Trouble with promoting lung cancer screening in never-smokers – Authors' reply
Authors: Chao-Hua Chiu, Chong-Jen Yu, Gee-Chen Chang, Pan-Chyr Yang
Journal: The Lancet Respiratory Medicine (2024)

The TALENT study is the first prospective low-dose CT (LDCT) lung cancer screening study in never-smokers. Therefore, it is not surprising to express concerns. We appreciate the valuable feedback in the Correspondence by Wayne Gao and H Gilbert Welch1Gao W Welch HG Trouble with promoting lung cancer screening in never-smokers.Lancet Respir Med. 2024; (published online Feb 28.)https://doi.org/10.1016/S2213-2600(24)00036-5Summary Full Text Full Text PDF Scopus (1) Google Scholar; however, it is essential to clarify several misconceptions. First, both sex and a family history of lung cancer are statistically significant risk factors for lung cancer after confounding adjustment. However, making inferences by directly comparing their respective odds ratios is not appropriate on the grounds of the overlap of the 95% CIs and omitting our stratified analysis of family history (an effect modifier) in the TALENT study2Chang G-C Chiu C-H Yu C-J et al.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: 141-152Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar. Neither are they adequate for the comparisons of these two risk factors with heavy smoking and the comparisons between detection and death. Gao and Welch compared two risk factors (sex and family history of lung cancer) used in our study with another risk factor (heavy smoking) in the other studies as well as comparing detection and death. The evidence for both comparisons is inadequate, and therefore, we believe these comparisons are inappropriate. Second, in addition to exploring a risk-based screening model, the aim of the TALENT study was to evaluate the effectiveness of early detection by LDCT screening. Therefore, comparing the detection rate in the TALENT study with those in National Lung Screening Trial and NELSON studies3Aberle DR Adams AM Berg CD et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (7969) Google Scholar, 4de Koning HJ van der Aalst CM de Jong PA et al.Reduced lung-cancer mortality with volume CT screening in a randomized trial.N Engl J Med. 2020; 382: 503-513Crossref PubMed Scopus (1768) Google Scholar was done to show a high early detection rate rather than compare the risk of lung cancer across different populations. Third, although overdiagnosis might have occurred, evaluating the extent of overdiagnosis in an observational study should be done with caution. The comparator using the pre-screening period, 15 years before the TALENT study, is scientifically unsound and would exaggerate overdiagnosis since lung cancer incidence before LDCT screening has increased over time. Fourth, our nodule management plan is more aggressive than that in 2024 guidelines, but the TALENT protocol, established in 2014, predominantly adhered to the National Comprehensive Cancer Network guidelines at that time5NCCN Clinical Practice Guidelines in Oncology, Lung Cancer Screening, Version 1, 2014.Google Scholar. Finally, the TALENT study is an ongoing study, and we presented the first results. It is still too early to infer whether risk-based LDCT screening can lead to a mortality reduction, as already shown in a similar risk-based UK Lung Cancer Screening trial.6Field JK Vulkan D Davies MPA et al.Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis.Lancet Reg Health Eur. 2021; 10100179 PubMed Google Scholar Therefore, long-term follow-up is required. We declare no competing interests. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published tables and institutional affiliations. Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort studyTALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. Full-Text PDF Trouble with promoting lung cancer screening in never-smokersWe read, with great concern, the finding from the TALENT study1 that family history is a sufficiently strong risk factor to warrant low-dose CT (LDCT) screening in never-smokers. In the data by Gee-Chen Chang and colleagues, family history of lung cancer is a weaker risk factor (odds ratio [OR] 1·67 [1·31–2·13]) than is female sex (2·06 [1·50–2·83]). On the basis of these data, one could equally argue that screening should be offered only to females who have never smoked—not males. Full-Text PDF