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The Female Asian Nonsmoker Screening Study (FANSS) showed a 1.3% lung cancer detection rate among 1000 Asian women with no smoking history.

The findings of FANSS, the largest lung cancer screening program involving a nonsmoking population in the US, were presented at World Conference on Lung Cancer (WCLC) 2025.

Presenter Elaine Shum, MD, of NYU Perlmutter Cancer Center, New York City, said the 1.3% detection rate in a population excluded from current guidelines raises questions about expanding screening criteria.

Rationale

Shum noted, during her talk, that lung cancer in individuals who have never smoked is the fifth most common cause of cancer-related deaths worldwide, with incidence expected to continue rising over the next years. Based on the National Lung Screening Trial (NLST), current guidelines in the US recommend low-dose CT screening only to individuals with current or former history of heavy smoking.

Shum explained that the research team chose to focus specifically on Asian nonsmoking women because this population faces a disproportionately high risk for lung cancer.

“As a thoracic medical oncologist in New York City, we have a fair amount of Asian patients, and unfortunately, the majority of them with lung cancer have no smoking history and were initially presenting with stage IV disease,” Shum said during an interview with Medscape Medical News.

Previous research has shown that 57% of Asian American women who have lung cancer have never smoked compared with about 15% of all other American women. Shum explained that the reasons behind the higher incidence of lung cancer among Asian women with no smoking history are unknown.

“Going back to the literature, it is well-recognized that Asian women with no smoking history are identified as having higher incidences of lung cancer, particularly associated with driver mutations, for unclear reasons; we felt that starting by screening this population made the most sense at the time,” Shum stated in her interview.

Regarding the potential reasons why Asian women with no smoking history are at a higher incidence of lung cancer, Shum said, “It is not simply a question of heredity, but there is another genetic component to this story that is not yet well-defined.”

Study Design and Population

The FANSS was designed as a pilot trial to assess the feasibility of lung cancer screening in Asian women with no smoking history. The study enrolled women aged 40-74 years who identified as being of Asian descent and never smoked (defined as fewer than 100 cigarettes in their lifetime). In the interview, Shum explained that the study did not require additional risk factors such as family history of lung cancer, making it a relatively unselected population compared with other screening studies.

One thousand of the 1041 participants who consented to the study completed baseline low-dose CT scans. The median age was 55.9 years, with the majority (84.7%) identifying as Chinese, followed by other East Asian (5.4%), Southeast Asian (4.6%), and South Asian (3.2%) populations. Only 29.7% of the participants reported a family history of lung cancer.

Key Findings

The baseline low-dose CT screening revealed a lung cancer detection rate of 1.3% (13 out of 1000 participants). All detected cancers were adenocarcinomas, which, according to Shum, are the kinds of cancers expected to be seen in never smokers. Most (69.2%) cancers were diagnosed at stage IA, 15.4% at stage IIB, and 15.4% at stage IIIB or IIIC.

During her talk, Shum emphasized that all 13 lung cancers harbored driver mutations: 12 had EGFR mutations (seven with L858R, five with exon 19 deletions) and two had HER2 exon 20 insertions. One participant had two separate primary lung adenocarcinomas with different EGFR mutations.

The Lung-RADS distribution showed that 38.8% of lesions were Lung-RADS 1, 52.1% Lung-RADS 2, 4.1% Lung-RADS 3, and 2.8% Lung-RADS 4. A positive screen was defined as Lung-RADS 3 or 4, occurring in 6.9% (69 of 1000) of participants.

The study also revealed differences in the characteristics of ground-glass nodules, especially in the Lung-RADS 2 group. The screening study detected 142 ground-glass nodules across different Lung-RADS categories, with 67 measuring ≤ 5 mm in the Lung-RADS 2 category, 44 measuring > 5-9 mm, and 11 measuring ≥ 10 mm.

Shum and her colleagues are collecting information about place of birth and time in the US of the study participants to determine if there may be differences in their screening results between participants based on these factors.

Comparison With Other Screening Studies

To put the FANSS findings into context, Shum compared the 1.3% detection rate in FANSS with those of three previous screening studies involving high-risk individuals: the NLST study involving individuals who have smoked at least 30 pack years and, if former, quit in the previous 15 years; the European NELSON trial involving current smokers; and the TALENT study from Taiwan, which screened Asian men and women who never smoked but had additional risk factors. Detection rates were 1.1% in the NLST trial, 0.9% in the NELSON trial, and 1.5% in the TALENT study.

“While our study is smaller in scale compared to NLST and TALENT, it still represents the largest known lung cancer screening study in the US performed only in a nonsmoking population,” Shum noted in the interview. “In comparison to the lung cancer detection rate in NLST, it is eye-opening to see a rate that is numerically higher than what was observed in a population with a heavy smoking history.”

However, David Baldwin, MD, of Nottingham University Hospitals, who served as discussant for the session, emphasized the need for caution when comparing the FANSS findings to those of the NLST trial.

“In NLST, almost all the overdiagnoses were in the previous pathological type of bronchoalveolar carcinoma, which are mostly sub-solid nodules,” he said in an interview.

Clinical Implications and Future Directions

According to Shum, the results of FANSS suggest that the development of specific screening and management guidelines for a nonsmoking population compared to a population with a smoking history is necessary.

However, Baldwin noted that for screening to be clinically useful, studies are needed to assess whether early detection will result in a reduction in mortality.

“The issue is whether the cancers detected are those that are responsible for mortality or not; they are all early stage, sub-solid, and mostly EGFR-driven, which have a much better prognosis,” he said in the interview.

During his talk, Baldwin emphasized the need for a better understanding of how to assess lung cancer mortality risk, identify which cancers cause high mortality, learn more about cancer biology, and understand the relationship between early detection and life-years gained.

In the interview, Shum commented on their next steps, noting that “FANSS has demonstrated it is feasible to perform low-dose CTs in a nonsmoking population, and we are excited to expand this concept to other nonsmoking populations as we try to define other high-risk groups.” She added that they are actively developing a larger multicenter study with the goal of generating evidence to inform national screening guidelines that will include a nonsmoking population.

“We have not yet looked at other high groups of nonsmokers, but this would be the plan in our multi-site study,” Shum noted, adding that there is a study that will be looking at those with a family history and screening those family members for lung cancer.

Shum said within the FANSS dataset, she and her colleagues are continuing to work on processing cell-free DNA blood samples and applying artificial intelligence and radiomic technology to the CT scans.

The FANSS was funded by private philanthropy, NYU Lung Cancer Center, Delfi Diagnostics, and the EGFR Resisters Distinguished Young Investigator Research Award. Shum reported financial relationships with AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, Genentech, Gilead, Regeneron (honoraria), and Delfi Diagnostics (research funding paid to institution). Baldwin reported financial relationships with AstraZeneca, MSD, Bristol Myers Squibb, and Roche (honoraria).

Christos Evangelou, PhD, is a freelance medical writer.