Bladder Cancer Mortality Research Articles

Basic Study on Gene Biology of Bladder Cancer Metastasis

Bladder cancer is a complex disease with distinct treatment approaches based on its progression. For non-muscle invasive bladder cancer, the primary treatment method involves complete tumor resection, followed by immunotherapy, intravesical chemotherapy, and regular monitoring. In cases of muscle-invasive bladder cancer, a multimodal approach-including radical cystectomy and neoadjuvant chemotherapy offers the best chance of cure; though some tumors still progress to metastatic disease, which is associated with high mortality rate. Metastasis remains the primary cause of bladder cancer mortality. Since research on tumor metastasis began in 1889, discoveries like the seed and soil hypothesis and the role of host factors have shaped the treatment strategies and contributed to our understanding of metastatic behavior. Advancing our knowledge of tumor biology, particulary in relation to metastasis, remains essential, and summarizing current findings in this area will support further progress in bladder cancer metastasis research.

Health care disparities and bladder cancer mortality in the United States: A closer look at the social vulnerability index.

150 Background: Bladder cancer is a significant public health concern, with various factors influencing mortality rates. The Social Vulnerability Index (SVI) measures community resilience to external health stresses. This study investigates the association between bladder cancer mortality (BCM) and county-level SVI in the United States (U.S.). Methods: Mortality data from U.S. counties were obtained from the Centers for Disease Control (CDC) and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database from 2015 to 2019 using the International Classification of Diseases-10th Edition (Code C67). The CDC and Agency for Toxic Substances and Disease Registry (ATSDR) county-level SVI was used as a composite measure of social vulnerability. The SVI includes several U.S. census variables grouped into four themes: Socioeconomic Status (SES), Household Characteristics, Racial and Ethnic Minority Status, and Housing Type and Transportation. Vulnerable SES variables include individuals with incomes below 150% of the federal poverty line, unemployment, those with housing cost burdens, and those without high school diplomas or health insurance. Vulnerable household variables include seniors over 65 years, children under 17 years, disabled civilians, single-parent households, and those with limited English proficiency. SVI Quartiles (Q1 being the least vulnerable and Q4 the most vulnerable) were compared to assess their impact on BCM. Negative binomial regression models were used to estimate Incidence Rate Ratios (IRRs) with 95% Confidence Intervals (CIs) using SAS software. Results: From 2015 to 2019, a total of 82,994 people died from bladder cancer, and the age-adjusted mortality rate per 1,000,000 was 42.4. A higher SVI in intermediate vulnerability quartiles was associated with a higher risk of BCM (Q2 and Q3: IRR = 1.06; 95% CI = 1.01-1.10; p = 0.009) compared to the least vulnerable quartile, Q1. Vulnerable SES had an increased risk of BCM (Q2 and Q3: IRR = 1.07; 95% CI = 1.03-1.12; p < 0.001) compared to Q1. BCM was also increased in individuals with vulnerable household characteristics (Q2 and Q3: IRR = 1.06; 95% CI = 1.02-1.10; p = 0.004) compared to Q1. Q4 was not significant in comparison to Q1 for the groups mentioned above. Interestingly, Racial and Ethnic Minority Status (Hispanic, Latino, African American, etc.) was associated with lower BCM in Q2 and Q3 (IRR = 0.88; 95% CI = 0.84-0.92; p < 0.001) and Q4 (IRR = 0.77; 95% CI = 0.73-0.81; p < 0.001) compared to Q1. No significant mortality differences were observed among vulnerable Housing Types and Transportation. Conclusions: Bladder cancer mortality is linked to vulnerable socioeconomic and household characteristics, while racial and ethnic minority status correlates with decreased risk. Future targeted public health interventions are needed to reduce bladder cancer mortality in vulnerable populations. Bladder cancer mortality and its association with social vulnerability quartiles. Bladder Cancer Mortality Characteristic IRR 95% CI p-value Social Vulnerability Index Q1 — — Q2&Q3 1.06 1.01, 1.10 0.009 Q4 0.98 0.93, 1.03 0.4 Socioeconomic Status Q1 — — Q2&Q3 1.07 1.03, 1.12 <0.001 Q4 1.00 0.95, 1.05 >0.9 Household Characteristics Q1 — — Q2&Q3 1.06 1.02, 1.10 0.004 Q4 1.05 1.00, 1.10 0.052 Racial & Ethnic Minority Status Q1 — — Q2&Q3 0.88 0.84, 0.92 <0.001 Q4 0.77 0.73, 0.81 <0.001 Housing Type & Transportation Q1 — — Q2&Q3 1.03 0.99, 1.08 0.2 Q4 0.98 0.93, 1.03 0.4 IRR = Incidence Rate Ratio, CI = Confidence Interval.

