NLST Reveals Details of First Round of Lung Cancer Screening

Fran Lowry

May 22, 2013

More detailed information about the initial round of screening by the National Lung Screening Trial (NLST), which found that screening with low-dose computed tomography (CT) was superior to chest x-ray in reducing deaths from lung cancer, has been published in the New England Journal of Medicine .

The new results highlight the fact that, despite a high false-positive rate, few subsequent follow-up diagnostic procedures are performed. They also provide important information for clinicians and their patients who may be considering undergoing lung cancer screening with CT.

The NLST results were published "backwards," after the trial's external Data and Safety Monitoring Board (DSMB) advised that its positive findings be reported immediately, William C. Black, MD, Professor of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told Medscape Medical News.

"What's a little bit confusing about the NLST is that we didn't publish the results in the normal sequence. What usually happens with screening studies is that as they progress, the relevant information is released, so the first paper might be on the design of the study, and the next paper would relate what happened during the first screening, and the next on subsequent screenings. Finally, the last paper would reveal the final results as they relate to mortality," Dr. Black said.

"But in this case, the DSMB decided that the final results were too important to the public to be held up and that the final paper should come out first, so we published the final paper before the intermediate paper," he said. The NSLT was halted early when the benefit from CT screening became apparent, and the top-line results were published in 2011.

Intermediate Results Important to Know

The current study reports the "excruciating details" about what actually happened during the first screening round. "These are very relevant to clinicians and patients who are making a decision about screening," Dr. Black said.

In the NLST first screening round, 26,309 participants underwent low-dose CT, and 26,035 participants underwent chest radiography.

A total of 7191 participants (27.3%) in the low-dose CT group and 2387 (9.2%) in the chest x-ray group had a positive screening result.

One issue of concern with CT screening for lung cancer has been that a positive result would generate a high number of subsequent diagnostic tests, which could be invasive and costly to patients and to the healthcare system.

Dr. William C. Black

As reported by Medscape Medical News , the "relatively high" level of false-positive findings, which were 96.4% in the CT group and 94.5% in the radiography group, would be an undue cause of anxiety in patients and increase the need for additional invasive tests such as lung biopsy.

However, the results of the first screening round of the NLST show that the majority of participants with positive screening results in both modalities underwent only one subsequent diagnostic test.

"We didn't do nearly as many follow-up procedures as people would assume," Dr. Black said. "Most of the positive CT scans led to just one additional procedure, on average, and that is highly relevant when you are trying to figure out how much testing you are going to eventually use and how much it is going to cost."

Specifically, 90.4% of the CT group and 92.7% of the radiography group had at least 1 follow-up diagnostic procedure.

This included additional imaging in 81.1% of the CT group and 85.6% of the radiography group, and surgery in 4.2% of the CT group and 5.2% of the radiography group.

"In many of the previous analyses people have assumed that there would be 3 or 4 or 5 additional diagnostic tests for every positive screen, and this has ramifications for the cost effectiveness of screening," Dr. Black said.

The issue of cost has been another area of concern. Critics of the NSLT have calculated that the number needed to screen to prevent 1 death from lung cancer is 300.

As previously reported by Medscape Medical News , Michael Kohn, MD, MPP, from the University of California at San Francisco, noted that to prevent that 1 death from lung cancer, these 300 people would have to undergo 900 screening CT scans at a total cost of around $300,000 and about 85 additional positive screening tests, at around $425,000, for a total of about $725,000 for the screening alone.

Interim Results a Benchmark for Other Screening

The results from the initial that have now been published will also be a benchmark for other screening programs, Dr Black said.

"If patients and their clinicians are trying to decide whether or not to get screened, they can always refer to these results. They will let patients know what they can expect, what are the likely outcomes, not just in terms of dying of lung cancer, which is only going to happen to a small percentage of people who get screened, but also in terms of the false positives and what happens afterwards," Dr. Black said.

Finally, lung cancer was diagnosed in 292 participants (1.1%) in the CT group compared with 190 (0.7%) in the radiography group.

The sensitivity of low-dose CT was 93.8% and specificity was 73.4%, and for chest radiography, sensitivity was 73.5% and specificity was 91.3%.

Eligible People Should be Offered Screening

Dr. Black emphasized that people who meet the criteria for lung cancer screening should be offered the opportunity to undergo such screening. These include men and women between the ages of 55 and 74 years, who have a 30-pack-peryear history of smoking, who have quit smoking in the last 15 years, and who are medically fit for surgery.

Screening for such individuals has been recommended by many medical groups, including the National Comprehensive Cancer Network and the American Cancer Society.

"You shouldn't be pushed into screening. The doctor shouldn't say 'I recommend screening,' the doctor should say 'I recommend that you listen to your options about screening.' It's an important subtlety and it is a challenge because it requires coordination between the referring physician and

radiology department. This is something that we are in the process of trying to implement here at Dartmouth-Hitchcock Medical Center," Dr. Black said.

Dr. Black reports no relevant financial relationships.

N Engl J Med. 2013;368:1980-1991. Abstract

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