RESEARCH PERSPECTIVES
1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA
Despite major advances in treatment, lung cancer remains the leading cause of cancer-related mortality in the United States and worldwide. Early detection via annual screening with low-dose computed tomography (LDCT) imaging has been shown to improve mortality in certain high-risk populations with a significant smoking history and is currently standard of care in the United States. However, a significant proportion of lung cancer occurs in people who have never smoked and do not meet the screening criteria, especially among women and individuals from countries in East Asia. There have been several observational studies conducted in East Asia that show LDCT screening detects lung cancer in never smokers, though they were not designed to show a mortality benefit and there is concern that the lung cancers detected largely represent overdiagnosis of indolent cancers. How to go about screening these populations requires careful consideration as every screening protocol needs to have its benefits balanced against the risks. More research is needed to determine the best screening strategy for this population.
Key Words: lung cancer ◾ screening ◾ never smokers ◾ Asians ◾ overdiagnosis
Citation: Journal of Asian Health. 2026;19:e119
Copyright: © 2026 Journal of Asian Health, Inc. is published for open access under the license Creative Commons CC BY-NC 4.0 License. Authors have full copyright.
Published: February 18, 2026.
Correspondence to: Weijia Chua, 300 Pasteur Dr, Stanford, CA 94305, USA. Email: wchua@stanford.edu
Competing interests and funding: The authors has not received any funding or benefits from industry or elsewhere to conduct this study.
Lung cancer remains the leading cause of cancer mortality in the United States and worldwide. In 2022, lung cancer was responsible for approximately 2.5 million new cases and over 1.8 million deaths globally.1,2 Despite major advances in immunotherapy and targeted therapies for lung cancer during the past decade, early detection remains the most effective strategy to reduce mortality with 5-year survival increasing from 9% for distant-stage disease to 64% for localized-stage disease.1 Since screening uptake in at-risk populations in the U.S. remains low, most lung cancers are unfortunately diagnosed at an advanced stage as patients often remain asymptomatic until late into the disease.3
The goal of lung cancer screening is to detect lung cancer at an early stage when it is more treatable and potentially curable. The largest randomized controlled trial evaluating low-dose computed tomography imaging (LDCT) screening for lung cancer in the U.S. was the National Lung Screening Trial (NLST) conducted during 2002–2004 under the auspices of the National Cancer Institute at the National Institutes of Health with results published in 2011. The trial showed that annual screening with LDCT in high risk current or former smokers for three years resulted in a 20% decrease in lung cancer mortality compared with chest radiograph at six years of follow up.4 Based on the results from this and other trials, the U.S. Preventive Services Task Force issued their first recommendation for annual screening for lung cancer with LDCT in 2013. It was updated in 2021 to expand eligibility criteria to those aged 50–80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.5,6
While tobacco smoking is the most well-established risk factor for lung cancer, there is a growing concern for lung cancer in people who have never smoked, especially among certain populations including women and individuals from countries in East Asia. It is estimated that 12–15% of lung cancers in the U.S. occur in never smokers and more than 50% of Asian American women who are diagnosed with lung cancer have never smoked.7–10 In certain subpopulations, the proportion is even higher, with more than 80% of lung cancer among Chinese women in both China and the U.S. occurring in those who have never smoked.9–11 Data from Taiwan’s National Cancer Registry indicated that more than 50% of lung cancer patients had never smoked, and of these patients nearly 60% had stage IV disease at diagnosis.12 Recent global data suggest that if lung cancer in never-smokers were a separate disease entity it would rank as the eighth leading cause of cancer mortality.13 Given the observed mortality reduction from screening among patients with a history of smoking, clinicians have been interested in whether screening can benefit those who have never smoked. While a U.S. based randomized controlled trial has yet to evaluate the benefits and harms of screening specifically in those who have never smoked, several observational studies and randomized screening trials have been conducted in East Asia. These studies primarily included a mixed population of individuals who have smoked and never smoked, and results indicate that LDCT screening detects lung cancer in never smokers. However, these studies were not designed to show a mortality benefit or evaluate the balance of harms to benefits of screening in never smokers.14–17
