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Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis
YGYNO-976614; No. of pages: 8; 4C: Gynecologic Oncology xxx (2017) xxx–xxx
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Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis Amy J. Bregar a, J. Alejandro Rauh-Hain a, Ryan Spencer b, Joel T. Clemmer a, John O. Schorge a, Laurel W. Rice b, Marcela G. del Carmen a,⁎ a b
Division of Gynecologic Oncology, Vincent Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
H I G H L I G H T S • White women were most likely to present with early stage disease. • African American women had lower all-cause survival compared to white women. • Hispanic women had higher all-cause survival compared to white women.
a r t i c l e
i n f o
Article history: Received 29 November 2016 Received in revised form 19 January 2017 Accepted 20 January 2017 Available online xxxx
a b s t r a c t Purpose. To examine patterns of care and survival for Hispanic women compared to white and African American women with high-grade endometrial cancer. Methods. We utilized the National Cancer Data Base (NCDB) to identify women diagnosed with uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma between 2003 and 2011. The effect of treatment on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. Results. 43,950 women were eligible. African American and Hispanic women had higher rates of stage III and IV disease compared to white women (36.5% vs. 36% vs. 33.5%, p b 0.001). African American women were less likely to undergo surgical treatment for their cancer (85.2% vs. 89.8% vs. 87.5%, p b 0.001) and were more likely to receive chemotherapy (36.8% vs. 32.4% vs. 32%, p b 0.001) compared to white and Hispanic women. Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had lower overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16–1.26). Conversely, Hispanic women had improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80–0.93). Conclusions. Among women with high-grade endometrial cancer, African American women have lower allcause survival while Hispanic women have higher all-cause survival compared to white women after controlling for treatment, sociodemographic, comorbidity and histopathologic variables. © 2017 Elsevier Inc. All rights reserved.
1. Introduction In the United States, endometrial cancer is the most common gynecologic malignancy, with 60,050 new cases estimated in 2016 [1]. While the majority of these cases are early stage and of low-grade
⁎ Corresponding author at: Division of Gynecologic Oncology, Vincent Obstetrics and Gynecology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 9 E, Boston, MA 02114, United States E-mail address: [email protected] (M.G. del Carmen).
endometrioid histology, a proportion of women will be diagnosed with an aggressive histologic subtype that confers a greater risk of disease recurrence and increased mortality [2]. African American women have a higher incidence of high-grade histology [3–7], which may contribute to the well-documented increase in overall mortality among African American women [8–12]. While the vast majority of research has focused on the comparison between white and African American women with endometrial cancer, a growing yet limited body of literature has examined differences in disease presentation, treatment patterns and outcomes between Hispanic and non-Hispanic women [7,13–16].
http://dx.doi.org/10.1016/j.ygyno.2017.01.024 0090-8258/© 2017 Elsevier Inc. All rights reserved.
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
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A.J. Bregar et al. / Gynecologic Oncology xxx (2017) xxx–xxx
“Hispanic or Latino” ethnicity is defined by the federal Office of Management and Budget as “a person of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race” [17]. Hispanics represent the largest ethnic minority group in the United States, and cancer is the leading cause of death among Hispanic women [18]. Hispanic women, similar to African American women, have a higher incidence of high-grade disease [13, 15] and are a vulnerable population disproportionately affected by lower socioeconomic status and barriers to healthcare. While there is substantial racial and cultural diversity within the Hispanic community and significant variation in the literature regarding how Hispanic ethnicity is characterized [19], cancer data are typically presented for Hispanics in aggregate [18]. Despite the heterogeneity within the Hispanic population, there is value in comparing the differences in treatment patterns and clinical outcomes among white women, African American women and Hispanic women with cancer, as such studies are lacking. The objective of this study is to compare the demographics, tumor characteristics, treatment course and overall survival of Hispanic women to non-Hispanic white women and nonHispanic African American women with high-grade endometrial cancer. 2. Materials and methods The National Cancer Data Base (NCDB) was used to identify women with high-grade endometrial cancer diagnosed between 2003 and 2011. The NCDB is a nationwide comprehensive clinical surveillance oncology system established by the American Cancer Society and the Commission on Cancer of the American College of Surgeons. Currently, this database captures approximately 70% of newly diagnosed malignancies in the United States, and receives over one million case reports from over 1500 hospitals annually [20]. The NCDB aggregates information about patient demographics, tumor characteristics, cancer-directed therapies, treating facility and overall survival. Data reported to the NCDB are retrospective and de-identified, ensuring confidentiality. This study was exempt from Institutional Review Board oversight. Women with grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma were considered to have high-grade endometrial cancer and were included in this study [6]. Women diagnosed by death certificate or at autopsy and patients who had other primary cancers were excluded. The variables of interest were race and ethnicity. For this, race and ethnicity variables were combined to construct single mutually exclusive raceethnicity variables (non-Hispanic white, non-Hispanic African American, Hispanic, other and unknown). Women of other or unknown race and/or ethnicity were excluded from this analysis. The primary outcome of interest was overall survival, defined as months from cancer diagnosis to death or date of the last contact. Secondary outcomes were the receipt of initial treatment after diagnosis of high-grade endometrial cancer. Initial treatment was defined as the first planned course of cancer-directed therapy used to manage the endometrial cancer and excludes treatments initiated for recurrence or relapse of disease [21]. The identification of chemotherapy through the NCDB has been shown in prior studies to be reliable [22–24]. Patients were considered to have been treated with combination adjuvant chemo-radiation if they had received both radiotherapy and chemotherapy within 6 months after diagnosis. We defined definitive surgery as procedures performed with curative intent or in anticipation of a subsequent curative treatment. Demographic, socioeconomic and clinical variables were categorized according to the NCDB Participant User File Data Dictionary [25]. Control variables included age at diagnosis, year of diagnosis (classified as 2003–2005, 2006–2008, 2009–2011), and geographic location of the treating facility (Northeast, Midwest, South and West). Tumor stage was determined using the revised 2009 staging criteria of the International Federation of Gynecologists and Obstetricians (FIGO)
[26]. Stage was determined based on available pathologic records depending on the type of surgery performed. Lymph node status was used to assign stage if lymphadenectomy was performed, otherwise pathologic stage was based on available pathologic data (e.g. depth of tumor invasion or evidence of metastatic disease). A residence was considered rural when the county of residence was “completely rural or had less than 2,500 urban population and was not adjacent to a metro area” as denoted by the United States Department of Agriculture's 2003 RuralUrban Continuum Codes classification scheme [27]. Median household income was categorized using the average income of the zip code of residence as estimated by either the 2000 census or the community survey data, categorized in quartiles (b$38,000, $38,000–$47,999, $47,000–$62,999 and ≥$63,000). Insurance status was categorized as uninsured, private insurance, Medicare or another type of government insurance (military or Medicaid). The treating facility was categorized according to the Commission on Cancer Accreditation Program as a Community Cancer Program, Comprehensive Community Cancer Program, Academic/Research Program or other. Education level for each patient's area of residence was estimated by matching the zip code of the patient recorded at the time of diagnosis against files derived from the 2012 American Community Survey data, thereby providing a measure of the proportion of adults in the patient's zip code who had attained a given education level. Comorbidity was analyzed using the Klabunde adaptation of the Charlson index; all subjects were assigned a score of 0, 1 or N2 [28,29]. 2.1. Statistical analysis Continuous variables were evaluated by ANOVA, and categorical variables were evaluated by chi square test. Pair-wise comparisons among continuous and categorical variables utilized the HolmBonferroni method to adjust for multiple comparisons. Logistic regression models were performed to describe predictors of treatment between racial groups, after adjusting for age, stage, histology, year of treatment, facility type, location, insurance type, education level, socioeconomic status and comorbidity score. Survival curves were calculated using the Kaplan-Meier method and used to compare between racial groups. Cox proportional hazards models were used to calculate adjusted group hazard ratios, and their 95% confidence intervals (CI) were utilized to assess the importance of adjuvant treatment options as an independent predictor of survival after adjusting for the same prognostic factors listed previously. All statistical tests were twosided, and differences were considered statistically significant at p b 0.05. All statistical analyses were performed using R 3.0.3 (R Foundation for Statistic Computing, Vienna Austria). 3. Results We identified 43,950 women from the NCDB diagnosed with highgrade endometrial cancer between 2003 and 2011 who met inclusion criteria. Table 1 summarizes the demographic and clinical characteristics of the study population. African American women were more frequently in the lowest quartile of income level (41.5% vs. 12.7% vs. 27.3%, p b 0.001) and had a higher comorbidity score of 2 or greater (7.1% vs. 4.7% vs. 4.3%, p b 0.001) when compared to white and Hispanic women. Hispanic women were more likely to be uninsured compared to white or African American women (10.9% vs. 2.9% vs. 5.0%, p b 0.001). Analysis of treatment patterns demonstrated that both Hispanic women and African American women were less likely to receive definitive surgical treatment compared to white women (87.5% vs. 85.2% vs. 89.8%, p b 0.001). While both Hispanic and African American women had lower rates of lymph node sampling compared to white women (71.9% vs. 69% vs. 75.3%, p b 0.001), African American women were the most likely to have positive lymph nodes (22.2% vs. 18.7% vs. 19.6%, p b 0.001) compared to white and Hispanic women. African American women were also more likely to receive adjuvant
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
A.J. Bregar et al. / Gynecologic Oncology xxx (2017) xxx–xxx
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Table 1 Demographics and clinical characteristics of the study population. Characteristic
White N = 34.035 (77.4%)
African American N = 7584 (17.3%)
Hispanic N = 2331 (5.3%)
p-Value
Median age at diagnosis, years (interquartile rage) Dates [N(%)] 2003–2005 2006–2008 2009–2011 Facility type [N(%)] Academic Community Cancer Program Comprehensive Cancer Program Other Area of residence [N(%)] Urban Rural Unknown Region [N(%)] Northeast Midwest South West Income [N(%)] Less than $38,000 $38,000–$47,999 $47,000–$62,999 $63,000 or more Unknown Insurance status [N(%)] None Medicare Other Government Private Unknown Charlson score [N(%)] 0 1 2 or more Histology [N(%)] Adenocarcinoma Carcinosarcoma Clear cell Papillary serous Pathologic stage [N(%)] I II III IV Unknown Surgery [N(%)] Yes Lymph node examination [N(%)] Yes Lymph node status [N(%)] Positive Adjuvant treatment [N(%)] None Chemotherapy Radiotherapy Chemotherapy and radiotherapy
66 (58–75)
66 (60–73)
63 (55–71)
*
9721 (28.6) 11,172 (32.8) 13,142 (38.6)
1899 (25.1) 2543 (33.5) 3142 (41.4)
601 (25.8) 757 (32.5) 973 (41.7)
p = 0.6 for African American vs. Hispanic
13,788 (40.4) 2032 (6.0) 18,195 (53.5) 20 (0.1)
4071 (53.7) 398 (5.2) 3113 (41.1) 2 (0.0)
1133 (48.6) 129 (5.5) 1069 (45.9) 0 (0.0)
31,718 (93.2) 748 (2.2) 1569 (4.6)
7192 (94.8) 110 (1.5) 282 (3.7)
2255 (96.7) 6 (0.3) 70 (3.0)
8118 (23.9) 9272 (27.2) 10,801 (31.7) 5844 (17.2)
1551 (20.5) 1351 (17.8) 4297 (56.7) 385 (5.0)
397 (17.0) 179 (7.7) 913 (39.2) 842 (36.1)
4327 (12.7) 7487 (22.0) 9315 (27.4) 12,093 (35.5) 813 (2.4)
3148 (41.5) 1673 (22.1) 1475 (19.4) 1092 (14.4) 196 (2.6)
637 (27.3) 570 (24.5) 571 (24.5) 512 (22.0) 41 (1.7)
1002 (2.9) 17,005 (50.0) 1431 (4.2) 13,986 (41.1) 611 (1.8)
378 (5.0) 3927 (51.8) 748 (9.9) 2370 (31.2) 161 (2.1)
255 (10.9) 836 (35.9) 339 (14.5) 803 (34.4) 98 (4.3)
25,905 (76.1) 6519 (19.2) 1611 (4.7)
5126 (67.6) 1921 (25.3) 537 (7.1)
1744 (74.8) 486 (20.8) 101 (4.4)
23,280 (68.4) 3703 (10.9) 1410 (4.1) 5642 (16.6)
3809 (50.2) 1409 (18.6) 395 (5.2) 1971 (26.0)
1538 (66.0) 253 (10.9) 104 (4.5) 436 (18.6)
13,674 (40.2) 2426 (7.1) 7578 (22.3) 3821 (11.2) 6536 (19.2)
2435 (32.1) 622 (8.2) 1749 (23.1) 1017 (13.4) 1761 (23.2)
830 (35.6) 185 (7.9) 537 (23.0) 303 (13.0) 476 (20.5)
30,568 (89.8)
6464 (85.2)
2040 (87.5)
25,633 (75.3)
5235 (69.0)
1675 (71.9)
6354 (18.7)
1681 (22.2)
456 (19.6)
14,619 (43.1) 7233 (21.3) 8403 (24.7) 3780 (11.1)
3227 (42.6) 1984 (26.2) 1563 (20.6) 810 (10.6)
1096 (47.0) 534 (22.9) 489 (21.0) 212 (9.1)
*
*
*
*
*
p = 0.11 for white vs. Hispanic
p = 0.04 for white vs. Hispanic
p = 0.01 for African American vs. Hispanic
* p = 0.03 for African American vs. Hispanic * *
* Unless otherwise indicated, p value for all pair-wise comparisons between groups b 0.001.
chemotherapy with or without radiation (36.8% vs. 32.4% vs. 32%, p b 0.001) compared to white and Hispanic women. We examined trends in disease presentation and adjuvant treatment in two-year increments over the time period of evaluation (2003–2005, 2006–2008 and 2009–2011). While rates of pathologic stage I disease remained relatively stable in white (39.7%, 39.0%, 41.5%) and Hispanic women (36.1%, 34.5%, 36.2%), an increased percentage of African American women were diagnosed with stage I disease over time (28.3%, 31.0%, 35.3%). Rates of lymphadenectomy increased over time in white (72.4%, 76.3%, 76.6%), African American
(65.4%, 69.1%, 71.2%) and Hispanic women (70.0%, 71.9%, 73.0%). Rates of adjuvant chemotherapy (with or without radiation) increased substantially for white (23.1%, 32.0%, 39.6%), African American (27.6%, 37.4%, 42.1%) and Hispanic women (20.6%, 30.1%, 40.5%) (Table 2). Multivariate analyses of treatment patterns controlling for clinical, pathologic and demographic factors demonstrated that African American women were less likely to receive surgical treatment compared to white women (Odds Ratio 0.65, 95% CI 0.51–0.83). There was no significant difference in surgical treatment between white and Hispanic women (OR 0.88, 95% CI 0.57–1.37). There was no racial or ethnic
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
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A.J. Bregar et al. / Gynecologic Oncology xxx (2017) xxx–xxx
Table 2 Stage and treatment stratified by date of diagnosis, race and ethnicity. White Pathologic stage [N(%)] I II III IV Unknown Lymph node dissection [N(%)] Yes Surgery [N(%)] Yes Adjuvant treatment [N(%)] None Chemotherapy Radiotherapy Chemotherapy and radiotherapy African American Pathologic stage [N(%)] I II III IV Unknown Lymph node dissection [N(%)] Yes Surgery [N(%)] Yes Adjuvant treatment [N(%)] None Chemotherapy Radiotherapy Chemotherapy and radiotherapy Hispanic Pathologic stage [N(%)] I II III IV Unknown Lymph node dissection [N(%)] Yes Surgery [N(%)] Yes Adjuvant treatment [N(%)] None Chemotherapy Radiotherapy Chemotherapy and radiotherapy
2003–2005 N = 9721
2006–2008 N = 11.172
2009–2011 N = 13.142
3859 (39.7) 768 (7.9) 2105 (21.7) 1118 (11.5) 1871 (19.2)
4355 (39.0) 877 (7.8) 2590 (23.2) 1247 (11.2) 2103 (18.8)
5460 (41.6) 781 (5.9) 2883 (21.9) 1456 (11.1) 2562 (19.5)
7039 (72.4)
8523 (76.3)
10,071 (76.6)
8671 (89.2)
10,105 (90.4)
11,792 (89.7)
4375 (45.0) 1421 (14.6) 3105 (31.9) 820 (8.5)
4712 (42.2) 2382 (21.3) 2887 (25.7) 1191 (10.7)
5532 (42.1) 3430 (26.1) 2411 (18.3) 1769 (13.5)
2003–2005 N = 1899
2006–2008 N = 2543
2009–2011 N = 3142
537 (28.3) 184 (9.7) 438 (23.1) 275 (14.5) 465 (24.4)
789 (31.0) 221 (8.7) 587 (23.1) 339 (13.3) 607 (23.9)
1109 (35.4) 217 (6.9) 724 (23.0) 403 (12.8) 689 (21.9)
1241 (65.4)
1757 (69.1)
2237 (71.2)
1599 (84.2)
2168 (85.3)
2697 (85.8)
878 (46.2) 368 (19.4) 498 (26.2) 155 (8.2)
1076 (42.3) 680 (26.7) 517 (20.3) 270 (10.7)
1273 (40.5) 936 (29.8) 548 (17.4) 385 (12.3)
2003–2005 N = 601
2006–2008 N = 757
2009–2011 N = 973
217 (36.2) 51 (8.5) 142 (23.6) 76 (12.6) 115 (19.1)
261 (34.5) 56 (7.4) 188 (24.8) 91 (12.0) 161 (21.3)
352 (36.2) 78 (8.0) 207 (21.3) 136 (14.0) 200 (20.5)
421 (70.0)
544 (71.9)
710 (73.0)
533 (88.7)
656 (86.7)
851 (87.5)
288 (47.9) 82 (13.6) 189 (31.5) 42 (7.0)
372 (49.1) 160 (21.1) 157 (20.8) 68 (9.0)
436 (44.8) 292 (30.0) 143 (14.7) 102 (10.5)
difference in rates of adjuvant chemotherapy or radiation; however, treatment at a Community Cancer Program was associated with a decreased likelihood of receiving surgery or chemotherapy (Table 3). Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had decreased overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16–1.26). Conversely, Hispanic women exhibited improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80–0.93). Such differences in survival by race/ethnicity were also apparent when analyzed by stage. African American women demonstrated worse survival in both early (stage I and II) and advanced (stage III and IV) disease compared to white women (Table 4). Hispanic
women, however, displayed improved survival compared to white women only in the case of early stage disease, yet there was no difference in survival in the case of advanced stage disease (Table 4). The Cox proportional hazards model identified higher stage, older age, histology other than adenocarcinoma, higher comorbidity index and lack of lymph node sampling as being independently associated with higher mortality (Table 4). In contrast, the highest income, private insurance, receipt of definitive surgery and adjuvant treatment with chemotherapy, radiation or both resulted in improved overall survival (Table 4).
4. Discussion In the United States, racial and ethnic disparities in receipt of care, as well as in mortality, are well established for a plethora of conditions. In this study of 43,950 women with high-grade endometrial cancer, after controlling for patient, tumor and treatment-related factors, African American women had lower all-cause overall survival compared to white women. While the root cause of this is undoubtedly multifactorial, unmeasured socioeconomic factors, compounded with measured factors such as insurance status, may play a significant role. While our study demonstrated decreased mortality in women with endometrial cancer of all stages with higher income and private insurance after controlling for various factors, socioeconomic disparity certainly cannot completely account for differences in endometrial cancer outcomes for African American women. Several studies have investigated the molecular differences in endometrial cancers between African American and white women, focusing on differences in p53 mutations, Her2/neu expression, and PTEN mutations [30–34]. A recent retrospective Gynecologic Oncology Group analysis furthermore demonstrated a trend towards worse survival for women of African ancestry as assessed by genotyping compared to women of European ancestral background, further supporting a biologic basis for the disparity in endometrial cancer outcomes [35]. In stark contrast to the decreased survival exhibited by African American women, Hispanic women exhibited improved overall survival after controlling for patient, tumor and treatment-related factors. There is no corresponding molecular data investigating the biologic difference in endometrial cancer for Hispanic women as there is for African American women, and it is thus a ripe field for study. Although also being a socioeconomically disadvantaged minority similar to African American women, Hispanic women have improved outcomes compared to white women. This discrepancy raises the issue of the “Hispanic paradox” and complicates the critical role socioeconomic status plays in accounting for differences in mortality [36–38]. A deeper and more nuanced understanding of racial and ethnic factors that influence women's survival is of the utmost importance. As noted in the study by Larisey et al. [39], however, entertaining only racial/ethnic group differences in survival overlooks the important contribution lifespan variability has in explaining health inequality. Lifespan variability measures dispersion and disparities within groups. Favorable longevity in the Hispanic population may in fact be the result of less individual variation in age at death, relative to other groups – that is, lower lifespan variability [39]. For example, in one of few studies addressing lifespan variability, the documented variability for Hispanics was 7% lower compared to the whites. Lower mortality among Hispanics from chronic lower respiratory disease and lung cancer accounts for an estimated 39% of their more favorable lifespan variability compared to whites. Importantly, Hispanic women were noted to have the lowest variance and white men the highest [39]. It also remains important to highlight that Hispanics in the United States remain a disadvantaged group, given their significantly lower socioeconomic status, even taking at face value their higher life expectancy [39,40]. That is, Hispanics may live longer and have more certainty in when they will die, due to their lower lifespan variability, yet they have fewer resources for support over a longer period of time [39].
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
A.J. Bregar et al. / Gynecologic Oncology xxx (2017) xxx–xxx
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Table 3 Multivariate logistic regression of factors associated with primary and adjuvant treatment modalities. Characteristic Race/ethnicity White African American Hispanic Date of diagnosis 2003–2005 2006–2008 2009–2011 Age b45 45–54 55–64 65–74 ≥75 Facility type Academic Community Cancer Program Comprehensive Cancer Program Other Area of residence Urban Rural Unknown Region Northeast Midwest South West Income Less than $38,000 $38,000–$47,999 $47,000–$62,999 $63,000 or more Unknown Insurance None Medicare Other Government Private Unknown Education (no HS) 21% or more 13%–20.9% 7%–12.9% b7% Unknown Charlson score 0 1 2 or more Histology Adenocarcinoma Carcinosarcoma Clear cell Papillary serous Pathologic stage I II III IV
Surgery
Chemotherapy
Radiation
Ref. 0.65 (0.51–0.83) 0.88 (0.57–1.37)
Ref. 1.02 (0.95–1.09) 1.01 (0.90–1.13)
Ref. 0.99 (0.93–1.06) 0.94 (0.85–1.04)
Ref. 0.97 (0.76–1.23) 1.06 (0.84–1.35)
Ref. 1.75 (1.65–1.87) 2.70 (2.54–2.87)
Ref. 0.86 (0.82–0.91) 0.75 (0.71–0.79)
Ref. 1.07 (0.58–1.96) 0.81 (0.47–1.40) 1.01 (0.56–1.82) 0.62 (0.34–1.13)
Ref. 0.93 (0.81–1.07) 0.91 (0.80–1.04) 0.82 (0.71–0.94) 0.33 (0.28–0.38)
Ref. 1.15 (1.01–1.32) 1.09 (0.97–1.24) 1.05 (0.92–1.20) 0.78 (0.68–0.89)
Ref. 0.37 (0.27–0.51) 1.06 (0.86–1.31)
Ref. 0.73 (0.65–0.81) 0.83 (0.79–0.87)
Ref. 1.31 (1.20–1.44) 1.09 (1.04–1.14)
Ref. 1.52 (0.73–3.18) 0.84 (0.42–1.65)
Ref. 1.05 (0.88–1.24) 1.18 (1.00–1.38)
Ref. 1.07 (0.92–1.25) 0.67 (0.58–0.78)
Ref. 0.93 (0.70–1.24) 1.11 (0.85–1.45) 1.78 (1.21–2.62)
Ref. 0.97 (0.90–1.04) 0.78 (0.73–0.84) 0.60 (0.55–0.65)
Ref. 1.02 (0.96–1.09) 0.66 (0.62–0.70) 0.62 (0.57–0.66)
Ref. 0.91 (0.68–1.21) 1.26 (0.90–1.77) 0.94 (0.63–1.39) 0.20 (0.02–2.66)
Ref. 1.01 (0.94–1.10) 0.97 (0.89–1.05) 0.97 (0.88–1.07) 0.69 (0.22–2.17)
Ref. 0.96 (0.90–1.03) 0.98 (0.91–1.05) 0.97 (0.89–1.05) 1.03 (0.42–2.57)
Ref. 1.42 (0.88–2.29) 1.25 (0.75–2.09) 1.88 (1.22–2.91) 0.48 (0.27–0.85)
Ref. 1.02 (0.89–1.17) 1.06 (0.91–1.23) 1.20 (1.06–1.35) 1.11 (0.91–1.37)
Ref. 1.16 (1.02–1.31) 1.10 (0.95–1.27) 1.19 (1.06–1.34) 1.30 (1.08–1.57)
Ref. 1.13 (0.85–1.50) 1.31 (0.93–1.84) 1.40 (0.92–2.15) 6.04 (0.41–88.70)
Ref. 1.07 (0.99–1.16) 1.18 (1.08–1.28) 1.28 (1.16–1.42) 1.29 (0.41–4.09)
Ref. 1.05 (0.98–1.13) 1.07 (0.99–1.15) 1.10 (1.01–1.21) 1.39 (0.55–3.52)
Ref. 0.98 (0.77–1.24) 0.73 (0.50–1.08)
Ref. 0.86 (0.81–0.91) 0.70 (0.63–0.78)
Ref. 0.81 (0.77–0.86) 0.82 (0.74–0.90)
Ref. 1.46 (1.08–1.97) 1.33 (0.82–2.16) 1.65 (1.30–2.10)
Ref. 1.83 (1.70–1.96) 1.91 (1.70–2.13) 3.17 (2.98–3.38)
Ref. 0.77 (0.72–0.83) 0.78 (0.70–0.86) 0.58 (0.55–0.62)
Ref. 0.09 (0.07–0.12)
Ref. 1.78 (1.62–1.96) 7.44 (6.98–7.92) 9.95 (9.20–10.77)
Ref. 2.21 (2.04–2.40) 1.09 (1.03–1.15) 0.27 (0.25–0.29)
Ref = Reference.
