The authors sought to understand the effect of patient sex, race, and socioeconomic status (SES) on outcomes for bladder cancer.
The authors sought to understand the effect of patient sex, race, and socioeconomic status (SES) on outcomes for bladder cancer.
The Florida Cancer Data System and the Agency for Health Care Administration data sets (1998-2003) were merged and queried. Survival outcomes for patients with bladder cancer were compared between different races, ethnicities, and community poverty levels.
A total of 31,100 people with bladder cancer were identified. Overall median survival time was 62.7 months. Statistically significantly longer survival times were observed in men (62.8 months vs 62.3 months for women), whites (63.0 months vs 39.6 months for African Americans [AAs], P < .001), non-Hispanics (62.9 months vs 56.4 months for Hispanics, P < .001), and patients from more affluent communities (74.0 months where <5% live in poverty vs 53.0 months where >15% live in poverty, P < .001). Surgery was associated with dramatically improved survival. AA women diagnosed with bladder cancer were significantly less likely to have endoscopic surgical resection compared with white women (P < .001). On multivariate analysis, independent predictors of poorer outcomes were older age, AA race, female sex, degree of community poverty, histologic tumor grade, advanced tumor stage, and lack of surgical treatment.
Racial and SES disparities in bladder cancer survival were not fully explained by late-stage presentation and undertreatment. Although earlier diagnosis and greater access to surgery would likely yield some improvement in outcomes for AA women, more research is needed to understand the remaining survival gap for this population. Cancer 2009. © 2009 American Cancer Society.
Disparities in diagnosis, treatment, and outcome for cancers in African Americans (AAs) and whites have been documented over the past 30 years.1 The Annual Report to the Nation on the Status of Cancer (1975-2002) showed that the incidence of urinary bladder cancer deaths is highest for AA males (9.3 per 100,000), followed by white and Hispanic males (8.0 per 100,000) and AA females (2.8 per 100,000).2 Many studies demonstrating disparities in cancer outcomes among different races and ethnicities have pointed to a lack of screening and therefore delays in diagnosis and treatment.3-12 The increased risk of death for AAs with bladder cancer has not so far been attributable to underutilization of cancer screening, as prior studies have demonstrated no effective screening method for this type of cancer.
The literature describing survival differences between Hispanics and non-Hispanics is sparse relative to that published regarding AA survival.13-15 Underwood et al,15 Prout et al,14 and Lee et al13 found that after adjustment for demographic and clinical factors, AA women with bladder cancer had an increased risk of death compared with their white counterparts; however, none of these studies commented on survival outcomes for Hispanic women. Watson and Sidor,16 in contrast, reported decreased survival rates for Native Americans and Alaskan Natives with bladder cancer. The lack of data on survival outcomes for Hispanic women bears further exploration to examine whether or not they too are subject to presentation at a later stage relative to their white counterparts.
Low socioeconomic status (SES) has also been linked to poor outcomes in cancer patients,16, 17 with bladder cancer being no exception.15 A clear relationship exists between race and SES, as evidenced by the finding that the median income of whites in the United States was approximately 60% more than that of AAs in 2006.18 Additional factors implicated in survival disparities among racial and ethnic minorities and the poor are advanced stage at presentation,15, 19-25 treatment differences,19-21, 23, 26, 27 and comorbidities.27
Bladder cancer represents the fourth most common malignancy diagnosed in the United States among men and the 12th most common malignancy among women. Approximately 68,810 new cases of bladder cancer were expected to be diagnosed in 2008, with 14,100 deaths directly related to these types of tumors.28 We sought to examine differences in survival observed in patients with bladder cancer based on race, sex, and SES in an ethnically diverse population. Although studies thus far have demonstrated relatively consistent results pointing to decreased survival times for AAs, the current study further elucidates survival disparities by including ethnicity and evaluating the independent effects of race and SES in a population-based sample. We hoped by revisiting this topic using a large state cancer registry, we might identify possible points of intervention that will lead to improved survival in these groups.