Bladder cancer incidence and mortality among men with and without castration therapy for prostate cancer - a nation-wide cohort study.

Bladder cancer (BC) is a common malignancy in the Western World with men being diagnosed almost four times as often as women. The etiology of bladder cancer may involve sex hormones. Prostate cancer (PCa) patients treated with chemical castration, such as androgen deprivation therapy, or surgical castration, may therefore have a lower risk of developing bladder cancer. In a nation-wide population-based cohort study using national Danish registry data, we included a cohort of men with a first-time PCa diagnosis between 2002 and 2018 divided according to antihormonal treatment in the first year after PCa diagnosis and a comparison cohort consisting of 10 age-matched persons for each PCa patient. Each individual was followed from 1 year after PCa diagnosis until death or end of follow-up. We computed cumulative incidences (risk) and hazard ratios (HRs) for BC. In a second cohort analysis, we determined overall survival and BC-specific mortality, determined from date of BC diagnosis until death. We included 48,776 PCa patients of whom 13,592 were treated with chemical castration, 2,261 with surgical castration, and 32,923 received no antihormonal treatment. The 5-year risk of BC for each PCa group was 1.1%, 0.7%, and 1.3%, respectively, corresponding to an adjusted HR of 1.13 (95% CI 0.98; 1.31), 0.95 (95% CI 0.62; 1.47), and 1.18 (95% CI 1.09; 1.28) compared to individuals without PCa. Patients receiving antihormonal treatment had a slightly lower incidence of BC compared to individuals without PCa, however, this was not supported by the HRs. The treatment, however, was not associated with overall survival.

Mitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer.

Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared with European American (EA) patients, but the molecular mechanism underlying race-specific differences are unknown. To address this gap, we conducted comprehensive RNA-Seq, proteomics, and metabolomics analysis of BLCA tumors from AA and EA. Our findings reveal a distinct metabolic phenotype in AA BLCA characterized by elevated mitochondrial oxidative phosphorylation (OXPHOS), particularly through the activation of complex I. The results provide insight into the complex I activation-driven higher OXPHOS activity resulting in glutamine-mediated metabolic rewiring and increased disease progression, which was also confirmed by [U]13C-glutamine tracing. Mechanistic studies further demonstrate that knockdown of NDUFB8, one of the components of complex I in AA BLCA cells, resulted in reduced basal respiration, ATP production, GLS1 expression, and proliferation. Moreover, preclinical studies demonstrate the therapeutic potential of targeting complex I, as evidenced by decreased tumor growth in NDUFB8-depleted AA BLCA tumors. Additionally, genetic and pharmacological inhibition of GLS1 attenuated mitochondrial respiration rates and tumor growth potential in AA BLCA. Taken together, these findings provide insight into BLCA disparity for targeting GLS1-Complex I for future therapy.

Impact of Age, Period, Cohort, Region, Race, and Health Services on Bladder Cancer Mortality in Brazil: A 23-Year Ecological Study.

Bladder cancer is one of the most economically costly types of cancer, but few studies have evaluated its mortality considering the factors that impact this outcome. This study aimed to investigate the impact of sociodemographic factors, period, cohort, and health services on bladder cancer mortality. This ecological study analyzed bladder cancer mortality data in Brazil from 2000 to 2022 and evaluated sociodemographic variables (race, region of residence), socioeconomic variables (gross domestic product per capita, Gini index of household income per capita, number of health professionals per inhabitant, expenditure on public health services, and consultations per inhabitant), and bladder cancer diagnosis and treatment procedures. These data were subjected to statistical analysis, which revealed that after the age of 50, there was a progressive increase in the risk of bladder cancer. Indigenous people had the lowest mortality rate, while white people had a significantly greater mortality rate than black and brown people. The North Region and Northeast Region presented the lowest mortality rates, whereas the South Region presented the highest mortality rates. In the South and Southeast Regions, a higher GDP was related to lower mortality. In the South, higher mortality was associated with a lower number of consultations per inhabitant per region. Fewer bladder punctures/aspirations and bladder biopsies were associated with higher mortality rates. In oncology, more procedures, such as total cystectomy, cystoenteroplasty, and total cystectomy with a single shunt, do not reduce the mortality rate. These results can serve as guidelines for adjusting public health policies.

Risk Factors Associated with Urothelial Bladder Cancer.

