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01 February 2025: Editorial  

Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-Smokers

Dinah V. Parums1F*

DOI: 10.12659/MSM.948255

Med Sci Monit 2025; 31:e948255

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Abstract

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ABSTRACT: In 2021, the US Preventive Services Task Force (USPSTF) called for increased efforts at tobacco control, smoking-cessation treatments, and annual lung cancer screening with low-dose computed tomography (LDCT), targeted at high-risk populations. In January 2024, the American Cancer Society (ACS) published an update on the previous 2013 lung cancer screening guidelines and recommends annual lung cancer screening with lung LDCT for individuals aged 50-80 years who are asymptomatic but who currently smoke or have previously smoked. Although rates of tobacco smoking have been falling in some countries, the incidence of lung cancer in individuals who have never smoked now represents the 7th most common cancer and the 5th leading cause of cancer-related death. Because there is evidence that lung cancer screening with LDCT reduces lung cancer mortality in individuals with a substantial smoking history, there is now increasing interest in evaluating LDCT for lung cancer screening in those who have never smoked. In 2024, the International Association for the Study of Lung Cancer (IASLC) published a five-year (2023-2027) roadmap for the global use of LDCT in screening for lung cancer. This editorial aims to highlight some recent guidelines and current approaches to lung cancer screening in smokers and non-smokers.

Keywords: Editorial, lung neoplasms, Mass Screening, Smoking, Tomography Scanners, X-Ray Computed

Population-based data from the US National Cancer Institute (NCI), the North American Association of Central Cancer Registries (NAACCR), and the Centers for Disease Control and Prevention (CDC) have shown that lung cancer remains the leading cause of cancer-related death in the US, despite decades of declining mortality rates [1]. However, between 2018 and 2023, the decline in lung cancer mortality was more significant than that of the annual incidence in men (5.0% vs 2.6%) and women (4.3% vs 1.1%), which indicates an absolute gain in two-year relative cancer survival of 1.4% per year [1]. This US trend may reflect improved patient outcomes due to advances in lung cancer treatment, increased access to care, and earlier-stage diagnosis [1]. In 2021, the US Preventive Services Task Force (USPSTF) recommended increased efforts at tobacco control, smoking-cessation treatments, and annual lung cancer screening with lung low-dose computed tomography (LDCT) targeted at high-risk populations [2]. Those at high risk for lung cancer include individuals with a 20-pack-year or more smoking history (a pack year = average number of cigarette packs smoked/day × number of smoking years), current smokers, or individuals who have quit smoking within the past 15 years and are between 50–80 years of age [2].

In January 2024, the American Cancer Society (ACS) published a 2023 update on the previous 2013 lung cancer screening guidelines [3]. Cancer of the lung and bronchus is the leading cause of mortality and years of life lost from cancer in men and women in the US [3]. There is evidence from controlled studies to support the reduction of mortality from lung cancer from early detection by screening [3]. The 2024 updated guidelines from the ACS for screening adults at high risk for lung cancer are intended to guide healthcare providers and patients [3]. The ACS Guideline Development Group undertook a systematic review of the literature on lung cancer and screening and included a 2021 update from the USPSTF and two lung cancer models validated by the Cancer Intervention and Surveillance Modeling Network (CISNET) consortium to assess the benefits and harms of screening [2,3]. The ACS guidelines recommend annual lung cancer screening with lung LDCT for individuals aged 50–80 years who are asymptomatic but who currently smoke or have previously smoked and have a ≥20 pack-year smoking history [3]. In 2024, the International Association for the Study of Lung Cancer (IASLC) published a five-year (2023–2027) roadmap for the global use of LDCT in screening for lung cancer [4]. The nine recommendations from the IASLC are summarized in Table 1 [4]. It is now clear that lung cancer screening, detection, prediction, and prognosis using lung LDCT in smokers and individuals who have never smoked will become increasingly driven by artificial intelligence (AI) (Table 1) [4,5].

