PURPOSE OF REVIEW: Upper tract urothelial carcinoma (UTUC) is a rare malignancy posing significant diagnostic and management challenges. This review provides an overview of the evidence supporting various imaging modalities and offers insights into future innovations in UTUC imaging. RECENT FINDINGS: With the growing use of advancements in computed tomography (CT) technologies for both staging and follow-up of UTUC patients, continuous innovations aim to enhance performance and minimize the risk of excessive exposure to ionizing radiation and iodinated contrast medium. In patients unable to undergo CT, magnetic resonance imaging serves as an alternative imaging modality, though its sensitivity is lower than CT. Positron emission tomography, particularly with innovative radiotracers and theranostics, has the potential to significantly advance precision medicine in UTUC. Endoscopic imaging techniques including advanced modalities seem to be promising in improved visualization and diagnostic accuracy, however, evidence remains scarce. Radiomics and radiogenomics present emerging tools for noninvasive tumor characterization and prognosis. SUMMARY: The landscape of imaging for UTUC is rapidly evolving, with significant advancements across various modalities promising improved diagnostic accuracy, patient outcomes, and safety.
- MeSH
- karcinom z přechodných buněk * diagnóza diagnostické zobrazování terapie patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- nádory ledvin diagnostické zobrazování terapie diagnóza patologie MeSH
- nádory močovodu diagnostické zobrazování diagnóza terapie patologie MeSH
- počítačová rentgenová tomografie metody MeSH
- pozitronová emisní tomografie metody MeSH
- staging nádorů MeSH
- urologické nádory diagnóza diagnostické zobrazování terapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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
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
Onkologie, ISSN 1802-4475 Ročník 18, 2024, Supplementum C
37 stran : barevné ilustrace ; 21 cm
Sborník prací, které se zaměřují na terapii urologických nádorů pomocí přípravku enfortumab vedotin (Padcev). Určeno odborné veřejnosti.
- Klíčová slova
- enfortumab vedotin, Padcev,
- MeSH
- cílená molekulární terapie MeSH
- cytostatické látky MeSH
- humanizované monoklonální protilátky MeSH
- imunokonjugáty MeSH
- karcinom z přechodných buněk MeSH
- protinádorové látky imunologicky aktivní MeSH
- urologické nádory MeSH
- Publikační typ
- kazuistiky MeSH
- sborníky MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- farmacie a farmakologie
- farmakoterapie
- onkologie
OBJECTIVE: Sparse data exist on the impact of upper urinary tract (UUT) decompression on the risk of UUT recurrence in patients with bladder cancer (BCa). This study aims to evaluate whether Double J stenting (DJS) can increase the risk of UUT recurrence compared to percutaneous nephrostomy (PCN) placement. MATERIALS AND METHODS: We retrospectively analyzed data from 1550 patients with cTa-T3NanyM0 BCa who underwent radical cystectomy (RC) between at 12 tertiary care centers (1990-2020). Patients with complete follow-up, no prior history of UUT cancer, and who required UUT decompression for preoperative hydronephrosis were selected. Hydronephrosis grade was defined according to established scoring systems. UUT recurrence was diagnosed through imaging, urinary cytology, and confirmed by selective cytology and ureteroscopy when possible. Propensity scores were computed to determine overlap weights and balance groups. Kaplan-Meier analyses estimated UUT recurrence-free survival (RFS), cancer-specific (CSS), and overall survival (OS) before and after weighting. Cox regression analyses before and after weighting were fitted to predict UUT recurrence. RESULTS: Of 524 included patients, 132 (25%) and 392 (75%) patients were managed with DJS and PCN placement, respectively. Patients who received PCN had higher grade (≥ 3) of obstruction (34% vs. 14%) and pT3-4 tumors (70% vs. 36%) than patients with DJS. During a median follow-up of 19 months, 2-years UUT-RFS did not differ between groups (95% for PCN vs 92% for DJS, weighted HR 1.41, 95% CI, 0.55-3.59). There was no difference in 2-years weighted CSS (74% vs. 74%) and OS (67% vs 69%). Main limitations were the short follow-up and inclusion of patients uniquely undergoing RC. CONCLUSIONS: These results suggest that ureteral DJS does not increase the risk of developing UUT recurrence in BCa patients with hydronephrosis requiring UUT decompression. However, UUT recurrence was rare, and associations were weak, with findings susceptible to bias. Randomized trials are needed to validate these results.
