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Originally published as JCO Early Release 10.1200/JCO.2005.03.7077 on December 19 2005 © 2006 American Society of Clinical Oncology.
Lung Cancer and Race: Equal Treatment Yields Equal Outcome Among Equal Patients, but There Is No Equal TreatmentWinship Cancer Institute, Emory University, Atlanta, GA In this issue of the Journal of Clinical Oncology, Blackstock et al1 report that they find no racial differences in outcome among patients receiving equal treatment for extensive stage small-cell lung cancer in an analysis of outcomes from four multi-institutional trials. Lathan et al2 use Medicare data, however, to demonstrate that there are significant differences in treatments offered to patients with early stage non–small-cell lung cancer (NSCLC). These findings help bring some clarity to an ongoing controversy in American medicine. It has been more than three decades since publication of the first academic paper discussing black-white racial differences in cancer survival and mortality rates.3 The fact that blacks have poorer survival and greater mortality compared with whites with a number of cancers has now been well documented in cancer registries. No other racial or ethnic group in the United States has lung cancer mortality rates as high as black Americans. Blacks have a death rate 17% higher than whites.4 Racial disparities in cancer have become the subject of much scientific and political controversy. Some have theorized that these disparities are due to biologic differences between blacks and whites.5 A few have gone so far as to refer to the differences in ways that imply that African Americans have an inherent biologic inferiority.6 Others have stressed disparities in socioeconomic status (SES) as most relevant to the disparities in health outcomes.7 Poverty is associated with decreased cancer survival and increased cancer mortality, and is also correlated with and may influence health outcome through environmental influences and behaviors that portend to a worse outcome. A wise oncologist once summed up the controversy by saying, "Some believe Blacks are harmed for life, while others believe Blacks are harmed by life?" In American medicine, there has been a concern that certain drugs are more effective in certain races. Some physicians use medical racial profiling in prescribing antihypertensive drugs. Certain drugs are believed effective in a larger proportion of whites, while other drugs are believed effective in a larger proportion of blacks.8 It should be noted that known enzymes and polymorphisms of enzymes responsible for the metabolism of certain drugs are more or less prevalent in certain racial and ethnic groups. Indeed, numerous enzyme polymorphisms and genetic mutations have been found to have varying prevalences among populations, no matter how one defines the population. While there are differences in the prevalence of certain enzymes, no racial or ethnic group monopolizes any enzyme. Race is a weak surrogate for pharmacogenetic differences. Race is only one way to categorize a people, and it is not a biologic categorization, it is sociopolitical. As with many cancers, black Americans present with both small-cell lung cancer and NSCLC at disproportionately higher stage and with disproportionately poorer performance status.1,9 This is, no doubt, part of the reason for the disparities in outcomes. It can be called evidence of racial biologic differences. One however, should not ignore the fact that social and economic influences can cause these disproportionate findings. SES and factors associated with SES, such as diet and education, can influence biologic findings. Poverty through different environmental stimuli can influence the biology of a tumor. A premise of the NIH Revitalization Act of 199310 is that some disparities are due to the fact that drugs have been developed that do not work as well in persons of certain races. The Revitalization Act is a federal law mandating that NIH funded clinical research includes minorities such that a so-called valid subset analysis of outcomes can be performed among the races. A valid subset analysis has been interpreted as distinctly different from a statistically significant subset analysis.10 Any subset analysis must be performed with extreme caution because subset analyses are fraught with the potential for erroneous findings with serious consequences. For example, early analysis of studies of zidovudine in HIV-infected patients suggested that zidovudine was less effective in blacks compared with whites. This finding was later proven wrong.11,12 A subset analysis of data from one study with a racially proportional and representative population may provide data, but is unlikely to provide statistically valid findings.10 Powering a trial for a statistically significant assessment of racial differences would add significant cost and disproportionately place far more minority patients in a trial, and therefore, at risk. A reasonable approach to this problem is to perform a meta-analysis of several studies and several different treatments. Previous studies of chemotherapy response in patients with NSCLC showed that equal treatment yields equal outcome among equal patients.9,13 Studies have also demonstrated that blacks and whites with NSCLC have similar outcomes when treated with surgery14 and radiation therapy.15 Taken together, this body of literature is quite compelling in that there are no racial differences in response to traditional lung cancer chemotherapy, radiation therapy, and surgery when black and white patients with identical prognostic factors are considered. Lathan et al2 identify what is an important