DENVER – An increasing share of patients with lung cancer report that they have never smoked, according to a pair of retrospective cohort studies reported at a world conference on lung cancer.
At three U.S. institutions serving geographically and racially diverse populations, the proportion of never-smokers rose from 9% to 15% over a 24-year period among patients with non–small-cell lung cancer (NSCLC), but did not change among those with small-cell lung cancer (SCLC). At a U.K. tertiary care institution, the proportion of never-smokers rose from 13% to 27% over a 7-year period among patients undergoing surgery for lung cancer.
Dr. Everett E. Vokes
Data further suggested that these trends were due at least in part to an increase in the absolute number of never-smokers with lung cancer, and not simply to a decline in the proportion of smokers with lung cancer, or to earlier, incidental detection of tumors resulting from better imaging technology.
More research will be needed to determine the specific factors driving this increase, according to Dr. Everett E. Vokes, cochair of the conference, moderator of a related press conference, and the John E. Ultmann Professor and Chair, department of medicine, University of Chicago.
“What is causing this, for me, would be very, very speculative,” he said. “Secondhand smoke is still there, and radon is mentioned. That shouldn’t necessarily justify an increase, because those are either constant or also decreasing [like smoking]. And of course it could be pollution and factors that have to do with small particles and carcinogens in the air.”
Dr. Lorraine Pelosof
In the first study, investigators led by Dr. Lorraine Pelosof of UT Southwestern Medical Center in Dallas used registries at three institutions – UT Southwestern Medical Center, Parkland Hospital in Dallas, and Vanderbilt University in Nashville, Tenn. – to identify patients who were diagnosed with lung cancer between 1990 and 2013.
Analyses were based on 10,593 patients with NSCLC and 1,510 patients with SCLC. The latter serve as an internal control given that cancer’s tight link with smoking, Dr. Pelosof noted.
In adjusted analyses, the proportion in the NSCLC group who reported never smoking increased from 9% to 15% during the study period (P less than .0001). In contrast, the proportion in the SCLC group held steady at roughly 2%.
Among patients with NSCLC, never-smokers were on average younger and more likely to be female compared with smokers, Dr. Pelosof reported at the conference, which was sponsored by the International Association for the Study of Lung Cancer.
In teasing out the cause for the rise in never-smokers with NSCLC, analyses showed that the absolute numbers of patients with NSCLC increased during the study period.
Preliminary data suggested that earlier, incidental detection did not explain the trend, as rates of stage I, II, and III disease in never-smokers were stable or decreased, while the rate of stage IV disease increased.
In addition, the trend did not appear to be explained by an influx to the institutions of patients with mutations seeking targeted therapies on clinical trials, as the trend persisted after adjustment for race/ethnicity, which was used as a surrogate for mutational status.
The investigators plan several avenues of additional research to sort this out, Dr. Pelosof said.
“We want to look at possibly other institutions that are geographically and demographically diverse. Additional institutions would be helpful,” she said. “And then to get at some of the mechanisms, [looking at] mutational status and biology I think would be very important.”
Dr. Eric Lim
In the second study, Dr. Eric Lim, a consultant thoracic surgeon at Royal Brompton Hospital, and a senior lecturer and reader in thoracic surgery at the National Heart and Lung Institute, Imperial College, London, and colleagues assessed smoking status among 2,170 patients who underwent surgery for lung cancer at the hospital between 2008 and 2014.
Overall, 20% of the patients in the cohort were never-smokers. Their mean age at presentation was 60 years, and two-thirds were women. The predominant tumor types were adenocarcinoma, seen in 54%, and carcinoid, seen in 27%.
The proportion who were never-smokers more than doubled during the study period, from 13% to 27%. The absolute annual number of such patients also rose, from about 60 to nearly 100.
Fully 52% of the never-smokers presented with only nonspecific symptoms of cough or chest infection, while 11% had hemoptysis. In the remaining 36%, the cancer was identified as an incidental finding on imaging done for other reasons.
“Nonsmoking lung cancer is increasing and now a significant proportion of the workload for surgeons across the United Kingdom,” concluded Dr. Lim. “Early detection in this group is challenging because they have no clear-cut symptoms, and serious symptoms were only present in a minority,” he said.