Health Letter, May 2014
By Elizabeth Barbehenn, Ph.D.
In December 2013, the U.S. Preventive Services Task Force (USPSTF) updated its recommendations relating to lung cancer screening. Lung cancer screening is one of several topics that the USPSTF examines periodically, but this is the first time the group has recommended screening for the early detection of the disease.
How the USPSTF works
The USPSTF is a volunteer panel working independently of the drug and medical device industries, which means that commercial influence is minimized. In preparing a recommendation, a group of health care experts, primarily doctors, critically examines the latest research in the medical literature on each topic covered by the USPSTF. They pick those studies that yielded the most valid data, analyze them and post their conclusions on the USPSTF website and in medical journals. The reviewers’ main interests are maintenance of health and quality of life. Their reviews provide basic information that primary care providers (for example, general internists, family physicians and pediatricians) can use in counseling and treating patients.
The USPSTF rates its recommendations using letter grades A through D, which denote, in descending order, the net benefit conferred by a medical intervention. For a recommendation to receive an A grade, there must be “high certainty that the net benefit [of a medical procedure or treatment] is substantial.” The December 2013 lung cancer screening guidelines received a B, a grade for which there must be “high certainty that the net benefit is moderate or … moderate certainty that the net benefit is moderate to substantial.”
Groundbreaking lung cancer screening recommendations
Besides age and smoking history (which are the primary risk factors), exposure to secondhand smoke, indoor cooking fumes, radon, asbestos, arsenic, chromium, and coal tar; family history; and pulmonary disease can also increase a person’s risk of lung cancer. (Readers who smoke can find a simple tool for assessing lung cancer risk on the Memorial Sloan Kettering Cancer Center’s website.) Since lung cancer is the third most common cancer in the U.S., as well as the leading cause of cancer-related death, early screening using a test with low-dose radiation has the potential to significantly reduce the number of deaths from the disease.
The USPSTF found and analyzed four randomized controlled trials that tested screening patients with personal smoking exposure with low-dose computed tomography (LDCT), a type of CT scan that exposes patients to lower doses of X-ray radiation than standard CT scans. However, only one of these trials was both very large and carried out using the highest-quality standards: the National Lung Screening Trial (NLST), which was funded by the National Cancer Institute, a part of the National Institutes of Health. The other three were much smaller, and the task force determined that the trials’ small size, short duration, and low-quality data made the trials insufficient as a basis for making recommendations. As a result, the data that form the basis for the current guidelines are primarily derived from the NLST.
Before the results of the NLST were published in 2011, no organization had recommended screening for lung cancer. Given that the trial showed that screening is beneficial, the USPSTF has used that study as the basis of the following recommendation supporting screening in certain individuals:
The USPSTF recommends annual screening for lung cancer with 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.
Other organizations have joined in recommending LDCT screening; these include the American College of Chest Physicians, the American Society of Clinical Oncology, the American Thoracic Society, the American Lung Association, the National Comprehensive Cancer Network and the American Cancer Society. However, their recommendations have a caveat that “screening should be offered only in clinical settings similar to those in the trial.” In particular, the CT equipment used for screening should conform to the standards of that used in the NLST, and those using it must have the qualifications needed to interpret the results correctly.
Results of the National Lung Screening Trial
The NLST randomized 53,454 people into two groups. One group received three annual screenings using LDCT (26,722 subjects) and the other received three annual screenings with standard chest X-rays (26,732 subjects). The subjects ranged from age 55 to 74 and had to be either a current smoker or someone who had quit within the past 15 years. They also had to have a smoking history of at least 30 pack-years (calculated by multiplying the average number of packs of cigarettes smoked per day by the number of years the person had smoked; for example, an individual who smoked an average of two packs daily for 15 years would have a 30-pack-year history of smoking).
Participants were followed for an average of six and a half years after entering the study. The primary endpoint of the trial was death from lung cancer, with secondary endpoints being death from any cause and lung cancer diagnosis.
The NLST found a 20 percent relative reduction in the risk of death from lung cancer. The “absolute” reduction, the actual percentage difference in lung cancer mortality between those undergoing at least one LDCT and those given at least one chest X-ray, was approximately 0.3 percentage points (1.62 percent in the chest X-ray group versus 1.31 percent in the LDCT group). In practice, this means that about 320 people would need to be screened annually for three years to prevent one death from lung cancer. The study also demonstrated that LDCT screening led to 6.7 percent fewer deaths from any cause compared with X-ray radiography.