The 2007 Florida Cancer Data System (FCDS) data set was used to identify all incident cases of invasive bladder cancer diagnosed in the state of Florida from 1998-2002. Patients with carcinoma in situ and benign bladder neoplasms were excluded from the analysis. The FCDS data set was enhanced with 2007 data linked from the Florida Agency for Health Care Administration (AHCA) data set. AHCA maintains 2 databases (Hospital Patient Discharge Data and Ambulatory Outpatient Data) on all patient encounters within hospitals and freestanding ambulatory surgical and radiation therapy centers in Florida. All hospitals have been required to report all discharges and outpatient encounters to AHCA since 1987. The AHCA data sets used in this study contain diagnoses and procedures performed during every hospitalization or outpatient encounter in the state of Florida, for the period 1998-2003. The comorbidity data obtained from the AHCA data set allowed for better correction of covariates. Tobacco and alcohol consumption data are self-reported at the time of cancer diagnosis, and information on duration of use was not available.
Cases in the FCDS and AHCA data sets were linked on the basis of unique identifiers.29, 30 These matches were confirmed with the patient's date of birth and sex. Postal codes listed in the FCDS-AHCA database were then used to determine community poverty levels according to the 2007 US Census Bureau report.31 Non-Florida residents were not included in the analysis, because follow-up for such patients, particularly survival information, may be inaccurate in up to 10% of such patients (FCDS personal communication). The University of Miami Miller School of Medicine Institutional Review Board approved this study.
The staging criteria used by the FCDS are consistent with the Surveillance, Epidemiology, and End Results (SEER) summary staging. In this study, local staging represents disease that does not extend beyond the primary organ, whereas those having positive lymph nodes at the time of resection were classified as having regional disease. Documentation of distant metastases during the perioperative period led to classification of affected patients as having distant disease.
Statistical analysis was performed with SPSS Statistical Package version 15.0 (SPSS Inc., Chicago, Ill). Correlations between categorical variables were made using the chi-square test. Median survival rates were calculated by the Kaplan-Meier method. Because the FCDS collects only primary cause of death, we analyzed only overall survival and not disease-specific survival. Survival was calculated from the time of the initial diagnosis to date of last contact, or date of death, which was the time of censoring. The univariate effects of demographic, clinical, and treatment variables on survival were tested by the log-rank test for categorical values. To estimate the impact of race, ethnicity, and SES on survival outcomes, we used a Cox proportional hazards model, adding demographic, clinical, and treatment variables in a stepwise fashion.
Over the 5-year period studied, 31,100 patients with bladder cancer were identified. Demographics, social, and tumor characteristics of the entire study population, including subset analysis, are summarized in Table 1. The majority of the patients were men (n = 23,432, 75.3%), white (n = 29,734, 96.6%), and non-Hispanic (n = 28,511, 92.6%). Most patients were also >65 years old (n = 23,766, 76.4%) and were smokers (n = 15,948, 64.7%). The majority of tumors were moderately differentiated (n = 9981, 39.0%) or poorly differentiated (n = 8232, 32.2%) in histology. Localized disease was most common (n = 7758, 82.2%). Approximately 36.6% of the study population lived in a community where >10% of the area population was living below the poverty line.
|Entire Cohort||Race, % of Total||Sex, % of Total||Community Poverty Level, % of Total|
|No.||% of Total||White||AA||Other||P||Men||Women||P||<5%||5%-10%||10%-15%||>15%||P|
|Median age at diagnosis, y||72.4||72.5||68.7||67.9||<.001||72.3||72.8||.002||72.2||72.7||72.8||71.7||<.001|
|Age groups, y|
|Community poverty level|
Median survival rates of the entire study population, including subset analyses, are summarized in Table 2. The median survival time (MST) for the entire cohort was 62.7 months. Significantly longer survival times were observed in younger patients at the time of diagnosis (median survival not yet reached vs 54.7 months for patients ≥66 years old, P < .001), men (62.8 months vs 62.3 months for women, P < .001), whites (63.0 months vs 39.6 months for AAs, P < .001), non-Hispanics (62.9 months vs 56.4 months for Hispanics, P = .048), and patients who live in communities where <5% of the population dwell in poverty (74.0 months vs 53.0 months where >15% live in poverty, P < .001). Survival was significantly longer in patients who did not drink alcohol (63.5 months vs 53.8 months, P < .001), but was not significantly different for smokers compared with nonsmokers (62.2 months vs 62.1 months, P = .895). Survival was significantly longer for patients with localized disease compared with distant disease (65.2 months vs 11.4 months, P < .001). Patients with well-differentiated tumors fared better than those with poorly differentiated tumors (median survival not reached vs 40.5 months, P < .001). Similarly, patients treated with only endoscopic surgical resection had significantly longer survival times than patients treated with open surgery or those who had no surgery (68.2 months vs 34.2 months vs 29.8 months, P < .001). This difference based upon surgical approach likely is because of differences in the use of laparoscopy versus open approaches based on tumor stage.
|Entire Cohort||Median Survival, mo|
|Median Survival, mo||P||Race||Sex||Community Poverty Level|
|Community poverty level|
Compared with whites, AAs tended to be diagnosed at an earlier age and lived in communities with significantly higher levels of poverty (Table 1). A smaller percentage of AAs reported tobacco usage compared with their white counterparts. With respect to clinical characteristics, AAs presented with more regional and distant disease and had more poorly differentiated tumors compared with whites. A greater proportion of AAs diagnosed with bladder cancer underwent radiation or chemotherapy treatment compared with whites. Univariate subset analysis demonstrated that AA race conferred a significantly poorer prognosis for bladder cancer (Table 2). MST of AAs with bladder cancer was significantly shorter than for whites among men and women; however, differences in median survival were particularly disparate for black women (63.4 months for whites vs 25.5 months for AAs; P < .001). For all tumor stages and grades, MST for AA patients was significantly less than for whites. At all poverty level strata, AAs had a shorter MST than whites.
Differences in treatment modality and outcomes between AA and white patients were also observed. Whereas more white patients underwent endoscopic surgical resection or open surgery (93.8% vs 88.1%), AA patients received more radiation therapy (6.6% vs 3.0%, P < .001) and chemotherapy (9.1% vs 6.2%; P = .002). Regardless of whether or not patients underwent endoscopic procedures, open surgical procedures, or no surgery at all, AA patients had decreased survival times compared with whites. Kaplan-Meier survival curves for white and AA patients are shown in Figure 1a.
Cancer of the urinary bladder was diagnosed in men almost 3 times more often than in women (Table 1). Male patients used alcohol and tobacco with higher frequencies, and had significantly higher proportions of localized disease compared with women. Men more frequently underwent endoscopic resection as opposed to open surgery or no surgery at all compared with women. They were also less likely to undergo chemotherapy or radiation treatment for their cancer.
Differences in outcomes for male and female patients were also observed in univariate subset analyses. More women with bladder cancer lived in communities with a >15% incidence of poverty compared with men (21.2% vs 18.6%, P < .001) and they had a significantly shorter MST than men. MST in female patients was significantly longer than in male patients who underwent endoscopic resection (68.7 months vs 67.8 months, P < .001).
Patients living in communities with >15% of the population living in poverty were more frequently younger, women, AA, Hispanic, and alcohol users compared with patients living in more affluent communities (Table 1). Patients living at greater poverty levels tended to have cancers that were more poorly differentiated, and had open surgery or no surgery at all as opposed to endoscopic resections, when compared with communities where <5% of the population lived in poverty. Univariate analysis demonstrated that community poverty level also affects MST in bladder cancer. Communities with greater percentages of the population living in poverty had significantly worse survival outcomes compared with communities with less poverty. For patients >65 years old, MST decreased significantly with increasing poverty level. Patients from communities where >15% of the population lives in poverty more frequently presented with advanced-stage disease compared with patients living in communities with a smaller proportion of poverty. Patients living in communities with the greatest amount of poverty were less likely to undergo endoscopic resection of their bladder cancer, and among all patients undergoing endoscopic procedures, those patients living in the poorest communities experienced worse survival outcomes compared with patients living in communities with the least amount of poverty (60.4 months vs 80.5 months; P < .001). Kaplan-Meier survival curves by area poverty level are shown in Figure 1b.
