Bladder Cancer Mortality Research Articles

Arsenic in Drinking Water and Urinary Tract Cancers: A Systematic Review Update

Problem: There remains uncertainty around cancer risk at lower levels of arsenic in drinking water. This study updates evidence from our previous review on the relationship between arsenic in drinking water and urinary bladder and kidney cancers (updated search January 2013 to February 2023). Method: Thirty-four studies were retained for review; six met criteria for inclusion in meta-analysis. Risk estimates for bladder and kidney cancer incidence and mortality were analyzed separately using Bayesian multilevel linear models. Results: For bladder cancer incidence, the estimated posterior mean relative risks (RRs) were 1.25 (0.92–1.73), 2.11 (1.18–4.22) and 3.01 (1.31–8.17) at arsenic concentrations of 10, 50 and 150 μg/L, respectively, with posterior probabilities of 92%, 99% and 100%, respectively, for the RRs to be >1. The corresponding RRs for kidney cancer were 1.37 (1.07–1.77), 1.95 (1.44–2.65) and 2.47 (1.74–3.52), with posterior probabilities of 100%. For bladder cancer, the posterior mean mortality ratios were 1.36 (0.35–6.39), 2.92 (1.24–7.82) and 4.88 (2.83–9.03) with posterior probabilities of 72%, 99% and 100%, respectively. Conclusions: The findings show increased bladder and kidney cancer risks at lower levels of arsenic in drinking water. Given that many people worldwide are exposed to lower levels of arsenic in drinking water, the public health impacts are substantial.

EPH24 Gender and Racial Disparities and All-Cause Mortality in Bladder Cancer Patients in the U.S.

Studies conducted up to two decades ago, suggest that sociodemographic characteristics affect bladder cancer mortality. African American race seems to be a strong predictor of poor survival. Female patients have higher bladder cancer mortality. The objective of this study is to examine recent data for sociodemographic differences in all-cause mortality among bladder cancer patients.

Tendencias de la mortalidad por cáncer de vejiga en España, 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 (≥75years) 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.

Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice.

Bladder cancer is among the ten most common cancers globally, causes considerable morbidity and mortality and is, therefore, a substantial burden for health-care systems. The incidence of bladder cancer is affected by demographic trends, most notably population growth and ageing, as well as exposure to risk factors, especially tobacco smoking. Consequently, the incidence has not been stable throughout the world over time, nor will it be in the near future. Further primary prevention efforts are of the utmost importance to reduce the medical and financial burden of bladder cancer on populations and health-care systems. Simultaneously, less-invasive and lower-cost approaches for the diagnosis of both primary and recurrent bladder cancers are required to address challenges posed by the increasing shortage of health-care professionals and limited financial resources worldwide. In this regard, urinary biomarkers have demonstrated promising diagnostic accuracy and efficiency. Awareness of the risk factors and symptoms of bladder cancer should also be increased in society, particularly among health-care professionals and high-risk groups. Studies investigating the associations between lifestyle factors and bladder cancer outcomes are scarce and should be a research priority. In this Review, we outline global trends in bladder cancer incidence and mortality, and discuss the main risk factors influencing bladder cancer occurrence and outcomes. We then discuss the implications, challenges and opportunities of these epidemiological trends for public health and clinical practice.

Occupational asbestos exposure and urinary bladder cancer: a systematic review and meta-analysis

