Characteristics Contributing to Survival Differences Between Black and White Patients Following Cystectomy.

PURPOSE: Examine patient, tumor, and treatment characteristics effect on the disparity between black and white patients with muscle-invasive bladder cancer (MIBC) who undergo radical cystectomy (RC). METHODS: 1,286 black patients in the 2004 to 2016 National Cancer Database fit inclusion criteria. A tapered match was performed from 17,374 white patients sequentially matched to the black cohort on demographics (age, gender, insurance, income, education, county, diagnosis year), presentation (demographic variables, stage, grade, tumor size, Charlson score), and treatment (demographic and presentation variables, lymph node count, hospital volume, neoadjuvant chemotherapy [NAC], treatment delay), creating 3 matched cohorts. Chi-square and Kruskal-Wallis tests were used to compare cohorts. Kaplan-Meier analysis was used to compare 5-year overall survival (OS). RESULTS: 5-year OS rate was 40.4% and 35.6% for unmatched white and black cohorts (P < 0.001), respectively. Following demographics and presentation match, 5-year OS rate for white patients decreased to 39.2% (P = 0.003) and 39.10% (P = 0.019), respectively. After treatment match, 5-year OS rate decreased to 36.7% for white patient (P = 0.32). Following presentation match, 7.2% of black patients vs. 5.8% of white patients had treatment delay, and 10.1% of black patients vs. 11.2% of white patients received NAC. The treatment match resulted in a 0.3% difference between groups for treatment delay and NAC. CONCLUSIONS: Our analysis demonstrates that disparity between black and white patients with muscle-invasive bladder cancer exists in demographic-, presentation-, and treatment-related variables. Treatment variables may be a large contributing factor to survival disparities. Further research is needed to identify social, biological, and organizational inputs that contribute to these disparities.

The centralization of bladder cancer care and its implications for patient travel distance.

OBJECTIVES: To evaluate the impact of centralized surgical and nonsurgical care (i.e., radiation and chemotherapy) on travel distances and survival outcomes for patients with advanced bladder cancer. Bladder cancer is a disease with high mortality for which treatment access is paramount and survival is superior in patients receiving surgery at high-volume centers. METHODS: Using SEER-Medicare, we identified patients 66 years or older diagnosed with bladder cancer between 2004-2013. We categorized patients as treated with either surgical (i.e., radical cystectomy) or nonsurgical (i.e., radiation or chemotherapy) care. We fit a linear probability model to generate the predicted proportion of patients treated at the top quintile of volume over time and assessed travel distance, 1-year all-cause mortality, and 1-year bladder cancer-specific mortality over time. RESULTS: A total of 6,756 and 10,383 patients underwent surgical and nonsurgical care, respectively. The percentage of patients treated at high-volume centers increased over the study period for both surgical care (53% to 62%) and nonsurgical care (47% to 55%), (both P< 0.001). Median travel distance increased (11.8 to 20.3 miles) for surgical care and (6.5 to 8.3 miles) for nonsurgical care, (both P < 0.001). The 1-year adjusted all-cause mortality and 1-year adjusted bladder-cancer specific mortality decreased significantly for both surgical and nonsurgical care (both P < 0.05). CONCLUSIONS: Over time, centralization of surgical and nonsurgical care for bladder cancer patients increased, which was associated with increasing patient travel distance and decreased all-cause and bladder-cancer specific mortality.

Ongoing risk of bladder cancer among former workers at the last benzidine manufacturing facility in the USA.

OBJECTIVE: To determine whether there is an ongoing risk of developing bladder cancer in a previously studied cohort of workers exposed to both benzidine and dichlorobenzidine or dichlorobenzidine only in the last benzidine manufacturing plant in the USA. METHODS: Workers (n=488) were identified from the quarterly 941 forms the employer was required to submit to the Social Security Administration from 1960 to 1977. Exposures were assigned based on dates worked and known benzidine/dichlorobenzidine production schedules. Incidence, vital status and cause of death were determined through 2014. Analyses were restricted to white men. RESULTS: Bladder cancer incidence and mortality were significantly increased (25 incident cases, standardised incidence ratio (SIR) 2.19, 95% CI 1.42 to 3.23, and 5 deaths, standardised mortality ratio (SMR) 3.79, 95% CI 1.23 to 8.84). There were significant increases in incidence and mortality in those exposed to both benzidine and dichlorobenzidine (SIR 3.11, 95% CI 1.97 to 4.67, SMR 4.10, 95% CI 1.12 to 10.50), but not among workers exposed to dichlorobenzidine only (two incident cases, SIR 0.89, 95% CI 0.11 to 3.23 and one death, SMR 2.90, 95% CI 0.07 to 16.15). Bladder cancer incidence and mortality were increased in individuals with >20 years since last exposure with >5 years worked (six observed, SIR 5.94, 95% CI 2.18 to 12.92 and two deaths, SMR 7.93, 95% CI 0.96 to 28.65). CONCLUSIONS: Incidence and mortality due to bladder cancer increased among workers exposed to benzidine but not among workers exposed only to dichlorobenzidine. The risk of incidence and death from bladder cancer remain elevated more than 20 years after last exposure to benzidine in those who worked >5 years.

