Eliminating disparities in endometrial cancer: adherence to high-quality care is not enough

Abstract

Related article, page 396. Related article, page 396. Disparities exist in cancer outcomes for many populations, most notably minorities (racial and ethnic), the poor, and those living in rural areas.1Ellis L. Canchola A.J. Spiegel D. Ladabaum U. Haile R. Gomez S.L. Racial and ethnic disparities in cancer survival: the contribution of tumor, sociodemographic, institutional, and neighborhood characteristics.J Clin Oncol. 2018; 36: 25-33Crossref PubMed Scopus (173) Google Scholar, 2Singh G.K. Jemal A. Socioeconomic and racial/ethnic disparities in cancer mortality, incidence, and survival in the United States, 1950-2014: over six decades of changing patterns and widening inequalities.J Environ Public Health. 2017; 2017: 2819372Crossref PubMed Scopus (267) Google Scholar, 3Zahnd W.E. Fogleman A.J. Jenkins W.D. Rural-urban disparities in stage of diagnosis among cancers with preventive opportunities.Am J Prev Med. 2018; 54: 688-698Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 4Zahnd W.E. James A.S. Jenkins W.D. et al.Rural-urban differences in cancer incidence and trends in the United States.Cancer Epidemiol Biomarkers Prev. 2018; 27: 1265-1274Crossref PubMed Scopus (147) Google Scholar Many studies have suggested that if those with cancer obtain equal treatment, the outcomes are similar, regardless of race, income status, or rural residence.5Blackstock A.W. Herndon 2nd, J.E. Paskett E.D. et al.Similar outcomes between African American and non-African American patients with extensive-stage small-cell lung carcinoma: report from the Cancer and Leukemia Group B.J Clin Oncol. 2006; 24: 407-412Crossref PubMed Scopus (38) Google Scholar, 6Bristow R.E. Chang J. Ziogas A. Campos B. Chavez L.R. Anton-Culver H. Sociodemographic disparities in advanced ovarian cancer survival and adherence to treatment guidelines.Obstet Gynecol. 2015; 125: 833-842Crossref PubMed Scopus (67) Google Scholar, 7Unger J.M. Moseley A. Symington B. Chavez-MacGregor M. Ramsey S.D. Hershman D.L. Geographic distribution and survival outcomes for rural patients with cancer treated in clinical trials.JAMA Netw Open. 2018; 1e181235Crossref PubMed Scopus (53) Google Scholar However, many of those studies have been conducted in the cooperative group setting, where patients (1) have made their way to places that offer high standard of care and (2) receive quality care per protocol.8Institute of Medicine (US)Committee on Cancer Clinical Trials and the NCI Cooperative Group Program.in: Nass S.J. Moses H.L. Mendelsohn J. A national cancer clinical trials system for the 21st century: reinvigorating the NCI Cooperative Group Program. National Academies Press (US), Washington, DC2010Google Scholar In addition, disparities are more likely to be seen in cancers that are “amenable to medical interventions,”9Tehranifar P. Neugut A.I. Phelan J.C. et al.Medical advances and racial/ethnic disparities in cancer survival.Cancer Epidemiol Biomarkers Prev. 2009; 18: 2701-2708PubMed Google Scholar such as breast, colorectal, cervical, prostate, and endometrial cancers. Tehranifar et al,9Tehranifar P. Neugut A.I. Phelan J.C. et al.Medical advances and racial/ethnic disparities in cancer survival.Cancer Epidemiol Biomarkers Prev. 2009; 18: 2701-2708PubMed Google Scholar in a landmark paper, defined this “amenability index,” which indicated survival differences in highly and moderately amenable cancer by racial group for overall cancer survival, even after adjusting for sex, age, stage of disease, and county-level poverty concentration. Quality of care, an important predictor of outcome, was not available for this analysis. The study by Huang et al10Huang A.B. Huang Y. Hur C. et al.Impact of quality of care on racial disparities in survival for endometrial cancer.Am J Obstet Gynecol. 2020; 223: 396.e1-396.e13Abstract Full Text Full Text PDF Scopus (10) Google Scholar, in this issue of the Journal, examines the influence of quality of care—as defined as adherence to 5 evidence-based treatment recommendations—on survival for endometrial cancer, one of the amenable cancers, by race, in black vs white women. Endometrial cancer is an ideal cancer type in which to examine this question, as black women have a lower incidence of endometrial cancer than white women but have a much higher mortality rate.11Mukerji B. Baptiste C. Chen L. et al.Racial disparities in young women with endometrial cancer.Gynecol Oncol. 