Landmark Trial Shows Potential of Low-Dose Computed Tomography for Lung Cancer Screening
By Joe Munch
The preliminary results of the National Lung Screening Trial (NLST) show that lung cancer screening can be beneficial to people at high risk for the disease. However, questions remain concerning who should be screened and how often.
Specifically, the NLST found that over the course of the study, low-dose helical computed tomography (CT) offered a lung cancer–specific mortality reduction of 20.3% and an all-cause mortality reduction of 6.9% compared with standard chest radiography in people considered to be at high risk for lung cancer. The clinical practice implications of these and other findings from the trial may not be known for some time, however.
Reginald Munden, M.D., a professor in the Department of Diagnostic Radiology at The University of Texas MD Anderson Cancer Center, was the study’s principal investigator at the institution.
“The trial provided a very rich repository of data, probably more data than we will ever be able to fully understand,” Dr. Munden said. “Even though we are in the very early phases of understanding lung cancer screening, this trial is still the most significant thing that’s ever happened in lung cancer because now we can detect a cancer early enough to cure somebody.”
Still, Dr. Munden said, “The trial may have raised more questions than it answered.”
Largest study of its kind
The NLST was a prospective randomized trial and the largest lung cancer screening trial to date, involving more than 30 institutions across the United States. When the NLST launched in 2002, it aimed to include 50,000 patients; more than 53,000 were enrolled within 18 months. Eligible participants were current or former smokers 55–74 years of age who had a smoking history of at least 30 pack-years and no history of lung cancer. (One pack-year is equivalent to 20 cigarettes smoked per day for a year.)
Participants were imaged at enrollment and annually for 2 years. Those in the study group underwent low-dose chest CT, while those in the control group underwent conventional chest radiography. In randomized trials, the control group typically gets the standard of care, but the standard of care in this case, Dr. Munden said, was to do no imaging. Chest radiography was performed in the control group because NLST researchers feared that not doing any imaging would cause some participants to drop out of the study. Although earlier trials had yielded no statistically significant data supporting the use of chest radiography for lung cancer screening, some researchers had interpreted those findings differently, saying that the benefit of screening with chest radiography, though small, was existent. Those researchers argued that radiographic screening of the control group could therefore obscure the true benefit of CT in the study group.
Even so, Dr. Munden said, “It’s probably better that we did chest radiographs in the control group because even if it has a benefit, we’ve far exceeded that with CT.”
Who should be screened?
The U.S. Food and Drug Administration has not approved CT for lung cancer screening. Although the NLST’s findings may change that, in the meantime, teams of researchers are scrambling to determine which populations are most likely to benefit from the screening protocol.
“It’s extremely important that we screen people who are truly at risk for lung cancer,” Dr. Munden said.
Yet opinions of what constitutes high risk can vary widely. Right now, the question of who should be screened—other than those meeting the criteria of the NLST—is open for interpretation.
For example, “We know that there’s a huge group of head and neck cancer survivors—long-term survivors—who smoke. They are at a much higher risk of developing lung cancer than a smoker who has never had head and neck cancer,” Dr. Munden said. “That kind of person is someone I’d consider at high risk and would probably screen, but that’s not the kind of person we screened in the trial.”
Most researchers, Dr. Munden said, agree that individuals at high risk are those who have had heavy exposure to smoking and have lived long enough to develop lung cancer. Many researchers believe such a person is one who has a smoking history of 20 or more pack-years and is at least 50 years of age.
“Part of the issue is who not to screen as much as it is who to screen,” Dr. Munden said. “What we do not want to do is screen a 40-year-old woman who has a casual or minimal smoking history, because the benefit does not justify the risk.”
Chief among the screening procedure’s risks is ionizing radiation exposure, which can increase a patient’s lifetime risk of developing cancer. (The risk is higher in women because breast tissue, which is highly radiosensitive, also receives the most radiation from chest CT.) In the United States, the average annual exposure to ionizing radiation is about 3.1 mSv—half from natural sources and half from manmade sources, mostly diagnostic medical procedures. Diagnostic CT delivers up to 8 mSv. Low-dose CT, which was used in the NLST, delivers about 1.5 mSv. By comparison, a series of conventional chest radiographs delivers about 0.06 mSv. In older patients with a long history of smoking—such as those included in the NLST—the benefit of identifying a cancer at a treatable stage is more likely to outweigh the risk a small dose of ionizing radiation conveys.
In the absence of established screening guidelines, Dr. Munden said, physicians should rely on their experience and judgment in determining which patients are at high risk. “If you think a patient of yours has a significant risk of lung cancer based on some criteria that you’re comfortable with, I encourage you to get the patient screened,” he said.
In addition to undergoing CT or chest radiography, more than 10,000 trial participants—including those enrolled at MD Anderson—submitted sputum, blood, and urine specimens as part of the NLST’s biomarker study. The goal of the biomarker study is to identify genetic differences between trial participants who developed lung cancer and trial participants who did not develop lung cancer. Although it is not yet under way, according to Dr. Munden, the biomarker study is integral to identifying the best candidates for lung cancer screening.
“To me, this will be the most important part of the trial,” Dr. Munden said. “If you think about who should be screened for lung cancer, the answer’s probably in a blood test that tells us this person has the genetic predisposition to develop lung cancer. That’s the person we’ll screen.” However, Dr. Munden added, “We’re not anywhere close to being there.”
Lung cancer screening at MD Anderson
Dr. Munden and other faculty members—including Therese Bevers, M.D., a professor in the Department of Clinical Cancer Prevention; Stephen Swisher, M.D., chair of and a professor in the Department of Thoracic and Cardiovascular Surgery; and George Eapen, M.D., an associate professor in the Department of Pulmonary Medicine—are in the initial phases of establishing a lung cancer screening program at MD Anderson.
“We’re not just going to screen people,” Dr. Munden said. “We want to collect data that can help answer some questions down the road, so the program will have a clinical research component as well.” He added that a smoking cessation program is offered as an integral part of the screening program.
The group has initiated the screening program at MD Anderson’s main campus in the Texas Medical Center and plans to eventually implement the program at the institution’s regional care centers. People aged 50 years and older with a smoking history of at least 20 pack-years are eligible. A physician referral is not required, Dr. Munden said, but patients must have a doctor who can be contacted in the event something is found. Physicians are encouraged to refer patients they believe to be at a high risk of developing lung cancer.
Dr. Munden said that the initial results of the NLST are expected to be published this summer. In the meantime—and for some time hereafter—NLST researchers will continue to grapple with the multitude of questions raised by the trial’s findings.
“The bigger questions now are, who do we screen and when do we screen them? And how often do we screen them?” Dr. Munden said. “As we discover answers to these and other questions, lung cancer screening programs will help us improve people’s health and save lives.”
MD Anderson Lung Cancer Screening Program
For more information, call Dr. Reginald Munden at 713-792-3492.
Other articles in OncoLog, July 2011 issue: