Screening for lung cancer

        Long before the 20th century, when it became a fact that smoking directly causes cancer, the tobacco plant, Nicotiana, was widely celebrated across Europe and South America for medicinal practices. For centuries tobacco was thought, without any evidence, to be a remedy for colds, fevers, and other illnesses. It wasn’t until the late 1800s, when smoking tobacco exploded in popularity, that doctors and scientists slowly began to notice the steady increase in lung cancer patients.¹ Decades later, overwhelming evidence that tobacco is extremely carcinogenic began to pile up, and smoking became a major public health concern.² 

        Today, lung cancer is the leading cause of cancer-related mortality in women the leading cause of cancer-related mortality remains breast cancer, but both groups combined, it’s true that it’s lung cancer worldwide. Modern medicine has come up with ways to detect and treat lung cancer, with one of the most commonly used prevention strategies being screening with low-dose CT scans. Two major studies, National Lung Screening Trial (NLST), and the Dutch-Belgian NELSON trial investigated the effect of low-dose CT scanning as a screening method on lung-cancer patient outcome. Two landmark randomized trials changed lung-cancer screening. The NLST showed approximately a 20% reduction in lung-cancer mortality with low-dose CT, while the NELSON trial subsequently found a reduction of approximately 24% among men, with an even larger, but less precise, benefit suggested among women. ^3,4,5 

        

        Although screening with low-dose CT lung imaging of high-risk individuals with a smoking history reduced lung cancer mortality, studies have shown that the current screening guidelines miss at least 50% of lung cancers.⁸ However, most of the public knowledge and research surrounding lung cancer has been directed at cases where the disease has been induced by heavy tobacco use. While it is true that most lung cancer cases are caused by smoking, up to one in four people diagnosed with lung cancer worldwide may have never smoked or have smoked fewer than 100 cigarettes in their lifetime. Lung cancer in never smokers (LCINS) disproportionately affects women, people of Asian descent and those with a family history, though the reason behind this increased risk is still poorly understood. Despite LCINS currently being the seventh leading cause of cancer related mortality worldwide, never-smokers remain excluded from current screening guidelines.¹ The question that arises is: if screening increases the rate of early detection, why doesn't everyone just get screened for lung cancer? After all, it is recommended for example, that all women above age 45 get screened for breast cancer. The reason is that not enough research has been done to demonstrate that widespread screening decreases the mortality rate of lung cancer among non-smokers. There is a cause for change in our approach to preventative medicine, specifically with regards to lung cancer, and further research must be done to address this issue. 

        Before a lung cancer screening program for non-smokers is implemented, some important questions must be addressed. The first is what are the biological causes behind LCINS, and how can they inform targeted prevention strategies? Some recent studies have highlighted the main drivers of LCINS, which include genetic susceptibility (ie: genetic variants or family history) or environmental factors like second hand smoke, radon exposure, air pollution and inflammatory diseases.¹    

        The second: what is the optimal screening model to identify which non-smoking individuals are at higher risk of developing lung cancer. There is currently no screening model in North America for never-smokers, because of lack of understanding of the biological mechanisms driving LCINS. In Taiwan, however, new steps towards the prevention and detection of lung cancer have led to the first program that includes individuals who have never smoked.  In 2022, Taiwan introduced a low-dose computed tomography (LDCT) screening program for high risk individuals, including those who were not smokers. The screening program was implemented based on the findings of the TALENT trial, as well as a review of global data and this approach may give us a glimpse of what the future could look like. The Taiwan lung cancer screening in never-smoker trial (TALENT) study screened 12,000 never-smokers aged 55-75 who had at least one risk factor for lung cancer, such as family history, secondhand smoke, or COPD. The study found occurrence of invasive lung cancer in 2.6% of participants, and more than three-quarters of those cancers were stage I. Family history emerged as a significant risk factor in the study. These results are remarkable, but they do not yet prove that screening never-smokers saves lives. TALENT was not a randomized mortality trial, and some of the cancers detected may represent overdiagnosis. Taiwan nevertheless took the unusual step of incorporating family history into its national screening program, making it one of the most interesting real-world experiments in lung-cancer prevention today.^6,7 

        The assumption that lung cancer is only a ‘smokers disease’ is slowly changing, and as public awareness of lung cancer risk increases, the current screening guidelines will continue to be challenged. It took decades for medicine to recognize that tobacco, once thought of as healthy, was in fact actually an aggressive carcinogen. Cancer screening is one of the most effective strategies against cancer, but medicine still has a long way to go for it to be used to its full potential. 

        By Milah Pipkey, student in biology, under the supervision of Dr Yahia Abdelali Lakehal, M.D., FRCPC, MPH.

    REFERENCES

1. Sindhu Bhaarrati Naidu, Allegra Wisking, Akul Karoshi, Sarah Burdett, Peter J. Godolphin, Sanjay Popat, Sam M. Janes, Neal Navani, Risk Factors Associated With Incidence of Lung Cancer in Never-Smokers: A Systematic Review and Meta-Analysis, JTO Clinical and Research Reports, Volume 6, Issue 12, 2025, 100910, ISSN 2666-3643, https://doi.org/10.1016/j.jtocrr.2025.10091
2. Charlton A. Medicinal uses of Tobacco in History. Journal of the Royal Society of Medicine. 2004;97(6):292-296. doi:10.1177/014107680409700614
3. National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395-409. doi:10.1056/NEJMoa1102873
4. De 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(6):503-513. doi:10.1056/NEJMoa1911793
5. Stephen Lam, Lung Cancer Screening in Never-Smokers, Journal of Thoracic Oncology, Volume 14, Issue 3, 2019, Pages 336-337, ISSN 1556-0864 doi:10.1016/j.jtho.2018.12.019
6. Pan-Chyr Yang et al. Taiwan national lung cancer early detection program for heavy smokers and non-smokers with family history of lung cancer.. J Clin Oncol 42, 8009-8009(2024). doi:10.1200/JCO.2024.42.16_suppl.8009
7. Pan-Chyr Yang et al.; TALENT 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):141-152. Doi: 10.1016/S2213-2600(23)00338-7
8. Parums DV. Editorial: Increasing Awareness of Lung Cancer in Non-Smokers and Never-Smokers Challenges Current Approaches to Prevention and Screening. Med Sci Monit. 2026 Jan 1;32:e952454. doi:10.12659/MSM.952454.