BACKGROUND AND OBJECTIVE: There are limited data on real-world outcomes for patients with advanced or metastatic urothelial cancer (mUC) since immune checkpoint inhibitors (ICIs) became available. Our objective was to analyze outcomes for patients with mUC since ICIs became available. METHODS: We performed a retrospective analysis of 131 patients with mUC attending the outpatient clinic of a single tertiary care center who received systemic therapy between June 2017 and July 2021 with follow-up up to December 2022. Summary and descriptive statistics were calculated for categorical and continuous variables. The Kaplan-Meier method was applied to calculate survival, and a Cox proportional-hazards model was used to explore associations between clinical variables and outcomes. KEY FINDINGS AND LIMITATIONS: The median patient age was 68 yr (range 35-90). The first systemic therapy administered was platinum-based in 79% of cases and ICI-based in 21%. Some 61% of the cohort received a second systemic treatment, with 75% of these an ICI. Median overall survival for the entire cohort was 24 mo (interquartile range 9-35). Patients on ICI therapy for ≥6 mo had median overall survival of 59 mo (95% confidence interval 39 mo-not reached). Metastatic sites on initiation of ICI therapy and C-reactive protein kinetics were prognostic in patients receiving ICIs. Limitations include the retrospective design and inherent selection bias. CONCLUSIONS AND CLINICAL IMPLICATIONS: More than 60% of patients with mUC received second-line treatment, and 75% of these received an ICI. Patients staying on immunotherapy for more than 6 mo have substantially better outcomes in comparison to patients with less time on immunotherapy and historical cohorts. PATIENT SUMMARY: We looked at the lines of therapy and outcomes for patients with advanced or metastatic cancer of the urinary tract, starting from when immunotherapy drugs called immune checkpoint inhibitors (ICIs) became available. We found that 60% of patients have received second-line therapy, which is a double the rate in comparison to historical groups of patients. Patients with long-term ICI therapy (>6 months) had significantly better outcomes, with a median survival of more than 3 years.

• MeSH
• dospělí MeSH
• imunoterapie * metody   MeSH
• inhibitory kontrolních bodů * terapeutické užití   MeSH
• karcinom z přechodných buněk * farmakoterapie   sekundární   patologie   MeSH
• lékařská praxe - způsoby provádění statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• míra přežití MeSH
• nádory močového měchýře * farmakoterapie   patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• urologické nádory farmakoterapie   patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Immune checkpoint inhibitors (ICIs) are an important therapeutic pillar in metastatic urothelial carcinoma (mUC). The occurrence of immune-related adverse events (irAEs) appears to be associated with improved outcomes in observational studies. However, these associations are likely affected by immortal time bias and do not represent causal effects. The aim of this study was to assess the effect of irAEs on outcomes while correcting for immortal time bias, using target trial emulation (TTE). METHODS: TTE was contrasted to adjusted naïve and time-updated Cox models. We performed a multi-institutional retrospective study involving mUC patients under ICI. The primary objective was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Secondary endpoints included the influence of irAEs on objective response rates (ORRs) to ICI and the influence of systemic corticosteroids on outcomes. RESULTS: Among 335 patients (median age: 69 yrs), 69.6% received ICI in the second line or further lines. During a median follow-up of 21.1 months, 122 (36.4%) patients developed irAEs of any grade (grade ≥ 3: 14.9%). Hazard ratios (HRs) for PFS ranged from 0.37 for naïve adjusted Cox model to 0.88 (95% confidence interval (CI), 0.59-1.30) with time-updated covariates, and from 0.41 to 1.10 (95% CI, 0.69-1.75) for OS. TTE accounting for immortal time bias yielded a HR of 1.02 (95% CI, 0.72-1.44) for PFS, and 0.90 (95% CI, 0.62-1.30) for OS. In contrast to the naïve Cox model (HR = 2.26, 95% CI 1.26-4.05), the presence of irAEs was no longer a predictive factor for improved ORR in time-updated Cox models (HR = 1.27, 95% CI 0.68-2.36) and TTE (HR = 1.43, 95% CI 0.89-2.29). In patients with irAEs, systemic corticosteroids did not negatively impact survival. CONCLUSION: Using TTE, we were able to show that the occurrence of irAEs is no longer associated with better survival or improved response rates to ICI in mUC patients, in contrast to the naïve analysis. These findings demonstrate that TTE is a suitable formal framework to avoid immortal time bias in studies with time-dependent non-interventional exposures.

• MeSH
• inhibitory kontrolních bodů * škodlivé účinky   terapeutické užití   MeSH
• karcinom z přechodných buněk farmakoterapie   mortalita   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory močového měchýře farmakoterapie   mortalita   imunologie   patologie   MeSH
• nežádoucí účinky léčiv etiologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• urologické nádory farmakoterapie   mortalita   imunologie   patologie   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
• multicentrická studie MeSH

BACKGROUND: Electronic patient-reported outcomes (ePROs) have been shown to enhance healthcare quality by improving patient symptom management or quality of life (QoL). However, ePROs data for urothelial cancer (UC) patients receiving systemic therapies are scarce, and the application of ePROs in this patient cohort may need specific setups. This study tested the feasibility of ePROs for UC patients receiving systemic therapies in the outpatient clinic of a tertiary care center. PATIENTS AND METHODS: From January 2022 to April 2023, 30 UC patients receiving systemic cancer therapies received ePROs based on the Common Terminology Criteria for Adverse Events (CTCAE) and European Organization for Research and Treatment of Cancer Core Quality of Life questionnaires (EORTC QLQ-30) to report their symptoms and QoL during systemic therapy, in total, 125 questions for every therapy cycle. The proportion of patients adherent to the ePROs was assessed to evaluate feasibility, with a preset threshold of 50%. At least half of all treatment cycles with a minimum of two consecutive ePROs (corresponding to two successive therapy cycles) had to be completed to be counted as adherent, and a maximum of six successive therapy cycles was followed by ePROs. Descriptive statistics were calculated for clinical and demographic patient characteristics. T-test and chi-square-test analyses were performed to study the association between ePROs adherence and clinical or demographic factors. The digital process was closely monitored for procedural impediments that could occur. RESULTS: 21 (70%) of the included 30 patients adhered to the provided ePROs, significantly higher than the predetermined threshold of 50%. Adherence remained above 70% until the end of the observation period. A significant negative effect of immigration background on ePROs compliance was observed (p = 0.006). No other variables were significantly associated with ePROs compliance. CONCLUSIONS: In this study, ePROs were a feasible method to assess symptoms and QoL during the systemic cancer therapy of UC patients at our center. The compliance of patients with immigration backgrounds was the most significant barrier to using ePROs in this setting. However, the study is limited by the exclusion of patients without email access and the lack of assessment of physician compliance with the ePROs data, which may affect the generalizability and implementation of the findings.

• MeSH
• emigrace a imigrace MeSH
• hodnocení výsledků péče pacientem * MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie proveditelnosti * MeSH
• urologické nádory terapie   psychologie   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

CONTEXT: The optimal therapeutic agent with respect to metastatic sites is unclear in advanced urothelial carcinoma (UC). OBJECTIVE: To investigate the metastatic organotropism differential treatment response in patients with advanced or metastatic UC. EVIDENCE ACQUISITION: A systematic search and network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The primary endpoints of interest were the objective response rate, overall survival (OS), and progression-free survival with respect to different metastatic sites. EVIDENCE SYNTHESIS: Twenty-six trials comprising 9082 patients met our eligibility criteria, and a formal NMA was conducted. Durvalumab plus tremelimumab as first-line systemic therapy was significantly associated with better OS than chemotherapy in visceral metastasis (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.67-0.98). Pembrolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with visceral metastasis (HR 0.75, 95% CI 0.60-0.95). Atezolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with liver metastasis (in the population of >5% of tumor-infiltrating immune cells) and lymph node metastasis (HR 0.51, 95% CI 0.28-0.96, and HR 0.59, 95% CI 0.37-0.96, respectively). CONCLUSIONS: Administration of immune-oncology treatments with respect to metastatic sites in patients with advanced or metastatic UC might have a positive impact on survival outcomes in both the first- and the second-line setting. Nevertheless, further investigations focusing on metastatic organotropism differential response with reliable oncological outcomes are needed to identify the optimal management strategy for these patients. PATIENT SUMMARY: Although the supporting evidence for oncological benefits of therapeutic systemic agents with respect to metastatic sites is not yet strong enough to provide a recommendation in advanced or metastatic urothelial carcinoma, clinicians may take into account tumor organotropism only in discussion with the patient fully informed on the optimal treatment decision to be taken.

• MeSH
• karcinom z přechodných buněk * farmakoterapie   sekundární   mortalita   patologie   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• randomizované kontrolované studie jako téma * MeSH
• síťová metaanalýza * MeSH
• urologické nádory farmakoterapie   patologie   mortalita   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

Úvod: Chirurgická stratégia liečby tzv. "pochovaného penisu" závisí od etiológie, kvality postihnutých a okolitých tkanív, ako aj od celkovej anatómie vonkajších genitálií. Materiál a metódy: Autori popisujú chirurgický princíp rekonštrukcie sekundárneho „pochovaného penisu“ po predchádzajúcich parciálnych amputáciách pre lokalizovaný karcinóm penisu, s použitím autológneho dermoepidermálneho štepu (STSG), lipektómie v prepubickej oblasti a skrotoplastiky. 65 ročný pacient s biopticky verifikovaným skvamóznym karcinómom penisu podstúpil primárne glansektómiu s rekonštrukciou "neo‑glansu" pomocou STSG. Vzhľadom na lokálnu recidívu ochorenia, bola vykonaná parciálna amputácia s rekonštrukciou neo‑glansu s použitím penilnej časti močovej trubice. V bezprostrednom pooperačnom období, v dôsledku sekundárnej infekcie tkanív penisu, bola u pacienta diagnostikovaná vyššie uvedená klinická entita. Výsledky: Primárnym cieľom chirurgickej revízie je upraviť mikčné obtiaže/možnosť pohlavného styku ako aj optimalizovať psychicku pacienta. Z pohľadu krátkodobého sledovania, bol dosiahnutý želaný efekt. Záver: STSG je valídnou alternatívou u pacientov s komplexných postihnutím penisu a kompromitovanou anatómiou mieška.

Background: Surgical strategy of buried penis depends on the etiology and quality of affected and surrounding tissues, as well as overall anatomy of the external genitalia. Patients and methods: The authors describe the surgical principle of aquired buried penis reconstruction after previous partial amputations while using principles of split‑thickness skin grafting (STSG), prepubic lipectomy and scrotoplasty. A 65 yrs old patient after biopsy proven squamous cell carcinoma of the penis, had undergone a glansectomy with neo‑glans reconstruction using STSG. A second procedure with neo‑glans reconstruction and urethral flap reconfiguration was done, because of local recurrence. Shortly thereafter, due to a secondary infection of the penis shaft tissues, the patient developed a buried penis. Results: The surgical goal should repair voiding/sexual functioning and psychological well being, which have been achieved during short term follow‑up. Conclusion: STSG is a valid alternative for advanced cases in patients with already compromised scrotum.

• Klíčová slova
• pochovaný penis,
• MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory penisu * chirurgie   MeSH
• výsledek terapie MeSH
• zákroky plastické chirurgie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH