Lung cancer is the biggest cancer killer of males and females in the United States and is a significant public health issue. Screening for lung cancer is important because most cases are diagnosed in the late stage (stage III and IV) and have low long-term survival. The U.S. Preventive Services Task Force currently provides a Grade B recommendation for yearly lung cancer screening with low-dose CT. Lung cancer screening is recommended for those 50-80 with a 20 pack-year or more smoking history (current smokers and those who quit within the past 15 years).
The lung cancer screening portion of the PLCO Cancer Screening Trial screened participants (smokers and non-smokers) with chest x-ray compared with no lung cancer screening. The PLCO trial did not show reduced mortality from lung cancer. The first study to demonstrate a reduction in mortality because of lung cancer screening was the National Lung Screening Trial. The National Lung Cancer Screening Trial was a randomized control trial of 53,000 high-risk participants aged 55-74 conducted from 2002-2009 and funded by the National Cancer Institute. Trial results were published in the New England Journal of Medicine in 2011. The National Lung Screening Trial showed a 20% decrease in mortality from lung cancer among participants screened with annual low-dose CT compared to screening with a chest x-ray. A similar randomized control trial looking at lung cancer screening with low-dose CT called the Nelson Trial was published in the New England Journal of Medicine in 2020. The study had similar results to the National Lung Cancer Screening Trial, demonstrating a 24% reduction in lung cancer mortality due to screening with low-dose CT compared to no lung cancer screening of high-risk participants.
A decrease in lung cancer mortality from screening was a terrific and impactful finding. However, lung cancer screening was also found to generate many false positives. Looking at the study results, at first glance, it is difficult to believe that almost all of the positive screening tests in the National Lung Cancer Screening Trial were due to false positives. False positives accounted for 96% of positive screenings in the low-dose CT group and 94% in the chest x-ray group. False positives from low-dose CT were also high in the Nelson Trial. The high-resolution capacity of low-dose chest CT increases the chances of flagging benign lesions as possible cancers. Most tiny lung lesions are either lymph nodes or non-calcified granulomas in lung tissue, often indistinguishable from tiny lung cancer lesions. False positives in the setting of lung cancer screening are problematic. False positives may result in additional radiation exposure from follow-up CT scans and unnecessary invasive procedures such as CT-guided fine-needle lung biopsies or bronchoscopy. For example, lung biopsy could result in a complication such as bleeding or pneumothorax.
Overdiagnosis and overtreatment are also relevant to lung cancer screening. Older adult smokers often have comorbidities such as cardiovascular disease or diabetes, which puts them at increased risk of dying from something other than lung cancer, such as a heart attack. It's hard to imagine that there are cases where it would be better to not know you have lung cancer. However, sometimes it's better to not be aware of cancer, even for lung cancer. Like other cancers, lung cancer is a spectrum of related cancers with different growth rates, also known as heterogeneous progression. Nonprogressive or indolent lung cancers will not metastasize or cause harm to an individual if left untreated. Lastly, to offer the most benefit, it is recommended that all lung cancer screening programs include smoking cessation education and treatment options for their patients.
References:
Aberle DR, Adams AM, Berg CD, et al.; 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.
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 Feb 6;382(6):503-513. doi: 10.1056/NEJMoa1911793.
Doria-Rose VP, Szabo E. Screening and prevention of lung cancer. In: Kernstine KH, Reckamp KL, eds. Lung cancer: a multidisciplinary approach to diagnosis and management. New York: Demos Medical Publishing, 2010:53-72.
National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873.
Marcus PM, Bergstralh EJ, Fagerstrom RM, et al. Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up. J Natl Cancer Inst 2000;92:1308-1316