Grade: B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.
The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery.
Frequency of Service
Annual screening. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery.
Risk Factor Information
Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the National Lung Screening Trial (NLST). Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit. A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening.
Patient Population Under Consideration
The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years.
The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years.
Screening may not be appropriate for patients with substantial comorbid conditions, particularly those who are in the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years5. Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program.
Assessment of Risk
Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke.
Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit6. A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening.
Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer.
Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery.
Other Approaches to Prevention
Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions.
Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit lines provide telephone-based behavioral counseling and support to tobacco users who want to quit smoking. Counseling is provided by trained cessation specialists who follow standardized protocols that may include several sessions and are generally provided at no cost to users. The content has been adapted for specific populations and can be tailored for individual clients. Strong evidence shows that quit lines can expand the use of evidence-based tobacco cessation treatments in populations that may have limited access to treatment options.
Combination therapy with counseling and medications is more effective at increasing cessation rates than either component alone. The U.S. Food and Drug Administration has approved several forms of nicotine replacement therapy (gum, lozenge, transdermal patch, inhaler, and nasal spray), as well as bupropion and varenicline. More information on the treatment of tobacco dependence can be found in the U.S. Public Health Service Reference Guide “Treating Tobacco Use and Dependence: 2008 Update”. The National Cancer Institute has developed a patient and physician guide for shared decision making for lung cancer screening based on the NLST (available at https://www.cancer.gov/types/lung/research/nlststudyguidepatientsphysicians.pdf). This 1-page resource may be a useful communication tool for providers and patients.
In addition, the National Comprehensive Cancer Network has developed guidelines for the follow-up of lung nodules7. The appropriate follow-up and management of abnormalities found on LDCT scans are important given the high rates of false-positive results and the potential for harms. Lung cancer screening with LDCT should be implemented as part of a program of care, as outlined in the next section.
Implementation of a Lung Cancer Screening Program
Screening Eligibility, Screening Intervals, and Starting and Stopping Ages
The NLST, the largest RCT to date with more than 50,000 patients, enrolled participants aged 55 to 74 years at the time of randomization who had a tobacco use history of at least 30 pack-years and were current smokers or had quit within the past 15 years4. The USPSTF recommends extending the program used in the NLST through age 80 years. Screening should be discontinued once the person has not smoked for 15 years.
The NLST enrolled generally healthy persons, and the findings may not accurately reflect the balance of benefits and harms in those with comorbid conditions. The USPSTF recommends discontinuing screening if a person develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery.
Clinicians will encounter patients who are interested in screening but do not meet the criteria of high risk for lung cancer as described previously. The balance of benefits and harms of screening may be unfavorable in these lower-risk patients. Current evidence is lacking on the net benefit of expanding LDCT screening to include lower-risk patients. It is important that persons who are at lower risk for lung cancer be aware of the potential harms of screening. Future improvements in risk assessment tools will help clinicians better individualize patients' risks6.
Smoking Cessation Counseling
All persons enrolled in a screening program should receive smoking cessation interventions. To be consistent with the USPSTF recommendation on counseling and interventions to prevent tobacco use and tobacco-caused disease, persons who are referred to a lung cancer screening program through primary care should receive these interventions before referral. Because many persons may enter screening through pathways besides referral from primary care, the USPSTF encourages incorporating such interventions into the screening program.
Shared Decision Making
Shared decision making is important for persons within the population for whom screening is recommended. The benefit of screening varies with risk because persons who are at higher risk because of smoking history or other risk factors are more likely to benefit. Screening cannot prevent most lung cancer deaths, and smoking cessation remains essential. Lung cancer screening has substantial harms, most notably the risk for false-positive results and incidental findings that lead to a cascade of testing and treatment that may result in more harms, including the anxiety of living with a lesion that may be cancer. Overdiagnosis of lung cancer and the risks of radiation are real harms, although their magnitude is uncertain. The decision to begin screening should be the result of a thorough discussion of the possible benefits, limitations, and known and uncertain harms.