PurposeThere is conflicting evidence on the association between asbestos exposure and bladder cancer. We performed a systematic review and meta-analysis to provide evidence on occupational asbestos exposure and the risk of mortality and incidence of bladder cancer.MethodsWe searched three relevant electronic databases (Pubmed, Scopus, and Embase) from inception to October 2021. The methodological quality of included articles was evaluated using the US National Institutes of Health tool. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) for bladder cancer, as well as respective 95% confidence intervals (CIs), were extracted or calculated for each included cohort. Main and subgroup meta-analyses according to first year of employment, industry, sex, asbestos type, and geographic region were performed.ResultsFifty-nine publications comprising 60 cohorts were included. Bladder cancer incidence and mortality were not significantly associated with occupational asbestos exposure (pooled SIR: 1.04, 95% CI: 0.95–1.13, P = 0.000; pooled SMR: 1.06, 95% CI: 0.96–1.17, P = 0.031). Bladder cancer incidence was higher among workers employed between 1908 and 1940 (SIR: 1.15, 95% CI: 1.01–1.31). Mortality was elevated in asbestos workers cohorts (SMR: 1.12, 95% CI: 1.06–1.30) and in the subgroup analysis for women (SMR: 1.83, 95% CI: 1.22–2.75). No association was found between asbestos types and bladder cancer incidence or mortality. We observed no difference in the subgroup analysis for countries and no direct publication bias evidence.ConclusionThere is evidence that workers with occupational asbestos exposure have a bladder cancer incidence and mortality similar to the general population.

Trends and risk factors of global incidence, mortality, and disability of genitourinary cancers from 1990 to 2019: Systematic analysis for the Global Burden of Disease Study 2019.

The incidence of kidney, bladder, and prostate cancer ranked ninth, sixth, and third in male cancers respectively, meanwhile, the incidence of testicular cancer also increased gradually in the past 30 years. To study and present estimates of the incidence, mortality, and disability of kidney, bladder, prostate, and testicular cancer by location and age from 1990 to 2019 and reveal the mortality risk factors of them. The Global Burden of Diseases Study 2019 was used to obtain data for this research. The prediction of cancer mortality and incidence was based on mortality-to-incidence ratios (MIRs). The MIR data was processed by logistic regression and adjusted by Gaussian process regression. The association between the socio-demographic index and the incidence or disease burden was determined by Spearman's rank order correlation. Globally in 2019, there were 371,700 kidney cancer cases with an age-standardized incidence rate (ASIR) of 4.6 per 100,000, 524,300 bladder cancer cases, with an ASIR of 6.5 per 100,000, 1,410,500 prostate cancer cases with an ASIR of 4.6 per 100,000 and 109,300 testicular cancer incident cases with an ASIR of 1.4 per 100,000, the ASIR of these four cancers increased by 29.1, 4, 22, and 45.5% respectively. The incidence rate of the four cancers and the burden of kidney cancer were positively correlated with the socio-demographic index (SDI), regions with a higher SDI faced more of a burden attributable to these four cancers. High body-mass index has surpassed smoking to be the leading risk factor in the past thirty years for kidney cancer mortality. Smoking remained the leading risk factor for cancer-related mortality for bladder cancer and prostate cancer and the only risk factor for prostate cancer. However, the contribution of high fasting plasma glucose to bladder cancer mortality has been increasing. The incidence of bladder, kidney, prostate, and testicular cancer is ever-increasing. High-income regions face a greater burden attributable to the four cancers. In addition to smoking, metabolic risk factors may need more attention.

5α-reductase inhibitors and the risk of bladder cancer in a large, population-based cohort.

The ability of 5α-reductase inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results. Our objective was to conduct a retrospective cohort population-based study to evaluate the association between 5ARI use, BC diagnosis, and BC mortality. We used routinely collected health care data from Ontario, Canada. Men ≥66 years of age with a prescription for a 5ARI were matched to non-5ARI users. Matching was done using a propensity score of selected covariates to make 96 different covariates comparable. We measured 5 additional baseline variables which may have impacted the risk of future BC diagnosis: prior cystoscopy, urine cytology, urinalysis, gross hematuria episodes, and transurethral resection of a bladder lesion. Only the first period of continuous usage of 5ARIs was considered. The prespecified at-risk period for outcomes started 1 year after initiating therapy and ended at the last date of 5ARI exposure + 1 year. We identified 93,197 men who initiated 5ARI therapy (52% dutasteride, and 48% finasteride) between 2003 and 2013 and matched them 1:1 to men who did not start a 5ARI. The median at-risk period for the 5ARI group was 1.68 years (interquartile range 1.00, 4.27). With adjustment for the variables related to prior BC investigations there was no significant difference in BC diagnosis (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.82-1.32) during the period of 0 to <2 years of 5ARI use; however, after ≥2 years of 5ARI use, the risk of BC diagnosis was significantly lower among the 5ARI group (HR 0.82, 95% CI 0.79-0.94). In a similarly adjusted model, BC mortality was lower among 5ARI users, but no longer statistically significant (HR 0.82, 95% CI 0.65, 1.02). When stratified by type of 5ARI, finasteride significantly reduced the risk of BC diagnosis after ≥2 years of continuous use (HR 0.86, 95% CI 0.76, 0.96); however, dutasteride did not (HR 0.92, 95% CI 0.83, 1.03). In a large cohort of men, the use of a 5ARI was associated with a significantly decreased the risk of BC diagnosis after more than 2 years of continuous therapy.