Urothelial bladder carcinoma (UBC) is the most frequent histologic form of bladder cancer, constituting 90% of the cases. It is important to know the risk factors of UBC to avoid them and to decrease its recurrence after treatment. The aim of this review was to provide an overview of the risk factors associated with UBC incidence. A comprehensive literature search from 2012 to 2024 was carried out in databases such as PubMed, Google Scholar, and Medline with potential keywords such as "bladder cancer", "urothelial bladder cancer", "incidence of urothelial bladder cancer worldwide", "mortality rate of bladder cancer", "incidence according to gender", "treatment for bladder cancer", and "risk factors of bladder cancer". Smoking tobacco was comprehended to be the major risk factor for UBC. Smoke from tobacco products contains polycyclic aromatic hydrocarbons (PAHs) and aromatic amines such as 4-aminobiphenyl, which are known to cause UBC. Smoking-related bladder cancer mortality ranks just second to smoking-related lung cancer mortality. For non-smokers, pollution became a major risk factor associated with UBC. Polycyclic aromatic hydrocarbons (PAHs) are linked to many cancers, especially to UBC. Indoor and outdoor pollution generates VOCs (volatile organic compounds) and PAHs. Small-particle matter < 2.5 is linked to UBC and lung cancers. Drinking chlorinated water is linked to UBC. Also, swimming in chlorinated pools that produce trihalomethanes increases the risk of many cancers, and especially of bladder cancer. Occupational exposure to carcinogens, specifically aromatic amines, is a significant UBC risk factor. It has been estimated that approximately 20% of all UBCs may be linked to this type of exposure, primarily in industrial settings that treat dye, paint, petroleum chemicals, and metal. The other risk factors included genetics, diet, and medical conditions. Alcohol, consumption of processed meat and whole milk, and higher intakes of selenium and vitamins A and E also contribute to the development of UBC. Further, chemotherapeutic agents, oral hypoglycemic drugs, and radiation therapy are positively associated with UBC. The significance of the initial prevention of UBC must be emphasized, and especially programs for quitting cigarettes should be encouraged and supported. However, smoking is not the only risk factor for UBC. For non-smokers, other risk factors should be investigated. Air and water pollution are linked to UBC. Indoor and outdoor pollution should be more controlled. Patients and people should be informed of the risk of drinking chlorinated water and swimming in chlorinated pools.

Trends in genitourinary cancer mortality in the United States: analysis of the CDC-WONDER database 1999-2020.

Sociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States. Mortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban-rural status, and geographic region using a significance level of p < 0.05. Overall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3-4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West. Significant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.

Disparities in trends in bladder cancer mortality between urban and rural patients: A 2000-2020 analysis.

4583 Background: Patients in rural areas in the US often have worse healthcare outcomes due to socioeconomic deprivation, higher rates of smoking, and limited access to medical care. Despite a general decline in bladder cancer mortality over the past two decades, comprehensive studies comparing these trends between urban and rural mortality are scarce. Methods: Utilizing the CDC WONDER database, we extracted mortality data for bladder cancer from 2000 to 2020. Age-adjusted mortality rates per 100,000 persons were standardized to the Year 2000 US standard population. Data segmentation by urbanity utilized the 2013 National Center for Health Statistics Urban-Rural Classification Scheme. The National Cancer Institute's Joinpoint Regression Program was employed to calculate average annual percent changes (AAPCs) and annual percent changes (APCs). Results: In our analysis, we identified a total of 306,750 bladder cancer death cases from 2000 to 2020. Significant improvements in bladder cancer mortality were observed in urban areas, with large central metros experiencing the most pronounced decrease (AAPC -1.0%, p&lt;0.001). This decline was moderate between 2000 and 2016 (APC -0.3, p&lt; 0.001) but accelerated between 2016 and 2020 (APC -3.8%, p&lt;0.001). Large fringe and medium metros also saw comparatively smaller but significant declines (AAPC -0.6%, P&lt;0.05) and also accelerated between 2016-2020. In contrast, small metro and rural areas (micropolitan and noncore) showed no significant improvement, with mortality rates remaining stable between 2000 and 2020 (AAPC 0.2%, P=0.099). Conclusions: This analysis, the largest to date comparing urban and rural mortality trends in bladder cancer, highlights significant disparities in outcomes between large urban and rural areas. The marked improvement in urban areas, especially noted around the time novel agents such as immunotherapy were introduced, underscores the potential impact of advanced treatments. However, the stable mortality rates in rural areas suggest that access to advanced care, environmental influences, socioeconomic status, and slower adaptation of new guidelines in rural settings may play critical roles. These findings underline the urgent need for strategies to close the urban-rural gap. [Table: see text]

Clinical characteristics and molecular mechanisms underlying bladder cancer in individuals with spinal cord injury: a systematic review

