Individuals who undergo lung cancer screening with low-dose computed tomography (LDCT) are at high risk for false-positive results, according to the results of a study presented here at the American Society of Clinical Oncology 45th Annual Meeting.
The risk for a false-positive result was 21% after undergoing 1 LDCT scan, and 33% after undergoing a second LDCT. The false-positive risk, however, was lower for screening with chest x-ray. People undergoing chest x-ray screening had a false-positive risk of 9% after 1 screen and of 15% after 2 screens.
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| Dr. Jennifer M. Croswell (Photo courtesy of ASCO) |
"The risks of false-positive lung cancer screening tests are substantial after just 2 exams," said lead author Jennifer M. Croswell, MD, acting director of the National Institutes of Health Office of Medical Applications of Research in Bethesda, Maryland. "There were only 2 rounds of screening, so this is a conservative risk of annual screening programs."
When evaluating whether or not lung cancer screening can reduce related mortality, several studies have reported a high incidence of noncalcified nodules in people who were screened. This study, however, is the first to quantify the cumulative risk for a false-positive result.
"We have seen an increasing promotion of LDCT screening to consumers, and the advertisements are saying that they can alleviate anxiety among smokers and former smokers," said Dr. Croswell, "but we don't have any real information about the efficacy of screening in early diagnosis."
Julie Gralow, MD, associate professor of medical oncology at the University of Washington in Seattle, pointed out that it is necessary to look at both the benefits and harms. "The gold standard in cancer screening should be an improvement in survival, but we haven't seen that yet in any screening for lung cancer," said Dr. Gralow, who moderated the press briefing in which the data were highlighted.
"However, depending on the benefit, some improvement in morbidity, such as finding it earlier so that you can have a smaller surgery or avoid chemotherapy — that counts too," she said.
But the gold standard is fewer deaths because it is found earlier, she emphasized. "Actually, very few screening tests have met that standard," she said. Mammography is 1 example in which multiple randomized studies have shown a reduction in death.
High Rate of Diagnostic Follow-Up
This study was a feasibility trial for the ongoing National Lung Screening Trial (NLST), a definitive randomized controlled trial comparing LDCT and single-view chest x-ray conducted at 6 NLST centers. The NLST itself was launched in 2002, has enrolled nearly 50,000 participants, is slated to collect and analyze data for 8 years, and will examine the risks and benefits of CT scans and chest X-rays. The goal of the NLST is to determine if either test is better at reducing lung-cancer-related mortality.
"We estimated the cumulative risk of receiving 1 false-positive test and other potential burdens associated with false-positive screening tests," explained Dr. Croswell.
The feasibility study looked at 3190 current or former smokers who were offered a baseline LDCT (n = 1610) or chest x-ray (n = 1580) and 1 repeat annual screen. The participants were followed for 1 year after their initial screening.
A positive screen was defined as any noncalcified nodule of 4 mm or more or any other radiographic finding deemed suspicious for cancer. A false-positive screen was defined as a completed negative work-up or a follow-up of 12 months or more without a cancer diagnosis.
There were a total of 38 screen-detected true cancers and 504 false positives. Of the people with false positives, 61% had at least 1 other type of screening exam, and 6.6% underwent some type of invasive procedure, Dr. Croswell pointed out.
Diagnostic Follow-Up of False-Positive Findings
| Procedure | Number of LDCT Scans | False-Positive LDCT Scans (%) | Number of Chest X-rays | False-Positive Chest X-rays (%) |
| Imaging exams | 307 | 61 | 110 | 51 |
| Minimally invasive procedure | 25 | 5.0 | 6 | 2.8 |
| Moderately invasive procedure | 20 | 4.0 | 7 | 3.2 |
| Major surgical procedure | 8 | 1.6 | 4 | 1.9 |
| Any invasive procedure | 33 | 6.6 | 9 | 4.2 |
On multivariable analysis, a higher risk for a false-positive result with LDCT was associated with increased age (>64 years), and being a current smoker vs a former smoker trended toward higher false-positive odds (odds ratio, 1.22; 95% confidence interval, 0.95 - 1.56).
"Given the high burden of false positives with LDCT for lung cancer screening, careful investigation of economic, psychosocial, and physical burdens is warranted," she said.
James Marshall, PhD, senior vice president for Cancer Prevention and Population Sciences, Roswell Park Cancer Institute in Buffalo, New York, agreed that advertising LDCT as a lung cancer screening tool to the public is problematic. "Some people will get the idea that they can go ahead with their 2 packs of Camels a day, and we can go ahead and catch it early, like polyps," said Dr. Marshall, who served as a discussant of the paper.
But he questioned the actual burden that receiving a false positive placed on the study participants. "These are modest burdens. Were they put at great risk by LDCT? I'm not sure."
The burden of false positives appears to be relatively modest, and consumers of screening services need to be fully informed, said Dr. Marshall.
More Emphasis Needed for Smoking Prevention/Cessation
Dr. Gralow feels it would be prudent to wait for the results from the National Lung Screening trial to see if there is a reduction in mortality. But the larger issue itself is tobacco use, she pointed out.
"Recent statistics suggest that 20% of adults in the [United States] smoke," she said, and lung cancer is just 1 of many risks that have been associated with smoking. "We should be putting efforts into prevention and cessation of smoking."
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