- MeSH
- cystektomie MeSH
- hydronefróza etiologie MeSH
- karcinom z přechodných buněk chirurgie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře * chirurgie patologie MeSH
- nádory močovodu chirurgie patologie MeSH
- následné studie MeSH
- perkutánní nefrostomie MeSH
- retrospektivní studie MeSH
- sekundární malignity chirurgie patologie MeSH
- senioři MeSH
- stenty * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- karcinom z přechodných buněk * farmakoterapie MeSH
- lidé MeSH
- monoklonální protilátky * terapeutické užití aplikace a dávkování MeSH
- nádory močového měchýře * farmakoterapie MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- urologické nádory farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Adjuvant immune checkpoint inhibitor therapies have radically altered the treatment landscape for renal cell carcinoma and urothelial carcinoma. However, studies have reported negative data regarding adjuvant immune checkpoint inhibitor therapies. Thus, this study aimed to assess the role of adjuvant immune checkpoint inhibitor therapy for both renal cell carcinoma and urothelial carcinoma. A systematic review and network meta-analysis were conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases were searched for articles published as of February 2023. Studies were deemed eligible if they evaluated disease-free survival in patients with renal cell carcinoma and urothelial carcinoma receiving adjuvant immune checkpoint inhibitor therapy. Five studies met the inclusion criteria. In a network meta-analysis, pembrolizumab was shown to be the most effective regimen for patients with renal cell carcinoma, whereas nivolumab was found to be the most effective regimen for patients with urothelial carcinoma. Additionally, these results were consistently observed in a sub-analysis of the T stage. The present analysis provides findings that support the usefulness of adjuvant nivolumab therapy in urothelial carcinoma and adjuvant pembrolizumab therapy in renal cell carcinoma, in agreement with the currently available guidelines. However, the caveat is that the randomized controlled trials included in this analysis differed in important respects despite being similar in study design. Therefore, with these differences in mind, care needs to be taken when selecting patients for these immune checkpoint inhibitor therapies to maximize their benefits.
- MeSH
- adjuvancia imunologická terapeutické užití MeSH
- imunoterapie metody MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- karcinom z přechodných buněk * farmakoterapie MeSH
- karcinom z renálních buněk * farmakoterapie MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie MeSH
- nádory močového měchýře * MeSH
- nivolumab terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- síťová metaanalýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
BACKGROUND: Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy. OBJECTIVE: The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2EV study. PATIENTS AND METHODS: The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. RESULTS: Median OS and PFS were 12.7 (95% CI 10.2-14.1) and 7.9 (95% CI 6.4-9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1-11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia. CONCLUSIONS: The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab.
- MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití farmakologie MeSH
- karcinom z přechodných buněk farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- monoklonální protilátky * terapeutické užití farmakologie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití farmakologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- urologické nádory farmakoterapie 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
Na akutní urologickou ambulanci se dostavil 93letý pacient stěžující si na obtékající permanentní močový katétr a bolesti podbřišku. Mezi pro případ relevantní pacientovy diagnózy patřily velmi vysoce rizikový uroteliální karcinom močového měchýře po opakovaných transuretrálních resekcích a recentně také výplaších intravezikální chemoterapií, diabetes mellitus druhého typu na dvojkombinaci perorálních antidiabetik a recidivující močové infekce. Pro suspekci na perforaci močového měchýře či komunikaci močového měchýře se střevem, při sterkorálně zapáchající moči, bylo doplněno kontrastní CT s vylučovací fází a CT cystogram. Perforaci či píštěl jsme neprokázali, avšak na základě zobrazovacích vyšetření jsme stanovili diagnózu emfyzematózní cystitidy. Tato kazuistika má za cíl upozornit na tuto vzácnou, mnohdy nenápadně se projevující, avšak potenciálně život ohrožující urologickou nosologickou jednotku.
A 93-year-old male presented to the urology outpatient clinic with complaints of a leaking indwelling urinary catheter and suprapubic pain. Our patient had a history of urothelial carcinoma of the bladder, for which he has undergone multiple transurethral resections and recent intravesical chemotherapy instillations. He also has type 2 diabetes mellitus, which is managed with a combination of oral antidiabetic medications and has a history of recurrent urinary tract infections. A CT scan with contrast and an excretory phase and CT cystogram were performed to rule out bladder perforation or a bladder-bowel fistula in the presence of foul-smelling urine. The CT scan did not show any evidence of colo-vesicalor fistula, but it did show evidence of emphysematous cystitis. This case report aims to highlight this rare, often presenting in a subtle manner, but life-threatening urological disease.
- Klíčová slova
- emfyzematózní cystitida,
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- aplikace intravezikální MeSH
- cystitida * diagnóza farmakoterapie terapie MeSH
- diabetes mellitus 2. typu farmakoterapie komplikace MeSH
- diagnostické zobrazování metody MeSH
- Escherichia coli patogenita MeSH
- hypoglykemika farmakologie terapeutické užití MeSH
- karcinom z přechodných buněk chirurgie farmakoterapie MeSH
- lidé MeSH
- nádory močového měchýře * chirurgie farmakoterapie MeSH
- senioři nad 80 let MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH