BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.
- MeSH
- antigeny nádorové MeSH
- dospělí MeSH
- karboanhydrasa IX metabolismus genetika MeSH
- karcinom z renálních buněk * patologie metabolismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitochondriální DNA genetika metabolismus MeSH
- mitochondrie * metabolismus patologie genetika MeSH
- mutace MeSH
- nádorový supresorový protein VHL genetika metabolismus MeSH
- nádory ledvin * patologie metabolismus genetika MeSH
- respirační komplex II * metabolismus genetika MeSH
- senioři MeSH
- sukcinátdehydrogenasa genetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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
PURPOSE OF REVIEW: This review explores the design and endpoints of perioperative platforms in clinical trials for muscle-invasive bladder cancer (MIBC). RECENT FINDINGS: The choice of clinical trial design in perioperative platforms for MIBC must align with specific research objectives to ensure robust and meaningful outcomes. Novel designs in perioperative platforms for MIBC integrate bladder-sparing approaches. Primary endpoints such as pathological complete response and disease-free survival are highlighted for their role in expediting trial results in perioperative setting. Incorporating patient-reported outcomes is important to inform healthcare decision makers about the outcomes most meaningful to patients. Given the growing body of evidence, potential biomarkers, predictive and prognostic tools should be considered and implemented when designing trials in perioperative platforms for MIBC. SUMMARY: Effective perioperative platforms for MIBC trials are critical in enhancing patient outcomes. The careful selection and standardization of study designs and endpoints in the perioperative platform are essential for the successful implementation of new therapies and the advancement of personalized treatment approaches in MIBC.
- MeSH
- cystektomie metody škodlivé účinky MeSH
- invazivní růst nádoru * MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- nádory močového měchýře * chirurgie patologie terapie mortalita MeSH
- perioperační péče metody normy MeSH
- stanovení cílového parametru MeSH
- výsledek terapie MeSH
- výzkumný projekt MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. PATIENTS AND METHODS: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). CONCLUSIONS: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.
- MeSH
- adjuvancia imunologická terapeutické užití MeSH
- aplikace intravezikální MeSH
- BCG vakcína * terapeutické užití MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * farmakoterapie patologie mortalita MeSH
- retrospektivní studie MeSH
- senioři MeSH
- statiny * terapeutické užití 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
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
PURPOSE OF REVIEW: The aim of the systematic review is to assess AI's capabilities in the genetics of prostate cancer (PCa) and bladder cancer (BCa) to evaluate target groups for such analysis as well as to assess its prospects in daily practice. RECENT FINDINGS: In total, our analysis included 27 articles: 10 articles have reported on PCa and 17 on BCa, respectively. The AI algorithms added clinical value and demonstrated promising results in several fields, including cancer detection, assessment of cancer development risk, risk stratification in terms of survival and relapse, and prediction of response to a specific therapy. Besides clinical applications, genetic analysis aided by the AI shed light on the basic urologic cancer biology. We believe, our results of the AI application to the analysis of PCa, BCa data sets will help to identify new targets for urological cancer therapy. The integration of AI in genomic research for screening and clinical applications will evolve with time to help personalizing chemotherapy, prediction of survival and relapse, aid treatment strategies such as reducing frequency of diagnostic cystoscopies, and clinical decision support, e.g., by predicting immunotherapy response. These factors will ultimately lead to personalized and precision medicine thereby improving patient outcomes.
- MeSH
- biologické markery MeSH
- lidé MeSH
- lokální recidiva nádoru genetika MeSH
- nádory močového měchýře * diagnóza genetika terapie MeSH
- prostata * MeSH
- recidiva MeSH
- umělá inteligence MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
BACKGROUND: In the era of standardized outcome reporting, it remains unclear if widely used comorbidity and health status indices can enhance predictive accuracy for morbidity and long-term survival outcomes after radical cystectomy (RC). PATIENTS AND METHODS: In this monocentric study, we included 468 patients undergoing open RC with pelvic lymph node dissection for bladder cancer between January 2009 and December 2017. Postoperative complications were meticulously assessed according to the EAU guideline criteria for standardized outcome reporting. Multivariable regression models were fitted to evaluate the ability of ASA physical status (ASA PS), Charlson comorbidity index (± age-adjustment) and the combination of both to improve prediction of (A) 30-day morbidity key estimates (major complications, readmission, and cumulative morbidity as measured by the Comprehensive Complication index [CCI]) and (B) secondary mortality endpoints (overall [OM], cancer-specific [CSM], and other-cause mortality [OCM]). RESULTS: Overall, 465 (99%) and 52 (11%) patients experienced 30-day complications and major complications (Clavien-Dindo grade ≥IIIb), respectively. Thirty-seven (7.9%) were readmitted within 30 days after discharge. Comorbidity and health status indices did not improve the predictive accuracy for 30-day major complications and 30-day readmission of a reference model but were associated with 30-day CCI (all P < .05). When ASA PS and age-adjusted Charlson index were combined, ASA PS was no longer associated with 30-day CCI (P = .1). At a median follow-up of 56 months (IQR 37-86), OM, CSM, and 90-day mortality were 37%, 24%, and 2.9%, respectively. Both Charlson and age-adjusted Charlson index accurately predicted OCM (all P < .001) and OM (all P ≤ .002) but not CSM (all P ≥ .4) and 90-day mortality (all P > .05). ASA PS was not associated with oncologic outcomes (all P ≥ .05). CONCLUSION: While comorbidity and health status indices have a role in predicting OCM and OM after RC, their importance in predicting postoperative morbidity is limited. Especially ASA PS performed poorly. This highlights the need for procedure-specific comorbidity assessment rather than generic indices.
Diagnostic work-up and risk stratification in patients with bladder cancer before and after treatment must be refined to optimize management and improve outcomes. MRI has been suggested as a non-invasive technique for bladder cancer staging and assessment of response to systemic therapy. The Vesical Imaging-Reporting And Data System (VI-RADS) was developed to standardize bladder MRI image acquisition, interpretation and reporting and enables accurate prediction of muscle-wall invasion of bladder cancer. MRI is available in many centres but is not yet recommended as a first-line test for bladder cancer owing to a lack of high-quality evidence. Consensus-based evidence on the use of MRI-VI-RADS for bladder cancer care is needed to serve as a benchmark for formulating guidelines and research agendas until further evidence from randomized trials becomes available.
