Low dose CT for lung cancer screening

Lung cancer is the leading cause of cancer-related death in both men and women, with 1,800,000 deaths per year worldwide (1). When symptoms appear, it is generally too late to offer curative treatment. Among all efforts made so far to reduce mortality from lung cancer, early screening has emerged since the early 2000s as a potential solution, thanks to the advent of multi-detector (so-called “volumetric”) computed tomography (CT) scanners. These scanners allow the acquisition of the entire thoracic volume in a single deep-inspiration breath-hold, enabling high-resolution reconstructions in all spatial planes while reducing the radiation dose delivered to the patient.

Three main pieces of evidence now justify organized low-dose CT (LDCT) screening for lung cancer. Two large randomized controlled trials (NLST in the USA and Nelson trial in Europe) conducted in smokers or former smokers demonstrated a significant reduction in lung cancer mortality in the group screened by LDCT compared to a control group (2,3). A large-scale, non-randomized, multinational, prospective program, named International Early Lung Cancer Action Program (I-ELCAP) conducted among 89,404 at-risk smokers showed that, after 10 annual screening scans, the 20-year lung cancer–specific survival was 81% [95% confidence interval (CI): 78%, 83%] which is considerably higher than that observed when cancer is diagnosed outside a screening program (4).

Although only a few countries have implemented national lung cancer screening programs, many others are actively evaluating the health economics and feasibility, with numerous pilot programs currently underway. Real-world data from these programs are accumulating and have been used to estimate the impact on target populations and the broader public. In the United States, despite the U.S. Preventive Services Task Force (USPSTF) recommending annual LDCT screening since 2013 (5), uptake remains low, with only 4.5% of eligible individuals screened in 2022 (6). In Europe, pilot lung cancer screening programs have been launched or are ongoing in several countries, including France (7,8), Germany (9), and Italy (10). In 2022, the UK National Screening Committee endorsed targeted screening for high-risk individuals aged 55 to 74 years (11). Regional pilots have been established in parts of England, with a national rollout planned in the coming years (12). In March 2025, Bhamani and colleagues published baseline findings from the SUMMIT study, a LDCT screening initiative for high-risk populations (13), regarded in UK as being a pragmatic, evidence-based, and practically deliverable lung cancer screening programme (14).

Screening uptake has been shown to vary based on socioeconomic status, ethnicity, age, gender, and both current and former smoking behavior (15-17). The SUMMIT study is embedded in a broader initiative aimed at optimizing LDCT screening uptake among high-risk individuals in anticipation of a national program in the UK. A key strength of the study lies in the formation of a screened cohort that is larger and more demographically representative than in prior studies. Conducted in socioeconomically and ethnically diverse areas of northeast and central London, the study reached underserved populations participants’ median deprivation rank placed them in the second most socioeconomically disadvantaged national quintile.

Individuals aged 55 to 77 identified as current smokers within the past 20 years in primary care records across 329 practices were invited by mail to attend a lung health check. Between April 8, 2019, and May 14, 2021, 18,581 individuals attended, of whom 12,773 were included in this analysis (Table 1). These participation rates were comparable to those in previous UK studies using open invitation with an opt-in model (17-19), although lower than the 52.6% rate reported in the Yorkshire Lung Screening Trial, which employed scheduled appointments and an opt-out model (16). Given the critical importance of uptake in the success of large-scale screening programs, any intervention that increases participation deserves careful consideration. Two other English pilot studies highlight the utility of mobile community-based scanning units, which address practical barriers such as travel-related issues and thereby improve uptake (17,20).