In 2024, the Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT), the largest prospective study to evaluate the use of LDCT screening in a risk enhanced population of primarily never smokers, published its results. During 2015–2019, TALENT enrolled 12,011 participants who had never smoked (93% of participants) or had smoked less than 10 pack-years and quit for more than 15 years and had an additional risk factor for lung cancer, including family history of lung cancer, passive smoking exposure, pulmonary tuberculosis, chronic obstructive pulmonary disease, a cooking index of 110 or higher, or cooking without using ventilation. The primary outcome was lung cancer detection rate, which was 2.6% with the first LDCT scan.18 Notably this is higher than the detection rate of 1.1% in the NLST, which enrolled high-risk individuals with a heavy smoking history.4
Based on this data, Taiwan initiated a nationwide screening recommendation that includes women aged 45–74 and men aged 50–74 with a family history of lung cancer.19 While screening in these populations has been shown to detect early-stage lung cancer, lung cancer screening experts have raised the concern that a large proportion of the lung cancers detected represent overdiagnosis or indolent cancers that would not have become clinically significant, thus not translating to a lung cancer mortality benefit.20 Of note, the 2.6% lung cancer detection rate in the TALENT study includes nodules that were diagnosed on pathology as minimally invasive adenocarcinoma and adenocarcinoma in situ. In addition, 97% of the diagnosed lung cancers were stage 1 or adenocarcinoma in situ, a stage distribution at diagnosis that is suggestive of overdiagnosis.18 An ecological cohort study using the Taiwan Cancer Registry noted that after the introduction and popularization of out-of-pocket LDCT screening (which was patient or provider initiated, prior to nationwide screening recommendations), there was a rise in early stage lung cancer diagnoses without a concomitant decrease in late stage diagnoses and no change in lung cancer mortality.21 These findings further support the concern that screening in this population is associated with overdiagnosis.
Overdiagnosis exposes patients to the harms associated with screening and subsequent treatment does not confer a mortality benefit (i.e. does not reduce the risk of death despite treatment). In the case of lung cancer screening, the potential harms include complications from biopsy procedures, radiation exposure from repeated imaging, psychological stress from finding a lung nodule, and consequences from unnecessary surgical and radiation treatments. In light of these potential harms, there needs to be careful consideration and evidence to support a benefit when defining a specific population to screen.
While screening very broad populations of Asian patients who have never smoked for lung cancer via traditional imaging screening may not be the answer, certainly the need for screening some subpopulation still exists. So how do we go about determining whom to screen? Randomized controlled trials to demonstrate a mortality benefit in this population are likely not practical due to the sample size and length of follow-up period needed. It is also not clear that clinical trials performed in Asia can be extrapolated to U.S. populations as there appears to be differences in lung cancer risk in never-smokers among different countries.
As outlined in the early detection committee report on screening individuals who have never smoked by the International Association for the Study of Lung Cancer (IASLC), the most promising strategy might be to develop a risk assessment tool that could be used in combination with a biomarker test as part of a precision medicine approach to identify high-risk subpopulations who would then undergo imaging screening.22 This approach could then be validated in different countries and different subpopulations.
However, as screening criteria becomes more complicated so does its implementation. As learned from experience with lung cancer screening in those with a smoking history, uptake and implementation has been a major barrier to screening success. Assessing complicated risk factors and interpreting a biomarker test raises several questions, including which providers have the bandwidth and expertise to perform these assessments and interpret these tests. In addition to risk assessment, also necessary is the need to define more specific guidelines for when to intervene and how to manage subsolid lung nodules, which are more common in Asian patients and those who have not smoked. As we strive to identify who best to screen, we must also plan for the how.
There is an increasing interest in the Asian American community to improve early detection of lung cancer and implement screening practices. The public health need in never smokers and in Asian Americans is a growing concern. However, while the benefits of screening are intuitive for patients to understand, the harms are more challenging to convey. Clinicians, researchers, and policymakers have a responsibility to make careful informed decisions about how to approach this in the best interests of each patient.