High-intensity end-of-life care among Medicare beneficiaries with bladder cancer.

OBJECTIVES: To quantify the proportion of patients receiving high-intensity end-of-life care, identify associated risk factors, and assess how receipt of palliative care impact end-of-life care; as the delivery of such care, and how it relates to palliative care, has not been reported in bladder cancer SUBJECTS AND METHODS: We conducted a retrospective cohort study of patients with bladder cancer who died within 1 year of diagnosis using Surveillance, Epidemiology, and End Results linked Medicare data. The primary outcome was a composite measure of high-intensity end-of-life care (>1 hospital admission, >1 ED visit, or ≥1 ICU admission within the last month of life; receipt of chemotherapy within the last 2 weeks of life; or acute care in-hospital death). Secondary outcomes included the use of such care over time and any association with the use of palliative care. A generalized linear mixed model assessed for independent determinants. RESULTS: Overall, 45% of patients received high-intensity end-of-life care. This proportion decreased over time. Patients receiving high-intensity care had higher rates of comorbidities, advanced bladder cancer, and nonbladder cancer cause of death. These patients more often received palliative care but, compared to those not receiving high-intensity care, this occurred farther removed from bladder cancer diagnosis and closer to death. CONCLUSIONS: Nearly half of Medicare beneficiaries with bladder cancer who die within 1 year of diagnosis receive high-intensity care at the end of life. Palliative care was seldom used and only very near the time of death.

Gender differences in trends of bladder cancer mortality-to-incidence ratios according to health expenditure in 55 countries.

The association between bladder cancer mortality-to-incidence ratios (MIRs) and healthcare disparities has gender differences. However, no evidence supports gender as an issue in the association between changes in the MIR and health expenditures on bladder cancer. Changes in the MIR were defined as the difference in data from the years 2012 and 2018, which was named δMIR. Current health expenditures (CHE) and the human development index (HDI) were obtained from the World Health Organization and the Human Development Report Office. The association between variables was analyzed by Spearman's rank correlation coefficient. In total, 55 countries were analyzed according to data quality and the exclusion of missing data. Globally, the MIR changed according to the HDI level in both genders. Among the 55 countries studied, a high HDI and CHE were significantly associated with a favorable age-standardized rate-based MIR (ASR-based MIR) in both genders and the subgroups according to gender (for both genders, MIR vs. HDI: ρ = -0.720, p < 0.001; MIR vs. CHE per capita: ρ = -0.760, p < 0.001; MIR vs. CHE as a percentage of gross domestic product (CHE/GDP): ρ = -0.663, p < 0.001). Importantly, in females only, the CHE/GDP but neither the HDI score nor the CHE per capita was significantly associated with a favorable ASR-based δMIR (ASR-based δMIR vs. CHE/GDP: ρ = 0.414, p = 0.002). In the gender subgroups, the association between the HDI and the CHE was statistically significant for females and less significant for males. In conclusion, favorable bladder ASR-based MIRs were associated with a high CHE; however, improvement of the ASR-based δMIR data was more correlated with the CHE in females. Further investigation of the gender differences via a cohort survey with detailed information of clinical-pathological characteristics, treatment strategies, and outcomes might clarify these issues and improve therapeutic and/or screening strategies for bladder cancer.

Triple-marker immunohistochemical assessment of muscle-invasive bladder cancer: Is there prognostic significance?

BACKGROUND: Bladder cancer is the ninth most common cancer worldwide, and the third most common cancer in Lebanon. Immunohistochemistry (IHC) has been used to stratify muscle-invasive bladder cancer (MIBC) into different subtypes. However, to our knowledge, there exists no study that investigates the use of this low-cost technique to predict prognosis in bladder cancer patients in our region. AIM: To examine the feasibility of low-cost triple-marker IHC assessment for MIBC subtyping in order to predict patients' survival and cisplatin sensitivity. METHODS AND RESULTS: We collected the specimens of deceased patients diagnosed with MIBC on pathology at our institution. For each case, tumor tissue blocks were retrieved and stained for hematoxylin and eosin in addition to three molecular markers by IHC: cytokeratin 5/6, cytokeratin 14 staining basal BC, and GATA3 staining luminal BC. A cut-off of ≥20% was set as positive. Kaplan-Meier curves were built, factored by BC subtype, to predict overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Hazard ratios in Cox regression were also created accounting for oncological factors and BC subtype. We categorized specimens as either luminal (GATA3 positive only) (n = 21; 56.7%) or as double-positive (GATA3 and basal cytokeratin 5/6 or cytokeratin 14 positive) (n = 16; 43.3%). The overall median survival was similar between the two categories (27.0 ± 4.82 months). Numbers favored luminal disease for PFS (Breslow P = .032). After adjusting for covariates, luminal molecular expression predicted PFS (0.28; [0.09-0.94]). Yet, the Cox model was not able to identify any predictors of OS or DSS. CONCLUSION: Specimens enriched with only a luminal molecular profile were more likely to exhibit cisplatin sensitivity. Despite the absence of guidelines recommending the utilization of molecular profiling in clinic practice, triple-marker IHC could serve as a potential low-cost prognostic indicator to identify patients at high risk of progression.

Recurrence Rate and Cost Consequence of the Shortage of Bacillus Calmette-Guérin Connaught Strain for Bladder Cancer Patients.

BACKGROUND: Between 2013 and 2016, global production of bacillus Calmette-Guérin (BCG) was dramatically reduced due to the collapse of the factory producing BCG Connaught. OBJECTIVE: To evaluate the clinical and economic impact of BCG shortage on a cohort of non-muscle-invasive bladder cancer (NMIBC) patients treated during the period of restricted supply. DESIGN, SETTING AND PARTICIPANTS: This retrospective, before and after, cost-consequence study included patients with intermediate- and high-risk NMIBC. Those resected between November 2011 and September 2013 (control group) were compared with those resected between October 2013 and December 2016 (study group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the rate of tumor recurrence from 30 d after transurethral resection to the end of follow-up at 24 mo; the secondary endpoints included the average cost of primary treatment, average cost of treatment of recurrence, and excess cost due to BCG shortage per patient. RESULTS AND LIMITATIONS: A total of 402 patients were included: 191 in the control group and 211 in the study group. The rate of recurrence at 24 mo was significantly higher in the study group than in the control group (46.9% vs 16.2%; relative risk: 0.7, 95% confidence interval [0.60; 0.82]; p < 0.001). The increased cost due to the decrease in BCG production was estimated to be €783 per patient with a new diagnosis of NMIBC during the period of restricted supply. This is a retrospective analysis at the level of our unit. A more precise evaluation would require a study of a larger cohort of patients. CONCLUSIONS: The shortage of BCG between October 2013 and December 2016 had a significant medical and economic impact; there was an increased rate of bladder cancer recurrence, and the total cost of care for intermediate- and high-risk NMIBC was higher. PATIENT SUMMARY: In this report, we analyzed the medical and economic impact of bacillus Calmette-Guérin (BCG) shortage that occurred between 2013 and 2016. We found a significant increase of bladder cancer recurrence and progression, and an increase in the number of patients who had to be treated by cystectomy. BCG shortage also had a significant impact on the total cost. Since there are no alternatives to BCG for high-risk non-muscle-invasive bladder cancer patients, BCG production has to be maintained by any means.

"Real-world" outcomes and prognostic indicators among patients with high-risk muscle-invasive urothelial carcinoma.

INTRODUCTION: There is no current standard of care for patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after neoadjuvant chemotherapy and surgical resection or for those who cannot receive or decline cisplatin-based perioperative chemotherapy. Understanding current, real-world treatment patterns may help inform decisions from clinical, research, and population health management perspectives. We examined real-world treatment patterns, survival outcomes, and prognostic factors among Medicare beneficiaries with high-risk MIUC who did not receive adjuvant treatment after surgical resection. METHODS: We identified patients with high-risk MIUC in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who underwent surgical resection (radical cystectomy and/or radical nephroureterectomy). Eligible patients had indicators of high-risk MIUC and surgical resection between 2001 and 2013. Demographic and clinical characteristics, including comorbidities, American Joint Commission on Cancer (AJCC) stage, tumor stage/grade and nodal status, and distribution of neoadjuvant treatment by the year of surgical resection were evaluated. Overall survival (OS) and disease-free survival (DFS) were assessed for the full cohort and by subgroups using Kaplan-Meier survival analysis. Adjusted Cox proportional hazards models were used to evaluate patient demographics and clinical characteristics associated with OS and DFS. RESULTS: A total of 665 patients were included in the analysis, with a mean age of 75.5 years; most were men (61%) and had AJCC stage IIIA disease (69%). Neoadjuvant treatment increased over the entire study period, both overall (from 12% to 46%) and cisplatin based (from 5% to 38%). Median OS for the entire cohort was 23.1 months (95% confidence interval: 18, 27); median DFS was 13.5 months (95% confidence interval: 11.3, 16.8). AJCC stage IIIB/IVA was the most significant predictor of poor prognosis for both OS and DFS, followed by non-white race and comorbidity burden. CONCLUSION: The prognosis for high-risk patients with MIUC remains poor, with significant risk of mortality within 2 years of radical cystectomy despite increasing use of neoadjuvant treatment. Unmet treatment needs persist for this difficult-to-treat patient population despite the increasing use of cisplatin-based neoadjuvant chemotherapy.

Comparing Costs of Radical Versus Partial Cystectomy for Patients Diagnosed With Localized Muscle-Invasive Bladder Cancer: Understanding the Value of Surgical Care.

OBJECTIVE: To compare costs associated with radical versus partial cystectomy. Prior studies noted substantial costs associated with radical cystectomy, however, they lack surgical comparison to partial cystectomy. METHODS: A total of 2305 patients aged 66-85 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer from January 1, 2002 to December 31, 2011 were included. Total Medicare costs within 1 year of diagnosis following radical versus partial cystectomy were compared using inverse probability of treatment-weighted propensity score models. Cox regression and competing risks analysis were used to determine overall and cancer-specific survival, respectively. RESULTS: Median total costs were not significantly different for radical than partial cystectomy in 90 days ($73,907 vs $65,721; median difference $16,796, 95% CI $10,038-$23,558), 180 days ($113,288 vs $82,840; median difference $36,369, 95% CI $25,744-$47,392), and 365 days ($143,831 vs $107,359; median difference $34,628, 95% CI $17,819-$53,558), respectively. Hospitalization, surgery, pathology/laboratory, pharmacy, and skilled nursing facility costs contributed largely to costs associated with either treatment. Patients who underwent partial cystectomy had similar overall survival but had worse cancer-specific survival (Hazard Ratio 1.45, 95% Confidence Interval, 1.34-1.58, P < .001) than patients who underwent radical cystectomy. CONCLUSION: While treatments for bladder cancer are associated with substantial costs, we showed radical cystectomy had comparable total costs when compared to partial cystectomy among patients with muscle-invasive bladder cancer. However, partial cystectomy resulted in worse cancer-specific survival further supporting radical cystectomy as a high-value surgical procedure for muscle-invasive bladder cancer.

Refining assessment of response to radiation-based therapy for muscle-invasive bladder cancer: Is post-treatment tumor bed biopsy always necessary?

INTRODUCTION: Radiation-based therapy (RT) has emerged as a suitable alternative to radical cystectomy (RC) and pelvic lymph node dissection for muscle-invasive bladder cancer (MIBC) patients. Routine biopsy after RT to rule out residual disease remains inconsistent across guidelines. Our objective was to review the significance of a bladder biopsy in terms of assessment of response post-RT and its potential impact on survival. PATIENTS AND METHODS: This was a single-center retrospective study on patients with MIBC (cT2-4aN0-2M0) treated with curative intent RT. A total of 169 patients with primary urothelial carcinoma were analyzed. Patients' demographic, clinical and pathological variables, imaging, cystoscopy, urine cytology, and biopsy reports after RT were collected and compiled. Whenever urine cytology was positive or cystoscopy showed any malignant-appearing lesion, the first assessment post-RT was considered suspicious for residual disease. A descriptive population analysis was reported. Cox regression multivariable analysis was performed to identify independent variables associated with survival outcomes. RESULTS: Median age was 75 years (interquartile range 66-82) and clinical staging was cT2 in 152 (90%) patients. Cytology and cystoscopy were normal in 140 (83%) after RT. Of patients with a control biopsy, residual MIBC was present in 3 (5%) and non-MIBC in another 6 (11%). On the contrary, a for-cause biopsy due to a suspicious assessment post-RT did not yield residual cancer in 45% of patients. Multivariable analysis showed that age (hazard ratio [HR] 1.04, P< 0.001), lymphovascular invasion (HR 1.68, P = 0.03) and a suspicious assessment after RT (HR 3.21; P< 0.001) were significantly associated with worse OS. This study was limited by its retrospective design. CONCLUSIONS: A routine biopsy after RT may be warranted to assess treatment response. This might be particularly important for patients who may benefit from early surgical intervention for residual MIBC. Further prospective studies are needed to confirm our findings.

Assessment of prognostic implication of a panel of oncogenes in bladder cancer and identification of a 3-gene signature associated with recurrence and progression risk in non-muscle-invasive bladder cancer.

This study evaluated the prognostic value of a panel of 29 oncogenes derived from the analysis of The Cancer Genome Atlas (TCGA data) or from the recent literature on bladder tumors on a well-characterized series of muscle-invasive bladder cancer (MIBC) and non-MIBC (NMIBC) samples and tried to identify molecular prognostic markers. Mutations of HRAS, FGFR3, PIK3CA and TERT were found in 2.9%, 27.2%, 14.9% and 76.7% of tumor samples, respectively. Concerning NMIBC, on multivariate analysis, RXRA and FGFR3 levels were associated with recurrence-free survival (RFS) (p = 0.0022 and p = 0.0069) and RXRA level was associated with progression to muscle-invasive disease (p = 0.0068). We identified a 3-gene molecular signature associated with NMIBC prognosis. FGFR3 overexpression was associated with reduced response to Bacillus Calmette-Guerin treatment (p = 0.037). As regards MIBC, on multivariate analysis, ERCC2 overexpression was associated with RFS (p = 0.0011) and E2F3 and EGFR overexpression were associated with overall survival (p = 0.014 and p = 0.035). RT-PCR findings were confirmed by IHC for FGFR3. Genomic alterations in MIBC revealed in TCGA data also concern NMIBC and seem to be associated with prognosis in terms of recurrence and progression. Correcting these alterations by targeted therapies seems a promising pharmacological approach.

Global Trends of Bladder Cancer Incidence and Mortality, and Their Associations with Tobacco Use and Gross Domestic Product Per Capita.

BACKGROUND: Bladder cancer is a major urological disease, with approximately 550 000 new cases diagnosed in 2018. OBJECTIVE: We examined gender-specific incidence and mortality patterns, and trends of bladder cancer from a global perspective. We further investigated their associations with tobacco use and gross domestic product (GDP) per capita. DESIGN, SETTING, AND PARTICIPANTS: We retrieved data on the incidence and mortality of bladder cancer from the GLOBOCAN database, Cancer Incidence in Five Continents, and the WHO mortality database. Data on the rate of tobacco use were retrieved from the WHO Global Health Observatory. Data on GDP per capita was retrieved from the United Nations Human Development Report. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed two sets of analyses. The first set of analysis is based on bladder cancer incidence and mortality data in 2018. The gender-specific age-standardised rates (ASRs) of incidence and mortality, and their correlations with the rate of tobacco use and GDP per capita were investigated. A multivariable linear regression analysis was also performed. In the second set of analysis, we examined the 10-yr temporal trends of bladder cancer incidence and mortality by average annual percent change using joinpoint regression analysis. A further exploratory analysis on GDP per capita in countries with decreasing trends of tobacco use was also performed. RESULTS AND LIMITATIONS: Wide variations in bladder cancer incidence and mortality were observed globally. There were positive correlations between the rate of tobacco use and the ASRs of bladder cancer incidence (r=0.20) and mortality (r=0.38) in men, and between the rate of tobacco use and the ASRs of bladder cancer incidence (r=0.67) and mortality (r=0.22) in women. There were positive correlations between GDP per capita, and the ASRs of bladder cancer incidence in men (r=0.48) and women (r=0.44). There was a weak positive correlation between GDP per capita and bladder cancer mortality in men (r=0.19), but no correlation with bladder cancer mortality in women (r=0.06). Upon multivariable linear regression analysis, tobacco use was significantly associated with bladder cancer incidence and mortality in men, and bladder cancer incidence in women. Regarding the 10-yr temporal trends of bladder cancer, Europe has an increasing incidence but decreasing mortality, and Asia has a decreasing incidence but increasing male mortality. Among countries with decreasing trends of tobacco use, the mean GDP per capita was higher in countries with decreasing trends of bladder cancer mortality than in those with increasing trends of bladder cancer mortality. A major limitation of the study is that cancer incidence might be underdetected and under-reported in less developed nations. CONCLUSIONS: There were observable trends of bladder cancer incidence and mortality globally. Tobacco use was significantly associated with both bladder cancer incidence and mortality. A certain level of economic capacity might be needed to further reduce bladder cancer mortality in countries with a decreasing trend of tobacco use. PATIENT SUMMARY: There are different trends of bladder cancer incidence and mortality globally. Smoking is significantly associated with the incidence and mortality of bladder cancer. A higher financial capacity may be needed to further improve the disease outcomes.