Other less likely explanations for the observed improved survival in our study include misclassification of Hispanic ethnicity on death certificates and some Hispanics returning to their country of origin at the end of life. Arias et al. [41], however, have shown that Hispanic ethnicity reporting on death certificates is sufficiently accurate, and adjusting for possible misclassification did not significantly impact mortality differences. Likewise, Turra et al. [42] found that the selective return of less-healthy Hispanics to their country of birth was too small in magnitude to explain the Hispanic mortality paradox in the United States.
The consideration of receipt of care, in addition to survival, is also important when assessing health disparities. In this study, we found that white women were more likely to present with early stage disease, receive surgery and undergo lymph node examination as compared to African American and Hispanic women. Interestingly, there was no significant difference observed in the administration of adjuvant treatment between racial and ethnic groups after controlling for various factors. Numerous studies have, however, demonstrated varying degrees of discrepancies in care for minority women [3,11,14–16,43,44] Despite the
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
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A.J. Bregar et al. / Gynecologic Oncology xxx (2017) xxx–xxx
Table 4 Multivariate cox proportional hazards model for overall mortality. Characteristic Race/ethnicity White African American Hispanic Date of diagnosis 2003–2005 2006–2008 2009–2011 Age b45 45–54 55–64 65–74 75+ Facility type Community Comprehensive community Academic Other Area of residence Urban Rural Unknown Region Northeast Midwest South West Income Less than $38,000 $38,000–$47,999 $47,000–$62,999 $63,000 or more Unknown Insurance None Medicare Other Government Private Unknown Education (no HS) 21% or more 13%–20.9% 7%–12.9% b7% Unknown Charlson score 0 1 2 or more Histology Adenocarcinoma (grade 3) Carcinosarcoma Clear Cell Papillary serous Pathologic stage I II III IV Adjuvant treatment None Chemotherapy Radiation Chemotherapy and radiation Surgery None Yes Lymph nodes examined Yes No
All
Early stage (I and II)
Advanced stage (III and IV)
Ref. 1.21 (1.16–1.26) 0.87 (0.80–0.93)
Ref. 1.22 (1.13–1.33) 0.80 (0.68–0.94)
Ref. 1.27 (1.20–1.34) 0.92 (0.83–1.02)
Ref. 0.97 (0.94–1.00) 0.94 (0.91–0.98)
Ref. 0.98 (0.91–1.05) 0.98 (0.90–1.06)
Ref. 0.99 (0.94–1.04) 0.97 (0.91–1.02)
Ref. 1.02 (0.91–1.15) 1.41 (1.27–1.57) 1.69 (1.51–1.88) 2.53 (2.27–2.83)
Ref. 1.10 (0.81–1.50) 2.14 (1.61–2.85) 2.97 (2.22–3.97) 5.37 (4.02–7.19)
Ref. 1.10 (0.95–1.27) 1.35 (1.18–1.54) 1.51 (1.31–1.74) 2.06 (1.78–2.37)
Ref. 0.96 (0.90–1.02) 1.02 (0.99–1.05) 1.54 (0.85–2.78)
Ref. 1.05 (0.92–1.19) 1.01 (0.95–1.08) 1.59 (0.66–3.84)
Ref. 0.99 (0.90–1.09) 1.06 (1.02–1.11) 1.35 (0.51–3.61)
Ref. 1.05 (0.95–1.16) 0.97 (0.87–1.07)
Ref. 1.00 (0.82–1.21) 0.91 (0.75–1.11)
Ref. 1.17 (1.02–1.35) 0.97 (0.84–1.13)
Ref. 1.07 (1.03–1.12) 1.04 (1.00–1.08) 1.00 (0.95–1.05)
Ref. 1.01 (0.93–1.11) 1.03 (0.95–1.12) 0.99 (0.89–1.09)
Ref. 1.07 (1.00–1.14) 1.03 (0.97–1.09) 0.95 (0.89–1.02)
Ref. 0.96 (0.92–1.01) 1.01 (0.96–1.06) 0.92 (0.87–0.98) 1.01 (0.63–1.60)
Ref. 0.90 (0.82–0.99) 0.92 (0.83–1.02) 0.89 (0.80–1.00) 0.41 (0.14–1.18)
Ref. 0.97 (0.90–1.03) 1.01 (0.94–1.08) 0.90 (0.83–0.98) 1.08 (0.53–2.20)
Ref. 0.90 (0.83–0.99) 0.99 (0.90–1.10) 0.78 (0.72–0.85) 0.76 (0.67–0.87)
Ref. 1.04 (0.84–1.29) 1.16 (0.91–1.48) 0.82 (0.67–1.01) 0.99 (0.75–1.32)
Ref. 1.00 (0.88–1.13) 1.08 (0.94–1.24) 0.94 (0.83–1.05) 0.80 (0.66–0.96)
Ref. 1.00 (0.96–1.05) 0.97 (0.92–1.02) 0.94 (0.89–1.00) 1.64 (1.03–2.60)
Ref. 0.96 (0.87–1.05) 0.98 (0.88–1.08) 0.92 (0.81–1.03) 4.60 (1.62–13.09)
Ref. 1.02 (0.96–1.09) 0.98 (0.91–1.05) 0.97 (0.88–1.05) 1.39 (0.68–2.82)
Ref. 1.17 (1.13–1.21) 1.44 (1.36–1.53)
Ref. 1.22 (1.14–1.30) 1.60 (1.43–1.79)
Ref. 1.10 (1.05–1.16) 1.28 (1.17–1.41)
Ref. 1.85 (1.78–1.93) 1.16 (1.08–1.24) 1.12 (1.07–1.16)
Ref. 2.27 (2.09–2.46) 1.07 (0.93–1.22) 1.14 (1.05–1.24)
Ref. 1.66 (1.56–1.76) 1.20 (1.09–1.32) 1.06 (1.01–1.12)
Ref. 1.84 (1.72–1.96) 3.27 (3.12–3.42) 6.08 (5.78–6.41)
Ref. 1.81 (1.70–1.94)
Ref. 0.82 (0.79–0.85) 0.80 (0.77–0.83) 0.70 (0.66–0.74)
Ref. 0.81 (0.72–0.90) 0.94 (0.88–1.00) 0.65 (0.57–0.75)
Ref. 1.99 (1.90–2.09)
Ref. 0.37 (0.35–0.39) Ref. 1.52 (1.46–1.57)
Ref. 0.63 (0.60–0.66) 0.68 (0.63–0.73) 0.55 (0.51–0.59) Ref. 0.52 (0.47–0.5)
Ref. 1.50 (1.39–1.61)
Ref. 1.46 (1.39–1.54)
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
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consistent finding that underserved minority women receive different care, a full understanding of the factors that influence treatment remains elusive. Several studies have attempted to investigate the impact that patient beliefs, culture, practice and provider-patient communication have on the offering and acceptance of cancer treatment in vulnerable populations [45–47]. Our study has several limitations. There was no central pathology review to assure that histologic sub-type and grade were correctly assigned to included cases. The NCDB only permits evaluation of allcause mortality and not cancer-specific mortality. Given the retrospective nature of the study, decisions regarding surgery and delivery of adjuvant therapies are susceptible to uncontrolled factors, making selection bias another study limitation. The database does not give detailed information regarding the specifics of adjuvant treatment regimens, scheduling and completion rates. Another limitation of the database is that it does not include standard comorbidities such as body mass index and diabetes, both of which have been shown to be relevant in the investigation of outcomes in patients with endometrial cancer [7,12,48–50]. Regardless of such limitations, this work highlights the need for further investigations of the differences in cancer outcomes between racial and ethic groups and for efforts to be made in closing existing socioeconomic disparity gaps and in eliminating barriers adversely affecting optimal cancer treatment among underserved minority populations. Conflict of interest statement The authors declare that there are no conflicts of interest.