Standardization of LDCT Screening and Follow-Up of Abnormal Findings
The evidence for the effectiveness of screening for lung cancer with LDCT comes from RCTs done in large academic medical centers with expertise in using LDCT and diagnosing and managing abnormal lung lesions. Clinical settings that have high rates of diagnostic accuracy using LDCT, appropriate follow-up protocols for positive results, and clear criteria for doing invasive procedures are more likely to duplicate the results found in trials. The USPSTF supports adherence to quality standards for LDCT8 and establishing protocols to follow up abnormal results, such as those proposed by the National Comprehensive Cancer Network[[7<]]. A mechanism should be implemented to ensure adherence to these standards.
In the context of substantial uncertainty about how best to manage individual lesions, as well as the magnitude of some of the harms of screening, the USPSTF encourages the development of a registry to ensure that appropriate data are collected from screening programs to foster continuous improvement over time. The registry should also compile data on incidental findings and the testing and interventions that occur as a result of these findings.
Research Needs and Gaps
Smoking prevalence and lung cancer incidence are higher among socioeconomically disadvantaged populations, and more research is needed in these groups. In addition, if lung cancer screening with LDCT is implemented more widely in diverse community settings, it is important to evaluate whether variability in follow-up protocols of positive results on LDCT scans results in a different balance of benefits and harms than that observed in RCTs.
More research is also needed on the use of biomarkers to focus LDCT efforts in persons who are at highest risk for lung cancer. The role of biomarkers in accurately discriminating between benign and malignant nodules and in identifying more aggressive disease needs to be determined.
Update of Previous USPSTF Recommendation
This recommendation updates the 2004 recommendation, in which the USPSTF concluded that the evidence was insufficient to recommend for or against screening for lung cancer in asymptomatic persons with LDCT, chest radiography, sputum cytologic evaluation, or a combination of these tests. In the current recommendation, the USPSTF recommends annual screening for lung cancer with LDCT in persons who are at high risk based on age and cumulative tobacco smoke exposure.
Lung cancer is the third most common cancer and the leading cause of cancer death in the United States1. The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases2. Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers 2. The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer.
Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage non–small cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection.
Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer3.
Benefits of Detection and Early Treatment
Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancer–related deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population4. The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancer–related deaths, and smoking cessation remains essential.
Harms of Detection and Early Intervention and Treatment
The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures.
The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosed—that is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging.
The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures4.
Recommendations of OthersIn 2012, the American College of Chest Physicians, the American Society of Clinical Oncology, and the American Thoracic Society19 recommended screening for lung cancer with LDCT primarily on the basis of results from the NLST, using eligibility criteria that closely modeled those of the NLST (persons aged 55 to 74 years who have a ≥30 pack-year smoking history and currently smoke or have quit in the past 15 years). The recommendations also stipulated that screening should be offered only in clinical settings similar to those in the trial. The American Association for Thoracic Surgery20 recommends annual screening with LDCT in current and former smokers aged 55 to 79 years who have a 30 pack-year smoking history. It also recommends annual screening starting at age 50 to 79 years in patients who have a 20 pack-year smoking history and additional comorbid conditions that produce a cumulative risk for cancer of at least 5% over the next 5 years. Furthermore, it recommends annual screening in long-term cancer survivors aged 55 to 79 years. In 2013, the American Cancer Society21 also began recommending screening for lung cancer with LDCT in high-risk patients who are in relatively good health and meet the NLST criteria (persons aged 55 to 74 years who have a ≥30 pack-year smoking history and currently smoke or have quit in the past 15 years). It recommends against the use of chest radiography and strongly suggests that all adults who receive screening enter an organized screening program that has experience in LDCT. In addition, the National Comprehensive Cancer Network7 recommends LDCT screening in selected patients who are at high risk for lung cancer. High risk is defined as persons aged 55 to 74 years who have at least a 30 pack-year smoking history and, if a former smoker, 15 years or less since quitting or persons aged 50 years or older who have at least a 20 pack-year smoking history and 1 additional risk factor. It does not recommend lung cancer screening in persons who are at moderate risk (aged ≥50 years and ≥20 pack-year smoking history or secondhand smoke exposure but no additional lung cancer risk factors) or low risk (younger than 50 years or smoking history of <20 pack-years).