Bladder Cancer最新文献

Background: Gene polymorphisms can lead to differential production of inflammatory proteins associated with cancer development. Prior explorations of the association of single nucleotide polymorphisms (SNPs) of monocyte chemoattractant protein (MCP-1/CCL2) and its receptor, CCR2, to bladder cancer, yielded conflicting findings.

Objective: To analyze the distributions of the polymorphisms CCL2 rs1024611 and CCR2 rs1799864 between healthy controls and bladder cancer patients to determine if they are associated with bladder cancer risk in a cohort of Hispanic White and non-Hispanic White men.

Methods: DNA was isolated from blood obtained from healthy male controls (CCL2 n = 447; CCR2 n = 612) and from male bladder cancer patients (CCL2 n = 233; CCR2 n = 227). The CCL2 rs1024611 SNP and CCR2 rs1799864 SNP were genotyped using the TaqMan methodology. Multivariable logistic regression was used to determine associations between SNP genotypes and bladder cancer in Hispanic and non-Hispanic White men.

Results: There were no significant differences in the genotype frequencies for either the CCL2 or CCR2 SNP and bladder cancer risk was equivalent regardless of CCL2 (NHW AA vs AG/GG, p = 0.7232; H AA vs. AG/GG, p = 0.5187) or CCR2 genotype (NHW AA vs GG/GG, p = 0.6826; H GG vs. AA/AG, p = 0.2425).

Conclusion: Prior studies have shown conflicting results regarding the association between bladder cancer risk and the CCL2 rs1024611 and CCR2 rs1799864 polymorphisms. We were unable to validate significant findings regarding any relationship between these polymorphism distributions across individuals with or without bladder cancer in a cohort of non-Hispanic White and Hispanic White men, suggesting no role of CCL2/CCR2 polymorphisms in bladder cancer.

Introduction: Radical cystectomy or trimodal therapy are treatment options for non-metastatic bladder cancer. However, there is limited evidence guiding post-treatment follow-up regimens, resulting in variations in care.

Objective: A Swiss consensus meeting aimed to identify gaps in follow-up strategies and subsequently tailoring follow-up protocols after curative treatment for bladder cancer.

Methods: A consensus meeting including participants from urology, oncology, radiation oncology, neuro-urology, international advisors, and patient representatives was held. 19 pre-formulated questions addressing follow-up duration, frequency, and modalities after radical cystectomy or trimodal therapy for bladder cancer were discussed and voted by participants.

Results: 42 experts from 22 institutions participated in the meeting. Agreement was reached on several important elements of oncological and functional follow-up like risk-adapted follow-up and regular usage of patient reported outcome measures (PROMs) and 3 novel personalized follow-up schedules were suggested, balancing oncological surveillance, and monitoring functional complications.

Conclusion: We agreed on 3 newly developed Swiss follow up schedules for patients with bladder cancer who underwent cystectomy or trimodal therapy with curative intent; these protocols include stage-specific recommendations for type and timing of investigations to detect relapse combined with balanced measures to monitor functional complications such as PROMS and specific clinical examinations. These protocols will be evaluated in a prospective national multicentric cohort study.

Background: Metastasis-directed therapy (MDT) for oligometastatic cancer is utilized for genitourinary malignancies including prostate and kidney cancers. Clinical research on MDT for urothelial carcinoma (UC) remains sparse, especially as systemic therapy advances have improved outcomes.

Objective: We investigated the role of MDT, specifically radiotherapy, for patients with oligometastatic bladder or upper-tract UC.

Methods: Data were collated on patients with metastatic UC with 5 or fewer metastatic sites undergoing MDT with ablative radiotherapy with or without preceding systemic therapy during January 2016 to July 2024. Endpoints were progression-free survival (PFS), and overall survival (OS). Cox proportional hazards analysis was conducted to determine the covariates associated with these endpoints.

Results: Fifty-two patients were included. Most were men (67%). Median age was 68 years (interquartile range, 62-78). Most had bladder primary tumors (79%). Patients had a median of 1 metastatic site. Most received ≥2 lines of systemic therapy before MDT (60%), whereas 8% received no systemic therapy before MDT. MDT was delivered to all metastases in 71% of cases, whereas the remaining cases (29%) had MDT delivered to select sites. Median follow-up from the diagnosis of metastasis was 32 months (interquartile range, 23-42). Median PFS and OS were 19 months (95% CI, 15-24) and 42 months (95% CI, 24-60), respectively.

Conclusions: MDT may serve as an effective adjunct to systemic therapy to improve outcomes of oligometastatic and oligoprogressive UC.

Background: In vivo modeling is essential to study bladder cancer biology. Orthotopic bladder tumor models involve direct introduction of tumor cells into the bladder of a laboratory animal. Common techniques for orthotopic tumor introduction include transurethral, ultrasound-guided, or surgical approaches.