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Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis Amy J. Bregar a, J. Alejandro Rauh-Hain a, Ryan Spencer b, Joel T. Clemmer a, John O. Schorge a, Laurel W. Rice b, Marcela G. del Carmen a,⁎ a b
Division of Gynecologic Oncology, Vincent Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
H I G H L I G H T S • White women were most likely to present with early stage disease. • African American women had lower all-cause survival compared to white women. • Hispanic women had higher all-cause survival compared to white women.
a r t i c l e
i n f o
Article history: Received 29 November 2016 Received in revised form 19 January 2017 Accepted 20 January 2017 Available online xxxx
a b s t r a c t Purpose. To examine patterns of care and survival for Hispanic women compared to white and African American women with high-grade endometrial cancer. Methods. We utilized the National Cancer Data Base (NCDB) to identify women diagnosed with uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma between 2003 and 2011. The effect of treatment on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. Results. 43,950 women were eligible. African American and Hispanic women had higher rates of stage III and IV disease compared to white women (36.5% vs. 36% vs. 33.5%, p b 0.001). African American women were less likely to undergo surgical treatment for their cancer (85.2% vs. 89.8% vs. 87.5%, p b 0.001) and were more likely to receive chemotherapy (36.8% vs. 32.4% vs. 32%, p b 0.001) compared to white and Hispanic women. Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had lower overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16–1.26). Conversely, Hispanic women had improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80–0.93). Conclusions. Among women with high-grade endometrial cancer, African American women have lower allcause survival while Hispanic women have higher all-cause survival compared to white women after controlling for treatment, sociodemographic, comorbidity and histopathologic variables. © 2017 Elsevier Inc. All rights reserved.
1. Introduction In the United States, endometrial cancer is the most common gynecologic malignancy, with 60,050 new cases estimated in 2016 [1]. While the majority of these cases are early stage and of low-grade
⁎ Corresponding author at: Division of Gynecologic Oncology, Vincent Obstetrics and Gynecology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 9 E, Boston, MA 02114, United States E-mail address: [email protected] (M.G. del Carmen).
endometrioid histology, a proportion of women will be diagnosed with an aggressive histologic subtype that confers a greater risk of disease recurrence and increased mortality [2]. African American women have a higher incidence of high-grade histology [3–7], which may contribute to the well-documented increase in overall mortality among African American women [8–12]. While the vast majority of research has focused on the comparison between white and African American women with endometrial cancer, a growing yet limited body of literature has examined differences in disease presentation, treatment patterns and outcomes between Hispanic and non-Hispanic women [7,13–16].
http://dx.doi.org/10.1016/j.ygyno.2017.01.024 0090-8258/© 2017 Elsevier Inc. All rights reserved.
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
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“Hispanic or Latino” ethnicity is defined by the federal Office of Management and Budget as “a person of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race” [17]. Hispanics represent the largest ethnic minority group in the United States, and cancer is the leading cause of death among Hispanic women [18]. Hispanic women, similar to African American women, have a higher incidence of high-grade disease [13, 15] and are a vulnerable population disproportionately affected by lower socioeconomic status and barriers to healthcare. While there is substantial racial and cultural diversity within the Hispanic community and significant variation in the literature regarding how Hispanic ethnicity is characterized [19], cancer data are typically presented for Hispanics in aggregate [18]. Despite the heterogeneity within the Hispanic population, there is value in comparing the differences in treatment patterns and clinical outcomes among white women, African American women and Hispanic women with cancer, as such studies are lacking. The objective of this study is to compare the demographics, tumor characteristics, treatment course and overall survival of Hispanic women to non-Hispanic white women and nonHispanic African American women with high-grade endometrial cancer. 2. Materials and methods The National Cancer Data Base (NCDB) was used to identify women with high-grade endometrial cancer diagnosed between 2003 and 2011. The NCDB is a nationwide comprehensive clinical surveillance oncology system established by the American Cancer Society and the Commission on Cancer of the American College of Surgeons. Currently, this database captures approximately 70% of newly diagnosed malignancies in the United States, and receives over one million case reports from over 1500 hospitals annually [20]. The NCDB aggregates information about patient demographics, tumor characteristics, cancer-directed therapies, treating facility and overall survival. Data reported to the NCDB are retrospective and de-identified, ensuring confidentiality. This study was exempt from Institutional Review Board oversight. Women with grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma were considered to have high-grade endometrial cancer and were included in this study [6]. Women diagnosed by death certificate or at autopsy and patients who had other primary cancers were excluded. The variables of interest were race and ethnicity. For this, race and ethnicity variables were combined to construct single mutually exclusive raceethnicity variables (non-Hispanic white, non-Hispanic African American, Hispanic, other and unknown). Women of other or unknown race and/or ethnicity were excluded from this analysis. The primary outcome of interest was overall survival, defined as months from cancer diagnosis to death or date of the last contact. Secondary outcomes were the receipt of initial treatment after diagnosis of high-grade endometrial cancer. Initial treatment was defined as the first planned course of cancer-directed therapy used to manage the endometrial cancer and excludes treatments initiated for recurrence or relapse of disease [21]. The identification of chemotherapy through the NCDB has been shown in prior studies to be reliable [22–24]. Patients were considered to have been treated with combination adjuvant chemo-radiation if they had received both radiotherapy and chemotherapy within 6 months after diagnosis. We defined definitive surgery as procedures performed with curative intent or in anticipation of a subsequent curative treatment. Demographic, socioeconomic and clinical variables were categorized according to the NCDB Participant User File Data Dictionary [25]. Control variables included age at diagnosis, year of diagnosis (classified as 2003–2005, 2006–2008, 2009–2011), and geographic location of the treating facility (Northeast, Midwest, South and West). Tumor stage was determined using the revised 2009 staging criteria of the International Federation of Gynecologists and Obstetricians (FIGO)
[26]. Stage was determined based on available pathologic records depending on the type of surgery performed. Lymph node status was used to assign stage if lymphadenectomy was performed, otherwise pathologic stage was based on available pathologic data (e.g. depth of tumor invasion or evidence of metastatic disease). A residence was considered rural when the county of residence was “completely rural or had less than 2,500 urban population and was not adjacent to a metro area” as denoted by the United States Department of Agriculture's 2003 RuralUrban Continuum Codes classification scheme [27]. Median household income was categorized using the average income of the zip code of residence as estimated by either the 2000 census or the community survey data, categorized in quartiles (b$38,000, $38,000–$47,999, $47,000–$62,999 and ≥$63,000). Insurance status was categorized as uninsured, private insurance, Medicare or another type of government insurance (military or Medicaid). The treating facility was categorized according to the Commission on Cancer Accreditation Program as a Community Cancer Program, Comprehensive Community Cancer Program, Academic/Research Program or other. Education level for each patient's area of residence was estimated by matching the zip code of the patient recorded at the time of diagnosis against files derived from the 2012 American Community Survey data, thereby providing a measure of the proportion of adults in the patient's zip code who had attained a given education level. Comorbidity was analyzed using the Klabunde adaptation of the Charlson index; all subjects were assigned a score of 0, 1 or N2 [28,29]. 