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Lung Cancer Screening Study Spurs Optimism, Caution
    Posted: 11/21/2006
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National Lung Screening Trial (NLST)
NLST, the National Lung Screening Trial, is a research study sponsored by the National Cancer Institute for men and women at risk for lung cancer.

Adapted from the NCI Cancer Bulletin, vol. 3/no. 42, Oct. 31, 2006 (see the current issue).

Results from a large, observational study suggest that using spiral computed tomography (CT) to screen people at increased risk for lung cancer can detect the disease at an early stage and may increase the number of people who can be cured. Currently, the vast majority of lung cancer diagnoses aren't made until the disease is well advanced, and most of these patients die within five years.

Among participants in the study who received a diagnosis of lung cancer based on spiral CT screening and a resulting biopsy, 85 percent had stage I lung cancer (412 of 484), and a statistically estimated 10-year survival among these patients was 88 percent. Among stage I patients who underwent surgery within one month of diagnosis, the estimated 10-year survival rate was 92 percent. Very few patients in the study, however, have been followed for 10 years.

Some researchers and members of the lung cancer advocacy community have suggested that the results represent a long-awaited breakthrough; others believe that the study, because it wasn't a randomized trial with an unscreened control arm, falls short of answering some critical questions.

The study was published in the October 26, 2006, New England Journal of Medicine (see the journal abstract).

"The results are potentially exciting," said Dr. Gary Kelloff, a special advisor to NCI's Cancer Imaging Program in the Division of Cancer Treatment and Diagnosis. "Although it isn't possible to determine whether CT screening actually decreases mortality based on these results," he said, "they do provide valuable information."

That includes data to help determine the percentage of screened patients with suspicious lesions that will be confirmed as cancers and evaluate the role of various tests, such as bronchoscopies and PET scans, in confirming spiral CT results.

The study - the International Early Lung Cancer Action Project (I-ELCAP) - involved 31,567 people without symptoms indicative of lung cancer but who were considered to be at increased risk for the disease. All participants underwent baseline screenings using spiral CT between 1993 and 2005. Based on specific protocols dictated by the baseline screening results, 27,456 patients underwent additional "annual" spiral CT screenings. Initially launched with a focus on current and former smokers in the United States, I-ELCAP was eventually expanded to include some international sites and a broader at-risk group, including people with heavy exposure to secondhand smoke or workplace contaminants linked to lung cancer, such as asbestos.

"In a population at risk for lung cancer, such screening could prevent 80 percent of deaths from lung cancer," wrote the study's lead author, Dr. Claudia Henschke of Weill Medical College of Cornell University, and colleagues.

The results, said Dr. Denise Aberle, a professor of radiology at the UCLA Jonsson Comprehensive Cancer Center, "raise great hope for CT screening" for the early detection of lung cancer. Along with Dr. Christine Berg from NCI's Division of Cancer Prevention, Dr. Aberle is a co-principal investigator on the NCI-sponsored National Lung Screening Trial (NLST), which is comparing spiral CT and chest x-ray in a population of more than 50,000 to determine which offers a stronger mortality benefit when used as a screening tool in current and former smokers.

Dr. Aberle cautioned that the findings can't be construed as proof that spiral CT decreases the risk of death from lung cancer because the study provides only an estimate of survival based on a median of 3.3 years of follow-up. "Survival statistics are entirely appropriate when used to compare differences in treatment modalities in patients with the same stage of a condition who are randomized to different treatment arms," she explained. But using a survival endpoint to infer a screening benefit can be misleading, she continued. For example, by diagnosing disease in advance of symptoms, survival will increase even if there is no delay in death.

"These results punctuate the critical necessity of addressing the effectiveness of screening by determining mortality differences in a randomized trial," said Dr. Kelloff.

By Carmen Phillips

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