Bladder Cancer-specific Mortality Research Articles

Impact of rural location on receipt of standard of care treatment and survival for locally advanced bladder cancer in Louisiana.

We aim to determine the effect of region of residence (urban vs. rural) on the odds of receiving standard of care treatment for locally advanced BCa in Louisiana and its impact on survival outcomes. Using the Louisiana Tumor Registry, we identified American Joint Committee on Cancer (AJCC) stage II or III, BCa diagnoses in Louisiana residents between 2010 and 2020. Treatment received was classified as standard or non-standard of care according to American Urological Association (AUA) guidelines and location of residence was determined using Rural Urban Commuting Area-Tract-level 2010 (RUCA). Multivariable logistic regression analyses and multivariate cox proportional hazard analyses were performed. Of 983 eligible patients, 85.6% (841/983) lived in urban areas. Overall, only 37.5% received standard-of-care (SOC) for the definitive management of locally advanced bladder cancer. Individuals living in rural areas (OR 0.53, 95% CI: 0.31-0.91, p = 0.02) were less likely to receive standard of care treatment. Both rural residence and receipt of non-standard of care therapy were associated with an increased risk of bladder cancer-specific (adj HR 1.53, 95% CI: 1.09-2.14, p = 0.01 and adj HR: 1.85, 95% CI: 1.43-2.39, <0.0001) and overall mortality (adj HR: 1.28, 95% CI: 1.01-1.61, p = 0.04 and adj HR: 1.73 95% CI: 1.44-2.07, p < 0.0001). Most patients with locally advanced bladder cancer in Louisiana do not receive SOC therapy. Individuals living in rural locations are more likely to receive non-standard of care therapy than individuals in urban areas. Nonstandard of care treatment and rural residence are both associated with worse survival outcomes for Louisiana residents with locally advanced bladder cancer.

Poorer Outcomes in Bladder Cancer Patients With Diabetes: A Systematic Review and Meta-analysis Addressing Over 226,472 Bladder Cancer Patients

Purpose: Diabetes mellitus, a frequent comorbid condition in cancer patients, has been shown to increase risk of all-site cancer mortality. This relationship has not been systematically studied in bladder cancer patients. This systematic review and meta-analysis aimed to identify, evaluate, and synthesize available evidence on the relationship between history of diabetes and outcomes in bladder cancer patients.Materials and Methods: Systematic searches interrogated OVID MEDLINE, Embase, Web of Science, Google Scholar, and Cochrane Library to identify scholarly reports relating diabetes to all-cause mortality, bladder cancer-specific mortality, recurrence, and progression in bladder cancer patients. After critical review, meta-analysis was used to quantitively synthesize qualifying data and assess potential influence of publication bias, clinical heterogeneity, and residual confounding.Results: We synthesized data on over 226,472 patients treated with curative intent uniquely represented in 28 studies that met quality metrics. Having diabetes was positively associated with each outcome. Hazard ratio estimates were indistinguishable for mortality from any cause, 1.22 (95% confidence interval [CI], 1.12–1.33) and bladder cancer-specific mortality, 1.28 (95% CI 1.17–1.41) and notably stronger in patients with muscle-invasive and high-risk non–muscle-invasive bladder cancer, 1.32 (95% CI, 1.15–1.50) and 1.48 (95% CI, 1.06–2.06). Neither publication bias, systematic error, nor confounding by factors such as smoking or obesity is likely to explain the observed associations.Conclusions: Bladder cancer patients with diabetes experience elevated mortality that is not explained by diabetes-related comorbidities or complications. Future research should explore type, severity, and duration of diabetes in relation to unfavorable bladder cancer outcomes.

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.

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.

ARTIA-Bladder: Daily Online Adaptive Short-Course Radiation Therapy (RT) and Concurrent Chemotherapy for Muscle-Invasive Bladder Cancer (MIBC): A Prospective Trial of an Individualized Approach for Reducing Bowel and Bladder Toxicity

