Low-Dose Computed Tomography Lung Cancer Screening for Individuals Who Have Never Smoked: A Review of Recent Updates in Taiwan and the United States

Abstract

Low-dose computed tomography (LDCT) screening is widely recognized as an effective tool for the early detection of lung cancer. However, its efficacy among individuals without a history of smoking continues to attract interest. Currently, nearly all lung cancer screening guidelines provide recommendations exclusively for individuals who currently smoke or have a history of smoking. Emerging research indicates that LDCT screening may also benefit individuals who have never smoked but are genetically predisposed to lung cancer or have been exposed to certain environmental risk factors. This underscores the need to consider expanding LDCT screening eligibility criteria to include carefully selected never-smokers at high risk, potentially preventing lung cancer-related deaths.

Introduction

Lung cancer is the leading cause of cancer-related mortality worldwide [1]. In 2022, approximately 2.5 million individuals were diagnosed with lung cancer, accounting for about 18.7% of all cancer-related deaths [2]. While cigarette smoking is the most well-known risk factor, other contributors include air pollution, family history, and occupational exposures such as second-hand smoke, household air pollutants, and asbestos [3,4]. International efforts have increasingly focused on early detection and intervention strategies for individuals at high risk of developing lung cancer [5].

In 2011, results from the landmark National Lung Screening Trial (NLST) were published [6]. This large-scale study randomized over 50,000 high-risk individuals across 33 US sites to 3 consecutive annual screenings with either low-dose computed tomography (LDCT) or chest radiography (CXR). After a median follow-up period of 6.5 years, the NLST revealed a significant 6.7% reduction in all-cause mortality and a 20.0% reduction in lung cancer-specific mortality in the LDCT group compared to the CXR group. These findings demonstrated the effectiveness of LDCT as an early detection tool. Subsequently, the United States Preventive Services Task Force (USPSTF) issued lung cancer screening guidelines recommending LDCT for individuals with a history of smoking [7].

Concerns regarding the risk of overdiagnosis associated with LDCT were substantiated when the NLST findings indicated high false-positive rates from LDCT scans. In a 2014 analysis of the NLST data, Patz et al. [8] estimated that approximately 18.5% of lung cancers detected by LDCT represented overdiagnosis. To further investigate incidence and mortality rates, NLST researchers published an extended follow-up study in 2019. The findings confirmed the capacity of LDCT to prevent, or at least delay for a decade, lung cancer-related deaths, and reported an LDCT false-positive rate of 3.1% [9]. Subsequently, in 2020, results from the European Nederlands–Leuvens Longkanker Screenings Onderzoek (NELSON) trial were released. This trial enrolled over 15,000 high-risk individuals who were randomized either to 4 rounds of LDCT screening conducted over a 6-year period or to a non-screening control arm [10]. With a minimum follow-up of 10 years, the results confirmed that LDCT effectively reduces lung cancer mortality, providing robust evidence in support of this conclusion. This association continues to be evaluated across various European countries [11-15]. Table 1 summarizes the relevant studies on LDCT lung cancer screening in individuals with active tobacco use.

Table 1.

Randomized controlled trials of LDCT lung cancer screening among individuals who smoke or have a history of smoking