Global changes in bladder cancer mortality in the elderly

BackgroundBladder cancer is the 14th most common cause of cancer deaths worldwide and has a mean age of diagnosis of 73 years. Elderly people have fewer curative treatment options for muscle invasive bladder cancer. The aim of this study is to investigate how bladder cancer mortality has changed over the past forty years in different world regions to assess discrepancies between elderly and younger patients with bladder cancer. MethodsBladder cancer mortality data were extracted from the World Health Organisation’s GLOBOCAN database. Age-standardised mortality rates (ASMR) for bladder cancer were computed by year, sex, region and Human Development Index (HDI) using the world standard population. ResultsOverall ASMR in all available countries with data between 1986 and 2014 for men aged ≥ 75 has decreased from 101.2 to 89.9 per 100,000 (−11.2%). The decrease in ASMR for men < 75 has been 0.3–2.0 per 100,000 (−39.4%). In women aged ≥ 75 ASMR has decreased from 26.9 to 22.5 per 100,000 (−16.4%) and in women < 75 the ASMR has decreased from 0.76 to 0.56 per 100,000 (−26.4%).Correlation analysis showed a positive linear relationship between Human Development Index (HDI) and improvement in age-standardised mortality rate in all ages. Pearson’s coefficient showed that correlation was strongest in the 60–74 age group (r = −0.61, p < 0.001) and weakest in those aged ≥ 75 (r = −0.39, p = 0.01). ConclusionBladder cancer mortality is not improving in the elderly at the same rate as the rest of the population. Particular focus should be applied in future research to enhance and expand treatment options for bladder cancer that are appropriate for elderly patients.

Competing mortality risk from second primary malignancy in bladder cancer patients following radical cystectomy: Implications for survivorship

IntroductionMuscle-invasive bladder cancer (BC) often occurs in patients with competing mortality risks, while also being associated with the highest rate of second primary nonurothelial cancers (SNUC) of all solid malignancies. We investigated the incidence, risk factors, and timing of SNUC as a competing mortality risk factor in patients with BC who were treated with curative intent radical cystectomy (RC). MethodsWe performed a retrospective cohort study assessing patients who underwent RC for cT2-4 N0M0 BC from January 1, 2005 to December 31, 2018 at a single, high volume tertiary care referral center. The Fine–Gray multivariable regression model was used to evaluate predictive factors for SNUC. Cumulative incidence of mortality (CIM) was estimated with modified Kaplan–Meier analysis. ResultsThe median follow-up time for the 693 patients who underwent RC was 3.7 years (interquartile range [IQR] 1.9–5.9 years). SNUC developed in 85 (12.3%) patients at a median 3.0 years post-RC (IQR 1.2–5.5 years). On multivariable analysis, the only significant predictor for developing SNUC was freedom from BC recurrence or metastasis (HR 1.54, 95% CI 1.12–1.76, P = 0.019). The most common SNUCs were primary lung cancer (24, 3.2% of cohort) and colon cancer (9, 1.3% of cohort). BC surveillance imaging diagnosed SNUC in 35/52 (67.3%) patients with solid-organ visceral primaries. The overall mortality rate for any SNUC was 38.8%, with the 3 most lethal cancer types being pancreatic, lung, and colon (62.5%, 54.2%, and 44.4% mortality, respectively). The incidence of SNUC uniformly increased postoperatively, with a cumulative incidence of 22.1% (95% CI, 16.8–27.9%) at 12-years post-RC. 163 patients (23.5%) died from BC, 33 patients (4.8%) died from SNUC, and 94 patients (13.6%) died from other causes. While the CIM for BC plateaued around 5-years post-RC at 24%, the incidence of other-cause mortality uniformly rose throughout the postoperative period. By post-RC year 9 there was no significant difference in CIM between BC (CIM 27.2%, 95% CI, 23.5–31.1%) and other-causes (CIM 20.0%, 95% CI, 15.8–24.6%). ConclusionsThe cumulative incidence of SNUC at 12-years post-RC was 22%, with the majority identified on BC surveillance imaging. While BC mortality plateaued around 5-years post-RC, mortality related to SNUC or other causes rose steadily in the postoperative period. These data have clinical significance with regards to patient counseling, survivorship and oncologic surveillance in the highly comorbid muscle-invasive BC population.

Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy

Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches. To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis. This prognostic study analyzed patients with MIBC pooled from 6 prospective phase I/II, II, or III trials of trimodality therapy (Radiation Therapy Oncology Group [RTOG] 8802, 8903, 9506, 9706, 9906, and 0233) across 37 participating institutions in North America from 1988 to 2007. Eligible patients had nonmetastatic MIBC and were enrolled in 1 of the 6 trimodality therapy clinical trials. Analyses were completed August 2020. Trimodality therapy with transurethral bladder tumor resection and cisplatin-based chemoradiation therapy. MRE11 expression and association with disease-specific (bladder cancer) mortality (DSM), defined as death from bladder cancer. Pretreatment tumor tissues were processed for immunofluorescence with anti-MRE11 antibody and analyzed using automated quantitative image analysis to calculate a normalized score for MRE11 based on nuclear-to-cytoplasmic (NC) signal ratio. Of 465 patients from 6 trials, 168 patients had available tissue, of which 135 were analyzable for MRE11 expression (median age of 65 years [minimum-maximum, 34-90 years]; 111 [82.2%] men). Median (minimum-maximum) follow-up for alive patients was 5.0 (0.6-11.7) years. Median (Q1-Q3) MRE11 NC signal ratio was 2.41 (1.49-3.34). Patients with an MRE11 NC ratio above 1.49 (ie, above first quartile) had a significantly lower DSM (HR, 0.50; 95% CI, 0.26-0.93; P = .03). The 4-year DSM was 41.0% (95% CI, 23.2%-58.0%) for patients with an MRE11 NC signal ratio of 1.49 or lower vs 21.0% (95% CI, 13.4%-29.8%) for a ratio above 1.49. MRE11 NC signal ratio was not significantly associated with overall survival (HR, 0.84; 95% CI, 0.49-1.44). Higher MRE11 NC signal ratios were associated with better DSM after trimodality therapy. Lower MRE11 NC signal ratios identified a poor prognosis subgroup that may benefit from intensification of therapy.

Secular trends of morbidity and mortality of prostate, bladder, and kidney cancers in China, 1990 to 2019 and their predictions to 2030

