In November 2010, the National Cancer Institute (NCI) ended one of the largest clinical trials ever conducted, the National Lung Screening Trial (NLST), after annual CT screenings of heavy smokers showed a 20 percent reduction in mortality compared with conventional x-ray screening. One year later, dozens of U.S. cancer centers have begun to offer screening for the nation's deadliest cancer, but few Americans are lining up for a chance at early detection.
NCI's decision to bring the NLST to an early close after screening 53,000 smokers signaled a major victory in the fight against lung cancer. Despite decades of decline in the number of U.S. smokers, lung cancer continues to kill 160,000 Americans each year. Notwithstanding NCI's abrupt action in response to CT's survival benefit, medical societies have yet to recommend the exam. As secondary analyses of the NLST trickle in, Medicare and private payors have yet to reimburse for CT screening, leaving lung cancer screening on the table at many centers, but patients off the gantry.
"The NLST results will have a significant impact on public health policy," Denise R. Aberle, MD, principal investigator for the NLST and vice chair of research for radiological sciences at University of California, Los Angeles (UCLA), predicted when early results were released in November 2010.
By the time Aberle and colleagues published a more comprehensive look at the NLST results in the Aug. 4 issue of The New England Journal of Medicine, cancer centers had already begun preparing, publicizing and, in many cases, implementing screening programs for high-risk patients.
"We had been talking for several months about implementing lung cancer screening. By the time the final report was published, we had already developed our lung CT program and were ready to begin screening," explains Stanton L. Gerson, MD, director of University Hospitals Seidman Cancer Center in Cleveland. University Hospitals' radiologists review approximately 100 low-dose lung CT screenings per month.
University Hospitals is not alone. At UCLA, lung CT screening has been available to the public for more than two years. "Even before the NLST results came out, there was a demand among patients to get screening CTs," points out Jay M. Lee, MD, surgical director of thoracic oncology at UCLA and head of the university's Lung Screening Clinic.
Public demand for lung CT has been the foundation of screening thus far. Without insurance coverage, cancer centers have instituted screening programs partly as services to their communities. "Lung screening can be a major contribution to fighting lung cancer, and we should be participating in anything that's helping reduce the number of people dying from cancer. But it's not going to be a margin-producing project," offers Reginald F. Munden, MD, MBA, head of the lung CT screening program at MD Anderson Cancer Center in Houston. Still, patient demand, or perhaps the ability to pay out of pocket, for CT screening is weak.
"We haven't seen a groundswell of people demanding screening," affirms Ella A. Kazerooni, MD, MS, head of the University of Michigan Comprehensive Cancer Center's lung screening program in Ann Arbor. Across the board, cost is the chief impediment to participation. At roughly $300 to $400 out-of-pocket per exam, the number of smokers getting screened remains low.
Too many false positives
Widespread lung screening hinges on reimbursement, which, experts say, will not come until Aberle and her team publishes a cost-effectiveness analysis of lung CT screening. At the root of the uncertainty is a high rate of false-positive screenings: 96 percent of all positive NLST screenings on CT were non-cancerous.
There is an overarching lack of guidance on how to manage abnormal lung nodules. "CT provides us with a powerful hint in the right direction, but the findings could still be many things, benign or malignant," Lee says.
The issue may come down to a matter of definition. The NLST defined positive screenings as non-calcified nodules 4 mm or larger. Different screening programs, as well as another large lung screening trial ongoing in Europe (NELSON trial), have opted for other definitions of positive findings. Thresholds range from 3D lesion quantifications of 500 mm3 in the NELSON trial to careful clinical judgments combining nodule size, density, borders and appearance.
"Generally speaking, the larger the lesion, the shorter the interval of follow-up,"