Publication year/country	Study title	Study cohort (total cases/LDCT group)	Malignant detection rate (under LDCT) (%)	Conclusion
2011/United States	NLST [6]	53,454/26,722	1.1	Compared to the chest radiograph group, NLST revealed a 20% relative reduction in lung cancer mortality and a 6.7% lower all-cause mortality in the LDCT group.
2012/Italy	MILD [11]	4,099/2,376	1.2	The LDCT group displayed a 39% decrease in lung cancer-specific mortality at the 10-year follow-up.
2016/Denmark	DLCST [12]	4,104/2,052	4.8	No significant differences were found in lung cancer mortality and all-cause mortality between screening and non-screening groups.
2016/United Kingdom	UKLS [13]	4,055/1994	2.1	Overall, 85.7% of screen-detected lung cancers were stage 1 or 2.
2017/Italy	ITALUNG [14]	3,206/1,613	4.2	The LDCT group displayed a nonsignificant 30% decrease in lung cancer-specific mortality and 17% decrease in overall mortality at the 9-year follow-up.
2020/Germany	LUSI [15]	4,052/2,092	3.1	LDCT screening displayed a 69% significant reduction in lung cancer mortality among women, but not men.
2020/The Netherlands, Belgium	NELSON [10]	15,792/a)6,583 (men); 1,317 (women)	0.9	Substantially lower lung cancer mortality was observed in the LDCT group compared to the control group (18.4% and 24.4%, respectively), after 10 years of follow-up.

LDCT, low-dose computed tomography; NLST, National Lung Screening Test; MILD, Multicentric Italian Lung Detection; DLCST, Danish Lung Cancer Screening Trial; UKLS, UK Lung Cancer Screening Trial; DANTE, Detection and Screening of Early Lung Cancer with Novel imaging Technology and Molecular Assays; ITALUNG, Italian Lung study; LUSI, Lung Cancer Screening Intervention; NELSON, Nederlands–Leuvens Longkanker Screenings Onderzoek.

^a)A total of 15,792 individuals were included in the NELSON study—13,195 men (primary analysis), 2,594 women (subgroup analyses), and 3 participants with unknown sex. Due to the lower prevalence and intensity among smoking among women compared to men, only a small number of women were eligible.

Also in 2020, the German Lung Cancer Screening Intervention trial demonstrated similar conclusions. Interestingly, it noted a significant 69% reduction in lung cancer mortality among women who smoked compared to a 6% reduction among male smokers, with a heterogeneity p- value of 0.09 [15].

In South Korea, results from the Korean Lung Cancer Screening Project (K-LUCAS) were published in 2019 [16]. The K-LUCAS findings further supported the efficacy of LDCT screening combined with smoking cessation counseling in saving lives. Based on these results, South Korea implemented the National Lung Cancer Screening Program (NLCSP). NLCSP guidelines recommend biennial LDCT screening for individuals aged 54 to 74 years who have a smoking history of ≥30 pack-years and currently smoke or have quit within the past 15 years [17]. To investigate 1-year mortality following NLCSP implementation, Kim et al. [18] utilized the difference-in-differences method using data from National Health Insurance Service claims between 2018 and 2020. Their analysis focused on 25,908 patients already diagnosed with lung cancer to assess the benefits of the NLCSP within this population. The results indicated that NLCSP implementation was associated with decreased 1-year mortality rates among patients with lung cancer, declining from 24.3% to 20.2%. Additionally, a 2020 study in South Korea reported that LDCT screening results displayed higher specificity among participants without tuberculosis sequelae, whereas those with tuberculosis sequelae exhibited higher false-positive rates [19].

Lung cancer screening guidelines continue to evolve as new studies highlight key limitations of current recommendations [20]. According to the most recent update of the USPSTF lung cancer screening criteria, published in 2021, annual LDCT screening is recommended for individuals aged 50 to 80 years with a smoking history of ≥20 pack-years who currently smoke or have quit within the past 15 years [21]. Compared to the 2013 USPSTF guidelines, the updated recommendations expanded the eligible age range from 55–80 years to 50–80 years and reduced the required smoking pack-year history from ≥30 to ≥20. In 2024, the National Comprehensive Cancer Network (NCCN) similarly updated their LDCT screening criteria [22,23]. The NCCN recommends LDCT lung cancer screening for individuals aged 50 and older with a smoking history of ≥20 pack-years, and based on a 2024 study by Potter et al. [24], the organization further recommended screening for any individual aged 50 or older with a smoking duration of ≥20 years. Currently, clear lung cancer screening guidelines exist for individuals who smoke or used to smoke (Table 2). However, no clear guidelines have yet been established for high-risk individuals without significant smoking histories. This gap highlights the need for further research to develop standardized screening protocols for never-smokers who face an elevated risk of developing lung cancer.

