Racial disparities in cancer care, an eyeopener for developing better global cancer management strategies

Abstract Background In the last few decades, advancements in cancer research, both in the field of cancer diagnostics as well as treatment of the disease have been extensive and multidimensional. Increased availability of health care resources and growing awareness has resulted in the reduction of consumption of carcinogens such as tobacco; adopting various prophylactic measures; cancer testing on regular basis and improved targeted therapies have greatly reduced cancer mortality among populations, globally. However, this notable reduction in cancer mortality is discriminate and reflective of disparities between various ethnic populations and economic classes. Several factors contribute to this systemic inequity, at the level of diagnosis, cancer prognosis, therapeutics, and even point‐of‐care facilities. Recent Findings In this review, we have highlighted cancer health disparities among different populations around the globe. It encompasses social determinants such as status in society, poverty, education, diagnostic approaches including biomarkers and molecular testing, treatment as well as palliative care. Cancer treatment is an active area of constant progress and newer targeted treatments like immunotherapy, personalized treatment, and combinatorial therapies are emerging but these also show biases in their implementation in various sections of society. The involvement of populations in clinical trials and trial management is also a hotbed for racial discrimination. The immense progress in cancer management and its worldwide application needs a careful evaluation by identifying the biases in racial discrimination in healthcare facilities. Conclusion Our review gives a comprehensive evaluation of this global racial discrimination in cancer care and would be helpful in designing better strategies for cancer management and decreasing mortality.