2.1. Statistical analysis Continuous variables were evaluated by ANOVA, and categorical variables were evaluated by chi square test. Pair-wise comparisons among continuous and categorical variables utilized the HolmBonferroni method to adjust for multiple comparisons. Logistic regression models were performed to describe predictors of treatment between racial groups, after adjusting for age, stage, histology, year of treatment, facility type, location, insurance type, education level, socioeconomic status and comorbidity score. Survival curves were calculated using the Kaplan-Meier method and used to compare between racial groups. Cox proportional hazards models were used to calculate adjusted group hazard ratios, and their 95% confidence intervals (CI) were utilized to assess the importance of adjuvant treatment options as an independent predictor of survival after adjusting for the same prognostic factors listed previously. All statistical tests were twosided, and differences were considered statistically significant at p b 0.05. All statistical analyses were performed using R 3.0.3 (R Foundation for Statistic Computing, Vienna Austria). 3. Results We identified 43,950 women from the NCDB diagnosed with highgrade endometrial cancer between 2003 and 2011 who met inclusion criteria. Table 1 summarizes the demographic and clinical characteristics of the study population. African American women were more frequently in the lowest quartile of income level (41.5% vs. 12.7% vs. 27.3%, p b 0.001) and had a higher comorbidity score of 2 or greater (7.1% vs. 4.7% vs. 4.3%, p b 0.001) when compared to white and Hispanic women. Hispanic women were more likely to be uninsured compared to white or African American women (10.9% vs. 2.9% vs. 5.0%, p b 0.001). Analysis of treatment patterns demonstrated that both Hispanic women and African American women were less likely to receive definitive surgical treatment compared to white women (87.5% vs. 85.2% vs. 89.8%, p b 0.001). While both Hispanic and African American women had lower rates of lymph node sampling compared to white women (71.9% vs. 69% vs. 75.3%, p b 0.001), African American women were the most likely to have positive lymph nodes (22.2% vs. 18.7% vs. 19.6%, p b 0.001) compared to white and Hispanic women. African American women were also more likely to receive adjuvant
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
A.J. Bregar et al. / Gynecologic Oncology xxx (2017) xxx–xxx
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Table 1 Demographics and clinical characteristics of the study population. Characteristic
White N = 34.035 (77.4%)
African American N = 7584 (17.3%)
Hispanic N = 2331 (5.3%)
p-Value
Median age at diagnosis, years (interquartile rage) Dates [N(%)] 2003–2005 2006–2008 2009–2011 Facility type [N(%)] Academic Community Cancer Program Comprehensive Cancer Program Other Area of residence [N(%)] Urban Rural Unknown Region [N(%)] Northeast Midwest South West Income [N(%)] Less than $38,000 $38,000–$47,999 $47,000–$62,999 $63,000 or more Unknown Insurance status [N(%)] None Medicare Other Government Private Unknown Charlson score [N(%)] 0 1 2 or more Histology [N(%)] Adenocarcinoma Carcinosarcoma Clear cell Papillary serous Pathologic stage [N(%)] I II III IV Unknown Surgery [N(%)] Yes Lymph node examination [N(%)] Yes Lymph node status [N(%)] Positive Adjuvant treatment [N(%)] None Chemotherapy Radiotherapy Chemotherapy and radiotherapy
66 (58–75)
66 (60–73)
63 (55–71)
*
9721 (28.6) 11,172 (32.8) 13,142 (38.6)
1899 (25.1) 2543 (33.5) 3142 (41.4)
601 (25.8) 757 (32.5) 973 (41.7)
p = 0.6 for African American vs. Hispanic
13,788 (40.4) 2032 (6.0) 18,195 (53.5) 20 (0.1)
4071 (53.7) 398 (5.2) 3113 (41.1) 2 (0.0)
1133 (48.6) 129 (5.5) 1069 (45.9) 0 (0.0)
31,718 (93.2) 748 (2.2) 1569 (4.6)
7192 (94.8) 110 (1.5) 282 (3.7)
2255 (96.7) 6 (0.3) 70 (3.0)
8118 (23.9) 9272 (27.2) 10,801 (31.7) 5844 (17.2)
1551 (20.5) 1351 (17.8) 4297 (56.7) 385 (5.0)
397 (17.0) 179 (7.7) 913 (39.2) 842 (36.1)
4327 (12.7) 7487 (22.0) 9315 (27.4) 12,093 (35.5) 813 (2.4)
3148 (41.5) 1673 (22.1) 1475 (19.4) 1092 (14.4) 196 (2.6)
637 (27.3) 570 (24.5) 571 (24.5) 512 (22.0) 41 (1.7)
1002 (2.9) 17,005 (50.0) 1431 (4.2) 13,986 (41.1) 611 (1.8)
378 (5.0) 3927 (51.8) 748 (9.9) 2370 (31.2) 161 (2.1)
255 (10.9) 836 (35.9) 339 (14.5) 803 (34.4) 98 (4.3)
25,905 (76.1) 6519 (19.2) 1611 (4.7)
5126 (67.6) 1921 (25.3) 537 (7.1)
1744 (74.8) 486 (20.8) 101 (4.4)
23,280 (68.4) 3703 (10.9) 1410 (4.1) 5642 (16.6)
3809 (50.2) 1409 (18.6) 395 (5.2) 1971 (26.0)
1538 (66.0) 253 (10.9) 104 (4.5) 436 (18.6)
13,674 (40.2) 2426 (7.1) 7578 (22.3) 3821 (11.2) 6536 (19.2)
2435 (32.1) 622 (8.2) 1749 (23.1) 1017 (13.4) 1761 (23.2)
830 (35.6) 185 (7.9) 537 (23.0) 303 (13.0) 476 (20.5)
30,568 (89.8)
6464 (85.2)
2040 (87.5)
25,633 (75.3)
5235 (69.0)
1675 (71.9)
6354 (18.7)
1681 (22.2)
456 (19.6)
14,619 (43.1) 7233 (21.3) 8403 (24.7) 3780 (11.1)
3227 (42.6) 1984 (26.2) 1563 (20.6) 810 (10.6)
1096 (47.0) 534 (22.9) 489 (21.0) 212 (9.1)
*
*
*
*
*
p = 0.11 for white vs. Hispanic
p = 0.04 for white vs. Hispanic
p = 0.01 for African American vs. Hispanic
* p = 0.03 for African American vs. Hispanic * *
* Unless otherwise indicated, p value for all pair-wise comparisons between groups b 0.001.
chemotherapy with or without radiation (36.8% vs. 32.4% vs. 32%, p b 0.001) compared to white and Hispanic women. We examined trends in disease presentation and adjuvant treatment in two-year increments over the time period of evaluation (2003–2005, 2006–2008 and 2009–2011). While rates of pathologic stage I disease remained relatively stable in white (39.7%, 39.0%, 41.5%) and Hispanic women (36.1%, 34.5%, 36.2%), an increased percentage of African American women were diagnosed with stage I disease over time (28.3%, 31.0%, 35.3%). Rates of lymphadenectomy increased over time in white (72.4%, 76.3%, 76.6%), African American
(65.4%, 69.1%, 71.2%) and Hispanic women (70.0%, 71.9%, 73.0%). Rates of adjuvant chemotherapy (with or without radiation) increased substantially for white (23.1%, 32.0%, 39.6%), African American (27.6%, 37.4%, 42.1%) and Hispanic women (20.6%, 30.1%, 40.5%) (Table 2). Multivariate analyses of treatment patterns controlling for clinical, pathologic and demographic factors demonstrated that African American women were less likely to receive surgical treatment compared to white women (Odds Ratio 0.65, 95% CI 0.51–0.83). There was no significant difference in surgical treatment between white and Hispanic women (OR 0.88, 95% CI 0.57–1.37). There was no racial or ethnic
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
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A.J. Bregar et al. / Gynecologic Oncology xxx (2017) xxx–xxx
Table 2 Stage and treatment stratified by date of diagnosis, race and ethnicity. White Pathologic stage [N(%)] I II III IV Unknown Lymph node dissection [N(%)] Yes Surgery [N(%)] Yes Adjuvant treatment [N(%)] None Chemotherapy Radiotherapy Chemotherapy and radiotherapy African American Pathologic stage [N(%)] I II III IV Unknown Lymph node dissection [N(%)] Yes Surgery [N(%)] Yes Adjuvant treatment [N(%)] None Chemotherapy Radiotherapy Chemotherapy and radiotherapy Hispanic Pathologic stage [N(%)] I II III IV Unknown Lymph node dissection [N(%)] Yes Surgery [N(%)] Yes Adjuvant treatment [N(%)] None Chemotherapy Radiotherapy Chemotherapy and radiotherapy
2003–2005 N = 9721
2006–2008 N = 11.172
2009–2011 N = 13.142
3859 (39.7) 768 (7.9) 2105 (21.7) 1118 (11.5) 1871 (19.2)
4355 (39.0) 877 (7.8) 2590 (23.2) 1247 (11.2) 2103 (18.8)
5460 (41.6) 781 (5.9) 2883 (21.9) 1456 (11.1) 2562 (19.5)
7039 (72.4)
8523 (76.3)
10,071 (76.6)
8671 (89.2)
10,105 (90.4)
11,792 (89.7)
4375 (45.0) 1421 (14.6) 3105 (31.9) 820 (8.5)
4712 (42.2) 2382 (21.3) 2887 (25.7) 1191 (10.7)
5532 (42.1) 3430 (26.1) 2411 (18.3) 1769 (13.5)
2003–2005 N = 1899
2006–2008 N = 2543
2009–2011 N = 3142
537 (28.3) 184 (9.7) 438 (23.1) 275 (14.5) 465 (24.4)
789 (31.0) 221 (8.7) 587 (23.1) 339 (13.3) 607 (23.9)
1109 (35.4) 217 (6.9) 724 (23.0) 403 (12.8) 689 (21.9)
1241 (65.4)
1757 (69.1)
2237 (71.2)
1599 (84.2)
2168 (85.3)
2697 (85.8)
878 (46.2) 368 (19.4) 498 (26.2) 155 (8.2)
1076 (42.3) 680 (26.7) 517 (20.3) 270 (10.7)
1273 (40.5) 936 (29.8) 548 (17.4) 385 (12.3)
2003–2005 N = 601
2006–2008 N = 757
2009–2011 N = 973
217 (36.2) 51 (8.5) 142 (23.6) 76 (12.6) 115 (19.1)
261 (34.5) 56 (7.4) 188 (24.8) 91 (12.0) 161 (21.3)
352 (36.2) 78 (8.0) 207 (21.3) 136 (14.0) 200 (20.5)
421 (70.0)
544 (71.9)
710 (73.0)
533 (88.7)
656 (86.7)
851 (87.5)
288 (47.9) 82 (13.6) 189 (31.5) 42 (7.0)
372 (49.1) 160 (21.1) 157 (20.8) 68 (9.0)
436 (44.8) 292 (30.0) 143 (14.7) 102 (10.5)
difference in rates of adjuvant chemotherapy or radiation; however, treatment at a Community Cancer Program was associated with a decreased likelihood of receiving surgery or chemotherapy (Table 3). Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had decreased overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16–1.26). Conversely, Hispanic women exhibited improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80–0.93). Such differences in survival by race/ethnicity were also apparent when analyzed by stage. African American women demonstrated worse survival in both early (stage I and II) and advanced (stage III and IV) disease compared to white women (Table 4). Hispanic
women, however, displayed improved survival compared to white women only in the case of early stage disease, yet there was no difference in survival in the case of advanced stage disease (Table 4). The Cox proportional hazards model identified higher stage, older age, histology other than adenocarcinoma, higher comorbidity index and lack of lymph node sampling as being independently associated with higher mortality (Table 4). In contrast, the highest income, private insurance, receipt of definitive surgery and adjuvant treatment with chemotherapy, radiation or both resulted in improved overall survival (Table 4).