Concurrent chemo-radiotherapy is commonly prescribed for muscle-invasive bladder cancer (MIBC). Post hoc analysis of two large, randomized trials found that hypofractionation improves loco-regional control (LRC) vs. standard fractionation in this population. A challenge in traditional image-guided radiotherapy of the bladder is that daily changes in bladder position and size requires large margins to ensure target coverage. This makes it difficult to spare uninvolved bladder from high-dose treatment, increases the risk of bowel toxicity, and results in historical rates of acute G3+ toxicity exceeding 20-30%. Daily online adaptive RT (ART) may enable reduced, personalized margins that maintain target coverage while reducing dose to OARs. This prospective clinical trial will test whether: 1) participants undergoing ART for MIBC have a lower rate of acute G3+ GI/GU toxicity compared with the 31% historical control rate (Stage III BC2001 trial), and 2) 2-year LRC with ART will be non-inferior to historical controls (75%). This multi-national trial will enroll 165 adult subjects with stage cT2-T4aN0M0 urothelial MIBC. Subjects will have undergone an attempt at maximal transurethral resection of bladder tumor. Patients with clinically involved nodes or G2+ GI or G3+ GU symptoms/conditions at baseline are ineligible. Concurrent with chemotherapy, participants will receive (at the discretion of the investigator) either 55 Gy in 20 fx to whole-bladder or 46 Gy in 20 fx to whole-bladder plus simultaneous in-field boost of 55 Gy in 20 fx to tumor bed. A personalized ITV will be derived for each subject based on bladder expansion, as assessed on two CT simulations separated by 30 min. Daily ART will be attempted for all subjects. The primary endpoint is acute G3+ GI/GU toxicity. Secondary endpoints are LRC; quality of life (EORTC QLQ-BLM30, EPIC 26 bowel and urinary); global function (EQ-5D-5L ); 2-year disease-free, bladder intact event-free, and overall survival; 2-year bladder cancer-specific mortality; NTCP model of acute GI toxicity for hypofractionated bladder RT; workflow feasibility of ART; improved target coverage ± reduced dose to critical OARs vs. non-ART dosimetry; acute G3+ GI/GU toxicity rate in subjects with ≥75% of their treatments as ART; and acute G3+ GI/GU toxicity in the cohort treated with partial bladder boost. Exploratory translational and correlative endpoints will also be examined. This trial opened to enrollment on Feb 2, 2023; the study duration is expected to be 4-5 years. This prospective clinical trial will provide robust clinical data to inform healthcare providers' decisions on the use of daily online ART and hypofractionation as a bladder preservation strategy for this population.

Insurance Type and Area Deprivation Are Associated With Worse Overall Mortality for Patients With Muscle-invasive Bladder Cancer

To examine the association of area-level socioeconomic status, rural-urban residence, and type of insurance with overall and cancer-specific mortality among patients with muscle-invasive bladder cancer. Using the Pennsylvania Cancer Registry, which collects demographic, insurance, and clinical information on every patient with cancer within the state, we identified all patients diagnosed with non-metastatic muscle-invasive bladder cancer between 2010 and 2016 based on clinical and pathologic staging. We used the Area Deprivation Index (ADI) as a surrogate for socioeconomic status and Rural-Urban Commuting Area codes to classify urban, large town, and rural communities. ADI was reported in quartiles, with 4 representing the lowest socioeconomic status. We fit multivariable logistic regression and Cox models to assess the relationship of these social determinants with overall and cancer-specific survival adjusting for age, sex, race, stage, treatment, rural-urban classification, insurance and ADI. We identified 2597 patients with non-metastatic muscle-invasive bladder cancer. On multivariable analysis, Medicare (hazards ratio [HR] 1.15), Medicaid (HR 1.38), ADI 3 (HR 1.16) and ADI 4 (HR 1.21) were independent predictors of greater overall mortality (all P < 0.05). Female sex and receipt of non-standard treatment were associated with increased overall mortality and bladder cancer-specific mortality. There was no significant difference in both overall and cancer-specific survival between patients who were non-Hispanic White compared to non-White or between those from urban areas, large towns, or rural locations. Lower socioeconomic status and Medicare and Medicaid insurance were associated with a greater risk of overall mortality while rural residence was not a significant factor. Implementation of public health programs may help reduce the gap in mortality for low SES at-risk populations.

PD29-05 ASSOCIATION OF AGE WITH NON-MUSCLE INVASIVE BLADDER CANCER: A BIOLOGICAL BASIS FOR EPIDEMIOLOGICAL DISPARITIES?

You have accessJournal of UrologyCME1 Apr 2023PD29-05 ASSOCIATION OF AGE WITH NON-MUSCLE INVASIVE BLADDER CANCER: A BIOLOGICAL BASIS FOR EPIDEMIOLOGICAL DISPARITIES? Niyati Lobo, Akshay Sood, Zhigang Duan, Wei Shen Tan, Valentina Grajales, Sia Viborg Lindskrog, Lars Dyrskjøt, Aarhus, Denmark, Hui Zhao, Sharon Giordano, Stephen B. Williams, and Ashish M. Kamat Niyati LoboNiyati Lobo More articles by this author , Akshay SoodAkshay Sood More articles by this author , Zhigang DuanZhigang Duan More articles by this author , Wei Shen TanWei Shen Tan More articles by this author , Valentina GrajalesValentina Grajales More articles by this author , Sia Viborg LindskrogSia Viborg Lindskrog More articles by this author , Lars DyrskjøtLars Dyrskjøt More articles by this author , Aarhus Aarhus More articles by this author , Denmark Denmark More articles by this author , Hui ZhaoHui Zhao More articles by this author , Sharon GiordanoSharon Giordano More articles by this author , Stephen B. WilliamsStephen B. Williams More articles by this author , and Ashish M. KamatAshish M. Kamat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003315.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Age disparity in patients with non-muscle-invasive bladder cancer (NMIBC) exists. Whether this is due to differences in cancer care or tumour biology is unclear. We sought to investigate age disparities in NMIBC using individual patient-level data from two cohorts: the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and the publicly available UROMOL dataset. METHODS: SEER-Medicare linked data was used to identify patients, aged ≥66 years, with clinical stage Ta, Tis and T1 NMIBC between 2005-2019 (n=32 225). Multivariable competing-risks Cox regression analyses were used to examine the association between age and recurrence (defined as receipt of TURBT ≥3 months after index diagnosis of NMIBC or progression), progression (defined as receipt of definitive treatment for bladder cancer) and bladder cancer-specific mortality rates after adjusting for demographic-, cancer- and treatment-related variables. Using the UROMOL cohort (n=834), age disparities across transcriptomic, genomic and spatial proteomic domains were assessed. Differences between groups were testing using Pearson’s Chi-square test or Fisher’s test for categorical variables. RESULTS: Analysis of the SEER-Medicare cohort revealed 10-year recurrence rates of 60.9%, 61.1% and 60.4% in patients aged 66-70 yrs, 71-80 yrs and ≥81 yrs, respectively; 10-year progression rates of 29.3%, 32.2% and 38.2%, respectively; and 10-year bladder-cancer specific mortality rates of 5.5%, 7.9% and 14.3%, respectively. Age ≥ 81 yrs was associated with a higher risk of progression (HR 1.32, 95% CI 1.25-1.40, p<0.001) and bladder cancer-specific mortality (HR 2.58, 95% CI 2.27-2.95, p<0.001). Analysis of UROMOL 2021 transcriptomic classes revealed that Class 2a was more frequently observed in older patients (34% in >75 yrs vs. 22% in ≤65 yrs; p=0.004). Compared to patients <65 yrs, those aged >75 yrs were more likely to have TP53 pathway change (54% vs. 38%; p=0.032). UROMOL genomic class 3 was more frequently observed in patients >75 yrs (42% vs. 24%; p=0.001), who also had higher amounts of altered genome (median: 337.7Mb vs. 168.2Mb; p<0.001). No significant differences were observed in immune cell infiltration scores between age groups. CONCLUSIONS: Among SEER-Medicare patients with NMIBC, advanced age is associated with higher risks of progression and bladder-cancer specific mortality. These results reflect age-related molecular biological differences observed across transcriptomic and genomic domains. Source of Funding: Niyati Lobo was supported by The Urology Foundation-Fulbright Scholar Award © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e826 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Niyati Lobo More articles by this author Akshay Sood More articles by this author Zhigang Duan More articles by this author Wei Shen Tan More articles by this author Valentina Grajales More articles by this author Sia Viborg Lindskrog More articles by this author Lars Dyrskjøt More articles by this author Aarhus More articles by this author Denmark More articles by this author Hui Zhao More articles by this author Sharon Giordano More articles by this author Stephen B. Williams More articles by this author Ashish M. Kamat More articles by this author Expand All Advertisement PDF downloadLoading ...

New Mental Health Diagnosis as a Prognostic Factor for Muscle-Invasive Bladder Cancer.

To examine differences in survival outcomes for muscle-invasive bladder cancer patients stratified by new mental health diagnosis. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients diagnosed with muscle-invasive bladder cancer between 2008 and 2014. Our primary outcome was cancer-specific and overall hazards of mortality. As a secondary outcome, we reported predictors of developing a new mental health diagnosis after bladder cancer diagnosis. We used Cox proportional hazards models to determine the impact of palliative care and mental health diagnoses on survival outcomes after adjusting for grade, stage, comorbidity index, and baseline demographics. Of the 3794 patients who met inclusion criteria, 1193 (31%) were diagnosed with a mental health illness after their bladder cancer diagnosis during the 6 years in the study period. The most common diagnoses were depression (13%), alcohol and drug abuse (12%), and anxiety (11%). Patients with a post-bladder cancer mental health diagnosis had a 57% higher hazard of overall mortality (HR 1.57, P=.048) and an 80% higher hazard of bladder cancer-specific mortality (HR 1.81, P=.037) CONCLUSIONS: New mental health diagnoses are associated with worse survival in patients with muscle invasive bladder cancer. This suggests that a multimodal approach to bladder cancer treatment should include addressing the non-oncologic needs of the patient to optimize survival outcomes.

