“There’s a lot we don’t know about lung cancer screening,” according to Denise Aberle, MD, who spoke at the recent American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research. However, certain measures can be taken to lower false-positive and overdiagnosis rates, lessen costs, ameliorate patient suffering, and correctly identify screening cohorts, she asserted.
Who Should Be Screened?
The National Lung Screening Trial (NLST) recommends lung cancer screening for adults aged 55 to 74 years who have at least a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. The US Preventive Services Task Force (USPSTF) has the same screening criteria, but has made revisions based on the Cancer Intervention and Surveillance Modeling Network (CISNET) models that are funded by the National Cancer Institute; they have extended the screening period up to individuals aged 80 years and do not recommend screening for individuals who have not smoked within the past 15 years.
The CISNET models that informed the USPSTF recommendations consist of 5 different consortiums, each having independent models for lung cancer, explained Aberle, vice chair of research and a professor in the Department of Radiological Science and professor of bioengineering at the University of California, Los Angeles. “When they looked across these 5 models they found a mortality reduction of anywhere from 8% to 24%. About half who went through screening had early-stage disease, and it is estimated that up to 500 per 100,000 lung cancer deaths across the population could be averted with the gain in life years,” she said.
“Many others have recommended that we use risk prediction models to try to better hone in on those individuals who should be screened,” said Aberle. Their premise is that we determine a threshold below which individuals will not be screened, and that doing so will improve on the existing NLST criteria. However, “using these risk predictors practically can be somewhat problematic,” she added.
What Can Be Done About False-Positivity Rates?
The false-positivity rate was one of the major limitations of the NLST, said Aberle. Consequences of this in a screening setting include additional unnecessary imaging and radiation exposure, unnecessary biopsies and the complications of those biopsies, unnecessary anxiety, and additional cost, she explained.
According to Aberle, if we look only at the published data from the NLST and stratify the nodules that factored into positive screens over each of the screening intervals, we can see that nodules that were ≤6 mm amounted to more than half of positive screenings but were responsible for less than 1% of lung cancers overall; if we look at increasing nodule size, the positive predictive value goes up so that the larger the nodule, the more likely it is that the person has cancer.
“This gives us a clue that size is important and might help us determine whether or not a screen is significant,” she suggested. “If we look at small nodules, 4-5 mm, we see that if we did nothing with those nodules but simply saw them one year later, we would suffer trivial effects with respect to the ability to diagnose lung cancer.”
When Is It Overdiagnosis?
“I understand the terms of overdiagnosis, and I understand the concept of overdiagnosis; I think where I stumble is when I look at the notion of overdiagnosis in the individual patient setting,” said Aberle. Questions concerning overdiagnosis are constantly raised, she noted. “But the only question for which there is a resounding answer is ‘we cannot assume a linear growth model.’”
“Some of these cancers are going to get worse over time, even over long periods of time. Some of these cancers are going to stay just the way they were. Some of these lesions may actually regress,” she noted. “We just don’t know enough and I think it makes it challenging to make these kinds of decisions in the individual patient setting.”
Next Steps in Screening
Aberle stated that it will behoove society to measure risk in individuals who are screened, redefine actionable nodules to lower false positives, maintain low radiation doses using current multidetector scanners, track smoking cessation efforts and rates, and collect the data via screening centers.
“Only in that way will we begin to understand what risk-to-benefit ratios are in the population setting and how we can maximize cost effectiveness,” she said.
“There’s a lot we don’t know about lung cancer screening; I personally find that exciting because I want to be able to help answer some of those questions,” she added.
Aberle DR. Lung cancer screening: from efficacy to effectiveness. Presented at: 13th Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research; September 28-October 1, 2014; New Orleans, LA.