In the National Lung Screening Trial, screening with 2 years of annual low-dose computed tomography (LDCT) achieved a 20% decrease in lung cancer mortality in high-risk populations when compared with chest radiography. A decade later, in March 2021, the U.S. Preventive Services Task Force (USPSTF) expanded the eligibility for U.S. adults to ages 50 to 80, including both people who currently smoke and people with at least a 20 pack-year smoking history; for those with a smoking history, they had to have quit within the prior 15 years to be eligible.1 By lowering the bottom age limit from 55 to 50 and the minimum pack-year history from 30 to 20, the USPSTF nearly doubled the number of people eligible for screening.2
Although LDCT screening has been shown to avert lung cancer mortality and increase life years, the expansion of the eligible population is also expected to lead to screening harms, including “unnecessary” biopsies, overdiagnosis of cancer, and anxiety.3 Recent work by Dr. Hui Zhao and colleagues4 evaluated the complication rates of invasive diagnostic procedures performed within 6 months of LDCT. This case-control research determined that 3.5% of patients underwent invasive diagnostic procedures after LDCT, with an overall complication rate of 16.6% in a real-world setting. Because the study lacked data on the smoking history of participants, we could not determine whether each enrolled patient met the screening eligibility criteria. Nevertheless, the 16.6% finding raises concern about the possibility of higher complication rates outside the NLST, giving rise to the key question of how to balance the benefits of lung cancer screening against the harms potentially associated with the follow-up investigations.
Identifying and recommending the optimal population for LDCT might be the first step toward creating this balance. Based on existing evidence from randomized controlled studies, the population at highest risk is clearly defined, composed mainly of people who smoke,5 ,6 but also including individuals with no smoking history but who might face an increased risk of lung cancer because of family history. Failing to include people who face a higher risk because of their ethnicity or gender should also raise concerns about the equity of screening guidelines. This can be avoided by integrating risk-prediction models that identify individuals who stand to gain a larger benefit from screening even though they do not meet 2021 USPSTF criteria. That strategy could nearly eliminate the disparity in life years gained between Black and White populations, although not the disparity between Asian and White groups.7 Hence, people of Asian descent might need to be given special consideration in lung cancer screening guidelines as an especially high-risk population. Yan et al. reported that Chinese people with a family history of lung cancer had a 3.2% increased risk of developing lung cancer.8 This cohort also showed an adjusted odds ratio of 7.31 for people with a family history of lung cancer compared to those without.8
In the United States, as in China, LDCT is relatively affordable and convenient. It costs approximately 400 Chinese yuan renminbi (CNY; US $60), can be performed within 1 week after an appointment; it is widely covered by health insurance plans as an annual service for those eligible. This has led to the diagnosis of early-stage lung cancer in a relatively large proportion of people with no history of smoking, particularly women. A Shanghai community health service study conducted in 11,332 individuals (7,144 men and 4,188 women) found that the incidence of primary lung cancer was 337 cases per 100,000 person-years among people of both genders who don’t smoke, compared with 159 cases per 100,000 person-years among the participants with smoking histories (p = 0.054).9 This apparent paradox suggests that there are more female patients with lung adenocarcinoma in East Asia who do not have a smoking history. Furthermore, according to recent research evaluating the results of regular health examinations among Chinese hospital employees, the detection rate of ground-glass nodules was significantly greater in women than in men (12.68% vs. 8.97%, p=0.004).10 Although the fundamental etiology is still unknown, a family history of lung cancer has been confirmed as the strongest predictor of the disease in people with no smoking history, especially in populations with a maternal history of lung cancer.8 ,11 Besides environmental risk factors such as second-hand smoke, kitchen fumes or hormones might be factors, as well. Genetic alterations may add insights that contribute to further epidemiologic research12 and necessitate the redefinition of the high-risk population eligible for lung cancer screening.
Another key issue will be how to deal with abnormal findings from thoracic imaging examinations, as most of the LDCT-detected lung abnormalities present as ground-glass opacity (GGO) lesions. In one study among 15,686 Chinese hospital employees, 95.5% of participants with screening-detected lung cancer presented with GGO.10 In addition to malignant tumors, the pathological features of GGO include inflammation as well as precancerous lesions such as atypical adenomatous hyperplasia. Thus, we have been trying our best to achieve accurate diagnoses and avoid unnecessarily invasive diagnostic procedures.
