NEJM: Cost-effectiveness chief barrier to implementing lung CT screening

CT scan of 72-year-old woman shows dominant pulmonary nodule (arrow) in right lower lobe that proved at pathology to be adenocarcinoma. Source: American Journal of Roentgenology, Ginsberg et al, 2004.

Despite an abrupt halt amid results that lung CT screening reduces mortality by 20 percent, researchers with the National Lung Screening Trial say it may be some time before the medical community can employ CT screening for the nation’s No. 1 cancer killer, owing in large part to a false-positive rate above 95 percent.  

This past November, the National Cancer Institute cut short its National Lung Screening Trial (NLST) after finding CT to be a dramatically more effective tool for lung cancer screening among current and former smokers. But as hundreds of researchers continue to labor over the troves of data and specimens collected from the trial’s 53,000-plus participants, additional findings published this week in the New England Journal of Medicine indicate that major medical and public policy challenges remain before CT can make its mark on the 94 million Americans at elevated risk for lung cancer.

Commenting on the latest NEJM study, Denise R. Aberle, national principal investigator for 23 of the 33 NLST sites and a researcher at University of California, Los Angeles' Jonsson Comprehensive Cancer Center, stated, “These findings confirm that low-dose CT screening can decrease deaths from lung cancer, which is expected to kill more than 150,000 Americans this year alone. This study also will provide us with a road map for public policy development in terms of lung cancer screening in the years to come.”

The findings

Between 2002 and 2009, 53,454 individuals with a history of smoking a pack of cigarettes a day for at least 30 years were screened and followed up for signs of lung cancer. Roughly half of the individuals underwent three annual chest x-rays, while the other half received three annual CT scans.

The results showed that low-dose CT (at an average dose of 1.5 mSv) produced a 20 percent reduction in lung cancer-specific mortality compared with conventional x-ray. For every 320 smokers screened via CT, one life was saved.

“The results demonstrated a definitive benefit in terms of lung cancer mortality and overall mortality for low-dose CT screening compared to x-ray,” explained Drew A. Torigian, MD, MA, an associate professor of radiology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia and the site’s principal investigator for the NLST. The University of Pennsylvania was one of 33 institutions to enroll patients in the NLST, contributing just fewer than 400 participants.

The findings are significant, Torigian indicated, because diagnoses of lung cancer tend to come so late in the disease’s progression that surgery and other treatments frequently are not curative. Early detection, then, constituted the operative difference between 356 deaths in the CT group and 443 deaths for the x-ray group, Torigian stated, despite the diagnosis of nearly 120 more cancers in the group that underwent CT.

Implementation: Challenges ahead, benefits certain

“For the 55 to 74 age group, the study definitively showed that CT decreases lung cancer-specific mortality. However, the question of whether CT can be used as a screening test we have yet to answer,” Torigian explained in an interview with Health Imaging News.

Despite demonstrating a 20 percent reduction in mortality, CT also resulted in a 96 percent false-positive rate: approximately one out of every four CT scans delivered a false-positive result, while more than one out of every three patients had at least one positive (false or true) CT scan. Positive results were defined as noncalcified lung nodules of at least 4 mm.

NLST researchers continue to investigate several avenues for minimizing the impact of the test’s low specificity. An important finding already recognized was that the rate of follow-up decreased with the accrual of additional scans, which allowed radiologists to track the progress of lesions and better assess their benignancy or malignancy. A critical part of any lung screening guidelines, Torigian suggested, would be the frequency with which CT scans are recommended.

In addition, physicians collected sputum, blood and urine specimens from roughly 10,000 participants as well as lung tissue samples from patients with confirmed malignancies. “If it turns out that the statistical analyses show that CT lung screening is not cost-effective for the entire population studied, then these laboratory biomarkers and tissue samples are really going to come into play. It is hopeful that these lab tests will enable us to narrow the screening criteria by better determination of risk factors, so that we can simultaneously further improve specificity and save costs,” Torigian added.

He estimated that it will likely take between six and 12 months before comprehensive cost-effectiveness studies on the NLST data are available. Until that time, the study indicated, the uncertainties of screening eligibility, frequency and follow-up only add to the unlikelihood that payors will reimburse screening CT anytime in the near future.

“How can we implement these findings in a uniform, reimbursed and cost-effective manner? That is really the crux of the matter, and it’s not simple,” Torigian emphasized.

Even with these challenges, there’s no overshadowing the excitement expressed by Torigian and other researchers, that, “For the first time, there is a screening test that has been shown to decrease the mortality rate caused by the most common cancer killer.”

Click to learn more about advanced visualization in CT screening or to review the initial results of the NLST.