Table 2.

LDCT lung cancer screening guidelines for individuals who smoke or have a history of smoking

Publication year	Guidelines	Recommendation
2021	USPSTF [21] (updated)	Recommends annual screening for lung cancer with LDCT in adults aged 50 to 80 years who have a ≥20 pack-year smoking history and currently smoke or have quit within the past 15 years.
2021	CHEST [33]	Recommendation #1: Annual screening for lung cancer with LDCT in adults ages 55 to 77 who have a ≥30 pack-year smoking history and currently smoke or have quit within the past 15 years. Recommendation #2: Annual screening for lung cancer with LDCT in adults ages 50 to 80 who have a ≥20 pack-year smoking history and currently smoke or have quit within the past 15 years. Recommendation #3: Annual screening for lung cancer with LDCT in adults who, based on risk prediction calculations or life-year gained calculations, may benefit from LDCT.
2025	NCCN [23] (updated)	Recommends annual lung cancer screening using LDCT for individuals ≥50 years old with a ≥20 pack-year smoking history or a ≥20-year history of smoking.

LDCT, low-dose computed tomography; USPSTF, United States Preventive Services Taskforce; CHEST, American College of Chest Physicians; NCCN, National Comprehensive Cancer Network.

The TALENT study and policy developments for never-smokers in Taiwan

In Taiwan, individuals who have never smoked account for more lung cancer cases than individuals who have smoked [25]. Notably, while the incidence of squamous cell carcinoma—a subtype of non-small cell lung cancer—has decreased, the rate of lung adenocarcinoma, the most common subtype, has paradoxically increased, particularly among women [26]. Some research indicates that lung adenocarcinomas are now more frequently detected in women than in men. Moreover, in Asia, these cancers exhibit a high frequency of EGFR mutations, although the underlying reasons remain unclear [15,27]. The TALENT study explicitly recommended biennial LDCT screening for members of specific age groups with a history of smoke exposure or a family history of lung cancer.

The International Association for the Study of Lung Cancer developed a predictive model indicating that lung cancer mortality among individuals who have never smoked is projected to rise over the next 50 years. While prior studies have demonstrated the life-saving benefits of LDCT screening for high-risk individuals who smoke, the impact on those who have never smoked remains under investigation.

In 2021, Taiwanese researchers published results from the Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT), which enrolled over 12,000 participants who had never smoked or had minimal smoking histories for LDCT screening. Participants had at least 1 risk factor for lung cancer, including cancer history among first- to third-degree relatives, secondhand smoke exposure, chronic lung disease, a cooking index of at least 110, or lack of home range hoods. Researchers found a lung cancer detection rate of 2.6% and an invasive lung cancer rate of 2.1%. At baseline, 3.3% of participants required biopsy or surgery for detected nodules. Participants with a family cancer history displayed higher invasive lung cancer detection rates compared to those without such a history (2.6% vs. 1.6%, respectively). TALENT notably revealed a positive correlation between lung cancer risk and the number of first-degree relatives diagnosed [28].

The TALENT study is highly regarded not only for confirming the importance of LDCT in early lung cancer screening but also for highlighting the value of screening high-risk never-smokers, thus raising awareness of lung cancer risk in this population. Notably, 96.5% of detected cancers were stage 0 or I, representing disease that is treatable and potentially even curable. The invasive lung cancer detection rate at baseline was 2.1%, compared to 1.1% in the NLST and 0.9% in the NELSON trial [28].

