MORE DETAILS FOR LUNG CANCER SCREENING TRIAL

November 10, 2010 (Philadelphia, Pennsylvania) — Five days after the landmark National Lung Screening Trial (NLST) was stopped, an official from the trial provided more detail on the study results, which were presented here at the Ninth Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research

The NLST, which was started in 2002, was conducted at 33 American sites with a cohort of 53,454 former and current heavy smokers. It represents the first time that a screening test has been shown to provide a significant reduction in lung cancer mortality in a randomized controlled clinical trial.

Screening with low-dose helical computed tomography (CT) provided a statistically significant 20.3% reduction in lung cancer mortality, compared with screening with chest x-ray, according to Christine Berg, MD, coleader of the NLST and chief of the Early Detection Research Group in the Division of Cancer Prevention of the National Cancer Institute (NCI). Dr. Berg spoke at a specially convened session at the conference, arranged after the news that the trial was stopped broke last week.

"This is not a fluke; it is a solid answer," said Dr. Berg, referring to the reduction in mortality findings. There were 245.7 lung cancer deaths per 100,000 person-years for CT, and 308.3 for chest x-ray. In terms of total number of deaths, there were 354 in the CT group and 442 in the chest x-ray group.

Participants in the trial were randomized to undergo screening annually for 3 years with either CT or chest x-ray, and were then followed for another 5 years.

At this point in the data collection, Dr. Berg and her NLST colleagues do not have details on what treatments patients diagnosed with lung cancer subsequently underwent, or on the breakdown of the cancers by stage and other characteristics. That data and much more will be forthcoming, she said.

However, Dr. Berg did provide information on the screen positivity rate for the different screening methods. Over the 8-year period that elapsed in the trial, there were 3 screening rounds. Of the participants who were screened with CT, 24.2% had a positive finding over the 3 rounds, compared with 6.9% who were screened with chest x-ray. These percentages were in accordance with the published literature, said Dr. Berg.

Across the 3 rounds of screening, the percentage of positive test results that turned out to be false ranged from 95% to 98% for CT and from 93% to 96% for chest x-ray. "Almost everyone who had a positive test result had a false positive," said Dr. Berg. She pointed out that the verification process for a positive result varied, but it included invasive biopsy.

The NCI is not issuing any advice to clinicians on the basis of the NLST results, noted Dr. Berg. However, when the trial stoppage was first announced, she said that results will "have implications for the screening and management of lung cancer for many years to come."

In the meantime, patients and healthcare providers are advised to discuss lung screening jointly. "There are lots of variables in the decision making," said Dr. Berg.

No Details on Harms Yet

At this point in the data collection, the NLST investigators do not have details on the harms, such as invasive biopsies and anxiety over false positives, that often accompany lung cancer screening.

However, Dr. Berg said that, as part of the safety monitoring process in the NLST, harms were tabulated and evaluated at each of the 6 points of planned interim analyses. "There was real concern that we would have to stop the study early due to the side effects of invasive biopsy," she said. "But the harms were not the reason for ending the study," she added triumphantly.

Other forthcoming data include information from planned substudies of specimens that attempt to validate biomarkers; quality of life, including the impact of screening; and the effect of screening on smoking behavior.

Across the 3 rounds of screening, there was a 91.2% rate of compliance among the participants. "We had outstanding screening compliance," beamed Dr. Berg. "We are very proud of this."

Dr. Berg heartily thanked the participants in the study. They included a high percentage of college-educated men and women (31.5%) and a strong number of former smokers (51%), which Dr. Berg called the "healthy volunteer effect." Men (59%) predominated, as did those 55 to 59 years of age (42.8%); the age limit for the study was 74 years. More than 20% of the participants had a first-degree relative with lung cancer.

The researchers have disclosed no relevant financial relationships.

Ninth Annual American Association for Cancer Research (AACR) International Conference on Frontiers in Cancer Prevention Research. Presented November 9, 2010.