The results of the multicenter Female Asian Nonsmoker Screening Study (FANSS) suggest that low-dose CT screening is feasible and has value for early lung cancer detection in the historically underserved demographic of Asian women with no history of smoking. These data from the largest United States–based lung cancer screening program dedicated to a nonsmoking population were presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer.1
Elaine Shum, MD
Although lung cancer in individuals who have never smoked is the fifth most common cause of cancer-related deaths worldwide, current U.S. guidelines recommend screening with low-dose CT scans only in those who currently or formerly smoked, based on the National Lung Screening Trial.2-4 Previously reported research found Asian American women who have never smoked to be twice as likely to develop lung cancer as their White counterparts, according to the investigators.
“Our findings show a lung cancer detection rate of 1.3%, which is higher than that reported in the National Lung Screening Trial for high-risk smokers,” commented presenting author Elaine Shum, MD, of NYU Langone Perlmutter Cancer Center, New York, in a news release issued by IASLC. “These results support the need to reconsider screening guidelines to include never-smoking high-risk groups.”
Study Details
Women between the ages of 40 and 74 who smoked fewer than 100 cigarettes in their lifetime and self-identified as Asian qualified for enrollment in this ongoing pilot study. However, Dr. Shum noted, “we did not include any other potential risk factors, such as family history.” Exclusion criteria included a history of lung cancer or treatment for any cancer within the prior 5 years.
After providing consent, eligible participants engaged in a shared decision-making discussion to review the benefits and risks of lung cancer screening. They subsequently underwent baseline low-dose CT of the chest, interpreted according to the Lung CT Screening Reporting and Data System (Lung-RADS; positive result defined as Lung-RADS 3 or 4) and clinical judgment, with plans for up to two additional scans during the study. The interval between scans was determined by Lung-RADS criteria or clinical judgment. A plasma-based assay to analyze cell-free DNA fragments for early detection of cancer was performed at the time of each scan.
All participants completed a questionnaire to self-report ethnicity, family history, and environmental and occupational exposures.
A total of 1,000 women (median age: 55.9 years), the target accrual for the study, had completed a baseline low-dose CT scan at the time of this analysis. Most of the population was of Chinese descent (84.7%) and reported no family history of lung cancer (68.6%).
The primary objective is to develop a database of clinical, demographic, and radiographic data of Asian nonsmokers who undergo low-dose CT. According to Dr. Shum, the secondary objectives include the lung cancer detection rate.
Lung-RADS Distribution at Baseline
Based on baseline screening results, most women had scans classified as Lung-RADS 1 (38.8%) or 2 (52.1%). Positive findings were identified in 6.9% of participants.
“To put into context, the National Lung Screening Trial reported Lung-RADS 1 in approximately over 50% of participants, and Lung-RADS 2 was in the 30% range,” Dr. Shum stated during a press briefing.
The baseline lung cancer detection rate was 1.3%. A total of 2.3% of the study population underwent biopsy or resection, including two participants who received the latter after their third low-dose CT scan.
Of the 13 lung cancers identified on the baseline scan, 69.2% were stage IA, 15.4% were stage IIB, and 15.4% were stage IIIB or IIIC. Dr. Shum reported that all were adenocarcinomas, which, she added, is “to be expected in a nonsmoking population with lung cancer.”
“It is important to note that there are 14 participants who [had scans classified as] Lung-RADS 3 or 4 and imaging findings that were highly suspicious for malignancy; however, they do remain in imaging follow-up,” she commented. “This suggests, perhaps, that our lung cancer detection rate recorded [at baseline] might be an underestimation.”
Detected Lung Cancers: A Closer Look
Of the 13 participants for whom lung cancer was detected at baseline, 12 had scans classified as Lung-RADS 3 or 4. One, whose baseline scan was classified as Lung-RADS 0, underwent a repeat scan, which showed a score of 2. “Putting together clinical characteristics and discussion at our nodule board, this patient was recommended to undergo biopsy,” Dr. Shum explained, which revealed “a lung adenocarcinoma.”
All detected lung cancers were found to harbor a driver mutation (EGFR exon 19 deletion [n = 5], EGFR L858R [n = 7], and HER2 exon 20 insertion [n = 2]; one participant had two primary lung adenocarcinomas, each with a distinct EGFR mutation from those listed). Most of the affected population (85%) did not report a family history of lung cancer.
Additionally, Dr. Shum highlighted two participants whose lung cancers were detected after the third low-dose CT scan, both of whom were classified as Lung-RADS 2 at baseline. The first showed Lung-RADS 4B due to a growing left lower lobe nodule, ultimately being diagnosed with stage IA EGFR L858R–mutated adenocarcinoma. The second, with a persistent ground-glass opacity, remained classified as Lung-RADS 2 but underwent resection due to a strong family history, revealing adenocarcinoma in situ. “Of note, the lesions of interest were present on their baseline CT scans,” Dr. Shum remarked.
Regional Practice Variations
“The definition of a positive screen varied between the three studies [FANSS, TALENT, and the National Lung Screening Trial],” Dr. Shum commented during a press briefing. She emphasized that in the Taiwanese TALENT study of nonsmokers with selected high-risk factors, it was defined as a solid nodule larger than 6 mm or a ground-glass opacity larger than 5 mm (vs FANSS: Lung-RADS 3 or 4 [solid/part solid nodule ≥ 6 mm or ground-glass opacity ≥ 30 mm]).
FANSS identified ground-glass opacities larger than 5 mm in 55 participants with scans classified as Lung-RADS 2. In the TALENT study, ground-glass opacities often underwent surgical resection, “so we are able to understand the histology,” according to Dr. Shum. Approximately one-third were invasive adenocarcinomas, another third were minimally invasive adenocarcinomas, and the others were adenocarcinomas in situ.5
“The [differences in] management practices between the United States and Asia might [have led to] an underestimation of the lung cancers detected in our cohort,” Dr. Shum remarked during a press briefing.
Insights and Opportunities
“FANSS is the largest lung cancer screening program that is dedicated solely to a nonsmoking population in the United States, and we have demonstrated that this is feasible,” stated Dr. Shum. “We reported a lung cancer detection rate from the baseline low-dose CT scan to be 1.3%, which is comparable to TALENT (1.5%) and higher than those reported in the National Lung Screening Trial (1.1%) and NELSON (0.9%). All the lung cancers detected in our program harbor a driver mutation, underlining that the biology of nonsmoking lung cancer is certainly different from that in a smoking population.”
Reflecting on the significance of the findings, Dr. Shum continued: “The development of specific screening and management guidelines for a nonsmoking population compared with a population with a smoking history is necessary, especially as we balance early detection and overdiagnosis. As lung cancer in those with no smoking history incidence continues to rise, expanding lung cancer screening guidelines to those with no smoking history warrants identification of [other] high-risk populations who may benefit.”
“With continued follow-up and pending biomarker analysis, FANSS may provide the data needed to expand evidence-based screening recommendations for nonsmoking populations,” Dr. Shum concluded in an IASLC statement.
DISCLOSURE: Dr. Shum has served as an advisor or consultant to AstraZeneca, Genentech, Boehringer Ingelheim, Janssen, Bristol Myers Squibb, Regeneron, and Gilead Sciences; and has received institutional research funding from Delfi Diagnostics.
REFERENCES
1. Shum E, Bell JL, Li W, et al: Female Asian Nonsmoker Screening Study (FANSS): A U.S. based lung cancer screening program in a non-smoking population. 2025 World Conference on Lung Cancer. Abstract OA15.03. Presented September 9, 2025.
2. LoPiccolo J, Gusev A, Christiani DC, et al: Lung cancer in patients who have never smoked —An emerging disease. Nat Rev Clin Oncol 21:121-146, 2024.
3. U.S. Preventive Services Task Force: Screening for lung cancer: U.S. Preventive Services Task Force Recommendation Statement. JAMA 325:962-970, 2021.
4. National Lung Screening Trial Research Team: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365:395-409, 2011.
5. Chang GC, Chiu CH, Yu CJ, et al: Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: A prospective cohort study. Lancet Respir Med 12:141-152, 2024.
EXPERT POINT OF VIEW
Invited discussant of the Female Asian Nonsmoker Screening Study (FANSS), David R. Baldwin, MD, FRCP, of the University of Nottingham and Nottingham University Hospitals NHS Trust, United Kingdom, described this lung cancer screening program dedicated to the at-risk population of female Asian nonsmokers in the United States as an “excellent idea.”
David R. Baldwin, MD, FRCP
Commenting on the study’s characteristics, he pointed out that the population had a “slightly lower median age than you would expect in other screening programs of people who smoke or have smoked.” He furthermore noted a “very high” early detection (ie, stage I or II) rate of approximately 86%, which “is also the highest rate among people who smoked,” matching that observed in the UK Lung Cancer Screening (UKLS) trial.1
“In people who have never smoked, in most health economic evaluations in the Western world, [screening] is not cost-effective,” Dr. Baldwin remarked. “However, in studies with people who have never smoked, we have comparable detection rates, because at-risk groups have been identified.” He also highlighted higher rates of early-stage detection and incidence of subsolid nodules, as well as high resection and survival rates.
According to Dr. Baldwin, “of course, there has been concern about overdiagnosis,” with considerable debate.“[There is] some real-world evidence suggesting reduction in mortality, but, unfortunately, there are also people who smoked in those data sets,” he continued. “We know we can detect early-stage disease, but can we influence mortality?”
Dr. Baldwin emphasized that future efforts should focus on understanding how to assess risk for lung cancer mortality, establishing at least some of the cancers that cause high mortality, determining whether mortality is reduced, learning more about the biology (ie, prognostic biomarkers), and understanding the relationship between early detection of cancer and life-years gained.
DISCLOSURE: Dr. Baldwin has received honoraria for lecturing from AstraZeneca and for an educational meeting from Boehringer Ingelheim; and has received numerous institutional research grants from CRUK, NIHR, Innovate UK, SBRI, Horizon Europe, and the Roy Castle Foundation.
REFERENCE
1. Field JK, Duffy SW, Baldwin DR, et al: UK Lung Cancer RCT Pilot Screening Trial: Baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening. Thorax 71:161-170, 2016.