BackgroundPatients with spinal cord injury have a relatively high risk for bladder cancer and often complicated with bladder cancer in advanced stages, and the degree of aggressiveness of malignancy is high. Most of the literature is based on disease clinical features while, our study reviews the clinical characteristics and molecular mechanisms of spinal cord injury patients with bladder cancer, so that it might help clinicians better recognize and manage these patients.MethodWe searched PubMed, Web of Science and Embase, using retrieval type like (“Neurogenic Lower Urinary Tract Dysfunction” OR “Spinal cord injury” OR “Spinal Cord Trauma”) AND (“bladder cancer” OR “bladder neoplasm” OR “bladder carcinoma” OR “Urinary Bladder Neoplasms” OR “Bladder Tumor”). In Web of Science, the retrieval type was searched as “Topic”, and in PubMed and Embase, as “All Field”. The methodological quality of eligible studies and their risk of bias were assessed using the Newcastle-Ottawa scale. This article is registered in PROSPERO with the CBD number: CRD42024508514.ResultIn WOS, we searched 219 related papers, in PubMed, 122 and in Embase, 363. Thus, a total of 254 articles were included after passing the screening, within a time range between 1960 and 2023. A comprehensive analysis of the data showed that the mortality and incidence rates of bladder cancer in spinal cord injury patients were higher than that of the general population, and the most frequent pathological type was squamous cell carcinoma. In parallel to long-term urinary tract infection and indwelling catheterization, the role of molecules such as NO, MiR 1949 and Rb 1. was found to be crucial pathogenetically.ConclusionThis review highlights the risk of bladder cancer in SCI patients, comprehensively addressing the clinical characteristics and related molecular mechanisms. However, given that there are few studies on the molecular mechanisms of bladder cancer in spinal cord injury, further research is needed to expand the understanding of the disease.

Abstract B001: Urinary bladder cancer incidence and mortality in the United States: 20-year trends and initial impact of the COVID-19 pandemic

Abstract Introduction: We examined nationwide trends in urinary bladder cancer incidence and mortality focusing on 1999-2019. A separate analysis of data from 2020 revealed how these rates were affected by the onset of the COVID-19 pandemic. Methods: State-specific bladder cancer (in situ and invasive) incidence and mortality rates were ascertained from the United States (US) Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database for 1999-2020 overall and according to age, gender, and geographic region. All rates were age-adjusted to the 2000 US Census population, except age-specific rates. We used Joinpoint software to calculate the 20-year average annual percent change and annual percent change for specific periods identified by data-driven joinpoint placement with 95% confidence intervals (CI). Results: In 2019, the US bladder cancer incidence rate was 18.8 (CI, 18.6 to 18.9) cases per 100,000. Bladder cancer incidence decreased 0.9% annually (CI, 0.8 to 1.0% decrease) during 1999-2019, with a 3.3% annual decrease (CI, 2.5 to 4.1% decrease) during 2016-2019 specifically. Among men, the 20-year annual decrease was 1.1% (CI, 1.0 to 1.1% decrease), with a 3.8% annual decrease (CI, 2.8 to 4.6% decrease) during 2017-2019 specifically. Among women, the 20-year annual decrease was 1.0% (CI, 0.9 to 1.2% decrease), with a 2.6% annual decrease (CI, 1.7 to 4.2% decrease) during 2016-2019 specifically. Largest annual decreases in incidence rates were seen among 55-59-year-olds (1.8%, CI, 1.6 to 2.0% decrease), and in the western US (2.3%, CI, 2.0 to 2.6% decrease). Conversely, some southern states showed an increase in incidence. In Tennessee, there was a 20-year annual increase of 1.2% (CI, 0.9 to 1.6% increase). In 2019, the US bladder cancer mortality rate was 4.1 (CI, 4.0 to 4.2) deaths per 100,000. Bladder cancer mortality decreased 0.4% annually (CI, 0.2 to 0.5% decrease) during 1999-2019, with a 2.5% annual decrease (CI, 1.3 to 4.7% decrease) during 2016-2019 specifically. Mortality rate trends were generally similar among men and women (0.4% and 0.7% decrease annually, respectively). Largest annual decreases in mortality rates were seen among 50-54-year-olds (1.5%, CI, 0.6 to 2.4% decrease) and in the northeast US (0.8%, CI, 0.7 to 1.0% decrease). Reflecting the initial impact of the COVID-19 pandemic, bladder cancer incidence decreased by 8.6% (CI, 7.7 to 9.6% decrease) and bladder cancer mortality decreased by 2.7% (CI, 0.6 to 4.8% decrease) comparing 2020 with 2019. Conclusions: After decades remaining relatively constant, bladder cancer incidence and mortality rates in the US began to decrease around 2016-2017. This trend was less apparent in the southern part of the country, where incidence trended upward in some states. As evident for other common cancers, bladder cancer incidence rates decreased sharply during the first year of the COVID-19 pandemic. Forthcoming data for 2021-2024 will provide a clearer picture of the magnitude of this disruption and the possibility of a rebound. Citation Format: Grace B. Gallant, Hugo Pomares-Millan, Judy R. Rees, Margaret R. Karagas, Michael N. Passarelli. Urinary bladder cancer incidence and mortality in the United States: 20-year trends and initial impact of the COVID-19 pandemic [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B001.