Following the release of findings from TALENT, started in July 2022, the Health Promotion Administration of Taiwan increased its emphasis on this issue (Fig. 1) [29]. Policy changes and educational initiatives expanded screening eligibility to individuals who had never smoked but were considered high-risk due to family history. Men aged 50–74 and women aged 45–74 with a family history of lung cancer (parent, sibling, or child), as well as individuals with ≥30 pack-year smoking histories who have quit within the past 15 years, are now eligible for subsidized biennial LDCT screening.

Fig. 1.

Starting in July 2022, the Health Promotion Administration of Taiwan began offering free biennial low-dose computed tomography (CT) lung cancer screening services to high-risk groups, specifically (a) individuals with a family history of lung cancer or (b) heavy smokers. Category (a) included men aged 50 to 74 or women aged 45 to 74 whose parent, child, or sibling had been diagnosed with lung cancer. Category (b) encompassed individuals aged 50 to 74 with a smoking history of at least 30 pack-years who either are willing to quit smoking or have quit within the past 15 years. From Taiwan National Lung Cancer Early Detection Program detects 85 percent of lung cancer cases at early phase [Internet]. International Association for the Study of Lung Cancer; 2023 [cited 2025 Feb 25]. Available from: https://www.iaslc.org/iaslc-news/press-release/taiwan-launches-national-lung-cancer-early-detection-program-detects-85 [29].

In 2023, an Asian meta-analysis assessed 141,396 smokers and 109,251 nonsmokers in LDCT cancer screening studies. The results revealed comparable risk of LDCT-detected lung cancer between women with no history of smoking history and men with such a history, although nonsmoking women displayed significantly lower overall and lung cancer-specific mortality rates [30].

LDCT screening raises concerns about overdiagnosis. Among the 2,094 TALENT participants with positive LDCT results, 392 underwent invasive procedures, such as lung biopsy or surgery; of these, 81 cases were ultimately identified as benign lesions or non-primary lung cancers. Overdiagnosis in LDCT screening remains challenging, as some indolent lesions may never progress to clinically significant disease. Refining intervention criteria, incorporating longitudinal follow-up strategies, and integrating molecular or radiomic biomarkers may reduce unnecessary invasive procedures while maintaining the benefits of early detection.

Current practices and consensus regarding lung cancer screening for never-smokers in the United States

Lung cancer incidence rates among individuals with no smoking history continue to rise, with an estimated 20% of patients diagnosed with lung cancer in the United States having never smoked [31,32]. Currently, the USPSTF lung cancer screening guidelines do not recommend LDCT scans for individuals with no prior tobacco smoking history, regardless of other risk factors they may have [21]. The 2021 USPSTF guidelines consider only age, pack-year smoking history, and years since quitting smoking (YSQ) as risk assessment factors. Under the Affordable Care Act, lung cancer screening in the United States is covered by most health insurance plans, but only for individuals meeting USPSTF eligibility criteria [21,23].

Other major medical associations have issued more expansive guidelines compared to the USPSTF. For instance, the 2024 NCCN criteria contain neither a YSQ criterion nor an upper age limit. Under the NCCN guidelines, LDCT screening can be recommended for high-risk individuals who are at least 50 years old with either a ≥20 pack-year or a ≥20-year history of smoking [23]. Additionally, the NCCN panel emphasizes the Tammemägi risk calculator, which includes variables such as chronic obstructive pulmonary disease and family history of lung cancer, to assist healthcare providers during the mandated shared decision-making process [33]. The NCCN panel also suggests that individuals who perceive themselves to be at high risk for lung cancer but who do not meet current screening guidelines should consult with their providers and consider participation in clinical trials [23]. Similarly, the American College of Chest Physicians (CHEST) guideline and expert panel report, released in 2021, acknowledged that LDCT screening may be advisable for individuals identified as high risk by risk prediction and life-gain calculators, even if they do not meet age or smoking history criteria [34].