Disparities in cause-specific mortality by race and sex among bladder cancer patients from the SEER database.

Previous literature shows that more bladder cancer patients overall die from causes other than the primary malignancy. Given known disparities in bladder cancer outcomes by race and sex, we aimed to characterize differences in cause-specific mortality for bladder cancer patients by these demographics. We identified 215,252 bladder cancer patients diagnosed with bladder cancer from 2000 to 2017 in the SEER 18 database. We calculated cumulative incidence of death from seven causes (bladder cancer, COPD, diabetes, heart disease, external, other cancer, other) to assess differences in cause-specific mortality between race and sex subgroups. We used multivariable Cox proportional hazards regression and Fine-Gray competing risk models to compare risk of bladder cancer-specific mortality between race and sex subgroups overall and stratified by cancer stage. 17% of patients died from bladder cancer (n = 36,923), 30% died from other causes (n = 65,076), and 53% were alive (n = 113,253). Among those who died, the most common cause of death was bladder cancer, followed by other cancer and diseases of the heart. All race-sex subgroups were more likely than white men to die from bladder cancer. Compared to white men, white women (HR: 1.20, 95% CI: 1.17-1.23) and Black women (HR: 1.57, 95% CI: 1.49-1.66) had a higher risk of dying from bladder cancer, overall and stratified by stage. Among bladder cancer patients, death from other causes especially other cancer and heart disease contributed a large proportion of mortality. We found differences in cause-specific mortality by race-sex subgroups, with Black women having a particularly high risk of dying from bladder cancer.

Impact of Age at Diagnosis of Bladder Cancer on Survival: A Surveillance, Epidemiology, and End Results-Based Study 2004-2015.

An older age contributes to the development of bladder cancer. However, the relationship between advanced age at the diagnosis and prognosis of bladder cancer has been few reported. This study aimed to determine the effect of age on survival in bladder cancer with different subgroups. 117,275 patients with bladder cancer, identified from the Surveillance, Epidemiology, and End Results database during 2004-2015 in America, were divided into 4 age groups (≤54, 55 to 64, 65 to 74, and ≥75 years). Multivariable Cox proportional-hazards model and competing risk model were conducted according to different age groups. Heat maps were plotted to show the impact of age on survival in subgroups classified by other clinicopathological variables. Moreover, restricted cubic spline was used to model the association between age and the risk of death. Patients aged ≥75years had shorter overall survival in comparison with those aged ≤54years (hazard ratio [HR] = 5.36, 95% confidence interval [CI] = 5.13-5.59). Compared with patients aged ≤54years, patients older than 75years experienced a decreased rate of bladder cancer-specific survival (subdistribution HR = 2.15, 95% CI = 2.04-2.25). Heat maps also showed that older ages were associated with worse overall cumulative mortality and bladder cancer-specific cumulative mortality. Similarly, restricted cubic spline verified the impact of age on survival of bladder cancer. Age at diagnosis of bladder cancer was found to be a significant predictor for the worse overall survival and bladder cancer-specific survival even in an era with more effective therapies. Exploring the reasons why older age contributes to poor outcomes for bladder cancer will be the focus of future research.

Competitive Risk Model for Specific Mortality Prediction in Patients with Bladder Cancer: A Population-Based Cohort Study with Machine Learning.

Noncancer death accounts for a high proportion of all patients with bladder cancer, while these patients are often excluded from the survival analysis, which increases the selection bias of the study subjects in the prediction model. Clinicopathological information of bladder cancer patients was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, and the patients were categorized at random into the training and validation cohorts. The random forest method was used to calculate the importance of clinical variables in the training cohort. Multivariate and univariate analyses were undertaken to assess the risk indicators, and the prediction nomogram based on the competitive risk model was constructed. The model's performance was evaluated utilizing the calibration curve, consistency index (C index), and the area under the receiver operator characteristic curve (AUC). In total, we enrolled 39285 bladder cancer patients in the study (27500 patients were allotted to the training cohort, whereas 11785 were allotted to the validation cohort). A competitive risk model was constructed to predict bladder cancer-specific mortality. The overall C index of patients in the training cohort was 0.876, and the AUC values were 0.891, 0.871, and 0.853, correspondingly, for 1-, 3-, and 5-year cancer-specific mortality. On the other hand, the overall C index of patients in the validation cohort was 0.877, and the AUC values were 0.894, 0.870, and 0.847 for 1-, 3-, and 5-year correspondingly, suggesting a remarkable predictive performance of the model. The competitive risk model proved to be of great accuracy and reliability and could help clinical decision-makers improve their management and approaches for managing bladder cancer patients.