2018; 148: 527-534Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Moreover, the authors used data from the National Cancer Database, thereby reducing any bias in sample selection owing to relying on cooperative group study samples alone. The sample size was large—310,208 women, of which 35,035 (11.3%) were black—and was further stratified by the stage at diagnosis, mainly stages I and III. The results shed light on important areas that explain differences in survival outcomes specifically. Although adherence to each of the 5 treatment quality metrics and overall adherence to treatment for which they were eligible (termed “perfect adherence”) were associated with improved survival in both racial groups, white women (1) were more likely to be adherent to all 5 metrics (50% of white and 38.3% of black women had perfect adherence) and (2) derived a greater survival advantage when receiving perfectly adherent treatment than black women (80.3% vs 62.5% alive at 5 years, white vs black women, respectively). Analysis by stage indicated the same trends. Multivariable analysis supported these findings with higher levels of adherence associated with lower mortality in a dose-dependent fashion, and black race being identified as an independent predictor of adverse short-term effects (eg, 30-day hospital readmission rates, death at 30 and 90 days) and long-term outcomes (eg, 5-year survival). Two important lessons are learned from this paper. First, black women were less likely to receive guideline-adherent treatment. This study examined age, insurance status, income, education, residence (ie, urban, rural, metropolitan), comorbidity score, clinical variables, and treating facility characteristics. Although differences were noted in univariable analyses between white and black women on all of these individual variables, analyses examining adherence were adjusted for these variables, indicating that disparities in adherence were not fully explained by these demographic, clinical, and facility variables. Second, even if they received guideline-appropriate treatment, black women still had inferior outcomes. Again, all reported analyses were adjusted for these same demographic, clinical, and treatment facility variables. One bright spot was the fact that black women who were adherent to treatment guidelines had similar outcomes to white women who did not, thus showing that adherence to guideline treatment improved but did not eliminate disparities in outcomes. How can disparities be eliminated? This is not an easy question to answer because there are multiple layers and factors that influence outcomes, many of which are not amenable to intervention. However, for the case of endometrial cancer, some can be explored, along the multilevel, social ecological model, the Warnecke framework for disparities.12Warnecke R.B. Oh A. Breen N. et al.Approaching health disparities from a population perspective: the National Institutes of Health Centers for Population Health and Health Disparities.Am J Public Health. 2008; 98: 1608-1615Crossref PubMed Scopus (303) Google Scholar The authors suggested 2 explanations that fall in the biology level of the social ecological model—tumor characteristics and genetics. Furthermore, studies have found that black women are less likely to respond to certain common chemotherapy regimens.13Killelea B.K. Yang V.Q. Wang S.Y. et al.Racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer: results from the National Cancer Data Base.J Clin Oncol. 2015; 33: 4267-4276Crossref PubMed Scopus (47) Google Scholar Tumor profiles of endometrial cancers from black women show a higher percentages of p53 vs PTEN mutations, with the former linked to poorer survival and the latter to better survival.11Mukerji B. Baptiste C. Chen L. et al.Racial disparities in young women with endometrial cancer.Gynecol Oncol. 2018; 148: 527-534Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar,14Daley-Brown D. Oprea-Ilies G.M. Lee R. Pattillo R. Gonzalez-Perez R.R. Molecular cues on obesity signals, tumor markers and endometrial cancer.Horm Mol Biol Clin Investig. 2015; 21: 89-106PubMed Google Scholar The next level includes biologic responses, such as obesity, depression, stress, hypertension, and comorbidities. Not all of these were included in this investigation, mainly because of the limitation of the data set. Other studies have demonstrated the negative impact of stress on cancer outcomes15Antoni M.H. Dhabhar F.S. The impact of psychosocial stress and stress management on immune responses in patients with cancer.Cancer. 