In the US, the incidence of lung cancer has declined steadily since 2006, by 2.5% annually in men and by 1% in women, with the downturn commencing later and being slower in women because women began cigarette smoking in large numbers later and were also slower to quit [6]. Estimates in 2024 for new cases and mortality for carcinoma of the lung and bronchus in the US were 234,580 new cases (116,310 men; 118,270 women) and mortality of 125,070 (65,790 men; 59,280 women) [6]. In 2023, Rumgay and colleagues published a study of the impact of preventable cancer deaths and years of life lost in Brazil, Russia, India, China, South Africa, the United Kingdom (UK), and the US, including tobacco smoking [7]. In 2020, an estimated 5.9 million preventable cancer deaths included 20.8 million years of life lost to tobacco smoking, with China having the highest years of life lost, followed by Russia [7].

Although rates of tobacco smoking have been falling in some countries, the incidence of lung cancer in individuals who have never smoked now represents the 7th most common cancer and the 5th leading cause of cancer-related death [8]. Lung cancer in individuals who have never smoked is sometimes termed ‘opportunistic lung cancer,’ but this terminology is not universally accepted [8]. What is known about lung cancer in never-smokers is that the most frequently reported associations include female gender, a family history of lung cancer, and Asian ancestry [8]. Also, smokers are more likely to develop squamous cell carcinoma of the lung, while patients who have never smoked predominantly present with peripheral adenocarcinoma of the lung [8].

A recently published modeling study by Anderer has shown that in the US, cancer prevention by screening has saved more lives from five main types of cancer than the treatment advances made during the past 45 years [9]. Analysis of population-level mortality data estimated that 5.9 million deaths from breast, colorectal, lung, cervical, and prostate cancer were avoided between 1975 and 2020 due to improved prevention, screening, and cancer treatment and that prevention and screening alone were responsible for preventing 4 out of 5, or about 4.8 million, deaths [9]. However, implementing screening programs for lung cancer has undergone several setbacks, including the choice of populations, choice of screening methods, and limited data from randomized trials regarding whether screening with LDCT lung imaging could reduce mortality from lung cancer in past and current smokers. Recent results from trials based in the Netherlands (the Dutch-Belgian Randomized Lung Cancer Screening Trial) and the US (National Lung Screening Trial) provided evidence in support of screening for lung cancer with LDCT imaging [10–12].

In 2020, de Koning and colleagues reported the findings from a study conducted with participants in Belgium and the Netherlands that included 13,195 men (primary analysis) and 2,594 women (subgroup analysis) between 50–74 years of age [10]. Study participants were randomized to undergo LDCT lung screening at baseline, 1 year, 3 years, 5.5 years, or no screening [10]. In the screening group, the incidence of lung cancer was 5.58 cases per 1,000 person-years [10]. In the control group, the incidence of lung cancer was 4.91 cases per 1,000 person-years [10]. Mortality from lung cancer was 2.50 deaths per 1,000 person-years in the screening group and 3.30 deaths per 1,000 person-years in the control group [10]. The study showed that mortality from lung cancer was significantly reduced in individuals who underwent LDCT lung screening compared with those with no screening [10].

The National Lung Screening Trial (NLST) began in 2002 and was conducted by the American College of Radiology Imaging Network (ACRIN) and the Lung Screening Study group [11]. The NLST research team was initially established by the US National Cancer Institute (NCI) to examine the feasibility of conducting an imaging trial in smokers [11]. The NLST enrolled 53,454 participants who were current or former heavy smokers aged between 55–74 years [11]. The study participants were former and current smokers who had a smoking history of at least 30 pack-years, but without signs, symptoms, or history of lung cancer [11]. The NLST research team compared two lung cancer screening imaging methods, including three rounds of low-dose helical (or spiral) CT and standard chest X-rays [11]. A standard chest X-ray provides an image of the whole chest with anatomic structures overlapping. However, helical LDCT uses lung X-rays to obtain multiple scan images of the entire chest. The study findings were published in 2011 [11]. The NLST research team showed that, during a 7-year follow-up, participants screened with low-dose helical CT scans had a 15–20% lower risk of death from lung cancer than participants screened using standard chest X-rays [11]. Therefore, there were approximately three fewer deaths per 1,000 individuals screened with lung LDCT imaging than those screened with chest X-rays (17.6 per 1,000 vs 20.7 per 1,000, respectively) [11]. After the three screening rounds, 24.2% of the LDCT screened images were positive, and 6.9% of the chest X-rays were positive, with most positive screens resulting in additional tests [11]. Importantly, primary early-stage lung adenocarcinomas and squamous cell carcinomas were detected more frequently by low-dose helical CT when compared to imaging with chest X-rays [11]. The more aggressive primary lung malignancy, small-cell lung cancer, was infrequently detected at early stages by low-dose helical CT or chest X-ray [11].