Beta-blocker use and urothelial bladder cancer survival: a Swedish register-based cohort study

Background Recent observational studies linked β-adrenergic receptor blocker use with improved survival in patients with several cancer types, but there is no information on the potential effects of β-blockers in patients with bladder cancer. Literature from pre-clinical studies is also limited, but urothelial cancer can exhibit significant overexpression of β-adrenergic receptors relative to normal urothelial tissue, suggesting that urothelial cancer may benefit from β-blockade therapy. We thus aimed to explore the possible association between β-blocker use and bladder cancer-specific mortality (BCSM) among patients with urothelial bladder cancer. Material and methods Patients diagnosed during 2006–2014 and identified from the Swedish Cancer Register (n = 16,669) were followed until 31 December 2015. Cox regression was used to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis with BCSM (primary outcome) and all-cause mortality, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and surgical procedures. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. Results Overall, β-blocker use was associated with lower BCSM [HR 0.88 (95%CI 0.81–0.96)]. Especially use of nonselective β-blockers showed a clear inverse association in comparison with both nonuse [0.66 (0.50–0.86)] and use of other antihypertensive medications [0.72 (0.54–0.95)]. The inverse association was most pronounced among patients with locally advanced/metastatic disease: [0.35 (0.18–0.68)]. A lower-magnitude inverse association was observed for selective β-blocker use [0.91 (0.83–0.99)]. Largely similar inverse associations were observed for hydrophilic [0.82 (0.70–0.95)] and lipophilic [0.91 (0.83–1.00)] β-blocker use. Conclusion β-blocker use, particularly of the nonselective type, was associated with lower BCSM, especially in patients with locally advanced/metastatic urothelial bladder cancer.

Longitudinal analysis of bladder cancer-specific mortality trends in the United States.

445 Background: Bladder cancer is the most common malignancy of the urinary system. Advances in diagnosis, imaging, and treatments have led to improvements in bladder cancer management. Recent data demonstrate decreasing bladder cancer-specific mortality (BCSM) rates between 2014-2018 for both males and females, however, these trends have not been further examined by race, ethnicity, or geographical location. Using a comprehensive dataset of BCSM over 2 decades, we sought to evaluate differences in BCSM rates overall and by sex, race, ethnicity, location and urbanization category in the United States (US). Methods: Age-adjusted mortality rates for bladder cancer (ICD10 code 67) were obtained for males and females of all ages in the US from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database. BCSM rates from 1999-2019 were estimated using linear regression. BSCM trends were evaluated by sex, race (White vs. Black), ethnicity (Hispanic vs. Non-Hispanic), urbanization category, and census region. BCSM rates were compared by F-test. Data analysis was performed using SAS 9.4. All p-values are based on a two-sided hypothesis test with values &lt; 0.05 considered statistically significant. Results: From 1999-2019, age-adjusted BCSM rate overall has decreased linearly by (-)0.0073 per 100,000 population/year (p &lt; 0.05). Evaluating by sex, both female [(-)0.131] and male [(-)0.022] BCSM rates decreased yearly (p &lt; 0.05). By ethnicity, male Hispanic and female Non-Hispanic patients had significantly decreasing BCSM rates [(-)0.021 and (-)0.011, respectively, p &lt; 0.05]. White patients had a slightly decreasing rate of BCSM [(-)0.0003, p = NS] while Black patients had an increasing BCSM rate [(+)0.022, p &lt; 0.05] – the difference between the two rates was significant (p &lt; 0.0001). BCSM rates were significantly decreasing in all census regions (Northeast, Midwest, South, Midwest, p &lt; 0.05). BCSM rate in micropolitan (rural) regions has increased yearly [(+)0.006], and rate differences between rural vs large fringe metro (suburban) and vs small metro (population &lt; 250,000) categories, both with significantly decreasing BCSM rates, were statistically significant (p = 0.03 and p = 0.047, respectively). Conclusions: Using comprehensive data on BCSM in the United States over two decades, we demonstrate that the overall mortality rate from bladder cancer has been decreasing. However, when disaggregating age-adjusted BCSM by sex, race, ethnicity, census regions, and urbanization categories, significant differences in mortality rates are found including worsening mortality for Black patients, demonstrating that improvements in BCSM are not equitable across variables. Further evaluation of these trends is important to understand how to target specific populations to improve BCSM and overall outcomes for all patients with bladder cancer.

Impact of selection bias on outcomes in veterans with muscle-invasive bladder cancer receiving bladder preserving trimodality therapy.

