While the incidence of lung cancer is decreasing in men, it continues to rise in women. With more than 19,000 new cases in France each year, lung cancer is now the third most commonly diagnosed cancer among women. This trend is also seen in other European countries but appears to be region-specific because other continents report a decline in incidence among women. Moreover, although overall prognosis remains better in the female population, the trend is worrying: Mortality associated with the disease is increasing in women, unlike in men with lung cancer. A session at the French-Language Pneumology Congress held from January 30 to February 1, 2026, in Lille, France, provided an opportunity to review the situation.

Efficacy and Toxicity

Lung tumors in women have a distinct tumor profile: Women have a higher proportion of adenocarcinomas than men and a higher frequency of somatic mutations (EGFR, BRAF, or HER2), including in nonsmokers. In addition, 65% of lung cancers in women are associated with smoking compared with 87% of those in men.

The role of estrogens is central because they interact directly with tumor growth signaling pathways. Moreover, “sex is the second leading factor of variability in drug pharmacokinetics after weight and accounts for 28% of anticancer drug kinetics,” emphasized Julien Mazières, pulmonologist, Toulouse University Hospital, Toulouse, France. Also involved in this equation are a higher body fat percentage, lower gastric acidity, and, above all, reduced renal and hepatic clearance.

As a result, exposure to drugs — represented by the area under the curve — is often greater in women and translates into not only improved progression-free survival with targeted therapies and chemotherapy but also increased toxicity. Carboplatin and paclitaxel are among the drugs whose kinetics are most affected by clearance. There are differences in clearance of more than 20% for these drugs in women vs men, though dosages are not systematically adjusted except for weight-based dosing. This vulnerability to adverse effects is particularly pronounced with targeted therapies, with more neuropsychiatric and gastrointestinal disorders. Data on the efficacy of immunotherapy in lung cancer by sex are contradictory. However, endocrine-related adverse effects and pneumonitis are more frequent in women, especially before menopause.

Women remain underrepresented in clinical trials, and sex-specific analyses of results are too rarely performed, which limits understanding of mechanisms and prevents tailoring management recommendations according to sex.

Impaired Quality of Life

Lung cancer most severely impairs physical functioning in women. “In the absence of sex-stratified studies, psycho-oncologists’ experience suggests that women have more cognitive disorders, anxiety, and depression associated with this disease. Its impact on quality of life is major, with deterioration of social relationships and reduced treatment adherence,” summarized Céline Mascaux, MD, PhD, pulmonologist, Strasbourg University Hospital, Strasbourg, France. Women also face social and family pressure — a mental burden that pushes them to “hold on” for their loved ones. Regarding sexual health, women with lung cancer who are sexually active often report dissatisfaction with the quality of their sexual relations because of fatigue, lack of energy, sadness, and shortness of breath, not to mention treatment-related sexual dysfunction. These problems are often not given sufficient attention by physicians.

Finally, fertility requires greater attention from the medical community: According to the VICAN study conducted by France’s National Health Insurance Fund, a discussion about fertility preservation did not take place at the time of cancer diagnosis for 60% of men and 67% of women of childbearing age. “In lung cancer specifically, the desire for children nevertheless exists in nearly 40% of patients of childbearing age,” regretted Jacques Cadranel, pulmonologist, Tenon Hospital, Paris, France. This desire does not appear to have influenced therapeutic strategy, and fertility preservation was ultimately proposed in only a third of cases and was carried out in only 3% of women compared with21% of men.

This story has been translated from Univadis France, part of the Medscape Professional Network.

Standard methods for calculating heart attack risk based on arterial plaque may be underestimating risks for women, according to a new study.

In the study, published Monday in Circulation: Cardiovascular Imaging, women had a similar risk for nonfatal heart attack, hospitalization for chest pain, or death from any cause as men, despite having less plaque in their arteries.

Women also faced elevated risk at lower levels of plaque than men, with risk beginning to rise at a 20% vs 28% plaque burden in women vs men. As plaque levels increased, women’s risk rose more sharply than men’s.

“Cardiovascular disease remains the leading cause of death in women, yet much of our risk prediction framework has historically been derived from predominantly male populations,” said Jan Brendel, MD, postdoctoral research fellow at Massachusetts General Hospital in Boston and lead author of the study. “Women have less coronary plaque overall, which can lead to the perception that they are lower risk.”

A Quantitative Approach

Following prior studies suggesting women may experience cardiovascular risk events even without large obstructive lesions, Brendel’s team became interested in whether quantitative imaging biomarkers, specifically plaque burden measured by coronary CT angiography, might reveal subtle, sex-related differences in how atherosclerosis translates into clinical risk.

The researchers analyzed data from 4267 patients enrolled in the PROMISE trial, a study comparing diagnostic strategies in stable outpatients with chest pain and no prior history of coronary artery disease. The patients were randomly assigned to coronary CT angiography.

Rather than simply assessing the degree of artery blockage, Brendel’s group measured each patient’s plaque volume and plaque burden. They then followed patients for a mean of 26 months to assess major adverse cardiovascular events (MACE).

“Quantitative plaque assessment is shifting the field toward imaging-based phenotyping and more individualized cardiovascular risk stratification, rather than binary obstructive versus nonobstructive classification of coronary plaque,” Brendel said.

While MACE incidence did not differ markedly between men and women, there was a difference in the pattern of the risk. In women, MACE risk rose steeply at low plaque levels and then leveled off, whereas men had a more delayed, gradual increase in risk with increasing plaque.

Interpreting Plaque Burden

One challenge Brendel and his collaborators faced was ensuring appropriate interpretation of subtle sex differences without overstating findings.

“We observed substantial overlap between women and men, particularly at higher levels of plaque burden, where statistical precision is more limited,” Brendel said. “Rather than indicating a dramatic divergence, the results point to nuanced differences in how coronary plaque relates to risk — with risk in women appearing to emerge at lower plaque levels.”

The findings suggest plaque measurements in women should be interpreted with nuance, and that those with low-to-moderate plaque burden should not automatically be assumed to be at low risk,” Brendel said.

“Integrating quantitative plaque assessment into cardiovascular risk stratification, with attention to sex, may help refine prevention strategies,” he added.

Outdated Practice Guidelines

Armin Arbab-Zadeh, MD, MPH, director of cardiac computed tomography in the Division of Cardiology at Johns Hopkins Hospital in Baltimore, published an editorial Monday in Circulation: Cardiovascular Imaging discussing the results of the study.

“I disagree with the authors’ interpretation of the study results because of the many potential confounding factors,” Arbab-Zadeh, who was not involved with the study, told Medscape Medical News. “I am not saying their conclusions are false but rather that the information is insufficient to draw these conclusions.”

Arbab-Zadeh emphasized it’s important that women with suspected coronary artery disease receive adequate testing and treatment.

“This is a much bigger concern than the minor differences outlined in the study,” he said. “Practice guidelines still focus on detecting obstructive rather than nonobstructive coronary artery disease, while the latter actually accounts for more myocardial infarctions, as shown in the PROMISE trial. Since women tend to have more nonobstructive [disease] compared to age- and risk-matched men, women are disproportionately affected by this outdated practice, which should be changed.”

“This study should raise awareness for evaluation and diagnosis for all women who present with symptoms of chest pain or symptoms concerning for angina,” said Sadiya Khan, MD, director of the Center for Population Science and Aging at Northwestern University Feinberg School of Medicine in Chicago. “The critical piece is that symptoms should not be dismissed.”

Khan, who also was not involved in the PROMISE trial analysis, added that in the future, use of the American Heart Association’s PREVENT risk score would be helpful because it is a more contemporary model for how plaque correlates with risk.

The study was funded by the National Institutes of Health and the National Heart, Lung, and Blood Institute. Some authors reported receiving funding from other research institutes and receiving consulting fees from pharmaceutical and device manufacturers. Borek Foldyna reported receiving institutional research support from AstraZeneca, MedImmune, Cleerly Health, and MedTrace.

Catherine Shaffer is a freelance science and medical writer with a background in molecular biology and pharmaceutical research. Her work has appeared extensively in scientific trade and mainstream publications and on public radio.

Two new modeling studies suggest that expanding lung cancer screening — to include more smokers or even lifelong nonsmokers — would save thousands more lives in the US every year. But not everyone is convinced the projected benefits would outweigh the harms.

In one study, published in JAMA, researchers at the American Cancer Society (ACS) found that only about 19% of currently eligible Americans underwent lung cancer screening in 2024.

That, the study projected, could translate to roughly 15,000 lung cancer deaths averted over 5 years. But 100% screening uptake would save three times as many lives.

“We estimated that about 62,000 deaths from lung cancer can be prevented [over 5 years] if everybody eligible for screening were to take it up,” said lead author Priti Bandi, PhD, scientific director of risk factors and screening research at the ACS.

She and her colleagues then took their projections a step farther, modeling what could happen if screening were expanded to everyone aged 50-80 years with a smoking history — or about 28 million Americans. Their conclusion: nearly 30,000 additional lung cancer deaths averted over 5 years.

