United We Stand, Divided We Fall: Addressing High Lung Cancer Rates, Mortality in Kentucky

Adam D. Lye, MD

Home to approximately 4.5 million Americans, more people in Kentucky die of cancer than in any other state in the country.¹

Cancer mortality in Kentucky is 17% higher than the overall United States, according to the Centers for Disease Control and Prevention. In addition to mortality, Kentucky is plagued with having the highest rate of lung cancer.^2,3

From scientists to oncologists and other clinicians in the community setting, years of research has grasped the big picture of lung cancer occurrence and outcomes in Kentucky, and some have begun to investigate potential causes, like regional disparities, smoking rates, and even discrepancies in legislation. In particular, research has highlighted that patients living in the Appalachian communities of Kentucky are heavily impacted by lung cancer.

“I take care of a lot of lung cancer, and it is definitely a challenge, but rewarding to be a part of their care,” said Adam D. Lye, MD, medical oncologists/hematologist, Norton Cancer Institute, Louisville, Kentucky, in an interview with Targeted Oncology™. “We typically see patients at a more advanced stage of lung cancer. This may be due, in some areas, to lack of education and lack of access to oncology care.

“Also, this issue has, unquestionably, been compounded during the pandemic with so many patients waiting to return for medical care and also avoiding going to the doctor, despite the presence of lung cancer symptoms,” he added. “Our organization has focused on the importance of lung cancer screening to detect these cancers as early as possible when treatment is more likely to result in curative intent treatment. Education and awareness of lung cancer screening continues to be a challenge throughout our state and others.

Kentucky Versus the United States

According to a recent study conducted by investigators at the University of Kentucky’s research department and physicians in the Markey Cancer Center in Lexington, Kentucky, considerable disparities exist between the population of patients with lung cancer in Kentucky compared with the rest of the United States. The disparities reportedly contribute to a higher cancer burden as well as poorer survival outcomes.⁴

Christine F. Brainson, PhD

“We do have the highest rate of lung cancer and because of that we also have a higher mortality. And it's interesting to note that there's many different types of lung cancer. In Appalachian Kentucky and Kentucky as a whole, we see a shift in subtype distribution, so we have more squamous cell carcinomas [and] more small cell lung cancer, which are particularly aggressive and deadly. That's an obvious concern for us here because not only do we have more lung cancer overall per person, but we also have an increase in these types of cancers that are harder to treat,” Christine F. Brainson, PhD, assistant professor of toxicology and cancer biology at the University of Kentucky College of Medicine told Targeted Oncology, in an interview.

The University of Kentucky study aimed to better understand the key differences in lung cancer between Kentucky and the greater US. The Surveillance, Epidemiology, and End Results (SEER) database was utilized to conduct the analysis. Investigators found 18 SEER registries for cases of patients with primary invasive malignant lung and bronchus disease who were diagnosed between 2012 and 2016. Cases included were from those aged 20 years or older who had common lung cancer subtypes like adenocarcinoma, small cell lung cancer (SCLC) squamous cell carcinoma (SCC), and neuroendocrine histology, along with others. Cases of patients with noninvasive lung cancers were excluded from the scope.⁴

“Overall, we had hundreds of cases in the SEER registry. The Kentucky cases, of course, have fewer but we still had thousands of cases that we looked at. So, we looked at the different types of lung cancers, by the pathologist code, and we also looked at incidence data, and survival. And all of those metrics were very different in Kentucky and especially Appalachian Kentucky. So, whatever we saw in Kentucky was skewed from the national averages,” Brainson said.

The study showed a significant difference in histological distributions and incidences of lung cancer in Kentucky compared with other states in the SEER database. Incidences of adenocarcinoma were lower in non-Appalachian Kentucky compared with other state registries (25% vs 45%; P =.0088), while cases of SCC (25% vs 19%; P <.0001) and SCLC (17% vs 12%; P <.0001) were notably higher. All other histologies appeared to occur at similar rates as shown in the other states’ SEER registries.