BackgroundProstate, bladder and kidney cancers are common age-related genitourinary cancers. China's population is aging at an increasing rate, so predicting the morbidity and mortality of prostate, bladder, and kidney cancer in China is of great significance to provide epidemiological evidence for forward planning and implementation of national health policies.MethodsNumbers of incidences and deaths by cancer (prostate, bladder and kidney), sex (male and female) and age groups from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study. We applied Bayesian age-period-cohort models to predict incidences and deaths to 2030. We also calculated Age-standardized incidence rate (ASIR) and mortality rate (ASMR), their trends were quantified by estimated average percentage change (EAPC) and 95% confidence interval (CI).ResultsPredictions suggest that by 2030, there will be 315,310 prostate cancer cases, 192,390 bladder cancer cases and 126,980 kidney cancer cases. The ASIRs will increase to 25.54/100,000 for prostate cancer (EAPC: 2.88, 95% CI, 2.84, 2.93), 7.54/100,000 for bladder cancer (EAPC: 2.58, 95% CI, 2.54, 2.61) and 5.63/100,000 for kidney cancer (EAPC: 4.78, 95% CI, 4.54, 5.02). Number of deaths in 2030 will be 81,540, 61,220, and 41,940, respectively. Different ASMR changes are observed, the ASMR for prostate cancer will drop to 7.69/100,000 (EAPC: -0.29, 95% CI, -0.31, -0.27), the ASMR for bladder cancer will stabilize at 2.49/100,000 (EAPC: 0.00, 95% CI, -0.02, 0.03), the ASMR of kidney cancer will increase to 1.84/100,000 (EAPC: 3.45, 95% CI, 3.22, 3.67). From 1990 to 2030, higher numbers of cases and rates are reported among males and in the 60 plus age group, both ASIR and ASMR of bladder and kidney cancers presents progressively widening differences between both males and females and between the < 60 and the ≥ 60 age groups.ConclusionMorbidity and mortality of the three genitourinary cancers are predicted to increase further over the next decade. It highlights the need for timely development and implementation of optimal health policies to curb the epidemic trends.

Temporal Trends and Projections of Bladder Cancer Burden in China from 1990 to 2030: Findings from the Global Burden of Disease Study.

Identifying disease burden and risk factors of bladder cancer and projecting its epidemiological trend in China, which can provide reference data to formulate measures for its management and prevention. We analyzed the incidence, mortality, and disability-adjusted life-years (DALYs) data of bladder cancer in China from 1990 to 2019 and predicted to 2030 based on the Global Burden of Disease Study 2019. We also estimated the proportion of risk factors contributing to bladder cancer DALYs. The average annual percentage change (AAPC) in both sexes was calculated to quantify the temporal trends. In China, the age-standardized incidence rate of bladder cancer increased from 3.3/100,000 in 1990 to 5.16/100,000 in 2019 (AAPC of 1.47), while the age-standardized mortality rate and age-standardized DALYs rate declined slightly (AAPC of -0.58 and -0.65, respectively). The burden of bladder cancer increased with age, which reached a peak over 85 years old. The main risk factor for bladder cancer was smoking, and the contribution of high fasting plasma glucose increased from 1990 to 2019, with an AAPC of 0.85 in males and 0.61 in females. We predicted total incident cases, deaths and DALYs will increase to 150,372 and 53,520 and 1043,688 in 2030, respectively. The disease burden of bladder cancer in males will consistently higher than that in females from 2020 to 2030. Although mortality and DALYs rates showed downward trends, the disease burden remained heavy in China at present. More effective and long-term health policies are needed to develop for early prevention and treatment of bladder cancer.

Identification of adenylate cyclase 2 methylation in bladder cancer with implications for prognosis and immunosuppressive microenvironment.