LDCT was performed without contrast, using 0.625 mm thin slices and radiation doses under 2 mSv. Nodule management followed the British Thoracic Society (BTS) screening-adapted guidelines (14). Of SUMMIT participants, 618 (4.8%) were referred to a lung cancer multidisciplinary team due to suspected malignancy, and 261 (2.0%) were diagnosed with lung cancer. These rates are higher than those reported in I-ELCAP (1.3%) (21), NLST (1.1%) (22), and the NELSON trial (0.9%) (23), confirming the value of LDCT screening in early lung cancer detection. At 12 months, the baseline LDCT scan showed an episode sensitivity of 97.0% (95% CI: 95.0–99.1%) and specificity of 95.2% (95% CI: 94.8–95.6%). The false positive rate was 4.8% (95% CI: 4.4–5.2%), higher than NELSON’s reported 1.7% (23), likely due to a lower volumetric threshold for defining positive solid nodules in SUMMIT (300 mm³ at baseline, 200 mm³ if growing) compared to 500 mm³ in NELSON (13). The interval cancer rate (0.6%) was similar to that observed in NELSON (0.5%) (23) and NLST (0.7%) (22).

Most prevalent lung cancers detected in SUMMIT (79.3%) were diagnosed at stage I or II, with 54.8% identified at the earliest stage IA (Table 2). The proportion of stage I diagnoses (70.1%) exceeded those in the NELSON trial (63.9%) (22), NLST (54.8%) (23), and other randomized trials (24-26), although it was lower than in some non-randomized studies (27). These findings reinforce the value of LDCT screening in facilitating curative-intent treatments, such as surgical resection, stereotactic ablative radiotherapy, or radical radiotherapy with or without chemotherapy, in 90.4% of cases (Table 2). Importantly, 74% of patients diagnosed with stage II or III disease underwent surgical resection, a significant outcome in light of recent guidelines endorsing neoadjuvant chemo-immunotherapy for resectable stage II and III lung cancer (28). However, 28 of 241 surgical resections (11.6%) were ultimately benign, including five lobectomies. Bahmani et al. suggested that this may reflect the high prevalence of mycobacterial disease in the study setting, supported by the common finding of necrotizing granulomatous inflammation in benign resections (13).

Given these results, the authors of SUMMIT concluded that large-scale lung cancer screening is both feasible and effective, providing a model for implementing a national, population-based screening program. Building on extensive pilot work, the English lung cancer screening program has been operational since February 1, 2025, with the goal of reducing socioeconomic disparities. Once fully implemented by 2030, it is projected to deliver nearly one million LDCT scans annually.

Despite this promising progress, several additional considerations warrant attention. One limitation of SUMMIT was the lack of assessment of participant perspectives on the acceptability of lung cancer screening. Participation and adherence are shaped by psychological and cognitive factors, which in turn may be influenced by the screening process itself. Barriers such as knowledge gaps, anxiety, stigma, cost, and logistical challenges can be addressed through patient-centered best practices, educational efforts, and behavioral interventions. Wood et al. recently reviewed these psychological and behavioral influences and proposed strategies to overcome them (29).

While SUMMIT reported suspected extrathoracic malignancies and urgent non-malignant findings in 2% of participants, it did not systematically assess thoracic abnormalities on LDCT scans linked to smoking-related comorbidities, such as coronary artery calcifications (CAC), emphysema, and osteoporosis (30). Smokers face increased risks of myocardial infarction, stroke, and heart failure. In NELSON, cardiovascular deaths after three LDCT rounds over ten years were comparable to lung cancer deaths (3). CAC is a strong predictor of cardiovascular events, with mortality rising in line with CAC burden (31). Chest CTs, even ungated, can reliably estimate CAC, presenting an opportunity to assess cardiovascular risk during lung cancer screening (32). Identifying emphysema on LDCT is also valuable. Centrilobular emphysema has been linked to elevated lung cancer risk, proportional to severity (33), and its detection contributes to risk stratification. Emphysema on CT, even without symptoms or abnormal spirometry, is associated with progression, declining lung function, and increased mortality (34-36). Bronchiectasis reporting is also now recommended in LDCT screening. Cai et al. found bronchiectasis in 24.4% of baseline scans, with 6.4% progression and 2.2% newly developed cases over five years (37). Osteoporosis, and associated vertebral fractures, is another key comorbidity in smokers with COPD (38,39). CT-measured bone attenuation correlates well with DXA-based bone mineral density (40). In the ECLIPSE cohort, low bone attenuation and existing vertebral fractures strongly predicted short-term fracture risk (41).