A cost-utility analysis of atezolizumab in the second-line treatment of patients with metastatic bladder cancer.

Background: Despite initial promising results, the IMvigor211 clinical trial failed to demonstrate an overall survival (os) benefit for atezolizumab compared with chemotherapy as second-line treatment for metastatic bladder cancer (mbc). However, given lessened adverse events (aes) and preserved quality of life (qol) with atezolizumab, there might still be investment value. To evaluate that potential value, we conducted a cost-utility analysis (cua) of atezolizumab compared with chemotherapy from the perspective of the Canadian health care payer. Methods: A partitioned survival model was used to evaluate atezolizumab compared with chemotherapy over a lifetime horizon (5 years). The base-case analysis was conducted for the intention-to-treat (itt) population, with additional scenario analyses for subgroups by IMvigor-defined PD-L1 status. Health outcomes were evaluated through life-year gains and quality-adjusted life-years (qalys). Cost estimates in 2018 Canadian dollars for systemic treatment, aes, and end-of-life care were incorporated. The incremental cost-effectiveness ratio (icer) was used to compare treatment strategies. Parameter and model uncertainty were assessed through sensitivity and scenario analyses. Per Canadian guidelines, cost and effectiveness were discounted at 1.5%. Results: For the itt population, the expected qalys for atezolizumab and chemotherapy were 0.75 and 0.56, with expected costs of $90,290 and $8,466 respectively. The resultant icer for atezolizumab compared with chemotherapy was $430,652 per qaly. Scenario analysis of patients with PD-L1 expression levels of 5% or greater led to a lower icer ($334,387 per qaly). Scenario analysis of observed compared with expected benefits demonstrated a higher icer, with a shorter time horizon ($928,950 per qaly). Conclusions: Despite lessened aes and preserved qol, atezolizumab is not considered cost-effective for the second-line treatment of mbc.

A mediation analysis to explain socio-economic differences in bladder cancer survival.

INTRODUCTION: This study aims to disentangle heterogeneity in the survival of bladder cancer (BC) patients of different socioeconomic status (SES) by identifying potential mediators of the relationship. METHODS: The Bladder Cancer Database Sweden (BladderBaSe) was used to select patients diagnosed between 1997 and 2014 with Tis/Ta-T4 disease. The education level was used as a proxy for SES. Accelerated failure time models were used to investigate the association between SES and survival. Mediation analysis was used to investigate potential mediators of the association also accounting for interaction. RESULTS: The study included 37 755 patients from the BladderBaSe. Patients diagnosed with both non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) who had high SES were found to have increased overall and BC-specific survival, when compared to those with low SES. In the NMIBC patients, Charlson Comorbidity Index was found to mediate this relationship by 10% (percentage of the total effect explained by the mediator) and hospital type by 4%. The time from referral to TURBT was a considerable mediator (14%) in the MIBC patients only. CONCLUSIONS: Mediation analysis suggests that the association between SES and BC survival can be explained by several factors. The mediators identified were not, however, able to fully explain the theoretical causal pathway between SES and survival, therefore, future studies should also include the investigation of other possible mediators to help explain this relationship further. These results highlight the importance of standardization of clinical care across SES groups.

Long-term trends in sex difference in bladder cancer survival 1975-2009: A population-based study in Osaka, Japan.

