‘Popularity paradox’: Evidence lacking to support lung cancer screening for never-smokers
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Current evidence does not support lung cancer screening for never-smokers or former light smokers with a family history of lung cancer, according to a commentary in Journal of Thoracic Oncology.
Gerard A. Silvestri, MD, MS, and colleagues examined several large-scale, single-arm observational trials conducted in Asia. The trials included individuals who never smoked or had a light smoking history.
Trial results showed lung cancer detection rates higher in this population compared with those previously reported among high-risk current or former smokers. More than 90% of cancers detected among those with a family history had been discovered at an early stage.
Based on these findings, the investigators of these trials concluded that screening first-degree relatives of people with lung cancer — regardless of smoking history — would yield a reduction in lung cancer mortality.
“On the surface, this seems like great news — early detection is what screening is supposed to do,” Silvestri, Hillenbrand professor of thoracic oncology at Medical University of South Carolina, told Healio. “However, the question is not whether those cancers were early stage. It’s whether at the same time we’ve decreased the number of late-stage cancers — a stage shift reported in randomized trials of heavy smokers accompanied with a decrease in lung cancer mortality in the screened group. What we saw at the population level, and in some of this research, was a rise in early-stage lung cancer with an incredibly high cure rate after surgery but no decrease in stage IV disease.”
Healio spoke with Silvestri about his motivation to write this commentary, the difference between cancer detection and cancer lethality, and the “popularity paradox” that may drive unnecessary screening and intervention.
Healio: What motivated you to write this paper?
Silvestri: I was one of the co-chairs of the screening sessions for last year’s World Conference on Lung Cancer. One of the abstracts selected for presentation was the Taiwan screening trial, which screened Asian patients— particularly women — with a light or never-smoking history but a family history of lung cancer.
The researchers believe their findings support screening this population. I felt differently, and I was asked to be the discussant after their presentation at the meeting. I pointed out some of the challenges with this observational study, as well as some of the dangers of screening a very low-risk group in hopes of detecting cancer. After I made my presentation, I was asked by the journal if we could put our ideas into a commentary.
Healio: Can you summarize the key points in your commentary?
Silvestri: Two issues are getting conflated in these trials. The first is the detection rate in this group of patients. If you screen this group — or any group — you can detect very small, indolent cancerous lesions. These are considered overdiagnosed cancers, ones can you live with but not die of. This is a hard concept to get people’s minds around, but the question is: Are these cancers lethal? The answer is most certainly not.
The Taiwan screening experience screened this group (light or never smokers with a family history of lung cancer), as well as a group of heavy-smoking men. Results showed the detection rate of cancer was higher in this group of Asian, never-smoking women. They saw a rise in the detection of lung cancers with very high cure rates — more than 90% — but no decrease in stage IV disease, which are the lethal cancers for which we should screen. So, the first part of this is the need to separate cancer detection and cancer lethality. Then there is what we call the “popularity paradox.”
Healio: What is the popularity paradox?
Silvestri: Imagine you are a woman who never smoked cigarettes, but someone said, “You probably ought to be screened for lung cancer,” so you got screened and they detected one of these small lesions. Then the surgeon resects that tumor. The patient recovers is discharged and is hugging the doctor, and everyone is happy that you were cured of your “cancer”. Then you go out and proselytize this screening to others. The paradox is, you may have actually been harmed by having major surgery for this lesion that would have never caused death, but you believed you were cured. It’s a tough concept.
Healio: Do you think your paper will put this debate to rest, or is more evidence needed?
Silvestri: There’s going to need to be much more evidence. I do think this might move the needle in terms of people thinking about it. We should have level one evidence, which is a randomized trial assigning people with a minimal smoking history with or without a family history of lung cancer to screening with a chest CT scan or no screening.
Healio: What should be the priority as far as maximizing the effectiveness of screening?
Silvestri: The science needs to push toward how to identify — through perhaps a blood-based biomarker or some other approach — a subgroup that might benefit, and then evaluate whether screening works in that subgroup.
Healio: Is there anything else you’d like to mention?
Silvestri: The authors of this article are huge advocates of lung cancer screening. In our individual programs — which include the Veterans Administration, the state of South Carolina and the state of Ohio — we’ve screened more than 50,000 people for lung cancer. We use the U.S. Preventive Services Task Force recommendations, which are to screen people aged 50 to 80 years who currently smoke, or who those who formerly smoked, are aged 50 to 80 with at least a 20 pack-year smoking history who either currently smoke or have quit in the last 15 years. That population is at high risk for developing lethal cancers.
We understand that screening is important, but this subgroup [of light or never-smokers with family history] has not been adequately studied. Although the outcomes of the studies in question might seem to support screening this group, we believe the evidence is just not there.
Reference:
For more information:
Gerard A. Silvestri, MD, MS, can be reached at silvestr@musc.edu.
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