DENVER — Lung cancer rates are increasing in people who have never smoked, according to two new studies presented here at the 16th World Conference on Lung Cancer.

In fact, at one institution, the incidence of never-smokers diagnosed with non-small-cell lung cancer (NSCLC) jumped from 13% to 28% during a 6-year period, Eric Lim, MD, from the Royal Brompton & Harefield NHS Foundation Trust in London, United Kingdom, and colleagues report in their study. And many of these patients initially presented with advanced-stage disease.

The second study demonstrated that the incidence of lung cancer in never-smokers is increasing in the United States. This was observed in three facilities, most significantly for NSCLC. At one institution, for example, the rate of never-smokers climbed from 8.9% in 1990–1995 to 19.5% in 2011–2013.

"When we think of lung cancer, we think of smoking," Dr Lim noted. But antismoking strategies implemented in the early 1980s have led to a decrease in smoking-related lung cancer.

Instead, "what we are seeing is an increase in the incidence of nonsmoking-related lung cancer," he explained during a press briefing. "We have seen more than double the amount of patients coming to us."

Annual Incidence Doubles

For their study, Dr Lim and his colleagues retrospectively analyzed data from a prospectively collected database of patients treated at their institution.

Of the 2170 patients who underwent lung cancer surgery from March 2008 to November 2014, 436 (20%) patients were never-smokers. The median age at presentation was 60 years, and 67% of the patients were women.

The annual increase in the incidence of never-smokers developing lung cancer rose from 13% in 2008 to 15%, 18%, 19%, 20%, and 28% in the subsequent years of the study, respectively. This was attributable to an absolute increase in number, not to a change in the ratio of never-smokers to current and exsmokers.

The most common histologic types of disease were adenocarcinoma (54%) and carcinoid (27%).

Early detection is important but challenging in this population, Dr Lim noted.

In this study, 52% of patients had no clear symptoms. Specific symptoms, such as hemoptysis, were experienced by only 11% of patients, and nonspecific symptoms, such as chest infection, were experienced by 18%. Cough was a presenting symptom in 34% of patients, and incidental imaging detected lung cancer in 36%.

"Clearly, it is not going to be cost-effective to screen the entire population of nonsmokers for lung cancer," Dr Lim pointed out. Instead, because this group of patients does not have established risk factors, research on early detection — ideally by noninvasive or molecular screening — is urgently needed to identify early lung cancer in nonsmokers, he added.

NSCLC Goes Up, SCLC Stays Constant

The second study presented assessed lung cancer in never-smokers at the University of Texas (UT) Southwestern Medical Center in Dallas, the Parkland Hospital in Dallas, and Vanderbilt University in Nashville, Tennessee.

To determine whether the incidence of non-small-cell lung cancer was increasing in never-smokers, "we looked at our tumor registry data and we queried year by year, from 1990 to 2013," said Lorraine Pelosof, MD, assistant professor at the UT Southwestern Medical Center, during a press briefing.

In their retrospective study, Dr Pelosof and her colleagues found that the incidence of NSCLC increased in never-smokers during the study period, even after confounders, such as age and sex, were controlled for (P < .0001).

"But in contrast, the number for small-cell lung cancer [SCLC] stayed the same," she reported. "The changes were quite small — typically 1% to 2%."

The changes in the incidence of NSCLC were significant, and Dr Pelosof pointed out that these increases were seen in a wide and diverse population. They were observed at two university medical centers and at the Dallas County Hospital.

Never-smokers with NSCLC tended to be younger and female. The increase in the proportion is not explained by any possible increase in early incidental diagnoses. "Patients were presenting with clinically significant later-stage disease," she said.

What Is Behind the Increasing Rates?

So what is causing never-smokers to develop lung cancer?

It is all very speculative at this time, said congress cochair Everett Vokes, MD, who is the John Ultmann professor and chair of the Department of Medicine at the University of Chicago.

"If the overall incidence of lung cancer is going down, which it likely will as smoking habits change, at least in this country, then proportions might change as other nonsmoking-related lung cancers rise," he said. "Historical perspectives on this are not easy because this type of computational analysis is new. It was introduced in the last 10 years, so the data are emerging."

That said, what is causing the increase in lung cancer in never-smokers is a matter of speculation, Dr Vokes explained. Some of it could be related to second-hand smoke, pollution, radon, and small particles in the air.

Efforts are needed to increase our understanding of the "mechanisms of carcinogenesis and the causes of cancers arising in never-smokers in order to implement strategies for prevention and treatment," said Giulia Veronesi, MD, from the division of thoracic surgery at the European Institute of Oncology in Milan.

Research using whole-exome sequencing might help in the effort to understand underlying mechanisms, she added.

The scientific community should not neglect the topic of nonsmoking-related cancers, said Dr Veronesi. "A common effort and collaboration between clinicians and scientists is required to identify new strategies for prevention, early detection, and treatment."

16th World Conference on Lung Cancer (WCLC). Presented September 8, 2015