Ralph Zinner, MD

“In almost every way, there are increases in absolute numbers and proportions,” Ralph Zinner, MD, professor, Division of Medical Oncology, University of Kentucky College of Medicine, in an interview with Targeted Oncology.

“But then in Appalachian Kentucky, it was even more dramatic of a change,” Brainson added.

HotSpot in the Appalachian Mountains

In comparison with non-Appalachian Kentucky at 34%, patients with lung cancer living in the Appalachian Mountains of Kentucky had a lower proportion of lung adenocarcinoma (29%) but had a higher number of SCC cases (25% vs 27%, respectively).⁴

Data also showed that women in Appalachian Kentucky were more likely to be diagnosed with SCLC than others in the US, including those in non-Appalachian Kentucky. Moreover, men living in Appalachian Kentucky had a significantly higher proportion of SCCs compared with the rest of the US.

What stood out the most about Appalachian Kentucky was the prevalence of SCLC, according to Brainson. The rates provide a signal to what 1 of the key contributors of the high lung cancer rates in the Appalachian region may be.

“There were very evident differences in total rates of small cell [lung cancer] in the Kentucky population compared to the SEER database overall. which is important for all kinds of reasons. It corroborates the understanding of the relationship between smoking and cancer with small cell [lung cancer] being especially attached to smoking,” said Zinner.

Lye agreed, adding, “I think that patient education on the importance of smoking cessation, lung cancer screening, and seeking medical care are a continued challenge and opportunity for growth. Access to oncology medical care has been a challenge in many of these rural areas. There is also data that shows even when correcting for smoking prevalence in some of these areas, the increased incidence of lung cancer may be influenced by other environmental factors. I think more research should be conducted in how the environment itself in these geographical areas may multiply the detrimental effects of cigarette use.”

However, in Kentucky, some communities may be hindered in pushing forth smoking cessation education considering that smoke-free ordinances are not implemented state-wide.

Unbridled Smoking and Other Contributing Factors

The road to regions having smoke-free areas in Kentucky has been long. It began in 2015 with U.S. HB145, a comprehensive smoke-free bill that was presented to the Kentucky General Assembly The bill passed the House after amendments were made, but it never made it to the state Senate.⁵

Kentucky’s problem was a key part of the American Lung Association’s (ALA) State of Tobacco Control 2021. The organization recommended that the state government repeal the rights of local governments to control tobacco ordinances, restore funding of $3.3 million to the Kentucky Tobacco Prevention and Cessation Program, and support and defend smoke-free laws across the state. The CDC recommended that Kentucky commit $56 million to tobacco use prevention and cessation. At the time ALA published its recommendations, the toll of smoking was quite remarkable with an estimated $1.9 million-negative impact on Kentucky’s economy, a 23.6% adult smoking rate, an 8.9% high school smoking rate, which accounts for more than 8,000 death known to be caused by smoking.⁶

The problem was and remains that tobacco production accounts for 50% of Kentucky agricultural economy and tobacco product sales make up a significant percentage of the overall economy.⁷ Big Tobacco began to lobby in response to the legislation in Kentucky and states with similar issues to address smoking in children in teens, which was raised by the FDA in 2019 as part of legislation called Tobacco 21.6 But many of the advertising from Big Tobacco in Kentucky left out adults and those impacted by second-hand smoking, according to an expert source. Tobacco 21 is just beginning to make its impact across the state in 2021.⁶

To-date, roughly 36% of residents in Kentucky are now protected by smoke-free ordinances.

“In my area of greater metropolitan Louisville, I am not aware of any areas that allow cigarette use inside a facility. However, I know that in other areas of the state smoking is still allowed inside some facilities. Unquestionably, the higher percentage of smokers in these areas is likely leading to pressure to resist smoke-free ordinances and policies. I think this can be improved with education and awareness in the local communities on the benefit for the entire population,” Lye explained.

Among the 63.4% of the Kentucky population that is not protected by smoke-free ordinances, many of them are in Appalachia. In some cases, entire counties have opted out of implementing smoke-free ordinances against the recommendation of health regulators in the country including, Daviess County, Franklin County, Hopkins County, Kenton County, and Letcher County. In all these counties, lung cancer is the leading cause of cancer death, according to the most up-to-date data from the Kentucky Cancer Registry.