Whites diagnosed with bladder cancer were significantly more likely to use tobacco compared with AAs (65.1% vs 55.5%, P < .001), and men diagnosed with bladder cancer were significantly more likely to use tobacco compared with women (67.7% vs 55.4%, P < .001). The survival of white smokers was significantly longer than that of their AA counterparts (62.3 months vs 40.3 months, P < .001). A survival advantage was also observed in whites who did not smoke when compared with AA nonsmokers (63.0 months vs 33.2 months, P < .001). Women who used tobacco had longer MST than men who used tobacco; however, this result was not statistically significant (65.9 months vs 61.0 months, P = .949). Smoking was not an effect modifier for race or sex. Among smokers and nonsmokers, women who lived in communities with >15% of the population living in poverty had significantly diminished median survival times.
The frequency of comorbidities in the study population is shown in Table 3. The most frequent comorbidity was hypertension (61.4%), whereas the most infrequent illness observed was human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) (0.2%). Compared with whites, AAs were more likely to be diagnosed with hypertension, diabetes, renal failure, liver disease, HIV/AIDS, anemia, and fluid and electrolyte disorders in addition to bladder cancer. Women were more often diagnosed with hypothyroidism, obesity, weight loss, anemia, depression, and fluid and electrolyte imbalances. Patients living in less affluent areas were more often diagnosed with congestive heart failure, hypertension, paralysis, pulmonary diseases, diabetes, renal failure, liver disease, obesity, weight loss, anemia, and depression. By univariate analysis, all listed comorbid conditions significantly affected MST, with the exception of hypertension and AIDS/HIV.
|Overall, %||Race, %||Sex, %||Poverty Level, %||Present, mo||Not Present, mo||P|
|Congestive heart failure||20.6||22.08||23.20||15.04||.109||22.9||19.4||<.001||20.0||22.0||23.6||23.9||<.001||39.5||77.5||<.001|
|Pulmonary circulation disorders||2.7||2.88||3.73||1.50||.226||2.9||3.0||.688||2.9||2.8||3.0||3.1||.687||37.4||64.1||<.001|
|Peripheral vascular disease||15.7||16.95||12.62||14.29||.003||18.1||12.7||<.001||16.1||17.1||17.6||16.6||.096||54.5||65.1||<.001|
|Chronic pulmonary disease||39.1||42.00||37.62||31.58||.002||43.4||36.7||<.001||37.9||41.1||43.9||46.3||<.001||50.1||78.5||<.001|
|Peptic ulcer disease||4.0||4.22||4.33||4.51||.975||4.3||4.0||.250||4.0||4.2||4.5||4.3||.606||54.2||63.5||.003|
|Rheumatoid arthritis/collagen vascular disease||22.8||24.42||24.04||23.31||.928||24.2||24.8||.295||24.4||23.2||25.8||24.8||.003||67.0||60.8||<.001|
|Fluid and electrolyte disorder||31.3||33.08||45.07||35.34||<.001||32.1||37.1||<.001||29.6||33.7||34.1||37.3||<.001||33.6||NA||<.001|
|Blood loss anemia||7.0||7.27||14.30||7.52||<.001||7.2||8.3||.002||6.4||7.4||7.5||8.7||<.001||32.8||66.2||<.001|
Results of multivariate analysis using the Cox regression model are summarized in Table 4. Independent predictors of survival of bladder cancer in the final model included age >65 years, AA race, female sex, community poverty level, histologic tumor grade, tumor stage, and surgical treatment. No differences were observed between ethnicity, alcohol consumption, tobacco usage, and chemotherapy.