462 Background: Retrospective studies using large registries comparing outcomes between radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) to trimodality therapy (TMT), which includes transurethral resection of bladder tumor followed by chemoradiation, often cannot distinguish whether patients receiving TMT were eligible for cystectomy but declined or simply ineligible for cystectomy. The objective of this study was to compare survival outcomes of patients with MIBC receiving TMT stratified by whether they were cystectomy-eligible to patients receiving RC +/- NAC. Methods: We used the national Veterans Affairs’ (VA) database to identify patients diagnosed between 2000-2017 with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent RC or TMT. Overall survival (OS) was evaluated with multivariable Cox proportional hazards model. Bladder cancer-specific mortality (BCSM) was evaluated with multivariable Fine-Gray regression. We conducted a chart review of clinical notes to ascertain if patients were eligible for cystectomy. Results: Overall 2306 Veterans with MIBC were included: 1472 (64%) with RC without NAC, 506 (22%) with RC-NAC, 107 (4.6%) with TMT eligible for RC, and 221 (9.4%) with TMT ineligible for RC. Median follow up time was 4.7 years. Patients receiving RC were on average 10 years younger, had higher creatinine clearance, and fewer comorbidities than those receiving TMT. Cystectomy-eligible TMT patients had higher creatinine clearance and fewer comorbidities than those ineligible for cystectomy. On multivariable analysis, compared to RC-NAC, TMT in cystectomy-eligible patients was associated with similar OS (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.76 - 1.28; p = 0.93) and BCSM (HR 1.02; 95% CI 0.71-1.47; p = 0.91). Compared to RC-NAC, TMT in cystectomy-ineligible patients was associated with inferior OS (HR 1.39; 95% CI 1.13 - 1.71; p = 0.002) and BCSM (HR 1.61; 95% CI 1.23 - 2.10; p &lt; 0.001). Conclusions: There is a significant selection bias among patients with MIBC receiving TMT. Cystectomy-eligible patients receiving TMT likely have similar survival outcomes as those receiving RC. Comparisons between RC and TMT in large registry data that lack information regarding eligibility for cystectomy in the TMT arm may be unreliable.

Geographic distribution of racial differences in mortality in muscle-invasive bladder cancer patients: an opportunity for improvement.

To determine the geographic distribution of muscle-invasive bladder cancer mortality according to race in the United States (US). African Americans (AAs) have up to two times the risk of bladder cancer mortality compared to Caucasians. Bladder cancer mortality increases exponentially once it invades the muscle. Geographic heterogeneity in bladder cancer mortality according to race remains to be determined. Analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data for 6,044 patients aged 66-85 diagnosed with clinical stage T2-T4 N0M0 bladder cancer from 1 January 2002 to 31 December 2011. Fine and Gray-competing risks regression models were used to assess the association of race with bladder cancer-specific mortality (BCSM) according to tumor registry. Out of 6,044 patients, 5,408 (89.5%) were Caucasian, 352 (5.82%) were non-Hispanic AA, 85 (1.4%) were Hispanic, and 199 (3.29%) were other. Of the 18 registries, AAs with bladder cancer were largely concentrated in Louisiana (19%), New Jersey (17.9%), and Georgia (17.6%). New Jersey was the only registry where AAs had increased risk of BCSM than Caucasians and only for stage T2 disease: (AHR, 1.74; 95% CI 1.22-2.47, p = 0.002). According to treatment, AAs in New Jersey had worse BCSM than Caucasians when they underwent radical cystectomy (AHR, 2.05; 95% CI 1.26-3.35, p = 0.0039) and radiotherapy or chemotherapy alone (AHR, 1.55; 95% CI 1.03-2.35, p = 0.0367). We observed geographic variation in bladder cancer mortality which impacted only one registry with one of the largest population of AAs. These findings support further investigation into the social determinants of race (i.e., socioeconomic status and distance to healthcare facility) and culturally centered healthcare decision making which may drive these results.

Risk of recurrence and long-term mortality following radical cystectomy for bladder cancer

Purpose To investigate the risk of recurrence and long-term mortality after radical cystectomy (RC) for bladder cancer (BC) at a high-volume tertiary referral center in Denmark over 19 years. Materials and methods Patients undergoing RC between the 1st of January 2000 to 31st of December 2018 were included. Patient data were manually retrieved from electronic patient files. Follow-up ended 18th of May 2020. Cumulative incidences were used to assess risk of recurrence and mortality using competing risk modelling. Cause-specific Cox regression models were used for multivariable analysis. Results A total of 1267 patients underwent RC of which 1042 were eligible for analysis. Overall mortality was 40% and 56% after 5 and 10 years, respectively. The cumulative incidence of recurrence and BC specific mortality was high within the first 2 years. Only 3.2% of the patients with recurrence were alive at the end of follow-up. The cumulative incidence of BC mortality after 5 years was 6.7% (95% CI 3.6–9.9) and 10% (95% CI 6.8–14) for patients with ≤ pT1bN0 and pT2N0, respectively. For patients with lymph node positive disease the cumulative incidence of BC mortality after 5 years was 65% (95% CI 58–71). Conclusions We found a significant risk of recurrence and disease-specific mortality following RC for BC, especially within the first 2 years following surgery. Our data seem comparable to other large cohorts. The chance of long-term survival following recurrence is low and there is a continuous need to improve adjuvant or salvage strategies following RC.