Comprehensive analysis and prognostic assessment of senescence-associated genes in bladder cancer

BackgroundThe prevalence and mortality of bladder cancer (BLCA) present a significant medical challenge. While the function of senescence-related genes in tumor development is recognized, their prognostic significance in BLCA has not been thoroughly explored.MethodsBLCA transcriptome datasets were sourced from the TCGA and GEO repositories. Gene groupings were determined through differential gene expression and non-negative matrix factorization (NMF) methodologies. Key senescence-linked genes were isolated using singular and multivariate Cox regression analyses, combined with lasso regression. Validation was undertaken with GEO database information. Predictive models, or nomograms, were developed by merging risk metrics with clinical records, and their efficacy was gauged using ROC curve methodologies. The immune response’s dependency on the risk metric was assessed through the immune phenomenon score (IPS). Additionally, we estimated IC50 metrics for potential chemotherapeutic agents.ResultsReviewing 406 neoplastic and 19 standard tissue specimens from the TCGA repository facilitated the bifurcation of subjects into two unique clusters (C1 and C2) according to senescence-related gene expression. After a stringent statistical evaluation, a set of ten pivotal genes was discerned and applied for risk stratification. Validity tests for the devised nomograms in forecasting 1, 3, and 5-year survival probabilities for BLCA patients were executed via ROC and calibration plots. IC50 estimations highlighted a heightened responsiveness in the low-risk category to agents like cisplatin, cyclopamine, and sorafenib.ConclusionsIn summation, our research emphasizes the prospective utility of risk assessments rooted in senescence-related gene signatures for enhancing BLCA clinical oversight.

Global burden of bladder cancer mortality in 2020 and 2040 according to GLOBOCAN estimates

IntroductionIn 2020, bladder cancer (BC) was the seventh most prevalent cancer in the world, with 5-year prevalence of more than 1.7 million cases. Due to the main risk factors—smoking and chemical exposures—associated with BC, it is considered a largely preventable and avoidable cancer. An overview of BC mortality can allow an insight not only into the prevalence of global risk factors, but also into the varying efficiency of healthcare systems worldwide. For this purpose, this study analyzes the national mortality estimates for 2020 and projected future trends up to 2040.Materials and methodsAge-standardized mortality rates per 100,000 person-years of BC for 185 countries by sex were obtained from the GLOBOCAN 2020 database, operated by the International Agency for Research on Cancer (IARC). Mortality rates were stratified according to sex and Human Development Index (HDI). BC deaths were projected up to 2040 on the basis of demographic changes, alongside different scenarios of annually increasing, stable or decreasing mortality rates from the baseline year of 2020.ResultsIn 2020, nearly three times more men died from BC than women, with more than 210,000 deaths in both sexes combined, worldwide. Regardless of gender, more than half of the total BC deaths were from countries with a very high HDI. According to our projections, while the number of deaths for men can only increase up to 54% (from 159 to around 163–245 thousand), for women it is projected to increase two- to three-fold (from 50 to around 119–176 thousand) by 2040. The burden of BC mortality in countries with a very high HDI versus high HDI appears to converge by 2040 for both sexes.ConclusionOpposite mortality trends by gender highlight the urgent need for immediate interventions to expand anti-tobacco strategies, especially for women. The implementation of more strict occupational health and safety regulations could also prevent exposures associated with BC. Improving the ability to detect BC earlier and access to treatment can have a significant positive impact on reducing mortality rates, minimizing economic costs, and enhancing the quality of life for patients.

Arab world's impact on bladder cancer research and opportunities for growth: A bibliometric review study.

Bladder Cancer (BC) is a widespread form of cancer that affects over 1.6 million people globally. The majority of cases are diagnosed as urothelial carcinoma, with a higher likelihood of diagnosis in men and with increasing age. The Arab world (AW) is one of the regions with the highest incidence and mortality rates of BC, and the average age of diagnosis is between 40 and 49 years in North Africa and the Middle East. This study aims to assess the activity and distribution of BC publications in the AW. A systematic search across MEDLINE and Embase databases spanning 2007 to 2021 identified 1208 English-language articles on bladder cancer with Arab affiliations. The dataset was normalized against the average population and GDP (2007-2020) for 22 Arab countries. Statistical analyses via SPSS and visualizations with VOSviewer unveiled collaboration patterns and thematic trends in Arab bladder cancer research. A total of 1208 BC publications were published in the AW, representing 0.24% of all biomedical publications. Egypt topped the list with the highest number of publications. The co-authorship analysis generated by VOSviewer revealed that out of 4766 authors, 161 met the minimum threshold of 5 publications. The findings reveal that Egypt and Jordan are at the forefront of BC research in the region, while other Arab countries are lagging behind despite being heavily impacted by the disease. To drive progress in the field, it's important to uncover the obstacles impeding BC research in these countries and implement effective solutions to overcome them.

