Denise R. Aberle, MD
Nearly 2 years after a landmark study supported computed tomography (CT) screening for people at high risk of developing lung cancer, questions persist about the complexities of implementing an early detection program and potentially conflicting results from European clinical trials now under way.
Denise R. Aberle, MD, who led the National Lung Screening Trial (NLST), remains convinced of the importance and validity of adding CT testing to the menu of preventive cancer screenings, yet notes that significant challenges loom in building a broad public health initiative.
“I think we’re looking at the beginning of a moderately long and evolving implementation for lung cancer screening,” Aberle said during an interview at the 13th International Lung Cancer Congress in Huntington Beach, California. “And I think it would probably be naïve of us to assume that this could happen easily over the course of a couple of years.”
In fact, Aberle believes that academic medical centers working through referrals from primary care physicians and pulmonology specialists will be best equipped to conduct screening programs.
Aberle, a professor of Radiology and Bioengineering at the David Geffen School of Medicine at the University of California, Los Angeles, discussed major issues facing CT screening during a presentation at the congress. Her key points included:
There is a need to reduce the rate of falsepositives in CT screening and the emphasis should be on better identifying individuals who should undergo testing. Strategies would include developing risk prediction models that include biomarkers, considering other health indicators such as cardiopulmonary disease, and integrating other imaging analyses into a diagnosis.
Screening programs should be designed that cut across disciplines, standardize radiology protocols, educate primary care physicians and pulmonologists, and integrate risk assessment into smoking cessation and chemoprevention therapies.
Clinical trial results from Europe Union (EU) nations are raising questions about CT screening programs. Initial results from approximately seven or eight randomized clinical trials conducted in Europe have not shown a mortality benefit or trend toward reducing the numbers of advanced lung cancers.
Conflicting European Trial Results Puzzling
While the challenges of setting up screening programs may be considerable, Aberle acknowledged conflicting trial results from Europe are concerning.
“You can imagine this is relatively disconcerting to those of us who did the National Lung Screening Trial, and I think we’re all, including in the United States and European Union, trying to figure out why that may be,” Aberle said.
Small sample sizes (typically <6000 participants), different risk factors among cohorts, and participant selection issues are among the factors that may account for the disparity in findings, said Aberle.
Another factor may be the experience level of surgeons removing lesions found through screenings. “In the NLST, the majority of the surgeons performing resections are dedicated lung cancer surgeons,” Aberle noted. “That is not necessarily the case in the EU trials, and this might also account for some of the differences in mortality.”
Aberle noted that findings from a larger cohort, the NELSON trial in the Netherlands involving approximately 20,000 participants, are expected in 2014 or later. Results from that trial and meta-analysis of aggregated data from the smaller trials might shed light on the outcomes.
“There is one other explanation and that is that screening doesn’t work, but I’m not ready to concede that because we’ve clearly shown a significant efficacy with both lung cancer–specific mortality and all-cause mortality in the NLST,” Aberle said.
NLST Findings Show Clear Benefits
The NLST involved 53,454 people randomized to receive three annual screenings with either low-dose helical CT or single-view chest x-ray (N Engl J Med
. 2011;365:395-409.) The participants, aged 55-74 years, had a cigarette-smoking history of ≥30 packyears and, if former heavy smokers, had quit within the prior 15 years.
The trial, which took place from August 2002 through September 2007, was conducted at two sets of centers consisting of one network for screening and another for imaging. The median follow-up period was 6.5 years.
In all, the screening effort resulted in the diagnosis of 1060 lung cancers among participants in the CT group, compared with 941 in the x-ray group. There were fewer deaths attributable to lung cancer and to all-cause mortality among those who were screened with CT versus x-ray.