Pulmonary Perspectives®

Are we there yet? Lung cancer screening – current landscape


Lung cancer is the second-most common cancer and one of the leading causes of mortality in the United States among both men and women. It accounts for almost 25% of all cancer deaths, and every year more people die of lung cancer than colon, breast, and prostate cancers combined. The American Cancer Society estimates about 235,760 new lung cancer cases and about 131,880 deaths from lung cancer in 2021.

Dr. Justin Stowell, Mayo Clinic, Rochester, Minn.

Dr. Justin Stowell

Smoking and increasing age are the two most important risk factors for lung cancer. Lung cancer has a higher incidence among Black men than White men, and among White women compared with Black women. These differences are likely related to smoking exposure. Early diagnosis of lung cancer can improve survival, and hence screening for lung cancer in high-risk populations is desired. Among the available cancer screening tests, radiology is primarily involved in breast and lung cancer screening (LCS). In 2011, the National Lung Screening Trial (NLST) showed a benefit of annual low- dose chest CT for LCS, with about 20% reduction in lung cancer-related mortality in high-risk participants compared with chest radiographs (Aberle DR, et al. N Engl J Med. 2011 Aug 4;365[5]:395-409).

Dr. Sushilkumar Sonavane, Mayo Clinic, Rochester, Minn.

Dr. Sushilkumar Sonavane

In 2013, the United States Preventative Services Task Force (USPSTF) issued a grade B recommendation in support of annual LCS by CT scan for individuals between the ages of 55-80 years with smoking history of 30 or more pack-years who are current smokers or had quit smoking in the last 15 years. Many other professional societies followed with their own recommendations with minor differences. In 2015, after the Centers for Medicare and Medicaid (CMS) decision of coverage, millions of Americans at high risk became eligible for CT LCS with no copayment or cost sharing by the patient.

The results from the European NELSON trial in 2020 augmented the NLST data showing a 24% decrease in lung cancer mortality. Nodules were measured using volume and volume doubling time rather than bidimensional axial measurements, reducing the false-positive results to 56% compared with 96% in NLST. With growing evidence of the benefits from LCS, recently USPSTF summarized with moderate certainty that annual LCS CT has moderate net benefit in people at high risk for lung cancer based on age, cumulative smoking exposure, and years since quitting smoking.

In March 2021, USPSTF has issued new recommendations with a decrease in the screening age to 50 years, and the smoking history that triggers screening to 20 pack-years (Screening for Lung Cancer: USPSTF Statement. JAMA. 2021 Mar 9;325[10]:962-70. doi: 10.1001/jama.2021.1117). These expanded eligibility criteria are projected to double the number of eligible candidates of LCS in the United States, reduce annual deaths by up to 50%, and benefit minorities and women. By widening the screening criteria to include younger individuals and who have smoked less tobacco, more lives will be saved by early detection of lung cancer. Since the NLST and NELSON trials enrolled relatively healthy people, USPSTF recommends discontinuation of screening once the person has not smoked for 15 years and in persons with any health problem that severely limits the life expectancy or the ability or willingness to undergo surgery. All screening programs must incorporate smoking cessation counseling and interventions for all the enrolled individuals who are current smokers. The USPSTF has also made recommendations on interventions to prevent the initiation of tobacco use in children and adolescents, including counseling and pharmacotherapy.

The decision to undergo LCS is inherently complex, and primary care and pulmonary physicians play a pivotal role by identifying the eligible patients, participating in shared decision-making (SDM), offering smoking cessation, ordering the CT, and managing follow-up. SDM between the patient and clinician includes a discussion of the benefits, risks, limitations, and potential harms of screening. The potential harms of screening include overdiagnosis, false-positive results, incidental findings, and the anxiety leading to further testing or follow-up. The risk of radiation exposure is markedly reduced using low-dose CT protocols compared with conventional chest CT. SDM visit also emphasizes the importance of adherence to annual screening and patient willingness and ability to undergo treatment if required. In 2015, CMS approved the addition of LCS counseling and SDM visits that are performed by physicians or qualified nonphysician practitioners (physician assistant, nurse practitioner, or clinical nurse specialist). Studies have shown that these visits improve the screening uptake rate.

To minimize the variations in the evaluation and management of screen-detected lung nodules, the American College of Radiology (ACR) developed the Lung Imaging Reporting and Data System (Lung-RADS) to be used in LCS CT reports. The latest revised version 1.1 of Lung-RADS was released in 2019. The Lung-RADS defines a positive screen and provides accepted nodule care pathways depending on their size, characteristics, and additional findings, and has been shown to decrease the rate of false-positive results in LCS. To be a designated LCS center, the department of radiology must comply with stringent requirements of technical and facility specification, with radiologist qualification, and with reporting and communication as outlined by the ACR. In addition, participation in the National LCS Registry to meet CMS quality reporting requirements is mandatory for facilities to be reimbursed by CMS.

After more than 10 years since its inception, the participation in LCS has been low. Out of 8 million eligible Americans, less than 4% have been screened (American Cancer Society, NSCLC statistics 2020) compared with breast cancer (up to 75%) (Breast Cancer: Facts and Figures 2019-2020). Adherence to annual LCS between 1-3 years in the US is only about 55%. Non-White patients, current smokers, those aged 65-73 years, and those who lack a college education are most likely to be less adherent to follow-up screening. There are hurdles at multiple levels including but not limited to patient and physician awareness, patient enrollment, adherence, follow-up, and insurance coverage. Expanding the reach of LCS in socially and economically disadvantaged, racial and ethnic minorities, and women has been even more challenging.

Significant differences exist in opinions and practices between primary care physicians (PCPs) and pulmonologists regarding referral for LCS and its benefits. Educational intervention at the PCP level aimed at awareness of USPSTF guidelines may improve utilization and adherence to screening. Increasing lung cancer awareness by community outreach programs, promoting related discussions, and providing information about available screening services to eligible population is crucial to derive the maximum benefits of LCS. Presenting decision aid tools on smartphones and online has shown to improve the participants’ knowledge of LCS, to reduce the decisional conflict, and to be acceptable among patients and providers. Implementation strategies such as involving a nonphysician provider, keeping the training on these tools brief and simple, and providing it to participants prior to the clinical encounter might be effective. Electronic medical record systems can be optimized to simplify the ordering procedure to ensure the eligibility criteria are met, to provide results to the physicians, and to direct further management of positive screen results. Most LCS programs have a nonphysician program coordinator to convey the results to the patients and physician, to send out reminders for scheduled follow up appointment, and to maintain the registry data.

In the future, newer imaging technology, and molecular biomarkers or other technologies to differentiate lung cancer more accurately from a benign nodule, and to determine its aggressiveness, will supplement the LCS to decrease false positive results. Better risk prediction models will influence screening eligibility and prognostication in a screen-detected cancer. Robust data collection from ongoing clinical programs will determine if the benefits of LCS seen in clinical trials are comparable when applied to diverse community settings.

Dr. Stowell and Dr. Sonavane are with the Mayo Clinic in Jacksonville, Fla.

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