In Japan, a study using population-based cancer registry data from six prefectures revealed a difference in bladder cancer survival between men and women. However, the period of the study was limited to 1993-2006. The recent introduction of immune checkpoint inhibitors, which have proved to be effective for the treatment for bladder cancer, has led to a rising demand for analysis of long-term trends in net survival in order to accurately assess the effect of the new treatment. The aim of the present study was to examine long-term trends in sex difference in bladder cancer net survival using large-scale population-based cancer registry data from Osaka, Japan (17,500 cases from 1975 to 2009). We also evaluated sex difference in bladder cancer survival after adjustment for stage, histologic type, and other prognostic factors. We showed the long-term trend of five-year net survival for each stage and found that women had poorer five-year net survival than men for the whole study period. The risk of death from bladder cancer was higher among men than women even after adjusting for period at diagnosis, histologic type, stage, age group, and treatment (Excess hazard ratios: 1.17; 95% Confidence interval: 1.10-1.25).

The Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival after radical cystectomy: external validation in a large bi-institutional cohort.

OBJECTIVE: To perform an external validation of the Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival (CSS) after radical cystectomy (RC) in a large bi-institutional cohort of patients. PATIENTS AND METHODS: Patients treated with RC and lymph node dissection (LND) between May 1996 and July 2017 were retrieved from the RC databases of Leuven and Turin. Collected variables were age at RC, tumour stage, lymph node (LN) density, neoadjuvant chemotherapy, the extent of LND, and nodal stage. The primary outcome was CSS visualised using Kaplan-Meier plots. Cox proportional hazard models were used to assess the impact of variables on CSS. We performed a pairwise comparison between the COBRA score levels using a log-rank test corrected by Bonferroni, and developed a simplified COBRA score with three risk categories. To compare models, we assessed concordance indices (C-indices), receiver operating characteristic curves with area under the curve (AUC), calibration plots, and decision curve analysis (DCA). Finally, we compared both COBRA and simplified COBRA models with the established American Joint Committee on Cancer (AJCC) model. RESULTS: A total of 812 patients were included. All COBRA score variables had a significant impact on CSS in a Cox proportional hazard model. However, pairwise comparison of the COBRA subscores could not differentiate significantly between all COBRA score levels. Based on these findings, we developed a simplified COBRA score by introducing three categories within the following COBRA score ranges: low- (0-1) vs intermediate- (2-4) vs high-risk (5-7). A pairwise comparison could discriminate significantly between all COBRA risk categories. When finally comparing COBRA and simplified COBRA models with the AJCC model, AJCC performed better than both. C-indices, AUCs, calibration plots and DCA for AJCC were all better compared with the original and simplified COBRA models. CONCLUSION: We performed an external validation of the COBRA score in a large bi-institutional cohort. We observed that several risk groups had overlapping CSS, demonstrating suboptimal performance of the COBRA score. Therefore, we constructed a simplified model with three COBRA score risk categories. This model resulted in demarcated risk groups with non-overlapping CSS and good predictive accuracy. However, both COBRA score models were outperformed by the AJCC staging system. Therefore, we conclude that the AJCC staging system should remain the current standard for stratifying patients after RC for CSS.

Geographical variations in cancer mortality and social inequalities in southern Spain (Andalusia). 2002-2013.

INTRODUCTION: Geographical variations in cancer mortality can be explained, in part, by their association with social inequalities. The objective of our study was to analyse the spatial pattern of mortality in relation to the most common causes of cancer in the Spanish autonomous community of Andalusia and its possible association with social inequalities. MATERIALS AND METHODS: A small area cross-sectional study in Andalusia, with census tracts as units of spatial analysis, for the period 2002-2013. Cases and person-years, sex and age group came from the Longitudinal Population Database of Andalusia. Standardized mortality rates and smoothed risk ratios were calculated using the Besag, York and Mollié model for lung, colorectal, breast, prostate, bladder and stomach cancer. In order to evaluate the association with social inequalities we included the deprivation index of the census tract as a covariate. RESULTS: The results show an East-West mortality pattern with higher risk in the west for lung and bladder cancer among men, and breast cancer among women. For all of Andalusia, the association between deprivation index of the census tract and mortality relative risks is positive and significant for lung, stomach and bladder cancers in men, while in women we observed a negative association for lung cancer and a positive for stomach cancer. CONCLUSIONS: Knowledge regarding the spatial distribution of cancer mortality and the socioeconomic inequalities related should contribute to the design of specific health and social policies-aimed at tackling cancer mortality and social inequalities in areas of high mortality and/or levels of deprivation.

