Despite mounting evidence that low-dose CT screening reduces lung cancer mortality in people at high risk, the uptake of screening in the United States has been slow, and some researchers caution that the risks involved need to be better understood.
It has been almost 10 years since the landmark National Lung Screening Trial (NLST) provided the scientific evidence used by the United States Preventive Services Task Force to recommend annual screening for adults 55 to 80 years of age who have a 30 pack-year smoking history and currently smoke or have quit in the previous 15 years.
But just 4.2% of Americans who qualified for screening in 2018 were tested, according to an American Lung Association report. If everyone at high risk had been tested, 48,000 American lives could have been saved.
Final results from the NELSON trial, published earlier this year, support those from NLST.
Mortality was 24% lower with low-dose CT screening than with no screening in the NELSON cohort, which consisted of 13,195 men and 2594 women at high risk for lung cancer because they were current or former smokers.
“With the NELSON results, the efficacy of low-dose CT screening for lung cancer is confirmed,” wrote the authors of an editorial accompanying the NELSON results. “Our job is no longer to assess whether low-dose CT screening for lung cancer works: it does. Our job is to identify the target population in which it will be acceptable and cost-effective.”
That sentiment is echoed by Michael Gould, MD, from Kaiser Permanente Southern California.
“Lo and behold, we have confirmation of NLST results from NELSON,” Dr. Gould said in an interview. “Now that we have consistent data from the NELSON confirmatory trial, can we finally believe NLST?”
Even though NELSON confirms the benefits of screening in clinical trials, many questions remain about how lung cancer screening translates into everyday practice, said Dr. Gould, who had been scheduled to discuss the trials and the state of lung screening at the American Thoracic Society 2020 International Conference, which will now run virtually in August.
For starters, the target population needs more scrutiny. Research has shown that, outside of clinical trials, the harms of screening can sometimes outweigh the benefits.
In 2018, the rate of overdiagnosis was shown to be 67.2% in the Danish Lung Cancer Screening Trial (DLCST).
And 56% of people screened with low-dose CT had false-positive results that required follow-up testing and procedures, according to a 2017 study of current and former heavy smokers. That rate is more than double the 18.5% false-positive rate in NLST.
“Only 20% of NLST participants were over age 65,” Dr. Gould said. “The NELSON cohort was younger.”
And although the USPSTF recommends lung screening in high-risk people, “there were some in the NLST cohort whose risk was not particularly high.” Others in the trial, he said, had a high risk, but some of those had one or more comorbid conditions, “so the risk was unbalanced.
“Risk is more complicated than simply saying that anyone who meets the NLST criteria should get scanned,” he added.
Weighing risks and benefits needs to be done on a patient-by-patient basis, Dr. Gould said. “Do they have the ability to tolerate surgery? What’s important to them? We can’t just say, ‘you have a 30-pack-year history, go get a test’.”
Often, he said, it’s the people who have the most to gain from screening who are also at highest risk from biopsies and surgical and nonsurgical treatments because of comorbidities.
The NLST population might also have cast a wider net for those eligible for screening; NELSON had a lower threshold for amount smoked (30 vs. 15 pack-years). “NLST points to scanning a bigger population and lighter smokers,” Dr. Gould said.