p = 0.002). Median CSM-free survival was 48 vs 38 months for RC treated vs RC not treated. Of metastatic patients, 22 (28%) underwent RC and 42 (52%) underwent chemotherapy. Both chemotherapy and RC improved CSM in metastatic PCV. Median CSM-free survival was 12 vs 7 months for RC treated vs RC not treated (HR: 0.27, p < 0.001). Median CSM-free survival was 11 vs 4 months for chemotherapy exposed vs chemotherapy naïve (HR: 0.32, p = 0.002). CONCLUSIONS: Although RC resulted in lower CSM, chemotherapy failed to show that effect in non-metastatic PCV patients. Conversely, both chemotherapy and RC resulted in statistically significantly lower CSM in metastatic PCV patients.

• Klíčová slova
• Bladder, Cancer, Chemotherapy, Plasmacytoid, Radical cystectomy, Signet ring cell,
• MeSH
• cystektomie metody   MeSH
• karcinom z přechodných buněk * farmakoterapie   chirurgie   MeSH
• lidé MeSH
• močový měchýř patologie   MeSH
• nádory močového měchýře * farmakoterapie   chirurgie   MeSH
• program SEER MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). METHODS: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. RESULTS: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). CONCLUSION: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.

• Klíčová slova
• CG, Immediate radical cystectomy, Immunotherapy, Non-muscle-invasive bladder cancer, T1,
• MeSH
• BCG vakcína terapeutické užití   MeSH
• cystektomie MeSH
• imunoterapie MeSH
• invazivní růst nádoru patologie   MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• močový měchýř patologie   MeSH
• nádory močového měchýře * farmakoterapie   chirurgie   MeSH
• retrospektivní studie MeSH
• spinocelulární karcinom * patologie   chirurgie   MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• BCG vakcína MeSH