Harms from screening
The benefits of LDCT screening must be weighed against the risk of harm for patients. For example, radiation exposure from LDCT, although at a low dose, slightly increases the risk of developing cancer. The actual exposure to radiation with LDCT in the NLST was 1.6 millisieverts (mSv) per scan. While the radiation exposure with each chest X-ray was not reported, the USPSTF reviewers noted that a standard diagnostic chest X-ray results in an exposure of approximately 0.02 mSv. (A millisievert is a measure of the dose of radiation based on its biological effects.) By comparison, the annual background radiation exposure in the U.S. averages 2.4 mSv, and the exposure to radiation from mammograms is estimated at 0.7 mSv. Because radiation exposure is cumulative and its harms often not evident for many years after exposure, the task force recommends starting annual LDCT screening at age 55. Modeling studies suggest that beginning screening before that age would confer more harms than benefits because of the rarity of cancer in younger populations (even smokers).
The most significant risks from LDCT are from false-positive results, overdiagnosis (finding lung cancers that would not eventually have killed the patient, such as a small, slow-growing cancer in an elderly patient), and the discovery of incidental findings (such as emphysema and calcium deposits in the coronary arteries), which can lead to additional unnecessary tests that can cause harm and psychological distress. Over the three rounds of screenings in the NLST, 24 percent of LDCT test results were positive, and of these, 96 percent were false positives. Most positive results led to additional investigations, and 50 percent of those required additional chest CT imaging (and therefore additional radiation exposure), 2.5 percent requiring additional invasive diagnostic procedures and 1.9 percent requiring a biopsy. None of the studies reviewed by the USPSTF reported on how incidental findings were handled, once discovered. Although no studies reported significant increases in anxiety or distress in patients who received positive results, this is inherently difficult to quantify, and assessment of the long-term consequences of screening was limited due to the short duration of the trials.
Before a particular patient is offered screening with LDCT, there should be a detailed discussion between the patient and health care provider of the benefits and risks of taking into account the age and overall health of the patient. Of note, modeling suggested that screening beyond age 80 would no longer offer benefits that outweighed the risks.
Catching lung cancer early
Usually by the time there are symptoms of lung cancer, it is too late for treatment. Almost 90 percent of diagnosed patients die of the disease. The hope now is that those who meet the characteristics of the NLST subjects — and those for whom the benefits outweigh the risks — can identify lung cancer in the early stages, when treatment is still possible.
Since approximately 85 percent of U.S. lung cancer cases are due to smoking, the most important thing that can be done to reduce the incidence of lung cancer (and other cancers triggered by cigarette use, as well as lung and heart diseases) is to stop smoking. The Centers for Disease Control and Prevention has material to help smokers quit (http://www.cdc.gov/tobacco/campaign/tips/). Worst Pills, Best Pills News, another publication from Public Citizen’s Health Research Group, also contains strategies for quitting smoking.
 Moyer VA on behalf of the USPSTF. Screening for Lung Cancer. http://www.uspreventiveservicestaskforce.org/uspstf/uspslung.htm.
 U.S. Preventive Services Task Force. USPSTF A-Z Topic Guide. http://www.uspreventiveservicestaskforce.org/uspstopics.htm.
 U.S. Preventive Services Task Force. Grade Definitions. http://www.uspreventiveservicestaskforce.org/uspstf/grades.htm. Accessed April 21, 2014.
 Moyer VA on behalf of the USPSTF. Screening for Lung Cancer. https://www.citizen.org/sites/default/files/lungcanes105.pdf
 Memorial Sloan Kettering Cancer Center. Lung Cancer Screening Decision Tool. http://nomograms.mskcc.org/Lung/Screening.aspx. Accessed April 8, 2014.
 American Cancer Society. What are the key statistics about lung cancer? http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-key-statistics. Accessed April 22, 2014.
 Memorial Sloan Kettering Cancer Center. http://www.mskcc.org/cancer-care/adult/lung/screening-guidelines-lung. Accessed April 21, 2014.
 Humphrey L, Deffebach M, Pappas M, Baumann C, Artis K, Priest Mitchell J, Zakher B, Fu R, Slatore C. Screening for Lung Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation. Evidence Synthesis No. 105. AHRQ Publication No. 13-05188-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2013. P. 42. https://www.citizen.org/sites/default/files/lungcanes105.pdf. Accessed April 22, 2014.
 Centers for Disease Control and Prevention. Smoking Cessation. http://www.cdc.gov/primarycare/materials/smokingcessation/
 Smoking Cessation: What Works and What Doesn’t. Worst Pills, Best Pills News. September 2012. http://www.worstpills.org/member/newsletter.cfm?n_id=813