In the United States, lung cancer screening faces 2 major issues. First, adoption rates of lung cancer screening have been low; in 2022, only about 18.1% of Americans eligible under the 2021 USPSTF guidelines received LDCT screening [23,24,35]. Second, the current guidelines are overly restrictive and exclude many individuals at high risk. For example, in the Detecting Early Lung Cancer (DELUGE) in the Mississippi Delta cohort, only 54% of 1,858 patients with lung cancer met USPSTF eligibility criteria for LDCT screening under the 2021 guidelines [36]. Similarly, in an examination of Boston Lung Cancer Study data by Potter et al. [37], only 46.1% of 7,186 patients with lung cancer fulfilled USPSTF screening inclusion criteria. The authors found the NCCN guidelines to be the most inclusive, covering 71.7% of the cohort [37]. Various factors contribute to the low screening uptake, including stigma associated with smoking, lack of awareness, and barriers to accessing screening services. However, the current USPSTF guidelines also exclude high-risk subsets of the population who either have lighter smoking histories or have never smoked [38].

In 2023, lung cancer among individuals who had never smoked was estimated to be the fifth leading global cause of cancer-related deaths [39]. Accumulating evidence indicates that air pollution substantially contributes to the rising incidence of lung adenocarcinoma among never-smokers [40]. The International Agency for Research on Cancer has classified outdoor air pollution and ambient particulate matter with a diameter ≤2.5 microns (particulate matter 2.5 [PM_2.5]) as Group 1 carcinogens [41]. In 2023, Hill et al. [42] reported that PM_2.5 may promote EGFR-driven lung tumorigenesis; furthermore, they found that just 3 years of exposure to high levels of PM_2.5 could increase an individual’s risk of developing lung cancer.

Ongoing research continues to evaluate the feasibility of lung cancer screening in high-risk subsets of the population currently excluded from standard guidelines. The MGH Fire Health Study in Boston screens current or retired firefighters aged 40 to 80 years or with at least 10 years of firefighting experience [43]. Instead of restricting eligibility solely based on age and tobacco use, this study assesses occupational exposures that may elevate lung cancer risk among firefighters compared to the general population. Another ongoing clinical study, the New York University Female Asian Nonsmoker Screening Study (FANSS), examines the feasibility of lung cancer screening in Asian American women who have never smoked [44]. Preliminary results of the FANSS in 2023 revealed an invasive adenocarcinoma detection rate of 1.5% among its 201 participants, comparable to rates of 1.52% from TALENT, also for invasive adenocarcinoma, and 1.1% from NLST for lung cancer. These early results highlight the potential benefit of LDCT for early lung cancer detection among Asian women who have never smoked. Similarly, the Female Asian Never Smokers study at the University of California San Francisco investigates lung cancer risk factors among Asian American women who have never smoked. This study analyzes saliva and blood samples from both diagnosed and undiagnosed Asian American women [45]. Building upon previous findings of metabolic changes in the oral cavity of patients with lung cancer, the study explores salivary biomarkers and multi-omics approaches for non-invasive early detection. These methods have shown promising sensitivity and specificity and could represent accessible alternatives to biopsy, although further validation research is necessary.

Advancing early detection requires improved identification of the individuals most at risk. As lung cancer rates among never-smokers increase and research into additional risk factors progresses, the question of how best to incorporate individual risk assessments into screening guidelines remains challenging and unresolved.

Global overview of lung cancer screening in never-smokers

Opportunistic LDCT lung cancer screening in individuals who have never smoked is currently not recommended [46]. Additional research must investigate risk factors, identify high-risk cohorts among never-smokers, and develop specific screening criteria tailored to these populations. Before the TALENT trial, a 2016 study from Taiwan explored additional predictors of lung cancer risk [47]. The retrospective study analyzed 1,615 asymptomatic adults ineligible for screening under the NLST criteria, as well as 148 participants who did meet NLST eligibility (aged 55–74 years; current or former smokers who had quit within the past 15 years; ≥30 pack-years of smoking history). Both groups underwent baseline LDCT screening, resulting in the detection of 25 lung cancers. This corresponded to a malignant baseline detection rate of 1.4%. Notably, only 1 detected cancer arose in an NLST-eligible participant, whereas the remaining 24 cases occurred among those deemed NLST-ineligible. These findings suggest that the current NLST criteria may exclude additional high-risk subgroups that could benefit from LDCT screening. Further characterization of the lung cancer diagnoses in the NLST-ineligible group revealed that 19 of the 24 cases occurred in women, and over half of the individuals diagnosed had a family history of lung cancer. Collectively, these data suggest that female sex and positive family history may confer a higher risk of developing lung cancer [48,49].