2022 2 and in 2020 there were about 10 million cancer deaths and an anticipated 19.3 million additional cancer incidences worldwide. 3 Cancer prevalence and cancer mortality are fortunately dropping in the world due to efficient healthcare facilities, better monitoring, early detection, and better cancer management. However, some populations continue to exhibit a greater risk of predominance and mortality concerning specific types of malignancies. Human populations all over the world are impacted by cancer but certain types of cancer are predominant in certain geographical locations. 4 Various factors have been attributed to the impact of this skewness, that include genetic, 5 socioeconomic, 6,7 and environmental factors. 8 The National Cancer Institute (NCI) specifies cancer health disparities as discrepancies in disease metrics, namely the occurrence rates, death rates, complications, survival rates, budgetary stress, and living standards [Courtesy: Cancer Disparities-NCI]. There appears to be a huge disparity in screening and early detection of cancer and the choice of treatment that is predominant among population subgroups. Disparities are apparent in the fact that although overall results show increasing awareness, better screening facilities, and significantly improved cancer mitigation, certain subgroups are not seeing the same gains as other groups. Such observations require a better understanding of the factors responsible for such differential mortality rates and improved cancer management and call for designing strategies for better implementation of the same.
These disparities are the outcome of complex and interconnected factors, making it challenging to separate them and analyze each factor's independent relative impact. Major cancer health disparities and associated mortality that have been noticed in different sections of the population are related to geographical locations, socioeconomic status, and genetics. 5,9 There is a large regional variation in both cancer cases, kind, and disease prognosis.
Breast cancer accounts for 25% of all women screened and leads to 16.6% of deaths due to cancer. 3 Incidence of breast cancer is significantly higher in developed countries like North America and Oceania ( Figure 1). The proportion of risk factors for breast cancer has been known to be impacted by significant alterations in diet, lifestyle, sociocultural, and architectural environments brought on by developing countries and an increase in the number of women in the industries. Lung cancer represents 11.4% of total cancer cases. 3 The incidence of lung cancer as seen in Figure 1 (the primary data to synthesize the following secondary data was obtained from GLOBOCAN, 2020) is reflective of greater exposure to pollutants and is an unfortunate outcome of industrialization, hence Africa and Latin America exhibit relatively lower incidences. The prevalence of colorectal cancer is about 10% of the total incidences of cancers. 3 Incidence rates of colorectal cancer in North America and Oceania are higher than in others due to the predominance of junk food in the diet and a sedentary lifestyle. Heavy alcohol use, tobacco consumption, and intake of red or processed meat are other contributing risk factors. Prostate cancer, being one of the most diagnosed cancers in men accounts for variable frequencies in incidence worldwide. Latin America, North America, Europe, and Oceania show greater incidence predominantly due to regular monitoring and marker-based screening. The greatest incidence rates for prostate cancer among black males are found in the Caribbean and the United States. 11 A higher mortality rate due to breast cancer in the African population, despite low incidence ( Figure 2) exemplifies the fact that due to a lack of regular screening early detection of breast cancer does not take place, resulting in higher mortality rates. Lung cancer is a very aggressive cancer and hence leads to higher mortality in all populations with a higher incidence of the disease. The incidence and consequently, mortality rates are highly impacted by the state of industrialization and exposure to associated pollutants. Mortality rates due to colorectal cancers are more or less similar in all regions; the underlying reason for this could be urbanization, dependence on processed foods, a sedentary lifestyle, and lack of physical activities.
Prostate cancer is curable if detected early, and hence, the lack of early detection of cancer in the African population due to a lack of 0 10 20 30  Genetic profiling for the determination of propensity to certain forms of cancer and prophylactic vaccination for cancer is followed in less than 1% of the global population and is also disparate in different ethnic groups. This is often due to a lack of awareness and also due to social deterrents.
Cardiovascular disease, diabetes, hypertension, obesity, and respiratory illness are more common comorbidities among low-income women, which restricts their treatment choices. 25 Black females are more inclined than white females to consume a diet rich in fat, deficient, in vegetables and fruits, and are less likely to engage in routine exercise, therefore, more prone to be overweight. 26 The discrepancy in breast carcinoma rates among females is, therefore, affected by nutritional and lifestyle factors that are indirectly linked to socioeconomic constraints. Further ignorance of disease, lower levels of education, and religious and cultural taboos are additional factors that often lead to late-stage diagnosis and inappropriate treatments, leading to deaths. 27 Contrary to white women, black women are more likely to depend on supernatural and spiritual intervention, instead of getting the proper medical care, which can be harmful to their survival. 28 In general, societal injustice, poverty, and other variables play a direct and indirect role in the gap in breast carcinoma rates among females. Similar socioeconomic discrepancies are also observed in various developing nations including India. 29 Interestingly in India, there is a steep rise in incidences of breast cancer in urban women, mainly due to stress, lifestyle choices, late pregnancies, and late menopause.
Among rural women, breast cancer incidences are however, lesser as compared to their urban counterparts, although there is a higher incidence of cervical cancer among them. 30,31 In rural India, the constraints leading to cancer mortality are often a lack of early diagnostics, advanced facilities and health care options. Hence, it is obvious that prudent cancer management is not only achievable by addressing economical and infrastructural constraints but also requires a holistic understanding of the factors in specific ethnic populations in addition to the uplifting of care facilities.
The unavailability of exposure to high-quality healthcare and therapeutic trials is considered to be the main cause of racial discrepancies in lung carcinoma survival. 32 It is significant to note that social determinants of wellness may contribute to differences in lung carcinoma therapy. These include, (1) both social and economic considerations, such as having health insurance or having the capacity to spend money for treatment, which affects the uninsured and disadvantaged populations, which comprises of many impoverished populations, in terms of access to effective adjuvant therapies. 33 Colorectal cancer (CRC) is the third most typical cancer in the United States, irrespective of gender. 36  which is connected to a worse prognosis. 61 The percentage mortality rate for US patients with respect to different stages of breast cancer is shown in Figure 3C and is indicative of the fact that late detection results in a very high probability of fatal consequences, thus necessitating the emphasis on biomarker screening and early detection.
One of the most inherited cancers is prostate cancer which can be easily diagnosed at early stages by marker-based screening. 62 Incidents of prostate cancer strike one in nine American men throughout the course of their lifetimes. However, this ratio is one in seven for Black males, whose mortality rate is 1.7 times higher than their white counterparts. 9 The mortality rate for prostate cancer concerning different stages of cancers in different racial cross sections of patients is shown in Figure 3D. Notably, in prostate cancer, there is a significantly low mortality rate at the regional and localized stages as compared to other types of cancer. Prostate cancer is generally curable if detected early when the cancer is at a localized or regional stage.
Black patients, however, often come for treatment only in the advanced stages of the disease and have high PSA values. 63 Black men had lower PSA screening rates than White men. 64,65 A similar scenario is seen in African men where lower incidence (Figure 1) is only reflective of poor screening and unfortunately results in a high mortality rate ( Figure 2) as a result of late diagnosis. Due to advances in screening technologies, more than 50% reduction in prostate cancer occurrence has been seen since 1992 with an increase of more than 2% in overall survival rates. 66

