"Never smokers," or people who've never smoked in their lives, account for an increasingly larger share of lung cancer cases, prompting experts to call for new cancer screening guidelines and treatments, Sharon Begley writes in STAT News—an article Begley, a never smoker herself, completed just five days before her death from complications of lung cancer on Jan. 16.

'But I never smoked': Lung cancer cases might be rising among never smokers, data suggests

Begley reports that Mandi Pike—a 33-year-old oil trader in Edmond, Oklahoma—was bewildered when she received the results of a PET scan revealing she had lung cancer in November 2019.

"But I never smoked," Pike, whom providers initially had misdiagnosed with pneumonia after she had been coughing, said. "It all seemed so surreal."

But research shows Pike's not alone, Begley reports. Although cigarette smoking remains the biggest risk factor for lung cancer, many Americans diagnosed with the disease have never smoked in their lives. According to a study published last month in JAMA Oncology, most Americans (90% of men and 84% of women) diagnosed with lung cancer have smoked, but 12% have never smoked.

"It is well-documented that approximately 20% of lung cancer cases that occur in women in the [United States] and 9% of cases in men, are diagnosed in never-smokers," surgeon Andrew Kaufman of Mount Sinai Hospital in New York, whose program for never smokers has treated about 3,800 patients in a decade, told Begley.

According to Begley, data also shows that 15% of male lung cancer patients and 50% of female lung cancer patients worldwide have never smoked. In addition, data shows that women who've never smoked are twice as likely to develop lung cancer as men who've never smoked, Begley reports.

Further, research shows that nonsmokers are now accounting for a larger share of cancer cases than ever before, according to Begley. For instance, a 2017 study involving 12,103 lung cancer patients at three U.S. hospitals showed that never smokers represented 8% of total cancer cases diagnosed from 1990 to 1995, but that percentage increased to 14.9% from 2011 to 2013. The study's authors found that statistical anomalies couldn't explain the increase, and they concluded that "the actual incidence of lung cancer in never smokers is increasing."

In addition, Begley reports that a separate study published the same year in the European Journal of Cancer arrived at a similar conclusion: The share of lung cancer patients who had never smoked increased from 13% in 2008 to 28% in 2014.

"Since the early 2000s, we have seen what I think is truly an epidemiological shift in lung cancer," Kaufman told Begley. "If lung cancer in never smokers were a separate entity, it would be in the top 10 cancers in the [United States]" in terms of both incidence and mortality, he said.

But Begley notes that some experts aren't sure whether lung cancer incidence has actually increased among never smokers over time. John Heymach, an oncologist at MD Anderson Cancer Center, said although there is data suggesting that absolute incidence of lung cancer has been increasing among never smokers, the data could be deceiving, because older datasets often don't include information on a patient's smoking status. That makes it impossible for researchers to determine what share of never smokers developed lung cancer in past decades, Heymach explained.

Similarly, Ahmedin Jemal, an epidemiologist at the American Cancer Society, said noted that current research does not show that never smokers have a higher a chance of developing lung cancer today than they had in the past, Begley reports.

Why do never smokers account for more lung cancer cases patients?

So why, then, do never smokers account for a growing share of lung cancer cases?

Jemal said simple math can largely explain the growth in cancer cases among never smokers. The percentage of Americans who smoke has decreased from 42% in 1965 to 15% in 2015—which means there are fewer smokers in the United States. Consequently, smokers are accounting for a smaller share of lung cancer cases than they had in the past, while never-smokers are representing a growing proportion of cases.

Josephine Feliciano, an oncologist at Johns Hopkins University School of Medicine, said that, other than a person's biological sex, "nothing stands out as a single large risk factor [for lung cancer among never smokers] that, if we only got rid of it, we would" explain the problem. "But air pollution, radon, family history of lung cancer, [and] genetic predispositions," chronic lung infections, as well as lung disease—such as chronic obstructive pulmonary disorder—appear to increase a person's risk of developing lung cancer, Feliciano told Begley.

However, none of those things—with the potential exceptions of indoor pollution and genetics—affect women more than men, which means it remains unclear what's causing women to have higher rates of lung cancer, Begley reports.

What does all this mean for lung cancer screenings and treatment?

Because never smokers now represent a larger share of lung cancer cases, experts are now calling for updated cancer screening guidelines and treatments designed with never smokers in mind, Begley reports.

The U.S. Preventive Services Task Force's (USPSTF) current guidance recommends CT scans to screen individuals ages 50 to 80 for lung cancer if they smoked at least 20 pack years, which is the equivalent of smoking about one pack of cigarettes per day for 20 years, two packs per day for 10 years, "and so on," or if they are still smoking or quit fewer than 15 years ago, Begley reports. According to Jemal, the guidelines don't recommend screenings for never smokers, because the costs of the screenings are considered to outweigh the benefits. He explained that screening thousands of never smokers likely would results in one identified case of lung cancer in any given year, Begley writes.

However, it might be time for that guidance to change, experts say. "It used to be that the high-risk group" for whom the lung cancer screening is recommended "was the vast majority of lung cancer patients," Heymach said. "But now that so many lung cancer cases are in nonsmokers, there is absolutely a need to reevaluate the screening criteria."

Heymach also noted that screening never smokers for cancer would help researchers figure out what the biggest risk factors for lung cancer are among those who haven't ever smoked.

Separately, the biotech industry is calling for the development of treatments for lung cancer patients who have never smoked, Begley reports. "A different disease needs a different drug," said Panna Sharma, co-founder and CEO of Lantern Pharma, which is working on a drug targeting lung cancer in female never smokers.

That's because tumors in never smokers can be different than those found in smokers, Sharma explained.

Ben Creelan, a thoracic oncologist at Moffitt Cancer Center, told Begley that current guidelines recommend that providers treat never smokers with lung cancer the same way they treat smokers with lung cancer. But "I think we should reconsider this," he said.

For instance, he noted that, because never smokers' tumors tend to have fewer mutations than those found in smokers, clinicians should be more bullish about identifying mutations that can be targeted with specific treatments in never smokers. "I keep looking for a mutation until I find something important," he said.

Overall, Heymach said more funding is needed for research into never smokers with lung cancer. It's "an area that's underserved and deserves more investment," Heymach told Begley. "It should be commensurate with the public health threat it represents" (Begley, STAT News, 1/26).