Smoking is just one of the potential causes of Kentucky’s high rate of lung cancer and lung cancer mortality.

When asked about contributing factors, Lye stated: “The first factor is the high smoking rate. I have seen estimates that as many as 1 in 4 Kentuckians smokes tobacco. A second factor is obesity and less than optimal lifestyles. Our state is currently in the top 5 states for obesity and the No. 1 state for childhood obesity. Poor overall health is undoubtedly an additional risk factor for many cancers. Finally…there is likely an environmental factor in play, as well, which could be magnifying the detrimental effects of tobacco. It would be interesting to see how the levels of radon, arsenic, lead, etc. are contributing to possible underlying DNA damage which could also be contributing to the increased prevalence of cancer, including lung cancer, in these areas.”

Brainson agreed, stating; “I think that smoking is a driver, but we can’t discount other possible causes, including radon gas that can build up in houses and radon has been shown to cause more adenocarcinoma, and small cell lung cancers. There are also other environmental exposures like indoor air pollution, coal mining and exposure to heavy metals in the water. Those are all things that people here at the Markey Cancer Center are actively researching.”

The issue in Kentucky is an ongoing challenge for oncologists and their patients. But cancer centers are working to make connections with the patients most heavily impacted.

“There are still some barriers in the fact that we just need to get out to the rural communities and have a build trust with them so that they really see that Markey Cancer Center is a great place to go, as are any of the affiliated hospitals. We hope they choose us if they did have a lung cancer diagnosis. But that's something that we're just going to have to work out over time to make sure that we keep the conversation going with the more rural communities,” said Brainson.

Kentucky is not alone is battling high rates of lung cancer. Right behind Kentucky in the rankings are Alabama, Arkansas, Louisiana, Mississippi, Tennessee, and West Virginia. The disparity overwhelmingly exists in Southern and rural communities.

Research shows that in the 15% to 20% of rural US regions, cancer morality is consistently higher, compared with urban and suburban areas. People who reside in rural communities are diagnosed in the later stages of disease more often and have high cancer incidence rates overall. Multiple studies looking into causes of the disparity in rural America have cited issues like poverty, lack of health insurance, and lack of access to primary care or specialty care.⁹

_References:

_{1. United States Census Bureau: Quick Facts Kentucky. Census.gov. Accessed October 31, 2021. https://www.census.gov/quickfacts/KY}

_{2. Cancer Mortality by State. CDC.gov. Accessed November 1, 2021. https://bit.ly/3qTRUNs}

_{3. Stats of the State of Kentucky. CDC.gov. Accessed November 1, 2021. https://bit.ly/3Cvkzun}

_{4. Brainson CF,, Huang B, Chen Q, et al. Description of a lung cancer hotspot: Disparities in lung cancer histology, incidence, and survival in Kentucky and Appalachian Kentucky. Clin Lung Cancer. 2021;S1525-7304(21)00061-9. doi: 10.1016/j.cllc.2021.03.007}

_{5. Kehler S and Hahn EJ. A policy analysis of smoke-free legislation in Kentucky. Policy Plit Nurs Pract. 2016; 17(2):66-75. doi: 10.1177/1527154416651406}

_{6. State of Tobacco Control 2021: Kentucky Highlights. Lung.org. Accessed November 2, 2021. https://bit.ly/3crNghg}

_{7. Snell W and Goetz S, et al. Overview of Kentucky’s tobacco economy. Uky.edu. Accessed November 2, 2021. http://www2.ca.uky.edu/agcomm/pubs/aec/aec83/aec83.pdf}

_{8. Percent of the Kentucky population covered by 100% smoke-free workplace laws. Uky.edu. Accessed November 2, 2021. https://bit.ly/3kROerY}

_{9. Murphy C, Evans S, Askelson N, et al. Extent of inclusion of “rural” in comprehensive cancer control plans in the United States. Prev Chron Dis. 2021;18:E866. doi. 10.5888/pcd18.210091}