In South Korea, a retrospective study analyzed 28,807 individuals who underwent LDCT screening between 2003 and 2016 at a single center. The findings revealed a lung cancer detection rate of 0.45% among never-smokers, and 92.7% of those cancers were diagnosed at stage 0 or I—compared with 63.6% in participants with a smoking history [48]. A separate South Korean analysis of LDCT scans from 2003 to 2019 assessed subsolid nodule detection at baseline and during follow-up. Most LDCT-detected subsolid nodules—both pure ground-glass opacity and part-solid—were identified at baseline. Never-smokers had a higher overall subsolid nodule detection rate (10.7%) compared to ever-smokers (7.7%) [50]. Nearly all nodules subsequently confirmed as lung cancer were adenocarcinomas, and 78.9% of new nodules detected on follow-up resolved spontaneously. Understanding the timing of nodule development in both never- and ever-smokers is therefore essential for determining the appropriate extent of follow-up management.

Over the years, many countries have initiated research into early LDCT lung cancer screening among never-smokers [28,47-56]. Table 3 summarizes the studies on LDCT screening in individuals without a smoking history.

Table 3.

LDCT lung cancer screening studies for individuals who have never smoked

Publication year/country	Study title	Study cohort (total cases/population)	Malignant detection rate (%)	Conclusion
2021/Taiwan	TALENT [28]	12,011/(INS=12,011)	2.6	TALENT confirmed the effectiveness of LDCT screening in a predefined, high-risk population of individuals who have never smoked.
2016/Taiwan	Selection Criteria for LDCT Among Asian Ethnic Groups [47]	1,763/(INS=1,615; S=148)	1.4 (INS=92.0; S=8.0)	Family history of lung cancer and female sex may be risk predictors of lung cancer development among individuals who have never smoked.
2018/Taiwan	Modified Lung-RADS Improves Performance of Screening LDCT [51]	1,978/(INS=1,440; S=538)	1.6 (INS=93.8; S=6.2)	Modified Lung-RADS may improve the sensitivity of detecting adenocarcinomas.
2019/South Korea	Role of LDCT among Never-Smokers [48]	28,807/(INS=12,176; S=16,631)	0.7 (INS=27.8; S=72.2)	Many LDCT-detected lung cancers were found at early stages among individuals who have never smoked.
2020/South Korea	LDCT screening and invasive diagnosis of pulmonary nodules for lung cancer [49]	37,436/(INS=17,968; S=19,468)	0.6 (INS=40.6; S=59.4)	High false-positive rates were found among both individuals who have and have not smoked who voluntarily underwent LDCT screening.
2020/Japan	LDCT screening in never-smokers and smokers [52]	12,114/(INS=6,021; S=6,090)	1.1 (INS=49.6; S=50.4)	Within the study population, 72.9% of individuals diagnosed with lung cancer would not have met NLST criteria.
2020/China	Results of LDCT as a regular health examination [53]	8,392/(INS=7,509; S=883)	2.1 (INS=93.3; S=6.7)	Provided assessments of lung cancer detection rates based on sex, age, and smoking history among hospital employees; additionally, found that most LDCT-detected lung cancers among the employees were diagnosed at early stages.
2021/China	LDCT screening at a tertiary hospital in Anhui, China [54]	9,084/(INS=4,102; S=4,973)	0.6 (INS=37; S=63)	An individual’s age, family history of cancer, and pulmonary nodule classification can influence their risk of developing lung cancer.
2021/South Korea	Lung cancer probability and clinical outcomes of subsolid nodules detected on LDCT [50]	50,132/(INS=22,631; S=27,501)	0.4 (INS=49.8; S=50.2)	Considering differences in lung cancer probability of baseline versus new subsolid nodules detected by LDCT may improve nodule management strategies.
2023/Taiwan	LDCT in relatives with a family history of lung cancer [55]	1,102/(INS=771; S=314)	4.5 (INS=80; S=20)	Maternal history of lung cancer may increase lung cancer risks.
2024/China	Opportunistic LDCT at National Cancer Center of China [56]	31,431/(INS=17,521; S=8,242)	0.6	Women who have never smoked but have secondhand exposure to smoke may benefit from LDCT.