Abstract 2239: Comparative effectiveness of cystoscopy surveillance strategies on mortality in non-muscle invasive bladder cancer: A target trial emulation using real-world data

Abstract Background: More than 60,000 U.S. adults are diagnosed with non-muscle invasive bladder cancer (NMIBC) each year. These patients are recommended to undergo surveillance via repeated cystoscopies. However, the ideal frequency of post-diagnostic cystoscopy surveillance remains unknown, and efforts are underway to de-escalate surveillance given uncertainty regarding its effect on mortality. We therefore aimed to compare the effectiveness of different post-diagnostic cystoscopy surveillance strategies on bladder cancer specific mortality. Methods: We used observational data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage to emulate a target trial, i.e., a hypothetical, pragmatic randomized trial that would answer our causal question. Eligible individuals were aged 66 years or older, diagnosed with NMIBC (Ta, Tis, or T1) classified as urothelial carcinoma between January 1, 2000 and December 31, 2017, and had completed their first post-diagnostic cystoscopy. We compared 10-year risks of bladder cancer specific mortality under cystoscopy surveillance every 3, 6, and 12 months separately among individuals at low, intermediate, and high risk. We estimated mortality risks using inverse probability weighted pooled logistic regression. Results: Among 58,004 eligible individuals, the median age at diagnosis was 77 years (interquartile range: 72, 82) and 75.6% were male. Over the 10 year follow-up period, 4,977 bladder cancer deaths occurred. Among individuals at high risk, the estimated 10-year bladder cancer mortality risks were 24.5% under the 3 month strategy, 26.6% under the 6 month strategy, and 27.3% under the 12 month strategy. Compared with cystoscopy every 3 months, the risk differences were 2.1% (95% confidence interval [CI]: -0.3, 3.8) for cystoscopy every 6 months, and 2.8% (95% CI: 1.0, 4.4) for cystoscopy every 12 months. For patients in the intermediate risk group, 10-year bladder cancer mortality risks were 14.4% under the 3 month strategy, 15.1% under the 6 month strategy, and 15.9% under the 12 month strategy. The risk differences were 0.7% (95% CI: -0.6, 2.0) for 6 vs. 3 months and 1.6% (95% CI: 0.3, 2.7) for 12 vs. 3 months. Among individuals at low risk, these mortality risks were 8.3% under the 3 month strategy, 9.2% under the 6 month strategy, and 9.6% under the 12 month strategy. Risk differences were 1.1% (95% CI: -0.1, 2.5) for 6 vs. 3 months and 1.5% (95% CI: 0.2, 3.0) for 12 vs. 3 months. Conclusions: We estimated that more frequent cystoscopy may result in clinically meaningful reductions in bladder cancer mortality among high risk patients. Among low and intermediate risk patients, more frequent cystoscopy may result in modest absolute risk reductions. Decision-makers should also consider the clinical and financial burden and risk of complications associated with more frequent surveillance. Citation Format: Emma E. McGee, Xabier García de Albéniz, A. Heather Eliassen, Kendrick Yim, Barbra A. Dickerman, Mark A. Preston, Miguel Hernán. Comparative effectiveness of cystoscopy surveillance strategies on mortality in non-muscle invasive bladder cancer: A target trial emulation using real-world data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2239.

