Differences By Sex in Lung Cancer Incidence and Mortality: What Is Known, and What Does It Mean?
The finding that women have a higher incidence of lung cancer than men of the same age and with the same smoking history was unexpected when it first emerged from studies in the 1990s. Just as unexpected was a subsequent finding. Even with their higher risk, women have a lower mortality and higher survival rates than men.
Both findings, confirmed in subsequent studies, have raised new questions for research and public health policy: What are the reasons for these differences between men and women? Could they offer clues to the cellular and other biologic mechanisms involved? Should there be different public health screening recommendations for women?
James L. Mulshine, MD
Answers have emerged over the past 3 decades. In a recent webinar,1 hosted by the International Association for the Study of Lung Cancer (IASLC) and moderated by James L. Mulshine, MD, of Rush University in Chicago, expert panelists described what is currently known about differences between men and women in lung cancer incidence and mortality; what questions remain; and how the answers could—or should—impact screening guidelines.
The Global Burden: What Do We Know?
Studies have shown that lung cancer is the leading cause of cancer death for men in 87 countries and for women in 28 countries. The webinar’s first speaker, Mary Pasquinelli, DNP, FNP-BC, Director of the Lung Screening Program at the University of Illinois Hospital and Health Science System, reported that the highest rates occur in the United States, Canada, Western Europe, Australia, China, and East Asia.
Mary Pasquinelli, DNP, FNP-BC
Using data and maps from the World Health Organization’s GLOBOCAN database, she pointed out that the highest mortality rates occur in higher-income countries and are associated with tobacco use. Smoking rates among women fell in most countries between 2000 and 2016, but women who still smoke have incidence and mortality rates that are 25 times higher than those for women who do not smoke. In China, Dr. Pasquinelli said, smoking rates were much lower for women than for men—2.7% vs 52.1—in 2015.
I-ELCAP Update in North America: 1992–2019
The International Early Lung Cancer Action Program (I-ELCAP) has been the source of much of the data on differences in men and women, based on its screening program with low-dose computed tomography. Panelist Claudia Henschke, MD, who heads I-ELCAP at the Icahn School of Medicine in New York, described data from the program’s baseline screenings, showing that women are at higher risk than men of a similar age and smoking history. In the program’s 2004 analysis of data for 2,202 women and 1,288 men, women were 2.7 times more likely than the men to have lung cancer. In an analysis 2 years later, involving 16,725 individuals screened, women had almost twice the risk as men. This study also looked at survival differences and found that women’s risk of dying of cancer was about half that of men, after adjusting for age, smoking history, disease stage, tumor cell types, and resection.
Claudia Henschke, MD
In a 2019 analysis of the cumulative I-ELCAP screening data, based on both baseline and repeat screenings, the findings are similar. Of 41,263 people screened (45% women, 55% men), the women were almost twice as likely to be diagnosed with lung cancer, after adjusting for age and smoking history. Women’s survival rates were 87.3% higher than the men’s survival rates, after adjusting for age, smoking history, disease stage, tumor cell types, and resection. The hazard ratio was 0.60, meaning that “the risk of dying of lung cancer among women is 40% lower than that of men, when adjusted for all these factors,” Dr. Henschke said.
Does Sex Matter?
The answer is an emphatic yes, said Andrea Wolf, MD, MPH, Associate Professor and Director of the New York Mesothelioma Program at the Icahn School of Medicine, who was the webinar’s final panelist. “Studies have repeatedly shown better survival for women than for men…. Treatment by treatment, women fare better than men,” she said. “The persistence of these findings suggests it is not by chance,” added Dr. Wolf, and “trying to tease out what the etiology is, who it applies to, and how this may impact treatment has been the subject of much research.”
Andrea Wolf, MD, MPH
Some of that research focused on differences in tumor subtypes. Researchers found that men and women with squamous cell lung cancer had the same survival rates. However, women with adenocarcinoma had different—and better—survival rates than men with adenocarcinoma.
Others have found that women with adenocarcinoma are more likely to have a mutation in the epidermal growth factor receptor (EGFR) than men. EGFR is a cell-surface glycoprotein found on non–small cell lung cancer (NSCLC) cells, and the most common mutation that causes uncontrolled activation of EGFR in 8% to 10% of NSCLCs. This type of lung cancer is more common in women, Asians, those who have never smoked, and patients with adenocarcinoma.
What Can Be Done?
This question—how to translate current knowledge into strategies to reduce risk and improve survival—was addressed at different times throughout the webinar, often with an emphasis on the need for screening. Dr. Pasquinelli’s summary slide included a recommendation to “modify criteria for lung cancer screening as evidence emerges.” Dr. Henschke’s final slide put it another way: “Women should be screened at a younger age and lower pack-years than men.”
And Dr. Mulshine concluded the webinar with a look ahead to next steps in screening. “What we have to do right now,” he said, “is help the general public to understand that this new, important, and life-saving option exists and remind our colleagues that the quality of delivered screening services matters intensely. We want to make sure, as we increase the uptake of screening in the nation and the world, that we also stay attentive to maintaining the high quality of the interdisciplinary team required to provide this demanding, but relatively safe, public health service.” ■
DISCLOSURE: Drs. Mulshine, Pasquinelli, Henschke, and Wolf reported no conflicts of interest.
1. International Association for the Study of Lung Cancer: Women and Lung Cancer: Screening, Treatment and Beyond. August 29, 2019, online. Available at https://www.iaslc.org/Conferences-Events/Event-Details/women-and-lung-cancer-screening-treatment-and-beyond. Accessed September 25, 2019.