Remarkable progress has been made in the treatment of lung cancer in the past 10 to 15 years; it is therefore not surprising that lung cancer mortality in the United States is declining consistently, at the rate of 2% to 4% annually in recent years. Long-term survival is possible even for patients with locally advanced and metastatic disease, though the best outcomes are observed in patients diagnosed with early-stage disease. Nevertheless, the majority of patients are still diagnosed at an advanced stage of the disease. Early detection of lung cancer is still attributable mainly to incidental diagnoses—and only to a small extent to screening.
The uptake of low-dose computed tomography (CT) screening, an evidence-based approach to detect lung cancer early and reduce mortality, remains low. The first evidence supporting the role for lung cancer screening was provided by the National Lung Screening Trial published in 2011.1 This study showed a 20% reduction in lung cancer mortality with annual low-dose CT scans in high-risk individuals. Consequently, the U.S. Preventive Services Task Force (USPSTF) and many other organizations recommend CT screening for lung cancer.
In 2020, the results of the NELSON study, which was conducted in Europe, were published in The New England Journal of Medicine.2 This trial confirmed the role of CT screening in reducing lung cancer mortality. The USPSTF updated its guidelines in 2021 to expand screening to adults aged 50 to 80 years with a 20 pack-year smoking history for up to 15 years after they quit smoking. Despite these developments, less than 10% of eligible subjects undergo CT screening in the United States.
Suresh S. Ramalingam, MD, FASCO
Barriers to Screening
Several factors could be contributing to this worrisome situation. An overall nihilism toward lung cancer (and its treatment) as well as the stigma associated with tobacco smoking are still pervasive factors. The fact that therapeutic advances in immunotherapy, targeted therapies, and local treatment modalities have all resulted in substantial gains in improving patient outcomes has not fully eliminated the nihilistic attitude many have toward lung cancer. This is substantiated by the fact that biomarker testing, which is critical to personalize therapy and improve outcomes in lung cancer, is performed in only about 60% of patients.
Some have questioned the safety and value of lung cancer screening; the fact that potential harm could result from invasive testing in patients with incidental, unrelated findings is often brought up as an argument against CT screening. Although there is merit to this consideration, there are algorithms in place to guide the appropriate workup for incidental nodules. Moreover, lung cancer screening itself is noninvasive and less time-consuming compared with screening for other malignancies such as breast, cervical, or colon cancer.
Cost-effectiveness is another important consideration when it comes to the adoption of screening programs. This is relevant since approximately 20% of the U.S. adult population born by the year 1960 is eligible for screening by current guidelines. An economic evaluation conducted by Toumazis et al estimated the incremental cost-effectiveness ratio per quality-adjusted life-year gained to be approximately $72,500, based on the 2021 USPSTF recommendations.3 This estimation supports the adoption of lung cancer screening as a cost-effective intervention. However, insurance coverage for screening is variable and could influence screening decisions.
Other Contributing Factors
Studies have shown that a majority of patients would undergo lung cancer screening if it were offered by their care teams. A common question that patients raise is whether the additional radiation exposure related to the CT screening will increase their risk of developing cancer. The radiation exposure that results from a low-dose CT scan is lower than that with standard CT scans; the total dose used for CT screening is highly unlikely to result in cancer. In fact, someone who flies on commercial airplanes a few times a year is likely to be exposed to a similar amount of radiation.
Lack of awareness continues to be a factor in the low uptake of lung cancer screening. There is a need to educate primary care and family practitioners on the appropriate indications for screening and to provide them with support for referring patients with abnormal findings for further workup. Educational programs targeted toward individuals at risk for lung cancer at a community level are also needed to elevate the level of awareness regarding the benefits associated with CT screening for lung cancer. There are disparities in screening based on socioeconomic and racial factors; underrepresented minority and economically weaker patients face additional barriers with regard to access, insurance coverage, transportation, and the inability to take time off from work.
Another contributing factor is the overall reduction in cancer screening in the initial years of the SARS–CoV-2 pandemic. Screening rates dropped substantially for breast and colon cancers in the year 2020. As patients begin to resume screening, health systems are struggling to meet the demand in a timely manner.
Smoking Behaviors
When individuals present for screening, it presents an opportunity to discuss the benefits of tobacco cessation and offer interventions as necessary. Evidence suggests that using this “teachable moment” to educate patients can result in improved smoking cessation rates for patients who undergo CT screening. On the other hand, we should guard against the sense of false security that may come from a normal scan for patients who are current smokers, which could perpetuate smoking.
As we galvanize our communities to overcome these factors to promote lung cancer screening, it should not be lost on us that nearly 15% of lung cancer cases are diagnosed in never-smokers. This group of individuals is not eligible for screening under the present guidelines. However, recent evidence suggests that CT screening may benefit never-smokers with a family history of lung cancer. Further studies are warranted to identify the optimal strategy for screening never-smokers at risk for lung cancer.
Conclusions
As treatment options for lung cancer improve, it is now possible to alter the natural history of the disease through early detection. Emerging approaches such as the use of cell-free DNA platforms for screening are in relatively early stages of evidence generation prior to adoption for routine use. Ongoing research on additional ways to identify patients at high risk is aimed at individualizing screening strategies for lung cancer, though none of these approaches have entered clinical practice. Thus, low-dose CT screening currently remains the best hope for reducing lung cancer mortality, in addition to improving tobacco control. A collective and concerted effort to increase the adoption of screening high-risk individuals should be an urgent priority for all of us.
Dr. Ramalingam is Professor of Hematology and Medical Oncology, the Roberto C. Goizueta Distinguished Chair for Cancer Research, Director of Medical Oncology, and Associate Vice-President for Cancer at the Woodruff Health Sciences Center of Emory University; and Executive Director of Winship Cancer Institute of Emory University, Atlanta.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO or The ASCO Post.
DISCLOSURE: Dr. Ramalingam has received institutional research support from Amgen, AstraZeneca, Bristol Myers Squibb, Merck, and Pfizer; and receives an honorarium from the American Cancer Society for his role as editor-in-chief of Cancer journal.
REFERENCES
1. National Lung Screening Trial Research Team: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365:395-409, 2011.
2. 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 382:503-513, 2020.
3. Toumazis I, de Nijs K, Cao P, et al: Cost-effectiveness evaluation of the 2021 U.S. Preventive Services Task Force recommendation for lung cancer screening. JAMA Oncol 7:1833-1842, 2021.