Today, artificial intelligence tools can simultaneously detect lung nodules and assess smoking-related comorbidities by integrating algorithms that analyze various imaging biomarkers (42). This “second reader” approach could maximize the clinical utility of LDCT screening by offering a comprehensive risk profile in smokers and former smokers.

The SUMMIT study focused on individuals at high risk for lung cancer based on smoking history, excluding never-smokers. However, lung cancer in never-smokers is now the seventh most common cancer and fifth leading cause of cancer-related death globally (43). This has sparked interest in LDCT screening for this group, although it is not currently recommended (44). In East Asia, countries/region like South Korea, Taiwan, China, and Japan have implemented opportunistic hospital-based programs of LDCT screening that routinely include non smokers. Several non-randomized studies have shown LDCT can detect lung cancer in never-smokers (45-48), though concerns about overdiagnosis remain (47-49). This issue was underscored by Gao et al., who examined the association between lung cancer incidence and the promotion of screening in a predominantly non-smoking population, using a population-based ecological cohort from the Taiwan Cancer Registry (48). Among approximately 12 million Taiwanese women, 57,898 were diagnosed with lung cancer. The introduction and promotion of LDCT screening were associated with a six-fold increase in the incidence of early-stage (stage 0–I) lung cancer between 2004 and 2018, while the incidence of late-stage (stage II–IV) disease remained unchanged. Although 5-year survival rates more than doubled to 40% during this period, lung cancer mortality remained stable, raising concerns about overdiagnosis.

In a multicenter South Korean cohort study involving 21,062 (76.6% women) asymptomatic never-smokers aged 50–80 years who underwent opportunistic LDCT screening, Kim et al. reported a lung cancer incidence of 0.8%, with 93.2% of cases detected at stage 0 or I. The five-year lung cancer-specific survival rates were 97.7% for women and 100% for men, with no significant differences in outcomes by gender (50). Notably, 80.1% of detected lung cancers presented as subsolid nodules. These findings highlight the potential risk of overdiagnosis in never-smokers undergoing LDCT screening. Surgical lung biopsy was the initial invasive diagnostic procedure in 83.5% of cases, underscoring a heavy reliance on this approach. Given that surgical lung resection carries mortality rates of up to 1–2%, the possible downstream harms associated with overdiagnosis in this population are substantial and warrant careful consideration. In the absence of high-quality randomized trial data to establish the clinical efficacy of lung cancer screening in never-smokers, concerns about overdiagnosis in this population will remain a significant and unresolved issue.

While there is evidence supporting the use of LDCT for lung cancer screening in individuals with a history of cigarette smoking, as well as emerging data in never-smokers, further long-term clinical studies are needed. This is particularly important given concerns about overdiagnosis in never-smoker populations and the variability in diagnostic practices across different countries and healthcare systems. To date, no active randomized clinical trials are assessing the effectiveness of LDCT screening specifically in never-smokers.

A promising strategy to reduce lung cancer mortality could involve identifying high-risk individuals among never-smokers, former smokers, and light smokers, and offering them LDCT screening. This approach would require validated risk-benefit assessments based on comprehensive risk prediction models. In this context, the development of future biomarkers enabling personalized lung cancer risk assessment, independent of age or smoking history, is highly anticipated. Such advancements would significantly enhance the identification of high-risk individuals and help define target populations for future lung cancer screening programs.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease. The article has undergone external peer review.

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1242/prf

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1242/coif). P.A.G. reports consulting fees from Sophia Genetics and Median Technology; and honoraria for speaking from Siemens Healthineers. The author has no other conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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