Abstract 7060: Mitochondrial metabolism and racial disparity of bladder cancer

Abstract Bladder cancer mortality is significantly higher in African American patients compared to their European American counterparts. This inferior survival of African American cancer patients is driven at least in part by distinctive intrinsic tumor biology, more specifically altered metabolic activity. However, underlying molecular mechanism for the African American bladder cancer mortality are largely unexplored. Our pioneering metabolomic findings demonstrate alterations in metabolic pathways between African American and European American bladder cancer, specifically those involved in driving energy metabolism. Along these line, we observed increased electron transport chain activity and ATP production in African American bladder cancer could be a result of distinctive rewiring of energy metabolism compared to their European American counterparts. We further performed gene set enrichment analysis by mapping metabolites to genes and observed that oxidative phosphorylation pathway was uniquely enriched in African American tumors compared to European American tumors. In addition, from in vitro assays, mitochondrial complex protein and activity were altered in African American bladder cancer. To determine the role of glutamine mediated increased electron transport chain activity and ATP production in African American bladder cancer, we evaluated the metabolic flux using 13C labeled tracers in both African American and European American bladder cancer cell lines. Metabolic flux analysis revealed that African American cell lines are more glutamine dependent and that producing increased tricarboxylic acid intermediates. Overall, our data indicate that elevated mitochondrial metabolism and oxidative phosphorylation driven by enhanced glutaminolysis may facilitate African American bladder cancer progression. These findings provide the rationale to use mitochondrial-specific inhibitors to target at least a subset of African American bladder cancer patients. Citation Format: Karthik Reddy Kami Reddy, Jun Hyoung Park, Roni J. Bollag, Martha K. Terris, Seth P. Lerner, Minhaj Siddiqui, Yair Lotan, Jianjun Gao, Benny Abraham Kaipparettu, Nagireddy Putluri. Mitochondrial metabolism and racial disparity of bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7060.

Identification and verification of anoikis-related gene markers to predict the prognosis of patients with bladder cancer and assist in the diagnosis and treatment of bladder cancer.

The recurrence and mortality rates of bladder cancer are extremely high, and its diagnosis and treatment are global concerns. The mechanism of anoikis is closely related to tumor metastasis. First, we obtained all the data needed for this study from a public database through a formal operational process. The data were then analyzed by bioinformatics technology. Through the limma package, we screened and obtained 313 anoikis-related genes [false discovery rate (FDR) <0.05, |log fold change (FC) | >0.585]. Then, through univariate independent prognostic analysis, we further screened 146 genes (P<0.05) related to the prognosis of bladder cancer from 313 differential genes. These 146 prognostically relevant differential genes were used for least absolute shrinkage and selection operator (LASSO) regression for further screening to obtain model-related genes and output model formulas. Through the nomogram, we can calculate the survival rate of patients more accurately. The accuracy of the nomogram was also confirmed by calibration curves, independent prognostic analysis, receiver operating characteristic (ROC) curves, decision curve analysis (DCA) curves. We then analysed the sensitivity of immunotherapy in bladder cancer patients with different risk scores via Tumor Immune Dysfunction and Exclusion (TIDE). Through bioinformatics technology and public databases, a prognostic model including 9 anoikis-related genes (KLF12, INHBB, CASP6, TGFBR3, FASN, TPM1, OGT, RAC3, ID4) was obtained. Integrating risk scores with clinical information, we obtained a nomogram that can accurately predict patient survival. By querying the immunohistochemical results of the Human Protein Atlas database, two of the nine model-related genes (FASN, RAC3) have the value of further research and are expected to become new biomarkers to assist the diagnosis and treatment of bladder cancer. Through immune-related analysis, we found that patients in the low-risk group appeared to be more suitable for immunotherapy, while drug sensitivity analysis showed that bladder cancer patients in the high-risk group were more sensitive to common chemotherapy drugs. In this study, a prognostic model that can accurately predict the prognosis of patients with bladder cancer was constructed. FASN and RAC3 are expected to become a new biomarker for the diagnosis and treatment of bladder cancer.

Transcriptome Analysis Reveals Anti-Cancer Effects of Isorhapontigenin (ISO) on Highly Invasive Human T24 Bladder Cancer Cells.

Bladder cancer, the most common malignancy of the urinary tract, has a poor overall survival rate when the tumor becomes muscle invasive. The discovery and evaluation of new alternative medications targeting high-grade muscle invasive bladder cancer (MIBC) are of tremendous importance in reducing bladder cancer mortality. Isorhapontigenin (ISO), a stilbene derivative from the Chinese herb Gnetum cleistostachyum, exhibits a strong anti-cancer effect on MIBCs. Here, we report the whole transcriptome profiling of ISO-treated human bladder cancer T24 cells. A total of 1047 differentially expressed genes (DEGs) were identified, including 596 downregulated and 451 upregulated genes. Functional annotation and pathway analysis revealed that ISO treatment induced massive changes in gene expression associated with cell movement, migration, invasion, metabolism, proliferation, and angiogenesis. Additionally, ISO treatment-activated genes involved in the inflammatory response but repressed genes involved in hypoxia signaling, glycolysis, the actin cytoskeleton, and the tumor microenvironment. In summary, our whole transcriptome analysis demonstrated a shift in metabolism and altered actin cytoskeleton in ISO-treated T24 cells, which subsequently contribute to tumor microenvironment remodeling that suppresses tumor growth and progression.

Longitudinal Analysis of Bladder Cancer-Specific Mortality Trends in the United States.