|<40 (reference group)|
|Caucasian (reference group)|
|Men (reference group)|
|Non-Hispanic (reference group)|
|Community poverty level|
|<5% (reference group)|
|Yes (reference group)|
|Yes (reference group)|
|Localized (reference group)|
|Well differentiated (reference group)|
|Endoscopic resection (reference group)|
|Yes (reference group)|
|Yes (reference group)|
AA patients were 27% more likely to die during the study period compared with white patients (P < .001), and women were 11% more likely to die during the study period compared with men (P < .001). Patients living in areas where >15% of the residents live in poverty were 17% more likely to die during the study compared with patients living in areas where <5% of the residents live in poverty (P = .001). Clinical and treatment characteristics proved to have the largest effect on survival outcomes. Patients with regional disease were 1.53 times more likely to die during the study period, and patients with distant disease were 2.73 times more likely to die during the study period compared with patients with localized disease (P < .001). A dose-response effect was observed between tumor grade and risk of death during the study period. Patients with poorly differentiated tumors were 2.18 times more likely to die during the study period compared with women with well-differentiated tumors. Patients who were not treated surgically had a 51% increased risk of death compared with those who received any surgical therapy (P < .001). Those who did not receive radiation treatment had a 34% decreased risk of death compared with patients who received radiation therapy (P < .001).
Differences in cancer survival based on race, ethnicity, and SES remain a major issue despite recognition of these inequalities for >30 years. In an effort to understand outcomes for bladder cancer patients and potentially improve survival, we examined a population-based registry to identify global prognostic factors important in the survival of patients diagnosed with urinary bladder cancer. In this analysis, emphasis was placed on the effects of race, sex, and area poverty level on overall survival. Although our report is consistent with others that have also found racial and socioeconomic disparities in cancer, this study is unique in that patients from all age groups, Hispanics and non-Hispanics, as well as their comorbid conditions, were included in the analysis. To our knowledge, this study represents the largest, most comprehensive analysis of these variables on the outcomes of patients with bladder cancer to date.
We observed that after controlling for sociodemographic, clinical, and treatment characteristics, as well as comorbidities, race, sex, and poverty were independent predictors of urinary bladder cancer survival. With respect to race, these results are supported by previous studies that lacked comorbidity data.13-15, 32 Prior published studies examining racial and gender disparities in bladder cancer have included data on patients diagnosed over many decades. The results of the current study suggest that despite the knowledge of existing disparities, little progress in improving survival of urinary bladder cancer has been made. In the cohort reported herein, AA patients had significantly more regional and distant disease and more poorly differentiated tumors compared with their white counterparts. AAs and women were also significantly less likely to have endoscopic resection compared with their white and male counterparts. Our comorbidity data did not indicate that AAs were more likely to be of increased operative risk secondary to poor health; however, the findings of more advanced disease at presentation may indicate that the extent of disease made these patients more likely to be inoperable at time of diagnosis, leading to more frequent use of chemotherapy or radiation treatment.
Survival of AA patients who underwent endoscopic resection was significantly shorter than that of whites by univariate analysis, whereas no difference in survival was noted with open procedures. After controlling for sociodemographic variables and clinical disease characteristics in multivariate analysis, endoscopic resection was associated with superior outcomes. These results indicate that for patients who receive surgical treatment for urothelial cancer, race, sex, and poverty were all independent predictors of survival. In part because bladder cancer is 3 times less common in women than in men, many health practitioners may overlook presenting symptoms of bladder cancer in women and reflexively attribute hematuria to cystitis or a variety of gynecologic pathologies. The findings of our study indicate that poor survival outcomes, particularly for AA women, regardless of poverty level, are at least in part the result of delays in diagnosis and treatment, or less than adequate treatment, and presentation of illness in advanced stages. These findings are particularly troubling considering that the incidence of bladder cancer in AA women is increasing. Previous studies from the 1980s and 1990s have also demonstrated that there is often a delay in diagnosis of bladder cancer, especially for women compared with men.33, 34
In a much smaller study, Prout et al14 found that black patients working in the most affluent occupations did not significantly differ in terms of survival compared with whites. Our study results suggest patients living in communities with >15% of the population living in poverty had significantly decreased MST compared with patients living in communities with less poverty, even when they had surgical treatment for their bladder cancer. After adjustment for confounding variables in the multivariate analysis, community poverty level continued to be an independent predictor of survival. These results suggest that when socioeconomically disadvantaged patients with bladder cancer are treated, their survival outcomes continue to be poorer relative to those of patients living in more affluent communities. Our findings are likely more robust, as we included a larger and more heterogeneous population of patients. Much like the association between AA race and survival, these results likely indicate poorer patients may be subject to incomplete follow-up of physician visits and treatment.
