Can the benefits of lung cancer screening be extended to never-smokers?

There is clear evidence for reduced mortality when low-dose computed tomography (LDCT) is used to screen high-risk current or former smokers for lung cancer (N Engl J Med. 2011;365:395–409; N Engl J Med. 2020:382:503–513). However, the incidence is rising in those with no smoking history such that lung cancer in individuals who have never smoked has been estimated to be the fifth leading cause of cancer-related deaths worldwide (Nat Rev Clin Oncol. 2024;21:121–146). This unique form of the disease is particularly common in Asia – where approximately one-third of all lung cancer cases are in never-smokers – and is related to the high prevalence of oncogenic drivers such as EGFR mutations (Transl Lung Cancer Res. 2018;7:450–463).

The question of whether LDCT provides benefit in non-risk-based screening is under investigation in the prospective Chinese Lung-Care Project study, with positive findings on mortality presented at the European Lung Cancer Congress (ELCC) 2026 (Copenhagen, 25–28 March) (LBA5). During a median follow-up of 7 years, screening of almost 12,000 individuals aged 40–74 years was associated with a significant 55% reduction in lung cancer deaths compared with 114,392 non-screened geographically matched individuals, with an impressive 72% reduction observed in women. Among patients diagnosed with lung cancer, screen-detected cases demonstrated significantly better overall survival compared with the non-screened group (hazard ratio 0.13; 95% confidence interval 0.09–0.19; p<0.001). In the screening group, 81.5% of cancers were diagnosed at stage I, compared with 25.1% in the non-screening group. In contrast, advanced-stage disease accounted for about 70% of cases in the non-screened group. Heavy smoking and chronic obstructive pulmonary disease were associated with worse outcomes, whereas other factors including environmental or occupational exposure to carcinogens, and family history of lung cancer showed no significant association.

These encouraging data, particularly on overall survival, highlight that the lifetime gained with non-risk-based screening could be even greater than in selected smoker populations, perhaps due to fewer comorbidities and earlier detection. Extended follow-up will be important to understand if the survival benefit expands even further.

The data presented add to evidence from the prospective TALENT study that demonstrated a high lung cancer diagnosis rate (2.6%) after LDCT screening among never-smokers in Taiwan (Lancet Respir Med. 2024;12:141–152). Female sex, a family history of lung cancer and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer. In addition, preliminary results from the U.S. FANSS study indicate that LDCT screening is feasible in female Asian non-smokers aged 40–74 years old (J Thorac Oncol. 2023;18:S81–S82). Invasive lung adenocarcinoma was detected in 3 out of 201 patients screened (1.5%). The tumours, which were all EGFR mutation positive, were resected and the patients received adjuvant targeted therapy.

The adoption of lung cancer screening has traditionally been slow, related to the financial burden of implementing LDCT programmes and the additional testing subsequently required. The potential for false-positives leading to unnecessary invasive procedures is another barrier, although the development of nodule-management strategies is helping to distinguish the malignant from the benign (Radiology. 2024;313:e240535). Education and emotional support may help to overcome the reluctance felt by some individuals invited to attend screening, and this may need to be tailored if screening is widened to include never-smoking individuals who may not perceive themselves to be at risk.

Large prospective screening trials can take many years to conduct so it is important that we use existing data to define biomarkers related to lung cancer detection in non- or light-smokers to guide who should get access to screening. Now that targeted agents are available to successfully treat early-stage lung cancer when detected, developing screening criteria and overcoming barriers to screening will be essential to halt the rising tide of lung cancer unrelated to smoking.