In 2019, the NLST research team published the findings from an extended follow-up of subjects by linkage to state cancer registries and the US National Death Index (NDI) [12]. The number needed to screen (NNS) to prevent one lung cancer death was calculated to be the reciprocal of the difference in the proportion of subjects dying from lung cancer across the arms of the study [12]. The results showed that the median follow-up after screening was 11.3 years for lung cancer incidence and 12.3 years for mortality from lung cancer [12]. Also, 1,701 and 1,681 lung cancers were diagnosed in the LDCT and chest X-ray arms, respectively [12]. The observed lung cancer deaths were 1,147 and 1,236 in the LDCT and chest X-ray arms, respectively [12]. This extended follow-up study of the NLST study participants showed a similar NNS as the original 2011 analysis, and there was no overall increase in lung cancer incidence in the participants screened with low-dose lung CT compared with the chest X-ray arm [12].

Because there is evidence that lung cancer screening with LDCT reduces lung cancer mortality in individuals with a substantial smoking history, there is now increasing interest in evaluating LDCT for lung cancer screening in those who have never smoked [13,14]. Currently, several non-randomized observational studies from Asia have supported lung cancer screening with LDCT to detect lung cancer in individuals who have never smoked [15,16]. However, whether screen-detected lung cancer in individuals who have never smoked predominantly represents early-stage aggressive lung cancer or low-grade cancer or has significant risks of false-positive diagnoses remains unclear but is under investigation [16,17].

Adenocarcinoma of the lung develops as a progression from atypical adenomatous hyperplasia to invasive adenocarcinoma, both of which can be detected by high-resolution lung LDCT [18]. Also, as the overall risk for lung cancer in individuals who have never smoked is lower than that of those with a smoking history, routine lung cancer screening with LDCT for individuals who have never smoked is not currently recommended [14,15]. However, some East Asian countries currently allow any individual to undergo privately financed lung cancer screening with LDCT [13,18].

A recently published multicenter cohort study from South Korea by Kim and colleagues of individuals who had never smoked and were aged between 50–80 years undergoing lung cancer screening with LDCT described screening-detected lung cancer incidence, associations, and outcomes [19]. This study included individuals who volunteered for LCDT lung cancer screening between 2009–2021, with at least 12 months of follow-up data and imaging results identified according to the American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) version 2022 [19,20]. There were 21,062 individuals in the screening study, and 0.8% (176) were diagnosed with lung cancer in individuals who had never smoked, of which 80.1% (141) had pulmonary nodules on LDCT, and 96% (169) had atypical adenomatous hyperplasia or adenocarcinoma, including 93.2% (164) diagnosed at either stage 0 or stage I lung cancer [19]. There were no gender differences in patient outcomes, with reported 5-year lung cancer-specific survival rates of 97.7% and 100% for women and men, respectively [19].

Data from the Taiwan Lung Cancer Screening for Never Smoker Trial (TALENT) also identified 96.5% of stage 0 or stage I lung cancer in individuals who have never smoked, with 81.1% of cancers presenting as lung nodules [15]. The false positive rate, or proportion of individuals without lung cancer with a Lung-RADS 3 or 4, was 5.5% compared with 12.8% in the NLST study, supporting possible screening overdiagnosis [15,21].

Conclusions

There is evidence to support the role of screening for lung cancer using LDCT in individuals with a history of cigarette smoking and also in non-smokers. Therefore, the recently updated recommendations for lung cancer screening are welcome recent developments. However, further long-term clinical studies are required due to the concerns with overdiagnosis when using screening in populations who have never smoked and the variability in diagnostic evaluation across different countries and healthcare systems.