BackgroundThe incidence and mortality of bladder cancer (BCa) are increasing, while the existing diagnostic methods have limitations. Therefore, for early detection and response prediction, it is crucial to improve the prognosis and treatment strategies. However, with existing diagnostic methods, detecting BCa in the early stage is challenging. Hence, novel biomarkers are urgently needed to improve early diagnosis and treatment efficiency.MethodsThe gene expression profile and gene methylation profile dataset were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), differentially methylated genes (DMGs), and methylation-regulated differentially expressed genes (MeDEGs) were gradually identified. A cancer genome map was obtained using online gene expression profile interaction analysis, and survival implications were produced using Kaplan-Meier survival analysis. GSEA was employed to predict the marker pathways where DEGs were significantly involved. The study used bisulfite PCR amplification combined with bisulfite amplicon sequencing (BSAS) to screen for methylation analysis of multiple candidate regions of the adenylate cyclase 2 (ADCY2) based on the sequence design of specific gene regions and CpG islands.ResultsIn this study, DEGs and DMGs with significantly up- or down-regulated expression were selected. The intersection method was used to screen the MeDEGs. The interaction network group in STRING was then visualized using Cytoscape, and the PPI network was constructed to identify the key genes. The key genes were then analyzed using functional enrichment. To compare the relationship between key genes and the prognosis of BCa patients, we further investigated ADCY2 and found that ADCY2 can be a potential clinical biomarker in BCa prognosis and immunotherapy response prediction. In human BCa 5637 and MGH1 cells, we developed and verified the effectiveness of ADCY2 primers using BSAS technology. The findings revealed that the expression of ADCY2 is highly regulated by the methylation of the promoter regions.ConclusionThis study revealed that increased expression of ADCY2 was significantly correlated with increased tumor heterogeneity, predicting worse survival and immunotherapy response in BCa patients.

Health and economic gain attributable to the introduction of the World Health Organization's drinking water standard on arsenic level in Hungary: A nationwide retrospective study on cancer occurrence and ischemic heart disease mortality

The World Health Organization (WHO) estimates that 140 million individuals are at risk from consumption of drinking water containing arsenic at concentrations above the WHO guideline value of 10 μg/l. Arsenic mitigation is considered to be the most effective way to prevent arsenic related diseases. After joining the European Union, Hungary implemented a Drinking Water Quality Improvement Programme (DWQIP) to reduce levels of arsenic in drinking water below the WHO guideline value. But what impact did this have on health? We estimated the change in lifetime excess skin, lung, and bladder cancer risks and mortality from ischaemic heart disease (IHD) associated with chronic arsenic intake among those exposed before (2004–2007) and after (2014–2017) the implementation of DWQIP. A population-based risk assessment approach was used to assess lifetime excess cancer risk applying two scenarios for lung and bladder cancers. The economic benefits of the DWQIP were estimated by the combination of cost of illness and value per statistical life methods. Compared to the period before the DWQIP, its implementation was associated with a significant reduction in arsenic in drinking water [median: 3.0 μg/l interquartile range (IQR): 1.5–12.0 μg/l to median: 2.15 μg/l IQR: 1.0–5.79 μg/l]. The two scenarios were estimated to be associated with 225.2 and 35.9 fewer cancer cases each year. The number of annually prevented IHD deaths was estimated to be 88.9. It was estimated that the benefits of the DWQIP will outweigh its costs. We conclude that reducing arsenic levels in drinking water to 10.0 μg/l resulted in significant health and economic benefits. Our study goes beyond the existing research, offering both new insights into the impact of arsenic mitigation and providing a methodological template for similar studies in the many parts of the world that have yet to reduce arsenic exposure.

Bladder cancer, inflammageing and microbiomes.

Ageing is correlated with elevated bladder cancer incidence, morbidity and mortality. Advanced age is also associated with elevated markers of chronic inflammation and perturbations in gut and urinary tract microbiota. One reason for the increased incidence and mortality of bladder cancer in the elderly might be that age-associated changes in multiple microbiomes induce systemic metabolic changes that contribute to immune dysregulation with potentially tumorigenic effects. The gut and urinary microbiomes could be dysregulated in bladder cancer, although the effect of these changes is poorly understood. Each of these domains - the immune system, gut microbiome and urinary microbiome - might also influence the response of patients with bladder cancer to treatment. Improved understanding of age-related alterations to the immune system and gut and urinary microbiomes could provide possible insight into the risk of bladder cancer development and progression in the elderly. In patients with bladder cancer, improved understanding of microbiota might also provide potential targets for therapeutic intervention.

AUTHOR REPLY

We thankDr. Schafer and Dr. Sundi for contributing to this timely discussion of the social and biological determinants of health disparities. As we hope to highlight, metastatic bladder cancer-specific survival has disparate outcomes between gender, race, and socioeconomic status. Given the high mortality and low overall survival of metastatic bladder cancer, this space has significant potential for improvement in care by targeting interventions for Black women and residents of high poverty areas.