According to Bandi, the findings underscore the importance of boosting the screening rate among Americans who meet current eligibility criteria — and argue for broadening eligibility.

Benefit-Risk Balance

Right now, the US Preventive Services Task Force (USPSTF) recommendsannual low-dose CT screening for adults aged 50-80 years who have a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

Those criteria are stricter than guidelines from the ACS, which dropped the 15-year rule in 2023. Earlier this year, the National Comprehensive Cancer Network did the same.

However, more screening is not necessarily better, cautioned H. Gilbert Welch, MD, of the Center for Surgery and Public Health at Brigham and Women’s Hospital in Boston.

Clinical trials, including the NLST in the US and NELSON trial in Europe, have proven that low-dose CT screening can reduce lung cancer mortality by about 20%. But those trials focused on people with a heavy smoking history.

Proof of a mortality benefit in lower-risk smokers is lacking, Welch pointed out, while the potential for harm is real.

“All of a sudden expanding to a whole new group of people — it’s just going to lead to a whole new set of procedures, a lot more false alarms, a lot more complications, and more overdiagnosis,” Welch told Medscape Medical News.

“I would say screening is not efficacious in the lowest-risk categories,” he said.

Screening Nonsmokers?

At the same time, interest in expanding lung cancer screening to patient populations other than heavy smokers is growing. That includes even lifelong nonsmokers, who account for between 10% and 20% of lung cancer cases in the US — partly due to other exposures such as secondhand smoke, air pollution, and radon.

The second modeling study, published on November 20 in JAMA Network Open, asked what could happen if lung cancer screening were strictly age-based. A team at Northwestern University in Chicago used data from published studies and 997 patients with lung cancer at their center — 65% of whom did not meet USPSTF screening criteria — to model the expanded scenario.

They calculated that universal screening of Americans aged 40-85 years would detect 94% of all lung cancers and prevent upward of 26,000 deaths annually.

“We moved to universal age-based screening for breast and colon cancer with tremendous success, and we need to move to the same approach for lung cancer,” study author Ankit Bharat, MBBS, professor of thoracic surgery at Northwestern, said in a press release.

However, the study also modeled the risks associated with age-based lung cancer screening: At 70% uptake (comparable to breast and colorectal cancer screening rates), there would be an estimated 16 million false positive results each year, leading to 1.2 million invasive procedures, with complications in 4900.

For context, breast cancer screening was estimated to yield 3.3 million false-positives, 33,000 biopsies, and 500 complications, while colorectal cancer screening yielded 2.1 million false positives, 420,000 polypectomies, and 3200 complications.

Real-World Issues

Welch pointed to the challenges of translating clinical trial findings to the real world, even to higher-risk smokers and former smokers. The NLST researchers “worked hard,” he said, to limit the harms of screening, including overdiagnosis.

“They had growth assessment protocols. They were careful about who they biopsied,” Welch said.

He believes those standards are too high a bar to be expected in routine clinical practice — meaning the benefits of screening may be less and the harms greater. And expanding eligibility to people who are at lower risk vs NLST participants would further shift the risk-benefit equation, according to Welch.

Bandi agreed that the potential for harm is a concern and said that clinicians need to provide patients with information about the risks of screening, in addition to the benefits.

As for why lung cancer screening rates remain low a decade on, Welch and Bandi agreed that heavy smokers often face barriers: They are disproportionately low-income and have less access to healthcare — and may be dealing with daily life issues that push lung cancer screening down on the priority list.

It’s possible, Welch said, that expanding screening eligibility to lower-risk groups would boost the screening adherence rate. But whether screening would be efficacious for those groups is another matter.

Better Data Needed

An editorial published with the ACS study said that as it stands, “lung cancer screening has realized only a fraction of its life-saving potential” — in part because of “overly restrictive” eligibility criteria.

However, worries about the harms of expanding screening — especially to nonsmokers — are valid, stressed Chi-Fu Jeffrey Yang, MD, and colleagues at Massachusetts General Hospital in Boston.

“It is unlikely,” they wrote, “that screening recommendations in the US will be expanded to include populations who have never used tobacco without high-quality randomized trial data.”

And while such trials have long been seen as prohibitively expensive, they noted, new risk-stratification tools may make them feasible by enabling researchers to enroll the highest-risk never-smokers.

The study was funded by the ACS Intramural Research Department. The authors disclosed having no conflicts of interest. Welch reported receiving royalties from books including Should I Be Tested For Cancer?

Ernie Mundell is a freelance medical journalist based in Los Angeles. He has more than 30 years of experience, including editorial positions at Reuters Health and HealthDay.