Effect of prior radiation on stage, differentiation, and survival in bladder cancer.

Clinically significant differences in radiation-related bladder tumors are not well-characterized, and survival analyses are needed. In this study, we aimed to utilize a national cancer database to evaluate the effect of prior radiation on tumor characteristics and survival in bladder cancer patients. The Surveillance, Epidemiology, and End Results (SEER) 9 database was queried to identify patients diagnosed with bladder cancer as a second malignancy. Patients having undergone radiation prior to developing bladder cancer were selected for comparative analysis. Logistic regression was used to generate odds ratios to evaluate differences in differentiation, stage, grade, and tumor size. Kaplan-Meier analysis and Cox non-proportional hazards regression models were used to assess the association between previous radiation and bladder cancer survival. A total of 25,408 patients were identified, of which 14,570 patients had sufficient data for analysis. Of these, 5968 (41.0%) received radiation for their primary malignancy. Prior radiation conferred a lower risk of developing moderately- or poorly-differentiated bladder tumors and muscleinvasive or node-positive disease. An increased risk of squamous cell carcinoma was noted (OR 1.43, CI 1.06-1.93). Prior radiation led to an increased risk of bladder cancer-specific (HR 1.13, CI 1.03-1.24) mortality at 5years. The greatest effect of prior radiation was an increased risk of bladder cancer-specific mortality for carcinoma in situ at 5years (OR 2.37, CI 1.45-3.86). Prior radiation is associated with lower grade and stage of bladder tumors in addition to worse cancer-specific survival.

Association of Health-Care System and Survival in African American and Non-Hispanic White Patients With Bladder Cancer.

African American patients with bladder cancer have inferior outcomes compared with non-Hispanic White (White) patients. We hypothesize that access to health care is a primary determinant of this disparity. We compared outcomes by race for patients with bladder cancer receiving care within the predominant hybrid-payer health-care model of the United States captured in the Surveillance, Epidemiology, and End Results (SEER) database with those receiving care within the equal-access model of the Veterans' Health Administration (VHA). African American and White patients diagnosed with bladder cancer were identified in SEER and VHA. Stage at presentation, bladder cancer-specific mortality (BCM), and overall survival (OS) were compared by race within each health-care system. The SEER cohort included 122 449 patients (93.7% White, 6.3% African American). The VHA cohort included 36 322 patients (91.0% White, 9.0% African American). In both cohorts, African American patients were more likely to present with muscle-invasive disease and metastases, but the differences between races were statistically significantly smaller in VHA. In SEER multivariable models, African American patients had worse BCM (hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.15 to 1.29) and OS (HR = 1.26, 95% CI = 1.20 to 1.31). In contrast within the VHA, African American patients had similar BCM (HR = 0.97, 95% CI = 0.88 to 1.07) and OS (HR = 0.99, 95% CI = 0.93 to 1.05). In this study of contrasting health-care models, receiving medical care in an equal-access system was associated with reduced differences in stage at presentation and eliminated disparities in survival outcomes for African American patients with bladder cancer. Our findings highlight the importance of reducing financial barriers to care to notably improve health equity and oncologic outcomes for African American patients.

Patterns of Failure After Definitive Chemoradiation for Muscle-Invasive Bladder Cancer