4. Discussion In the United States, racial and ethnic disparities in receipt of care, as well as in mortality, are well established for a plethora of conditions. In this study of 43,950 women with high-grade endometrial cancer, after controlling for patient, tumor and treatment-related factors, African American women had lower all-cause overall survival compared to white women. While the root cause of this is undoubtedly multifactorial, unmeasured socioeconomic factors, compounded with measured factors such as insurance status, may play a significant role. While our study demonstrated decreased mortality in women with endometrial cancer of all stages with higher income and private insurance after controlling for various factors, socioeconomic disparity certainly cannot completely account for differences in endometrial cancer outcomes for African American women. Several studies have investigated the molecular differences in endometrial cancers between African American and white women, focusing on differences in p53 mutations, Her2/neu expression, and PTEN mutations [30–34]. A recent retrospective Gynecologic Oncology Group analysis furthermore demonstrated a trend towards worse survival for women of African ancestry as assessed by genotyping compared to women of European ancestral background, further supporting a biologic basis for the disparity in endometrial cancer outcomes [35]. In stark contrast to the decreased survival exhibited by African American women, Hispanic women exhibited improved overall survival after controlling for patient, tumor and treatment-related factors. There is no corresponding molecular data investigating the biologic difference in endometrial cancer for Hispanic women as there is for African American women, and it is thus a ripe field for study. Although also being a socioeconomically disadvantaged minority similar to African American women, Hispanic women have improved outcomes compared to white women. This discrepancy raises the issue of the “Hispanic paradox” and complicates the critical role socioeconomic status plays in accounting for differences in mortality [36–38]. A deeper and more nuanced understanding of racial and ethnic factors that influence women's survival is of the utmost importance. As noted in the study by Larisey et al. [39], however, entertaining only racial/ethnic group differences in survival overlooks the important contribution lifespan variability has in explaining health inequality. Lifespan variability measures dispersion and disparities within groups. Favorable longevity in the Hispanic population may in fact be the result of less individual variation in age at death, relative to other groups – that is, lower lifespan variability [39]. For example, in one of few studies addressing lifespan variability, the documented variability for Hispanics was 7% lower compared to the whites. Lower mortality among Hispanics from chronic lower respiratory disease and lung cancer accounts for an estimated 39% of their more favorable lifespan variability compared to whites. Importantly, Hispanic women were noted to have the lowest variance and white men the highest [39]. It also remains important to highlight that Hispanics in the United States remain a disadvantaged group, given their significantly lower socioeconomic status, even taking at face value their higher life expectancy [39,40]. That is, Hispanics may live longer and have more certainty in when they will die, due to their lower lifespan variability, yet they have fewer resources for support over a longer period of time [39].
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
A.J. Bregar et al. / Gynecologic Oncology xxx (2017) xxx–xxx
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Table 3 Multivariate logistic regression of factors associated with primary and adjuvant treatment modalities. Characteristic Race/ethnicity White African American Hispanic Date of diagnosis 2003–2005 2006–2008 2009–2011 Age b45 45–54 55–64 65–74 ≥75 Facility type Academic Community Cancer Program Comprehensive Cancer Program Other Area of residence Urban Rural Unknown Region Northeast Midwest South West Income Less than $38,000 $38,000–$47,999 $47,000–$62,999 $63,000 or more Unknown Insurance None Medicare Other Government Private Unknown Education (no HS) 21% or more 13%–20.9% 7%–12.9% b7% Unknown Charlson score 0 1 2 or more Histology Adenocarcinoma Carcinosarcoma Clear cell Papillary serous Pathologic stage I II III IV
Surgery
Chemotherapy
Radiation
Ref. 0.65 (0.51–0.83) 0.88 (0.57–1.37)
Ref. 1.02 (0.95–1.09) 1.01 (0.90–1.13)
Ref. 0.99 (0.93–1.06) 0.94 (0.85–1.04)
Ref. 0.97 (0.76–1.23) 1.06 (0.84–1.35)
Ref. 1.75 (1.65–1.87) 2.70 (2.54–2.87)
Ref. 0.86 (0.82–0.91) 0.75 (0.71–0.79)
Ref. 1.07 (0.58–1.96) 0.81 (0.47–1.40) 1.01 (0.56–1.82) 0.62 (0.34–1.13)
Ref. 0.93 (0.81–1.07) 0.91 (0.80–1.04) 0.82 (0.71–0.94) 0.33 (0.28–0.38)
Ref. 1.15 (1.01–1.32) 1.09 (0.97–1.24) 1.05 (0.92–1.20) 0.78 (0.68–0.89)
Ref. 0.37 (0.27–0.51) 1.06 (0.86–1.31)
Ref. 0.73 (0.65–0.81) 0.83 (0.79–0.87)
Ref. 1.31 (1.20–1.44) 1.09 (1.04–1.14)
Ref. 1.52 (0.73–3.18) 0.84 (0.42–1.65)
Ref. 1.05 (0.88–1.24) 1.18 (1.00–1.38)
Ref. 1.07 (0.92–1.25) 0.67 (0.58–0.78)
Ref. 0.93 (0.70–1.24) 1.11 (0.85–1.45) 1.78 (1.21–2.62)
Ref. 0.97 (0.90–1.04) 0.78 (0.73–0.84) 0.60 (0.55–0.65)
Ref. 1.02 (0.96–1.09) 0.66 (0.62–0.70) 0.62 (0.57–0.66)
Ref. 0.91 (0.68–1.21) 1.26 (0.90–1.77) 0.94 (0.63–1.39) 0.20 (0.02–2.66)
Ref. 1.01 (0.94–1.10) 0.97 (0.89–1.05) 0.97 (0.88–1.07) 0.69 (0.22–2.17)
Ref. 0.96 (0.90–1.03) 0.98 (0.91–1.05) 0.97 (0.89–1.05) 1.03 (0.42–2.57)
Ref. 1.42 (0.88–2.29) 1.25 (0.75–2.09) 1.88 (1.22–2.91) 0.48 (0.27–0.85)
Ref. 1.02 (0.89–1.17) 1.06 (0.91–1.23) 1.20 (1.06–1.35) 1.11 (0.91–1.37)
Ref. 1.16 (1.02–1.31) 1.10 (0.95–1.27) 1.19 (1.06–1.34) 1.30 (1.08–1.57)
Ref. 1.13 (0.85–1.50) 1.31 (0.93–1.84) 1.40 (0.92–2.15) 6.04 (0.41–88.70)
Ref. 1.07 (0.99–1.16) 1.18 (1.08–1.28) 1.28 (1.16–1.42) 1.29 (0.41–4.09)
Ref. 1.05 (0.98–1.13) 1.07 (0.99–1.15) 1.10 (1.01–1.21) 1.39 (0.55–3.52)
Ref. 0.98 (0.77–1.24) 0.73 (0.50–1.08)
Ref. 0.86 (0.81–0.91) 0.70 (0.63–0.78)
Ref. 0.81 (0.77–0.86) 0.82 (0.74–0.90)
Ref. 1.46 (1.08–1.97) 1.33 (0.82–2.16) 1.65 (1.30–2.10)
Ref. 1.83 (1.70–1.96) 1.91 (1.70–2.13) 3.17 (2.98–3.38)
Ref. 0.77 (0.72–0.83) 0.78 (0.70–0.86) 0.58 (0.55–0.62)
Ref. 0.09 (0.07–0.12)
Ref. 1.78 (1.62–1.96) 7.44 (6.98–7.92) 9.95 (9.20–10.77)
Ref. 2.21 (2.04–2.40) 1.09 (1.03–1.15) 0.27 (0.25–0.29)
Ref = Reference.