References

1. Kratzer TB, Bandi P, Freedman ND, Lung cancer statistics, 2023: Cancer, 2024; 130(8); 1330-48

2. Krist AH, Davidson KW, Mangione CMUS Preventive Services Task Force, Screening for lung cancer: US Preventive Services Task Force recommendation statement: JAMA, 2021; 325(10); 962-70

3. Wolf AMD, Oeffinger KC, Shih TY, Screening for lung cancer: 2023 guideline update from the American Cancer Society: CA Cancer J Clin, 2024; 74(1); 50-81

4. Lam S, Bai C, Baldwin DR, Current and future perspectives on computed tomography screening for lung cancer: A roadmap from 2023 to 2027 from the International Association for the Study of Lung Cancer: J Thorac Oncol, 2024; 19(1); 36-51

5. Quanyang W, Yao H, Sicong W, Artificial intelligence in lung cancer screening: Detection, classification, prediction, and prognosis: Cancer Med, 2024; 13(7); e7140

6. Siegel RL, Giaquinto AN, Jemal A, Cancer statistics, 2024: Cancer J Clin, 2024; 74(1); 12-49

7. Rumgay H, Cabasag CJ, Offman J, International burden of cancer deaths and years of life lost from cancer attributable to four major risk factors: A population-based study in Brazil, Russia, India, China, South Africa, the United Kingdom, and United States: EClinicalMedicine, 2023; 66; 102289

8. LoPiccolo J, Gusev A, Christiani DC, Jänne PA, Lung cancer in patients who have never smoked – an emerging disease: Nat Rev Clin Oncol, 2024; 21(2); 121-46

9. Anderer S, Cancer prevention, screening averted several million more deaths than treatment over 45 years: JAMA Jan 3, 2025, doi: 10.1001/jama.2024.26879 Epub ahead of print

10. de Koning HJ, van der Aalst CM, de Jong PA, Reduced lung-cancer mortality with volume CT screening in a randomized trial: N Engl J Med, 2020; 382(6); 503-13

11. Aberle DR, Adams AM, Berg CDNational Lung Screening Trial Research Team, Reduced lung-cancer mortality with low-dose computed tomographic screening: N Engl J Med, 2011; 365(5); 395-409

12. National Lung Screening Trial (NSLT) Research Team, Lung cancer incidence and mortality with extended follow-up in the national lung screening trial: J Thorac Oncol, 2019; 14(10); 1732-42

13. Kim RY, Insights into opportunistic lung cancer screening for individuals who have never smoked: JAMA Netw Open, 2025; 8(1); e2454009

14. Kerpel-Fronius A, Tammemägi M, Cavic MMembers of the Diagnostics Working Group; ED Screening Committee, Screening for lung cancer in individuals who never smoked: An International Association for the Study of Lung Cancer Early Detection and Screening Committee report: J Thorac Oncol, 2022; 17(1); 56-66

15. Chang GC, Chiu CH, Yu CJTALENT Investigators, 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, 2024; 12(2); 141-52

16. Gao W, Wen CP, Wu A, Welch HG, Association of computed tomographic screening promotion with lung cancer overdiagnosis among Asian women: JAMA Intern Med, 2022; 182(3); 283-90

17. Silvestri GA, Young RP, Tanner NT, Mazzone P, Screening low-risk individuals for lung cancer: The need may be present, but the evidence of benefit is not: J Thorac Oncol, 2024; 19(8); 1155-63

18. Succony L, Rassl DM, Barker AP, Adenocarcinoma spectrum lesions of the lung: Detection, pathology and treatment strategies: Cancer Treat Rev, 2021; 99; 102237

19. Kim YW, Joo DH, Kim SY, Gender disparities and lung cancer screening outcomes among individuals who have never smoked: JAMA Netw Open, 2025; 8(1); e2454057

20. Christensen J, Prosper AE, Wu CC, ACR Lung-RADS v2022: Assessment categories and management recommendations: Chest, 2024; 165(3); 738-53

21. Pinsky PF, Gierada DS, Black W, Performance of lung-RADS in the National Lung Screening Trial: A retrospective assessment: Ann Intern Med, 2015; 162(7); 485-91

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