| DISPARITIES IN TREATMENT
Due to population expansion as well as improvements in early identification and treatment, there are more cancer survivors than ever before. As of Jan 1, 2022, over 4000000 females in the United States were projected to have a background of metastatic breast carcinoma, and an additional 287850 females will receive a new diagnosis.
According to a study, three-fourths of the 150000 approx. breast car-  [68][69][70] Trends in the treatment of breast cancer are shown in Figure 4A,B.  ing them prone to early detection and 100% cancer regression. 79 However, although there is not much racial discrepancy as per genetic predisposition, regular screening remains to be the only determinant between 100% cancer recovery versus fatal outcome upon late diagnosis. [80][81][82] Hence the greatest solution to the racial discrepancy in its mortality lies in greater awareness and screening outreach measures that need to be implemented on a global scale. 83

| DISPARITIES IN TARGETED TREATMENTS AND IMMUNOTHERAPY
Cancer health disparities have continued to increase despite advancements in treatment strategies. Cost and availability are the major factors that widen this gap. 84 Immunotherapy is currently regarded as a regular part of the first and foremost therapy for metastatic tumors which lack targetable mutations. 85 92 Similar trends were also seen in prostate tumors for increased expression of proinflammatory genes among this population. 93 All these findings suggest better immunotherapeutic options for black patients but the reality is contrasting, due to patient-level factors (SES, behavior toward treatment and ethnicity, etc.), provider-level factors (cost of immunotherapy, knowledge, beliefs, and attitude toward patient, etc.) and system level factors (reimbursement and infrastructure quality, etc.).
Regulatory bodies play a role in specialized therapies like immunotherapy. It has been found that the percentage of patients having immunotherapy before and after approval by the FDA is increased to 12.4% in NSCLC. 94  investigator-initiated trials is from community centers. 84 Geographical accessibility to a clinical study may affect its enrollment. There is evidence that unequal geographical accessibility to health care is correlated to adverse consequences and inferior quality of life as well as inadequate treatment compliance. 101 Syed et al. 102 129 This societal outlook toward palliative care also must be acknowledged and weighed against scientific rationale with compassionate patient management and the spread of awareness. State-of-the-art palliative treatment techniques need to be more uniformly distributed to ease pain and suffering, notwithstanding racial discrimination globally. 130 To evaluate and eradicate racial/ethnic inequities in hospice and palliative care, investigational strategies are required and the financial burden needs to be effectively managed.

| CONCLUSION
Growing industrialization is often associated with drastic changes in behavioral changes, such as tobacco control, should also be supported.
Most crucially, government-driven schemes for improvements that support health equity, ubiquitous insurance policies, and availability of standard treatment for all must be ensured if the aforementioned disparities are to be erased.

ACKNOWLEDGMENTS
The work has been supported by the Department of Biotechnology, Delhi Technological University.

CONFLICT OF INTEREST
The authors have stated explicitly that there are no conflicts of interest in connection with this article.

DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.

ETHICS STATEMENT
The present work has been done in compliance with the ethical guidelines of Delhi Technological University.