Lung Cancer and Race: Equal Treatment Yields Equal Outcome Among Equal Patients, but There Is No Equal Treatment

In this issue of the Journal of Clinical Oncology, Blackstock et al 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 multiinstitutional trials. Lathan et al 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. 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. 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. A few have gone so far as to refer to the differences in ways that imply that African Americans have an inherent biologic inferiority. Others have stressed disparities in socioeconomic status (SES) as most relevant to the disparities in health outcomes. 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. 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. 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 1993 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. 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. 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. 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. Studies have also demonstrated that blacks and whites with NSCLC have similar outcomes when treated with surgery and radiation therapy. Taken together, this body of JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 24 NUMBER 3 JANUARY 2