LDCT, low-dose computed tomography; TALENT, Taiwan Lung Cancer Screening in Never-Smoker Trial, the TALENT Study; INS, individuals who have never smoked; S, individuals who smoke or have a smoking history.

In China, Japan, South Korea, and Taiwan, LDCT screening is widely available and relatively affordable for those willing to pay out of pocket [57]. With the growing popularity of opportunistic screening in these regions, it must be noted that indiscriminate testing may lead to overdiagnosis and pose risks from invasive downstream procedures. In a multicenter cohort study spanning 2009 to 2021, Kim et al. [58] reported no significant sex-based differences in lung cancer detection among participants undergoing opportunistic screening, concluding that men and women share comparable overdiagnosis risks.

A 2020 South Korean single-center retrospective cohort study analyzed 37,436 individuals—both ever- and never-smokers—who underwent LDCT between 2009 and 2018. Among never-smokers, 0.77% underwent invasive biopsy, of whom 36.0% were found to have benign nodules. Although false-positive rates after biopsy did not differ significantly between never- and ever-smokers, the overall rate was higher than reported in other studies. The authors hypothesized that this elevated false-positive rate reflects the high regional prevalence of mycobacterial disease, which can mimic lung nodules on LDCT images. Ultimately, more research is required to develop specific inclusion criteria for never-smokers and to establish tailored management strategies for LDCT-detected nodules in Asian never-smoker populations [49].

Currently, no robust risk models exist for lung cancer in never-smokers. In 2014, research using the PLCOall2014 model suggested that the benefit of screening never-smokers was negligible [59]. Subsequently, Wu et al. [60] developed a Taiwan-based model incorporating age, sex, body mass index (BMI), family history, lung function, alpha-fetoprotein, and carcinoembryonic antigen, identifying a subset of never-smokers with risk levels comparable to those of heavy smokers. Similarly, the NCC-LCm2021 model from China includes age, sex, BMI, family history, and chronic respiratory disease, while another Chinese model extends its variables to include height, physical activity, cough frequency, and other factors [61,62]. Despite these advances, existing models remain suboptimal in predicting lung cancer among Asian never-smokers, likely reflecting unmeasured genetic or environmental factors. Accordingly, further research is required [63].

Conclusion

Currently, lung cancer screening guidelines apply almost exclusively to current and former smokers. Emerging evidence suggests that never-smokers with identifiable risk factors may also derive substantial benefit from screening. Multiple studies have demonstrated significantly higher detection rates in women than in men among never-smokers who undergo LDCT, particularly among those with a multiplex family history of lung cancer. Moreover, the cancers detected through screening in high-risk never-smokers are predominantly adenocarcinomas and are most often diagnosed at an early stage. While early detection can save lives, indiscriminate screening without consideration of individual risk factors is not advised. Future research should aim to refine and expand LDCT criteria to include never-smokers at elevated risk, as early detection and intervention within these populations could markedly improve prognoses.

Funding Statement

Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.