For pure or subsolid lung nodules that are less than 5 mm, a follow-up period is strongly recommended. If, after that period, GGOs persist or have grown, surgical intervention should be recommended, especially for anxious or young patients. Because of continuous advancements in minimally invasive thoracic surgery and the Enhanced Recovery After Surgery (ERAS) approach, surgical trauma has been reduced and survival and quality of life significantly improved. Furthermore, peripheral tumors with a diameter of 2 cm or less and/or a cardiothoracic ratio of more than 0.5 are now considered candidates for sublobular resection.13 For help locating such a tumor, 3D-reconstruction can be used, along with watershed analysis of the target pulmonary artery for real-time localization.14 For patients strongly suspected to have early-stage lung cancer, surgery is considered a better option than percutaneous biopsy.
Beyond the challenges of implementing lung cancer screening in eligible populations, the optimal management of lung abnormalities following LDCT detection is a major dilemma. Shared decision-making may offer opportunities to maximize benefits, reduce harms, and improve lung cancer screening.15 Conversations between physicians and patients about lung cancer screening should include a discussion of the risks of abnormal findings and of subsequent courses of action, such as the potential adverse events associated with surgical intervention or other invasive diagnostic procedures. Moving forward, genomic features, such as circulating tumor DNA—evaluated in the context of the natural history of lung cancer—may help to individualize risk assessment and better facilitate screening applications.
- 1. Henderson LM, Rivera MP, Basch E. Broadened Eligibility for Lung Cancer Screening: Challenges and Uncertainty for Implementation and Equity. JAMA. 2021;325:939-941.
- 2. Potter AL, Bajaj SS, Yang C-FJ. The 2021 USPSTF lung cancer screening guidelines: a new frontier. Lancet Respir Med. 2021;9(7):689-691.
- 3. Meza R, Jeon J, Toumazis I, et al. Evaluation of the Benefits and Harms of Lung Cancer Screening With Low-Dose Computed Tomography: Modeling Study for the US Preventive Services Task Force. JAMA. 2021;325:988-997.
- 4. Zhao H, Xu Y, Huo J, et al. Updated Analysis of Complication Rates Associated With Invasive Diagnostic Procedures After Lung Cancer Screening. JAMA Netw Open. 2020;3:e2029874.
- 5. Church TR, Black WC, Aberle DR, et al. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013;368:1980-1991.
- 6. 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;382:503-513.
- 7. Landy R, Young CD, Skarzynski M, et al. Using Prediction-Models to Reduce Persistent Racial/Ethnic Disparities in Draft 2020 USPSTF Lung-Cancer Screening Guidelines. J Natl Cancer Inst. 2021. [Epub ahead of print].
- 8. a. b. c. Lin H, Huang YS, Yan HH, et al. A family history of cancer and lung cancer risk in never-smokers: A clinic-based case-control study. Lung Cancer. 2015;89:94-98.
- 9. Luo X, Zheng S, Liu Q, et al. Should Nonsmokers Be Excluded from Early Lung Cancer Screening with Low-Dose Spiral Computed Tomography? Community-Based Practice in Shanghai. Transl Oncol . 2017;10:485-490.
- 10. Ouyang B, Li M, Li L, et al. Characteristics of Ground-Glass Nodules Detected by Low-Dose Computed Tomography as a Regular Health Examination Among Chinese Hospital Employees and Their Parents. Front Oncol. 2021;11:661067.
- 11. Pan-Chyr Y. National Lung Cancer Screening Program in Taiwan: The TALENT Study. J Thorac Oncol. 2021;16(3):S58.
- 12. Zheng D, Chen H. Lung cancer screening in China: early-stage lung cancer and minimally invasive surgery 3.0. J Thorac Dis. 2018;10:S1677-S1679.
- 13. Asamura H, Okada M, Saji J, et al. Randomized Trial of Segmentectomy Compared to Lobectomy for Small-Sized Peripheral Non-small Cell Lung Cancer (JCOG0802/WJOG4607L). Paper presented at: American Association for Thoracic Surgery 101st Annual Meeting [virtual]; May 2, 2021.
- 14. Chu XP, Chen ZH, Lin SM, et al. Watershed analysis of the target pulmonary artery for real-time localization of non-palpable pulmonary nodules. Transl Lung Cancer Res. 2021;10:1711-1719.
- 15. Hoffman RM, Reuland DS, Volk RJ. The Centers for Medicare & Medicaid Services Requirement for Shared Decision-making for Lung Cancer Screening. JAMA. 2021;325:933-934.