People often use the expression, “Where there is smoke, there is fire.” Unfortunately for lung cancer patients, the opposite is almost always assumed to be true. Where there is fire (in this case, lung cancer), it is assumed that smoking must have preceded it. This assumption often leads to the question, “Did you smoke?” following almost every personal revelation of lung cancer. Few questions engender such anger and annoyance in patients as that one, particularly in the 10%-20% of lung cancer patients who are “never smokers.”
A history of tobacco use is the most common risk factor for the development of lung cancer. To deny that would be to deny the reality and epidemiology of the disease. However, as smoking rates have decreased, other risk factors for the development of lung cancer have been recognized, including:
# Environmental and occupational causes
# Radon gas
# Indoor heating and cooking fumes
# Other lung diseases
# Potential genetic associations
Among these risk factors, air quality is perhaps the most alarming factor globally. It is estimated that living in a polluted city may increase a person’s risk of lung cancer by 27%-40% compared to living in a clean city. Despite these epidemiologic hints, we still clearly have much to learn about why never-smokers get lung cancer.
One assumption that we have tried to debunk is that lung cancer in never smokers is somehow an indolent disease. This theory began to surface as CT screening for lung cancer increased and incidentally detected nodules became more common on CT scans performed for other reasons. In that context, it was suggested that we are over-diagnosing lung cancer and finding cancers that would never harm patients—an idea that is often suggested in never smokers.
Over-diagnosis argument rings hollow, however, when one considers that the overall 5-year survival for all stage IA lung cancer patients still hovers in the 70%-80% range. No evidence exists to suggest that never-smokers have indolent cancers. In fact, we recently compared stage-specific overall and cancer-specific survival in groups of never smokers and smokers and found no difference in outcomes. We, therefore, feel strongly that suspicious lung nodules in never-smokers should not be ignored and that prompt protocol-based diagnosis and standard-of-care treatment is critical for this group of patients.
One thing that is apparent is that lung cancer in never smokers more often affects a different type of patient than the traditional “Marlboro Man” stereotype. Never smokers tend to be:
And, because never smokers with lung cancer don’t fit the stereotype, it is unclear how this affects time to diagnosis. Some have suggested that never-smokers are at risk for delayed diagnosis, leading to finding cancer at an advanced stage.
We have found that never-smokers with metastatic cancer tend to have gene abnormalities (EGFR mutations, ALK, and ROS1 rearrangements) that can be treated with targeted drug therapies—sometimes with remarkable success. Because of this, never smokers are more commonly represented in news stories and among advocacy groups, making them the new face of lung cancer. Fortunately, these are faces of hope, rather than the traditional nihilism associated with late-stage lung cancer.
Finally, it should be noted that lung cancer in never smokers appears to be on the rise. It is unclear whether this is due to a decrease in smoking-associated cancers and a proportional rise in lung cancer in never smokers or due to an actually increased incidence of lung cancer in never smokers. Either way, health care providers will increasingly encounter never-smokers with lung cancer. At my institution, never smokers composed 29% of our most recent surgical cohort (2013–2016). We clearly need to devote more attention to these patients. We need funding for the research community to perform studies that will allow us to better understand the descriptive epidemiology of this disease and the molecular mechanisms that lead to lung cancer in never smokers.
And everyone needs to better understand that, sometimes, there can be fire without the smoke.