Bladder cancer is the tenth leading cause of cancer death in the United States (US). Advances in diagnosis, imaging, and treatments have led to improvements in bladder cancer management. To evaluate longitudinal bladder cancer mortality trends from 1999-2020 in the US by gender, race, ethnicity, age, geographic region, and urbanization category. Age-adjusted bladder cancer death and incidence rates of individuals in the US of all ages between 1999-2020 were obtained using the CDC WONDER and NAACCR databases. Trends and average annual percent changes (AAPC) in age-adjusted Bladder Cancer-Specific Mortality (BCSM) and incidence rates were estimated. Data were analyzed from May 2023 to October 2023. From 1999-2020, overall BCSM decreased by 0.4% annually, with a dramatic decrease in deaths between 2015-2020 (AAPC: -2.0% [95% CI: -2.6,-1.3]). However, BCSM rates and metastatic malignant bladder cancer incidence rates from 1999-2020 increased for individuals≥85 years old (AAPC for BCSM: 0.8% [95% CI:0.5,1.1]; AAPC for metastatic malignant incidence: 2.5% [95% CI: 2.0,2.9]). Increases in BCSM were found for certain years in the South, in rural areas, and for Non-Hispanic White and Asian or Pacific Islander individuals. Overall mortality from bladder cancer has been decreasing in the US over two decades. Upon disaggregation, increasing trends were found for BCSM and for metastatic malignant bladder cancer incidence for individuals≥85 years old from 1999-2020. Further evaluation of these trends is essential to understand how to target specific populations to improve patient outcomes.

The global landscape of bladder cancer incidence and mortality in 2020 and projections to 2040.

Bladder cancer (BCa) is one of the most common urological malignancies worldwide. This study examines the global epidemiological profile of BCa incidence and mortality in 2020 and the projected burden to 2040. The estimated number of BCa cases and deaths were extracted from the GLOBOCAN 2020 database. Age-standardised incidence rates (ASIRs) and age-standardised mortality rates (ASMRs) were calculated using the world standard. The predicted BCa incidence and mortality in 2040 was calculated based on demographic projections. Globally, approximately 573 000 new BCa cases and 213 000 deaths occurred in 2020, corresponding to ASIRs and ASMRs of 5.6 and 1.9 per 100 000, respectively. The incidence and mortality rates were approximately 4-fold higher in men (9.5 and 3.3 per 100 000, respectively) than women (2.4 and 0.9, respectively). Across world regions, incidence rates varied at least 12-fold among men and 8-fold among women, with the highest ASIRs for both men and women detected in Southern Europe (26.5 and 5.8 per 100 000, respectively) and Western Europe (21.5 and 5.8, respectively) and the lowest in Middle Africa (2.2) in men and South-Central Asia (0.7) in women. The highest ASMRs for both men and women were found in Northern Africa (9.2 and 1.8 per 100 000, respectively). By 2040, the annual number of new BCa cases and deaths will increase to 991 000 (72.8% increase from 2020) and 397 000 (86.6% increase), respectively. Geographical distributions of BCa incidence and mortality uncovered higher risk of BCa incidence in Southern and Western European populations and higher risk of mortality in Northern African populations. Considering the predicted 73% and 87% increase in annual BCa cases and deaths by 2040 globally, respectively, there is an urgent need to develop and accelerate BCa control initiatives for high-risk populations to tackle global BCa burden and narrow its geographical disparities.

Bladder cancer mortality trends in Spain: 1980–2021

ObjectiveWe propose to update bladder cancer mortality rates in Spain from 1980 to 2021, by sex and age-group, by autonomous community (AC). Materials and methodsThe public online databases of the National Statistical Institute were used to obtain data on population and bladder cancer mortality. Age-standardised mortality rates (ASMRs), all ages and truncated (<75 and ≥75) were estimated and reported as rates per 100,000 persons. Joinpoint regression software was used for estimation and trend analysis of ASMRs bladder cancer. ResultsIn the last decade, the ASMR for bladder cancer (all ages, <75 years and ≥75 years) decreased significantly in Spain for both sexes. This trend was observed in 12 ACs for men and in 4 ACs (Andalusia, Canary Islands, Catalonia and Madrid) for women, although to different degrees. For men, ASMR remained stable in Castilla-León and La Rioja (<75 years), Cantabria, Castilla-La Mancha and Valencia (≥75 years) and the 2 Castilian regions (all ages). For women, ASMR also decreased in Valencia (<75 and ≥75), Castilla-León (≥75), Galicia (≥75 and all ages) and Navarre (<75 and all ages). ConclusionOur results reveal significant variations in trends by AC, sex and age group, emphasizing the need for continued follow-up and targeted interventions to further reduce bladder cancer mortality rates in Spain.