logistical question in medicine: How do we get adequate high quality care to a population that does not get it? In a population-based study, they demonstrate that a substantial fraction of black Americans with early stage NSCLC do not receive potentially curative treatments when compared with whites. Even black patients, who are physically able to tolerate lung surgery, are less likely to receive it. Several other studies have found that blacks in the United States are less likely to receive optimal therapy for lung cancer when compared with whites. Indeed, there are studies showing that blacks are less likely to receive surgical resection,14,16,17 radiation therapy,13 and chemotherapy.18 The population-based Lathan study not only demonstrates that there is not equal treatment, it demonstrates that equal treatment yields equal outcome among equal patients. These disparate treatment patterns likely relate to racial differences in SES. In some instances, the poorer patients do not have access to physicians capable of performing more complicated lung cancer treatments.14 Compared with whites, a larger proportion of black patients are poor. Important questions in health disparities research include: (1) What is the role of poverty and social conditioning on cancer stage and presentation? (2) What factors related to SES status affect cancer outcomes? (3) Why are some patients not offered resection and other standard treatments? (4) Why do a higher proportion of blacks refuse surgical and possibly other needed medical interventions? Numerous studies demonstrate racial differences in patterns of care.19 While there has been tremendous emphasis on the study of drugs possibly having less effect in blacks, there seems little interest in the fact that many studies show that blacks are at greater risk to receive less than optimal treatment for a number of cancers. No drug works when it is not given. While the two studies published in the journal1,2 help to bring some clarity to a controversy in American medicine, they also demonstrate the most pressing question in health disparities research: How can we give optimal medical care to the many people who do not receive it? Indeed this is a social imperative. Author's Disclosures of Potential Conflicts of Interest The author has indicated no potential conflicts of interest. Author Contributions
ACKNOWLEDGMENTS Supported by Grant No. P60MD000525 from the National Center for Minority Health and Health Disparities, NIH. REFERENCES
1. Blackstock AW, Herndon JE, Paskett ED, 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 24:407-412, 2006 2. Lathan C, Neville BA, Earle CC: The effect of race on invasive staging and surgery in non–small-cell lung cancer. J Clin Oncol 24:413-418, 2006 3. Henschke UK, Leffall LD Jr, Mason CH, et al: Alarming increase of the cancer mortality in the U.S. Black population (1950-1967). Cancer 31:763-768, 1973[CrossRef][Medline] 4. Reis LAG, Eisner MP, Kosary CL, et al: SEER Cancer Statistics Review, 1975-2002. National Cancer Institute, Bethesda, MD, 2005. www.seer.cancer.gov/csr/1975_2002/ 5. Bach PB, Schrag D, Brawley OW, et al: Survival of blacks and whites after a cancer diagnosis. JAMA 287:2106-2113, 2002 6. Goldson A, Henschke U, Leffall LD, et al: Is there a genetic basis for the differences in cancer incidence between Afro-Americans and Euro-Americans? J Natl Med Assoc 73:701-706, 1981[Medline] 7. Freeman HP: Cancer in the socioeconomically disadvantaged [see comments]. CA Cancer J Clin 39:266-288, 1989 8. Brawley OW: Some perspective on black-white cancer statistics. CA Cancer J Clin 52:322-325, 2002 9. Blackstock AW, Herndon JE, Paskett ED, et al: Outcomes among African-American/non-African-American patients with advanced non-small-cell lung carcinoma: Report from the Cancer and Leukemia Group B. J Natl Cancer Inst 94:284-290, 2002 10. Freedman LS, Simon R, Foulkes MA, et al: Inclusion of women and minorities in clinical trials and the NIH Revitalization Act of 1993–the perspective of NIH clinical trialists. Control Clin Trials 16:277-285, 1995[CrossRef][Medline] 11. Easterbrook PJ, Keruly JC, Creagh-Kirk T, et al: Racial and ethnic differences in outcome in zidovudine-treated patients with advanced HIV disease. Zidovudine Epidemiology Study Group. JAMA 20:2713-2718, 1991 12. Lagakos S, Fischl MA, Stein DS, et al: Effects of zidovudine therapy in minority and other subpopulations with early HIV infection. JAMA 20:2709-2712, 1991 13. Akerley WL, Moritz TE, Ryan LS, et al: Racial comparison of outcomes of male Department of Veterans Affairs patients with lung and colon cancer. Arch Intern Med 153:1681-1688, 1993 14. Bach PB, Cramer LD, Warren JL, et al: Racial differences in the treatment of early-stage lung cancer. N Engl J Med 341:1198-1205, 1999 15. Graham MV, Geitz LM, Byhardt R, et al: Comparison of prognostic factors and survival among black patients and white patients treated with irradiation for non-small-cell lung cancer. J Natl Cancer Inst 84:1731-1735, 1992 16. Greenwald HP, Polissar NL, Borgatta EF, et al: Social factors, treatment, and survival in early-stage non-small cell lung cancer. Am J Public Health 88:1681-1684, 1998 17. Smith TJ, Penberthy L, Desch CE, et al: Differences in initial treatment patterns and outcomes of lung cancer in the elderly. Lung Cancer 13:235-252, 1995[CrossRef][Medline] 18. Earle CC, Venditti LN, Neumann PJ, et al: Who gets chemotherapy for metastatic lung cancer? Chest 117:1239-1246, 2000 19. Shavers VL, Brown ML: Racial and ethnic disparities in the receipt of cancer treatment. J Natl Cancer Inst 94:334-357, 2002
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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