2019; 125: 1417-1431Crossref PubMed Scopus (73) Google Scholar and obesity. Moreover, it is well known that black women are at an increased risk for obesity, and obesity creates an inflammatory milieu in the body, which is procarcinogenic and potentiates poor outcomes.14Daley-Brown D. Oprea-Ilies G.M. Lee R. Pattillo R. Gonzalez-Perez R.R. Molecular cues on obesity signals, tumor markers and endometrial cancer.Horm Mol Biol Clin Investig. 2015; 21: 89-106PubMed Google Scholar Although most individual factors, such as demographics, were included, others such as individual risk factors (eg, tobacco use, alcohol use, diet, and trust in the healthcare system) could not be measured. Again, all these factors have been shown to affect either outcomes or treatment adherence.16Greer J.A. Pirl W.F. Park E.R. Lynch T.J. Temel J.S. Behavioral and psychological predictors of chemotherapy adherence in patients with advanced non-small cell lung cancer.J Psychosom Res. 2008; 65: 549-552Crossref PubMed Scopus (100) Google Scholar, 17Hillen M.A. de Haes H.C. Smets E.M. Cancer patients’ trust in their physician-a review.Psychooncology. 2011; 20: 227-241Crossref PubMed Scopus (154) Google Scholar, 18Kohler L.N. Garcia D.O. Harris R.B. Oren E. Roe D.J. Jacobs E.T. Adherence to diet and physical activity cancer prevention guidelines and cancer outcomes: a systematic review.Cancer Epidemiol Biomarkers Prev. 2016; 25: 1018-1028Crossref PubMed Scopus (108) Google Scholar, 19Land S.R. Cronin W.M. Wickerham D.L. et al.Cigarette smoking, obesity, physical activity, and alcohol use as predictors of chemoprevention adherence in the National Surgical Adjuvant Breast and Bowel Project P-1 Breast Cancer Prevention Trial.Cancer Prev Res (Phila). 2011; 4: 1393-1400Crossref PubMed Scopus (49) Google Scholar, 20Theofilou P. Panagiotaki H. A literature review to investigate the link between psychosocial characteristics and treatment adherence in cancer patients.Oncol Rev. 2012; 6: e5Crossref PubMed Scopus (22) Google Scholar The physical and social context level, which includes where women live, was not measured and could affect the ability to obtain adherent care and influence response to care, such as social support, employment, and transportation; however, surrogates, such as income and education, were obtained. Finally, some of the fundamental causes of disparities such as the healthcare system and poverty were measured; however, factors such as the family dynamic, norms, and discrimination were not. The relative importance of each of these levels to poor outcomes is difficult to determine, much less measure. However, previous work by teams such as those from the University of Chicago21McClintock M.K. Conzen S.D. Gehlert S. Masi C. Olopade F. Mammary cancer and social interactions: identifying multiple environments that regulate gene expression throughout the life span.J Gerontol B Psychol Sci Soc Sci. 2005; 60 Spec No 1: 32-41Crossref PubMed Google Scholar,22Sighoko D. Murphy A.M. Irizarry B. Rauscher G. Ferrans C. Ansell D. Changes in the racial disparity in breast cancer mortality in the ten US cities with the largest African American populations from 1999 to 2013: the reduction in breast cancer mortality disparity in Chicago.Cancer Causes Control. 2017; 28: 563-568Crossref PubMed Scopus (22) Google Scholar have demonstrated that these social factors (poverty, crime, abuse)—many of which are linked to the social determinants of health23Marmot M. Social determinants of health inequalities.Lancet. 2005; 365: 1099-1104Abstract Full Text Full Text PDF PubMed Scopus (2626) Google Scholar—do “get under the skin” of black women and cause higher stress and inflammation. These social factors coupled with higher rates of triple-negative breast cancer lead to poorer outcomes, in terms of breast cancer mortality. The same could be said for endometrial cancer. For example, if the rates of poorer tumor biology and genetic mutations are then influenced by stress owing to worry about income, crime, or abuse, and there are difficulties obtaining timely diagnosis (lack of screening) and treatment because of transportation or inability to get off work for appointments, coupled with higher rates of comorbidities that affect survival, disparities will persist and grow. Thus, to eliminate disparities, we need to identify the root causes and develop and implement interventions that are relevant, culturally appropriate, and delivered to women in an atmosphere that is safe, friendly, and welcoming. Patient navigators have been suggested as interventions to address disparities across the cancer control continuum among underserved populations and those who suffer from disparities.24Bernardo B.M. Zhang X. Beverly Hery C.M. Meadows R.J. Paskett E.D. The efficacy and cost-effectiveness of patient navigation programs across the cancer continuum: a systematic review.Cancer. 