Objective: We systematically collected data from published studies that have utilized orthotopic bladder tumor models in mice or rats to identify trends and outcomes across techniques. We used these data to optimize a surgical orthotopic technique.

Methods: A PubMed search was performed to identify articles involving orthotopic implantation of tumor cells into mouse or rat bladders for research purposes. Results were individually reviewed and filtered. All studies reporting preclinical models established via a surgical, transurethral, and/or ultrasound-guided approach were included. Surgical orthotopic tumor implantation experiments were performed and data collected.

Results: A total of 254 studies were identified, of which 187 met criteria and were included in the analysis. Data regarding each orthotopic technique was reviewed and trends were identified. Transurethral installation was the most commonly used method but had the lowest tumor take rate. The surgical approach had the highest metastatic rate. These data were used to inform optimization of the surgical orthotopic approach in our laboratory. The study is limited by its retrospective design and heterogeneity of data reporting across studies.

Conclusions: Tumor take rates vary across orthotopic implantation techniques. Optimization of a surgical implantation approach is feasible. These findings can inform best practices for orthotopic bladder cancer models.

Background: Neighborhood Deprivation (ND) indices serve as indicators of socioeconomic status and are recognized determinant of survival across multiple cancer types.

Objective: To determine the potential effect of ND on urothelial bladder cancer survival outcomes using a California-specific measure, the Healthy Places Index (HPI).

Methods: We queried our institutional database for patients who underwent radical cystectomy from 2013 to 2019. Patients were categorized into HPI quartiles based on their residential areas, with Q1 representing the most disadvantaged and Q4 the least disadvantaged. Multivariable logistic regression was used to identify predictors of adverse pathological features. Multivariable cox regression was utilized to evaluate the association of HPI with overall survival (OS) and recurrence free survival (RFS).

Results: A total of 729 patients were included in our analysis. Belonging to the most disadvantaged quartile (Q1) was associated with higher odds of lymphovascular invasion (HR 1.94, p < 0.001), and extravesical disease (HR 1.87, p < 0.001) at presentation, compared to the least deprived quartile (Q4). Survival analyses showed that worse ND was independently associated with worse OS (Q1 vs Q4: HR: 1.76, 95% CI: 1.18-2.62, p = 0.006) after adjusting for age, extravesical disease, node-positivity, and lymphovascular invasion. OS was positively associated with the education, economic, and transportation subdomains of HPI in univariable analyses.

Conclusions: Greater ND is associated with adverse pathology on presentation and worse OS following radical cystectomy for UBC. Larger prospective studies are warranted to further assess the influence of social disparities on survival outcomes following RC.

Background: Recently, urinary extracellular vesicles (uEVs) have emerged as promising biomarkers for early diagnosis, prognosis, and treatment monitoring in urothelial carcinoma (UC). uEVs encapsulate nucleic acids, proteins, and other bioactive molecules that reflect the tumor microenvironment, potentially offering a non-invasive approach for real-time cancer assessment.

Methodology: A comprehensive literature review was conducted, focusing on recent studies evaluating uEVs in UC, particularly regarding their molecular contents, such as microRNA (miRNA), long non-coding RNAs (lncRNAs), circular RNA (circRNA), messenger RNA (mRNA), and proteins. Studies that assessed the clinical utility of uEVs for diagnosis, prognosis, and individualized treatment guidance in UC were emphasized.

Results: Studies have identified a variety of EV-RNAs and EV-proteins as potential diagnostic and prognostic biomarkers, with some showing promise for treatment response. However, challenges in validation, limited cohort sizes, and inconsistent findings have hindered their clinical application. Liquid biopsies using uEVs are advancing UC precision medicine by improving diagnostic accuracy, identifying molecular subtypes, and potentially predicting therapeutic responses.

Conclusions: UEVs are promising for UC management, offering a minimally invasive, accessible source of biomarkers for diagnosis, prognosis, and treatment monitoring. Although further research and large-scale validation are needed, the integration of uEVs into clinical practice has the potential to transform UC patient care by providing precise personalized management strategies. Continued advances in EV research and biomarker discovery may ultimately lead to more effective targeted UC therapies.

Alterations in mRNA splicing play a critical role in driving the molecular heterogeneity of many cancers, including urothelial carcinoma, by contributing to disease progression, treatment response, and clinical outcomes. These splicing changes can arise from somatic mutations in core spliceosomal components or through alternative splicing events affecting cancer-associated genes. In this review, we examine how dysregulation of pre-mRNA splicing influences key aspects of urothelial carcinoma biology, including cell proliferation, invasion, metastasis, modulation of the immune microenvironment, metabolism, and therapeutic resistance. We highlight frequently observed splicing-factor mutations and discuss the impact of aberrant splicing and cancer-specific isoforms on prognosis. We also explore splicing alterations associated with susceptibility to urothelial carcinoma and review emerging therapeutic strategies, such as splice-switching oligonucleotides and small molecule spliceosome inhibitors, that offer promising avenues for precision medicine in this disease.