The American Cancer Society (ACS) has suggested that low SES in AAs is responsible for many inequalities.35 Moreover, the ACS, in collaboration with the National Cancer Institute and Center for Disease Control, issued a landmark report highlighting the key issues.36 The poor were found to have worse outcomes because of financial hardship and lack of insurance, and therefore poor access to healthcare. This report also suggested that the poor endured more pain and suffering when diagnosed with cancer and that they did not benefit from cancer education and outreach programs. Finally, the report suggested that poor patients regard cancer diagnoses with a sense of resignation and futility, and therefore are less likely to seek medical treatment.36 In our final Cox regression model, race, sex, and poverty remained independent predictors of survival, along with lack of surgical treatment for bladder cancer.
In light of the finding that access to care has been highlighted as a major factor affecting cancer survival, many organizations have increased their efforts to level the playing field in the burden of cancer. The ACS has made this issue the centerpiece of their goal to be attained by the year 2015,37 and the US Department of Health and Human Services has made a commitment to reduce cancer disparities with the Healthy People 2010 initiative. These efforts are primarily focused on modifiable, socioeconomic factors such as poverty level, education, and healthcare. The results of our study suggest programs that increase the likelihood of AAs and the poor to seek treatment and education programs aimed at better compliance with treatment programs may have the most substantial impact on bladder cancer survival.
Although significant differences in survival by race and SES were observed, no survival disparities were observed for Hispanic men and women with bladder cancer. No significant difference in survival times was observed relative to white non-Hispanic patients. Ethnicity also failed to reach significance in the final multivariate regression model. Previous studies examining bladder cancer survival have not commented on possible ethnic differences outside that of the Native American and Native Alaskan populations.16 Although only 7.4% of our sample identified themselves as Hispanic, this observation may reflect the finding that ethnicity does not play as large a role as race or sex in predicting bladder cancer survival. In addition, the predominately Cuban population of South Florida has been shown to have more favorable health outcomes relative to other Hispanics, and therefore these results may not be generalizable to other Hispanic subgroups, such as Mexican Americans. These results may also point to improving awareness of signs and symptoms of bladder cancer in the Hispanic population and earlier identification of the disease at more treatable stages. Previously we have also failed to observe disparate outcomes for Florida Hispanics for several other cancers.29, 38, 39
We have provided the most comprehensive analysis of bladder cancer to date using a linked FCDS and AHCA database. This linkage dramatically improved the power of the study, as it provided additional data such as comorbidities, enhanced follow-up, socioeconomic information, and improved treatment information. Our study was restricted to 1998-2003, as linkage of these data sets was not possible in data sets for prior years. The FCDS, which currently includes over 2.7 million records, is a population-based registry of all cancer cases diagnosed or treated in the state of Florida, which represents about 6% of the total US population. The data collected from large cancer registries provide insight into tumor behavior and allow us to examine outcomes from current treatment strategies.40-45 Although this represents an excellent database for comparative outcomes analysis, it is not without limitations. By using area poverty as a proxy for SES may result in misclassification of some patients whose postal codes do not accurately reflect the true income level of the individual. In addition, FCDS records only primary cause of death; as a result, we were unable to include disease-specific survival in our examination. Furthermore, although data on radiotherapy and chemotherapy were examined, information on specific regimens and dosages were also not available.
In conclusion, after controlling for socioeconomic factors, clinical characteristics, and treatment modality, we demonstrate significant racial, gender, and SES disparities exist in bladder cancer survival. The inequalities were observed in both the univariate and multivariate analysis. Programs geared toward diminishing disparities in bladder cancer survival should be aimed both at providing earlier diagnosis and assuring optimal delivery of therapies, including increased use of minimally invasive surgical treatment to patients, particularly AAs and women whose diagnosis is often under-recognized.
Supported in part by a grant from the James and Ester King Tobacco Grant from the State of Florida.