A Flexible Reduced Logarithmic-X Family of Distributions with Biomedical Analysis.

Statistical distributions play a prominent role in applied sciences, particularly in biomedical sciences. The medical data sets are generally skewed to the right, and skewed distributions can be used quite effectively to model such data sets. In the present study, therefore, we propose a new family of distributions to model right skewed medical data sets. The proposed family may be named as a flexible reduced logarithmic-X family. The proposed family can be obtained via reparameterizing the exponentiated Kumaraswamy G-logarithmic family and the alpha logarithmic family of distributions. A special submodel of the proposed family called, a flexible reduced logarithmic-Weibull distribution, is discussed in detail. Some mathematical properties of the proposed family and certain related characterization results are presented. The maximum likelihood estimators of the model parameters are obtained. A brief Monte Carlo simulation study is done to evaluate the performance of these estimators. Finally, for the illustrative purposes, three applications from biomedical sciences are analyzed and the goodness of fit of the proposed distribution is compared to some well-known competitors.

Occupational disparities in bladder cancer survival: A population-based cancer registry study in Japan.

BACKGROUND: Little is known about occupational disparities in bladder cancer survival. METHODS: Using data from a population-based cancer registry (1970-2016), we identified 3593 patients with incident bladder cancer diagnosed during 1970-2011 who completed occupational information. The patients were followed for 5 years (median follow-up time 5.0 years). Their longest-held occupations at incident bladder cancer diagnosis were classified according to a national standardized classification. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall death were estimated by Cox proportional hazard model, adjusted for age, sex, and year of diagnosis. Clerical workers served as the reference group. RESULTS: Overall prognosis was fair in this population (5-year overall survival, 61.9%). Compared with patients in clerical jobs, survival was poorer for those in professional and managerial jobs (mortality HR 1.36; 95% CI 1.09-1.69), sales and service jobs (HR 1.25, 95% CI 1.01-1.56), construction jobs (HR 1.83, 95% CI 1.40-2.38), and manufacturing jobs (HR 1.32, 95% CI 1.05-1.66), as well as those not actively employed (HR 1.27, 95% CI 1.02-1.58). A similar pattern was observed in the subgroup analyses restricted to male patients as well as additional analyses adjusted for potential prognostic variables (eg, stage) with multiple imputation. CONCLUSION: We documented occupational disparities in bladder cancer survival in Japan. However, the pattern of disparity did not favor highest occupational groups.

Socioeconomic Status-Related Parameters as Predictors of Competing (Non-Bladder Cancer) Mortality after Radical Cystectomy.

OBJECTIVE: To investigate the impact of socioeconomic status-related parameters on competing (non-bladder cancer) mortality after radical cystectomy. PATIENTS AND METHODS: A total of 1,268 consecutive patients who underwent radical cystectomy for urothelial or undifferentiated bladder cancer at our institution between 1993 and 2016 with a mean age of 69 years (median 70 years) were studied. The mean -follow-up of the censored patients was 7.2 years (median 5.7 years). Proportional hazard models for competing risk were used to identify predictors of non-bladder cancer (competing) mortality. The following parameters were included into multivariate analyses: age, American Society of Anesthesiologists physical status classification, Charlson score, gender, level of education, smoking status, marital status, local tumour stage, lymph node status, adjuvant and neoadjuvant chemotherapy. RESULTS: Besides age and both comorbidity classifications, the socioeconomic status-related parameters gender (female versus male, hazard ratio [HR] 0.58, 95% CI 0.40-0.84, p = 0.0042), level of education (university degree or master craftsman versus others, HR 0.76, 95% CI 0.56-0.1.03, p = 0.0801), smoking status (current smoking versus others, HR 1.47, 95% CI 1.10-1.96, p = 0.0085) and marital status (married versus others, HR 0.68, 95% CI 0.50-0.92, p = 0.0133) were independent predictors of competing mortality after radical cystectomy. If considered in combination (multiplication of HRs), the prognostic impact of socioeconomic parameters superseded that of the investigated comorbidity classifications. CONCLUSION: Socioeconomic status-related parameters may provide important information on the long-term competing mortality risk after radical cystectomy supplementary to chronological age and comorbidity.