<h3>Purpose/Objective(s)</h3> Outcomes for muscle-invasive bladder cancer (MIBC) treated with definitive chemoradiation (CRT) have largely remained stagnant in recent decades. To understand how best to improve outcomes for this population, we investigated patterns of failure after CRT for MIBC within the national Veterans Affairs' (VA) database. <h3>Materials/Methods</h3> In the VA database, we identified patients diagnosed between 2000 and 2018 with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent CRT (defined as at least 50% of an intended definitive radiation regimen in conjunction with at least 1 cycle of chemotherapy). All patients' electronic health records were chart reviewed to obtain detailed clinical, pathologic, treatment (radiation dose, type of chemotherapy), and outcomes (dates and locations of recurrences, cause-specific death) data. Median times to recurrence are reported along with 25th-75th percentiles. Endpoints of local recurrence (LR, defined as recurrence in the bladder or upper tract), distant recurrence (DR, defined as recurrence beyond regional lymph nodes), overall mortality (OM), and bladder cancer-specific mortality (BCM) were evaluated in multivariable Cox and Fine-Gray models. <h3>Results</h3> Overall, 356 patients were included: median age 76, T2 disease 85%, lymph node positive (LN+) disease 5%. 12% of patients had carcinoma in situ, 32% had multifocal disease, and 33% had pretreatment hydronephrosis. Median follow up time was 77 months. 5-year OM was 69% (95% CI 64-74%) and 5-year BCM was 39% (95% CI 34-44%). 155 (44%) patients had no recurrence. In the 135 (38%) patients that developed DR, the median time to DR was 12.1 mo (8.0-23.4 mo). 106 (79%) patients of the DR group developed DR as a first recurrence with either DR only (n = 73) or DR and LR simultaneously (n = 33). In the 123 (35%) patients that developed LR, median time to LR was 11.1 mo (7.3-20.9 mo). Of the 92 patients who developed LR first without a simultaneous DR, 26 (28%) went on to develop DR. Median time from LR to DR in this group was 12.4 mo (3.0-27.0 mo). In multivariable models, LN+ disease, pretreatment hydronephrosis, and creatinine clearance (CrCl) ≤ 50 were associated with higher rates of DR, inferior OM, and inferior BCM. No patient, tumor, or treatment variables were associated with LR. <h3>Conclusion</h3> 44% of patients with MIBC treated with CRT had no recurrence while 35% developed LR and 38% developed DR. These results highlight the need for continued local surveillance after CRT as over a third of patients developed LR. Given the high proportion of DR and the advent of novel agents (antibody drug conjugates, immunotherapy, etc.) for advanced urothelial carcinoma, these data emphasize the need for clinical trials exploring such agents to improve outcomes for patients with MIBC undergoing definitive intent CRT. Our identified clinical markers (LN+ disease, hydronephrosis, decreased CrCl) as well as novel biomarkers (e.g., circulating tumor DNA) may help delineate populations most likely to benefit from additional therapy.

Factors Associated With Treatment Discontinuation in Patients With Muscle-Invasive Bladder Cancer Undergoing Chemoradiation

Radiation treatment with concurrent chemotherapy (CRT) is a definitive treatment option for muscle-invasive bladder cancer (MIBC). Despite its effectiveness, CRT is underutilized given perceptions regarding fitness of patients for treatment and subsequent utility. Within the national Veterans Affairs' (VA) database, we investigated the factors associated with and the impact of treatment discontinuation in patients with MIBC treated with CRT.In the VA database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 and 2018 and treated with definitive intent CRT. Patients' electronic health records were chart reviewed to document if they completed definitive radiation (defined as at least 55 Gy). Preferred chemotherapy regimen was defined as containing cisplatin or combination mitomycin/5-fluorouracil. Primary endpoint of discontinued radiation was evaluated in a multivariable logistic regression. Secondary endpoints of 30/90-day mortality, overall mortality (OM), bladder cancer-specific mortality (BCM), non-bladder cancer-specific mortality (NCM), locoregional failure (LRF), and distant failure (DF) were evaluated in multivariable Cox and Fine-Gray models.Of an identified 369 veterans with MIBC who underwent CRT, 30 (8.1%) patients did not complete definitive radiation. The most common reasons for treatment discontinuation included comorbidities/infections necessitating hospital admission (63.3%) and treatment intolerance/declining performance status (26.7%). In multivariable logistic regression, the only significant sociodemographic or clinical variables associated with radiation discontinuation were creatinine clearance (CrCl) ≤ 50 (OR 3.61, 95% CI 1.51-8.66, P < 0.01) and non-preferred chemotherapy regimen (OR 3.43, 95% CI 1.36-8.67, P = 0.01). In the discontinued radiation cohort, 30-day mortality was 33.3% and 90-day mortality was 50.0% with the majority of deaths due to non-bladder cancer-specific causes. In this cohort, no patient or tumor variables were associated with either endpoint. In the completed radiation cohort, 30-day mortality was 2.7% and 90-day mortality was 6.8%. In multivariable analysis, radiation discontinuation was significantly associated with worse OM (HR 2.50, 95% CI 1.37-4.56, P < 0.01) and worse NCM (HR 2.29, 95% CI 1.21-4.32, P = 0.01). It was not associated with inferior BCM (HR 0.56, 95% CI 0.25-1.26, P = 0.16), LRF (HR 0.93, 95% CI 0.44-1.97, P = 0.85), or DF (HR 0.60, 95% CI 0.28-1.28, P = 0.19).More than 90% of patients with MIBC who undergo definitive intent CRT are able to complete their radiation course. Decreased creatinine clearance and receipt of non-preferred chemotherapy notably increased the odds of not completing radiation. Further research is required to develop evidence-based guidelines on patient selection to ensure curative therapy is offered to appropriate patients.