2019; 125: 2747-2761PubMed Google Scholar In collaboration with community health educators (CHEs) or workers, navigators can help all populations receive timely and adherent care.24Bernardo B.M. Zhang X. Beverly Hery C.M. Meadows R.J. Paskett E.D. The efficacy and cost-effectiveness of patient navigation programs across the cancer continuum: a systematic review.Cancer. 2019; 125: 2747-2761PubMed Google Scholar,25Ginsburg O. Yip C.H. Brooks A. et al.Breast cancer early detection: a phased approach to implementation.Cancer. 2020; 126: 2379-2393Crossref PubMed Scopus (59) Google Scholar We have demonstrated that CHEs from minority or underserved populations can speak to community residents and engage them in cancer prevention, screening, and treatment services and link them to navigators who can arrange the needed care including how to pay for care, where to get care, and how to travel to the care facility. Furthermore, CHEs can continue to provide translation services and support for care, and navigators can continue to follow up patients through screening, diagnostic follow-up, and treatment—to survivorship. Our model has demonstrated excellent return on institutional investment and reduced no-shows and delays in diagnostic resolution and start of treatment.24Bernardo B.M. Zhang X. Beverly Hery C.M. Meadows R.J. Paskett E.D. The efficacy and cost-effectiveness of patient navigation programs across the cancer continuum: a systematic review.Cancer. 2019; 125: 2747-2761PubMed Google Scholar,25Ginsburg O. Yip C.H. Brooks A. et al.Breast cancer early detection: a phased approach to implementation.Cancer. 2020; 126: 2379-2393Crossref PubMed Scopus (59) Google Scholar Unfortunately, patient navigation is not a reimbursable service. Although bills have been introduced into Congress to add a billing code for these vital services, this has not yet been approved.26Congress.govH.R.6808 - Patient Navigation Assistance Act of 2018. 115th Congress (2017-2018).https://www.congress.gov/bill/115th-congress/house-bill/6808?s=1&r=7Google Scholar Moreover, definitions of how navigators function, while clearly stated in all material about navigation,27Parker V.A. Clark J.A. Leyson J. et al.Patient navigation: development of a protocol for describing what navigators do.Health Serv Res. 2010; 45: 514-531Crossref PubMed Scopus (61) Google Scholar are not implemented the same across institutions, thus limiting the effectiveness in some settings. If we as a society care about eliminating disparities, especially for cancers that are amenable to care, then investments need to be made to implement these proven interventions. If not, black women will continue to die needlessly, driving more families into greater depths of poverty and despair. Although appropriate care is an important and essential factor, it cannot on its own completely eliminate disparities in survival from a cancer that can have good outcomes. Action needs to be taken to address the other factors. Studies such as the one by Huang et al10Huang A.B. Huang Y. Hur C. et al.Impact of quality of care on racial disparities in survival for endometrial cancer.Am J Obstet Gynecol. 2020; 223: 396.e1-396.e13Abstract Full Text Full Text PDF Scopus (10) Google Scholar provide the needed evidence to support such action. Impact of quality of care on racial disparities in survival for endometrial cancerAmerican Journal of Obstetrics & GynecologyVol. 223Issue 3PreviewBlack women experience poorer survival compared with white women across all endometrial cancer stages and histologies. The incidence of endometrial cancer is 30% lower in black women compared with white women, yet mortality is 80% higher in black women. Differences in adherence to evidence-based guidelines have been proposed to be major contributors to this disparity. Full-Text PDF