November 3, 2011 (Boston, Massachusetts) — Results from the National Lung Screening Trial (NLST) provided provocative evidence that screening with low-dose helical computed tomography (CT) could reduce lung cancer mortality by more than 20%.

This landmark study showed that, compared with screening with chest x-rays, CT screening could significantly reduce deaths from lung cancer in a population of heavy smokers; however, a number of questions remain unanswered.

A special session, held here at the Tenth Annual American Association for Cancer Research (AACR) International Conference on Frontiers in Cancer Prevention Research, followed-up on the NLST and addressed the next steps.

There are a number unresolved issues with respect to CT screening for lung cancer, explained John L. Field, MA, PhD, BDS, FRCPath, who chaired the session.

"These need to be resolved before a national screening program can be implemented in any country," he said. Dr. Field is director of research at the Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, United Kingdom.

"These issues include defining optimal risk populations, cost effectiveness, and harmonization of CT screening protocols; the whole area of work-up techniques is still an open question," he noted. In addition, "optimal surgical management...screening intervals, and screening rounds" must still be defined for Europe.

Defining Parameters

As previously reported by Medscape Medical News, the NLST is the first randomized controlled trial of lung cancer screening to show a significant mortality benefit. The study was halted after 8 years, when the results clearly showed the benefit of CT screening. The findings have potential implications for the screening and management of lung cancer.

At that time, Michael Unger, MD, FACP, FCCP, director of the pulmonary cancer detection and prevention program at the Fox Chase Cancer Center in Philadelphia, Pennsylvania, said that "screening is not a test. It is a process involving correct diagnosis and most appropriate management."

"The most important question is: "Who is really at high risk?" he told Medscape Medical News."Other questions include when and how long we should study the subjects." Then there is the issue of false positives, where the CT screen picks up lesions that are not lung cancer, he explained. Previous studies have reported high rates of false positives with CT screening for lung cancer, ranging from 25% to 70%."

Christine Berg, MD, chief of the Early Detection Research Group at the National Cancer Institute's Division of Cancer Prevention, and codirector of the NLST, agreed that although lung cancer screening has a lot of promise, "there is a lot of work to be done before it is rolled out into cancer screening programs around the world."

"The National Lung Screening Trial was designed to answer one question only: Does screening with low-dose helical CT lower lung-cancer-specific mortality," she said during the AACR session. "We designed the study to have the shortest time period, the fewest number of participants, the fewest number of screens, and the lowest cost to answer that question."

There are numerous questions that need to be answered, she said, but those will have to be the domain of future research.

Screening Offered

Despite remaining questions and the need for further validation, some centers in the United States are already offering lung cancer screening. At the World Conference on Lung Cancer held earlier this year, Roy Herbst, MD, from the Yale Cancer Center in New Haven, Connecticut, noted that his center is offering CT screening for lung cancer.

"We have made the decision to offer such screening," he said during the conference, and so have several other centers, including the University of Texas M.D. Anderson Cancer Center in Houston.

The National Comprehensive Cancer Network (NCCN) has just come out in favor of lung screening in individuals who are at high risk in a newly published set of guidelines — the first from any professional society to address the issue of lung cancer screening.

Trials Ongoing

There are a number of ongoing trials in Europe that have reported preliminary results, said Dr. Field. The largest is the Dutch–Belgian NELSON (Nederlands-Leuvens Longkanker Screenings Onderzoek) trial, but other trials are being conducted in France, Germany, and Italy.

In addition, "the United Kingdom has just launched its pilot study," said Dr. Field. "We need to improve control of lung cancer in the United Kingdom because, unfortunately, we have one of the highest instances in Europe. It is a major public health problem."

That British trial will randomize 4000 individuals who have at least a 5% risk of developing lung cancer over 5 years, as predicted by the Liverpool lung project risk prediction model. If the pilot demonstrates that a trial is feasible, they will move to a full randomized controlled trial, explained Dr. Field.

"The study is designed for 32,000 subjects," he said. "There will be 1 round of screening in the intervention arm, and then a 10-year follow-up will give us 90% power for a 25% to 30% mortality reduction."

Need for Guidelines

Dr. Field noted that after a workshop held just before the World Lung Cancer Congress, a position paper was developed that has now been accepted for publication. "One of the main points to come from this is that we have now set up a strategic CT advisory committee," he said. "What we're involved in at this moment is engaging societies and organizations, at an international level, that are stakeholders in CT screening; therefore, we can develop future recommendations and guidelines in a unified way."

A statement released in July by the International Association for the Study of Lung Cancer notes that screening for lung cancer "can be improved through ongoing research, which is essential, as the resolution of spiral CT imaging continues to improve, and this can drive further progress with safer and more effective surgical management. Additional research will define risk profiles of individuals who would benefit most from screening."

They point out in their statement that "a crucial factor required in the implementation of future national screening programs will be the participation of multidisciplinary groups of trained specialists in the relevant aspects of early lung cancer."

Tenth Annual American Association for Cancer Research (AACR) International Conference on Frontiers in Cancer Prevention Research. Special session 3. Presented October 23, 2011.

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