BACKGROUND AND OBJECTIVE: Non-muscle-invasive bladder cancer (NMIBC) poses a significant clinical challenge, particularly when failing bacillus Calmette-Guérin (BCG) therapy, necessitating alternative treatments. Despite radical cystectomy being the recommended treatment, many patients are unfit or unwilling to undergo this invasive procedure, highlighting the need for effective bladder-sparing therapies. This review aims to summarize and report the evidence on the efficacy and to estimate the costs of bladder-preserving strategies used in NMIBC recurrence after failure of intravesical BCG therapy. METHODS: We systematically searched online databases for prospective studies investigating intravesical therapy, systemic therapy, or combination of both in patients treated previously with BCG. Owing to significant heterogeneity across the studies, a meta-analysis was inappropriate. A sensitivity analysis was performed in an exploratory manner. We used a decision-analytic Markov model to compare novel U.S. Food and Drug Administration-approved treatments with a 2-yr time horizon. KEY FINDINGS AND LIMITATIONS: A total of 57 studies published between 1998 and 2024, with 68 unique study arms and consisting of 2589 patients, were identified. The 3-mo overall response rate (ORR) across all studies, complete response rate (CRR) in concomitant carcinoma in situ (CIS) or CIS only disease, and recurrence-free rate (RFR) in papillary disease were estimated to be 52.4% (95% confidence interval [CI]: 45.4-59.2), 52.8% (95% CI: 42.9-62.6), and 26.4% (95% CI: 13.3-45.6), respectively. The 12-mo ORR, CRR, and RFR were estimated to be 78% (95% CI: 52.9-91.8), 27.8% (95% CI: 21.3-35.4), and 25.4% (95% CI: 18.2-34.2), respectively. The progression rate was estimated to be 13% (95% CI: 9-18.2). The mean proportion of patients treated with radical cystectomy was estimated to be 24.7 (range 0-85.7). The reported toxicity grades were overall mild, with a median of 3.4% (range 0-33.3%) participants experiencing a dose limiting toxicity. Compared with using radical cystectomy to treat patients failing BCG therapy, at a willingness-to-pay threshold of 100 000 USD, nadofaragene firadenovec was cost effective, with an incremental cost-effectiveness ratio (ICER) of 10 014 USD per quality-adjusted life year (QALY), while nogapendekin alfa inbakicept was less cost effective than nadofaragene firadenovec (ICER of 44 602 USD per QALY). Pembrolizumab, which dominated, was both less costly and more effective than the other strategies. CONCLUSIONS AND CLINICAL IMPLICATIONS: Salvage bladder-sparing therapies show a response rate of around 50% at 3 mo in patients with NMIBC failing BCG. However, long-term data are heterogeneous. Nevertheless, recently developed agents show promising tumor control activity. In the rapidly evolving landscape of urothelial cancer, some of these treatment strategies might be cost effective and improve patients' quality of life. The findings of our review highlight the need for novel, more effective therapeutic strategies. PATIENT SUMMARY: In this study, we reviewed the evidence on the efficacy of bladder-preserving strategies used in patients with bladder cancer recurrence after failing bacillus Calmette-Guérin (BCG) therapy. We found that these strategies show a response rate of around 50% at 3 mo. However, long-term data are heterogeneous. Nevertheless, recently developed agents show promising tumor control activity. In the rapidly evolving landscape of urothelial cancer, some of these treatment strategies might be cost effective and improve patients' quality of life.
- MeSH
- adjuvancia imunologická * terapeutické užití ekonomika MeSH
- analýza nákladů a výnosů * MeSH
- aplikace intravezikální MeSH
- BCG vakcína * terapeutické užití ekonomika MeSH
- invazivní růst nádoru MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * farmakoterapie patologie terapie ekonomika MeSH
- neúspěšná terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
BACKGROUND: Androgen-receptor signaling inhibitors (ARSIs) significantly improve survival in systemic therapy for advanced/metastatic prostate cancer (PCa) patients; however possible central nervous system (CNS) toxicity is an unaddressed concern. We aimed to assess and compare the incidence of CNS-related adverse events (AEs) secondary to the treatment of PCa patients with different ARSIs. MATERIALS: In August 2023, a comprehensive seach was conducted in three databases for randomized controlled trials (RCTs) of PCa patients receiving ARSIs plus ADT. The primary endpoints included mental impairment, cognitive impairment, seizure, fatigue, and falls. RESULTS: Twenty-six RCTs, comprising 20,328 patients, were included in meta-analyses and network meta-analyses (NMAs). ARSIs increased the risk of mental impairment (RR: 1.72; 95% CI, 1.09-2.71), cognitive impairment (RR: 2.25; 95% CI, 1.78-2.86), seizure (RR: 2.20, 95% CI, 1.09-4.45), fatigue (RR: 1.31, 95% CI, 1.20-1.43), and falls (RR: 2.07, 95% CI, 1.60-2.67) compared to standard of care (SOC). Based on NMAs, Enzalutamide showed a significant increase in risk for all assessed CNS-related AEs, while Abiraterone demonstrated significant risk increases in cognitive impairment, fatigue, and falls. Conversely, Darolutamide did not exhibit significant increases in risk for any CNS-related AEs, except for fatigue. CONCLUSIONS: The addition of ARSIs to ADT increased all examined CNS-related AEs compared to SOC. Each ARSI is associated with a distinct profile of CNS-related AEs. Careful patient selection and monitoring for CNS sequelae is necessary to achieve the best quality of life in patients on ARSI + ADT for PCa.
- MeSH
- antagonisté androgenních receptorů * škodlivé účinky aplikace a dávkování terapeutické užití MeSH
- benzamidy MeSH
- fenylthiohydantoin škodlivé účinky aplikace a dávkování MeSH
- lidé MeSH
- nádory prostaty * farmakoterapie patologie MeSH
- nemoci centrálního nervového systému chemicky indukované MeSH
- nitrily MeSH
- pyrazoly MeSH
- randomizované kontrolované studie jako téma MeSH
- síťová metaanalýza * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled 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
Limited evidence exists about preserving neurovascular bundles during radical prostatectomy (RP) for high-risk prostate cancer (HRPCa) patients. Hence, we validated an existing algorithm predicting contralateral extraprostatic extension (cEPE) risk in unilateral high-risk cases. This algorithm aims to assist in determining the suitability of unilateral nerve-sparing RP. Among 264 patients, 48 (18%) had cEPE. The risk of cECE varied: 8%, 17.2%, and 30.8% for the low, intermediate, and high-risk groups, respectively. Despite a higher risk of cECE among individuals classified as low-risk in the development group compared to the validation group, our algorithm's superiority over always/never nerve-sparing RP was reaffirmed by decision curve analysis. Therefore, we conclude that bilateral excision may not always be justified in men with unilateral HRPCa. Instead, decisions can be based on our suggested nomogram.
- MeSH
- algoritmy * MeSH
- hodnocení rizik metody MeSH
- léčba šetřící orgány * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty * chirurgie patologie MeSH
- nomogramy MeSH
- prostata chirurgie inervace patologie MeSH
- prostatektomie * metody MeSH
- roboticky asistované výkony * metody MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie 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 AND OBJECTIVE: The role of genetic variants in response to systemic therapy in muscle-invasive bladder cancer (MIBC) is still elusive. We assessed variations in genes involved in DNA damage repair (DDR) before and after cisplatin-based neoadjuvant chemotherapy (NAC) and correlation of alteration patterns with DNA damage and response to therapy. METHODS: Matched tissue from 46 patients with MIBC was investigated via Ion Torrent-based next-generation sequencing using a self-designed panel of 30 DDR genes. Phosphorylation of γ-histone 2A.X (H2AX) was analyzed via immunohistochemistry to evaluate DNA damage. Genetic variants were analyzed along with clinical data and quantitative phospho-H2AX data using the Kaplan-Meier method, Cox regression analysis, and factor analysis of mixed data. KEY FINDINGS AND LIMITATIONS: Twenty-five patients (54%) had a response (
- Publikační typ
- časopisecké články 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.
Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.