Other less likely explanations for the observed improved survival in our study include misclassification of Hispanic ethnicity on death certificates and some Hispanics returning to their country of origin at the end of life. Arias et al. [41], however, have shown that Hispanic ethnicity reporting on death certificates is sufficiently accurate, and adjusting for possible misclassification did not significantly impact mortality differences. Likewise, Turra et al. [42] found that the selective return of less-healthy Hispanics to their country of birth was too small in magnitude to explain the Hispanic mortality paradox in the United States.
The consideration of receipt of care, in addition to survival, is also important when assessing health disparities. In this study, we found that white women were more likely to present with early stage disease, receive surgery and undergo lymph node examination as compared to African American and Hispanic women. Interestingly, there was no significant difference observed in the administration of adjuvant treatment between racial and ethnic groups after controlling for various factors. Numerous studies have, however, demonstrated varying degrees of discrepancies in care for minority women [3,11,14–16,43,44] Despite the
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
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A.J. Bregar et al. / Gynecologic Oncology xxx (2017) xxx–xxx
Table 4 Multivariate cox proportional hazards model for overall mortality. Characteristic Race/ethnicity White African American Hispanic Date of diagnosis 2003–2005 2006–2008 2009–2011 Age b45 45–54 55–64 65–74 75+ Facility type Community Comprehensive community Academic Other Area of residence Urban Rural Unknown Region Northeast Midwest South West Income Less than $38,000 $38,000–$47,999 $47,000–$62,999 $63,000 or more Unknown Insurance None Medicare Other Government Private Unknown Education (no HS) 21% or more 13%–20.9% 7%–12.9% b7% Unknown Charlson score 0 1 2 or more Histology Adenocarcinoma (grade 3) Carcinosarcoma Clear Cell Papillary serous Pathologic stage I II III IV Adjuvant treatment None Chemotherapy Radiation Chemotherapy and radiation Surgery None Yes Lymph nodes examined Yes No
All
Early stage (I and II)
Advanced stage (III and IV)
Ref. 1.21 (1.16–1.26) 0.87 (0.80–0.93)
Ref. 1.22 (1.13–1.33) 0.80 (0.68–0.94)
Ref. 1.27 (1.20–1.34) 0.92 (0.83–1.02)
Ref. 0.97 (0.94–1.00) 0.94 (0.91–0.98)
Ref. 0.98 (0.91–1.05) 0.98 (0.90–1.06)
Ref. 0.99 (0.94–1.04) 0.97 (0.91–1.02)
Ref. 1.02 (0.91–1.15) 1.41 (1.27–1.57) 1.69 (1.51–1.88) 2.53 (2.27–2.83)
Ref. 1.10 (0.81–1.50) 2.14 (1.61–2.85) 2.97 (2.22–3.97) 5.37 (4.02–7.19)
Ref. 1.10 (0.95–1.27) 1.35 (1.18–1.54) 1.51 (1.31–1.74) 2.06 (1.78–2.37)
Ref. 0.96 (0.90–1.02) 1.02 (0.99–1.05) 1.54 (0.85–2.78)
Ref. 1.05 (0.92–1.19) 1.01 (0.95–1.08) 1.59 (0.66–3.84)
Ref. 0.99 (0.90–1.09) 1.06 (1.02–1.11) 1.35 (0.51–3.61)
Ref. 1.05 (0.95–1.16) 0.97 (0.87–1.07)
Ref. 1.00 (0.82–1.21) 0.91 (0.75–1.11)
Ref. 1.17 (1.02–1.35) 0.97 (0.84–1.13)
Ref. 1.07 (1.03–1.12) 1.04 (1.00–1.08) 1.00 (0.95–1.05)
Ref. 1.01 (0.93–1.11) 1.03 (0.95–1.12) 0.99 (0.89–1.09)
Ref. 1.07 (1.00–1.14) 1.03 (0.97–1.09) 0.95 (0.89–1.02)
Ref. 0.96 (0.92–1.01) 1.01 (0.96–1.06) 0.92 (0.87–0.98) 1.01 (0.63–1.60)
Ref. 0.90 (0.82–0.99) 0.92 (0.83–1.02) 0.89 (0.80–1.00) 0.41 (0.14–1.18)
Ref. 0.97 (0.90–1.03) 1.01 (0.94–1.08) 0.90 (0.83–0.98) 1.08 (0.53–2.20)
Ref. 0.90 (0.83–0.99) 0.99 (0.90–1.10) 0.78 (0.72–0.85) 0.76 (0.67–0.87)
Ref. 1.04 (0.84–1.29) 1.16 (0.91–1.48) 0.82 (0.67–1.01) 0.99 (0.75–1.32)
Ref. 1.00 (0.88–1.13) 1.08 (0.94–1.24) 0.94 (0.83–1.05) 0.80 (0.66–0.96)
Ref. 1.00 (0.96–1.05) 0.97 (0.92–1.02) 0.94 (0.89–1.00) 1.64 (1.03–2.60)
Ref. 0.96 (0.87–1.05) 0.98 (0.88–1.08) 0.92 (0.81–1.03) 4.60 (1.62–13.09)
Ref. 1.02 (0.96–1.09) 0.98 (0.91–1.05) 0.97 (0.88–1.05) 1.39 (0.68–2.82)
Ref. 1.17 (1.13–1.21) 1.44 (1.36–1.53)
Ref. 1.22 (1.14–1.30) 1.60 (1.43–1.79)
Ref. 1.10 (1.05–1.16) 1.28 (1.17–1.41)
Ref. 1.85 (1.78–1.93) 1.16 (1.08–1.24) 1.12 (1.07–1.16)
Ref. 2.27 (2.09–2.46) 1.07 (0.93–1.22) 1.14 (1.05–1.24)
Ref. 1.66 (1.56–1.76) 1.20 (1.09–1.32) 1.06 (1.01–1.12)
Ref. 1.84 (1.72–1.96) 3.27 (3.12–3.42) 6.08 (5.78–6.41)
Ref. 1.81 (1.70–1.94)
Ref. 0.82 (0.79–0.85) 0.80 (0.77–0.83) 0.70 (0.66–0.74)
Ref. 0.81 (0.72–0.90) 0.94 (0.88–1.00) 0.65 (0.57–0.75)
Ref. 1.99 (1.90–2.09)
Ref. 0.37 (0.35–0.39) Ref. 1.52 (1.46–1.57)
Ref. 0.63 (0.60–0.66) 0.68 (0.63–0.73) 0.55 (0.51–0.59) Ref. 0.52 (0.47–0.5)
Ref. 1.50 (1.39–1.61)
Ref. 1.46 (1.39–1.54)
Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024
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consistent finding that underserved minority women receive different care, a full understanding of the factors that influence treatment remains elusive. Several studies have attempted to investigate the impact that patient beliefs, culture, practice and provider-patient communication have on the offering and acceptance of cancer treatment in vulnerable populations [45–47]. Our study has several limitations. There was no central pathology review to assure that histologic sub-type and grade were correctly assigned to included cases. The NCDB only permits evaluation of allcause mortality and not cancer-specific mortality. Given the retrospective nature of the study, decisions regarding surgery and delivery of adjuvant therapies are susceptible to uncontrolled factors, making selection bias another study limitation. The database does not give detailed information regarding the specifics of adjuvant treatment regimens, scheduling and completion rates. Another limitation of the database is that it does not include standard comorbidities such as body mass index and diabetes, both of which have been shown to be relevant in the investigation of outcomes in patients with endometrial cancer [7,12,48–50]. Regardless of such limitations, this work highlights the need for further investigations of the differences in cancer outcomes between racial and ethic groups and for efforts to be made in closing existing socioeconomic disparity gaps and in eliminating barriers adversely affecting optimal cancer treatment among underserved minority populations. Conflict of interest statement The authors declare that there are no conflicts of interest.
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Please cite this article as: A.J. Bregar, et al., Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis, Gynecol Oncol (2017), http://dx.doi.org/10.1016/j.ygyno.2017.01.024