Lipidomic Profiling Identifies a Novel Lipid Signature Associated with Ethnicity-Specific Disparity of Bladder Cancer.

Bladder Cancer (BLCA) is the ninth most frequently diagnosed cancer globally and the sixth most common cancer in the US. African Americans (AA) exhibit half the BLCA incidence compared to European Americans (EA), but they have a 70% higher risk of cancer-related death; unfortunately, this disparity in BLCA mortality remains poorly understood. In this study, we have used an ethnicity-balanced cohort for unbiased lipidomics profiling to study the changes in the lipid fingerprint for AA and EA BLCA tissues collected from similar geographical regions to determine a signature of ethnic-specific alterations. We identified 86 lipids significantly altered between self-reported AA and EA BLCA patients from Augusta University (AU) cohort. The majority of altered lipids belong to phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), ly sophosphatidylcholines (lysoPCs), phosphatidylserines (PSs), and diglycerides (DGs). Interestingly, levels of four lysoPCs (lyso PCs 20:3, lyso PCs 22:1, lyso PCs 22:2, and lyso PCs 26:1) were elevated while, in contrast, the majority of the PCs were reduced in AA BLCA. Significant alterations in long-chain monounsaturated (MonoUN) and polyunsaturated (PolyUN) lipids were also observed between AA and EA BLCA tumor tissues. These first-in-field results implicate ethnic-specific lipid alterations in BLCA.

Immune Checkpoint Inhibitors as a Neoadjuvant/Adjuvant Treatment of Muscle-Invasive Bladder Cancer: A Systematic Review.

Simple SummaryBladder cancer is the ninth most common cancer worldwide. Immune checkpoint inhibitors, a novel class of immunotherapy drugs that restore natural antitumoral immune activity, have been applied to improve the overall survival and to reduce the morbidity and mortality of bladder cancer both in neoadjuvant and adjuvant settings. However, some patients do not respond to checkpoint inhibitors. Consequently, the capability for identifying patients eligible for this type of immunotherapy represent one of the efforts of ongoing studies. We aim to summarize the most recent evidence on immune checkpoint inhibitors in neoadjuvant and adjuvant setting in the treatment of muscle-invasive bladder cancer.Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25% of patients undergo radical cystectomy or radiotherapy. Immune checkpoint inhibitors represent a novel class of immunotherapy drugs that restore natural antitumoral immune activity via the blockage of inhibitory receptors and ligands expressed on antigen-presenting cells, T lymphocytes and tumour cells. The use of immune checkpoint inhibitors in bladder cancer has been expanded from the neoadjuvant setting, i.e., after radical cystectomy, to the adjuvant setting, i.e., before the operative time or chemotherapy, in order to improve the overall survival and to reduce the morbidity and mortality of both the disease and its treatment. However, some patients do not respond to checkpoint inhibitors. As result, the capability for identifying patients that are eligible for this immunotherapy represent one of the efforts of ongoing studies. The aim of this systematic review is to summarize the most recent evidence regarding the use of immune checkpoint inhibitors, in a neoadjuvant and adjuvant setting, in the treatment of muscle-invasive bladder cancer.

MP42-03 5α-REDUCTASE INHIBITORS AND THE RISK OF BLADDER CANCER IN A LARGE, POPULATION-BASED COHORT

You have accessJournal of UrologyCME1 May 2022MP42-03 5α-REDUCTASE INHIBITORS AND THE RISK OF BLADDER CANCER IN A LARGE, POPULATION-BASED COHORT Snir Dekalo, Eric McArthur, Jeff Campbell, Michael Ordon, Nicholas Power, and Blayne Welk Snir DekaloSnir Dekalo More articles by this author , Eric McArthurEric McArthur More articles by this author , Jeff CampbellJeff Campbell More articles by this author , Michael OrdonMichael Ordon More articles by this author , Nicholas PowerNicholas Power More articles by this author , and Blayne WelkBlayne Welk More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002608.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The ability of 5α-Reductase Inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results. As such, our aim was to conduct a retrospective cohort population-based study to evaluate the association between 5ARI use, BC diagnosis, and BC mortality. METHODS: We used routinely collected health care data from Ontario, Canada. Men ≥66 years of age with a prescription for a 5ARI were matched to non-5ARI users. Matching was done using a propensity score of selected covariates to make 96 different covariates comparable. We also measured an additional five baseline variables which may have impacted the risk of future BC diagnosis: cystoscopy, cytology, Urine-dip, hematuria, and transurethral resection of bladder lesion. Only the first period of continuous use of 5ARIs was considered. The prespecified at-risk period for outcomes started 1 year after initiating therapy (this lag period allowed time for a biologically plausible effect from the 5ARI to occur) and ended at the last date of 5ARI exposure + 1 year (to allow time for BC to be diagnosed, and due to the residual effects of 5ARIs). RESULTS: We identified 93,197 men who initiated 5ARI therapy (52% dutasteride, and 48% finasteride). between 2003-2013 and matched them 1:1 to men who did not start a 5ARI. The median at-risk period for the 5ARI group was 1.68 years (IQR 1.00, 4.27). Both BC diagnosis and BC mortality were significantly less common during the at-risk period among the 5ARI group (HR 0.76, 95%CI 0.70-0.83; and HR 0.66, 95%CI 0.53-0.82 respectively). With adjustment for the variables related to prior BC investigations there was no significant difference in BC diagnosis (HR 1.05 95%CI 0.82-1.32 during the period of 0-<2 years of 5ARI use; however after ≥2 years of 5ARI use the risk of BC diagnosis was significantly less among the 5ARI group (HR 0.82, 95%CI 0.79-0.94). In the adjusted model, BC mortality was lower among 5ARI users, but no longer significant (HR 0.82, 95%CI 0.65, 1.02). CONCLUSIONS: In a large cohort of men using 5ARI, we demonstrated a decreased risk of BC diagnosis. This risk reduction was present after ≥2 years of continuous therapy. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e730 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Snir Dekalo More articles by this author Eric McArthur More articles by this author Jeff Campbell More articles by this author Michael Ordon More articles by this author Nicholas Power More articles by this author Blayne Welk More articles by this author Expand All Advertisement PDF DownloadLoading ...

Race, ethnicity, and gender reporting in North American clinical trials for BCG-unresponsive non-muscle invasive bladder cancer.

The National Institutes of Health (NIH) Revitalization Act of 1993 established guidelines for the inclusion of racial/ethnic minorities and women in clinical research. However, the reporting rate of such patient demographic data in clinical trials for BCG-unresponsive non-muscle invasive bladder cancer is not well characterized. We identified published clinical trials of all phases (I -III) for BCG-unresponsive non-muscle invasive bladder cancer conducted in the US and/or Canada. We calculated the proportion of studies reporting patient gender and race/ethnicity, tabulating these data when present. We compared reported trial participant race, ethnicity and gender with the number of new bladder cancer cases and deaths using the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI) U.S. Cancer Statistics data from 2013 -2017. We identified 27 trials published from 1998 -2021 enrolling a total of 1673 patients. While all trials included data on patient gender (22% women overall), only 40.7% included any data on patient race/ethnicity. Among those that did, trial participants were reported as white (94%), Black (2.1%), Hispanic (0.6%), Asian (0.9%), and Other (2.3%). Racial/ethnic minorities were underrepresented in clinical trials relative to their proportion of new bladder cancer cases and deaths. Most clinical trials that have been conducted for BCG-unresponsive non-muscle invasive bladder cancer do not report data on patient race or ethnicity despite NIH guidelines advocating for inclusion of such data. Racial/ethnic minorities remain underrepresented in these trials relative to the burden of bladder cancer prevalence and mortality faced by these groups.