“Unfortunately, the trial is too small to have a clear-cut result,” said Harry J. de Koning, MD, PhD, of Erasmus Medical Center in Rotterdam, The Netherlands, who was one of the authors of the NELSON study. “You see the [mortality] curves diverge only after year 7 or so.” For comparison, he said, the NLST and the NELSON trial show an improvement in mortality with screening after only 1-2 years. “That’s what you would expect.”

Removing that nonrandomized group of patients from the analysis further weakened the observed effect, said Richard Hoffman, MD, MPH, of the University of Iowa Holden Comprehensive Cancer Center, Iowa City. “When they looked at the people who were randomized to CT or control, what they found was that the difference was not significant.”

Others, however, hope that despite the flaws, the study stimulates further research on the impact of long-term screening.

Under the current recommendations, clinicians don’t stop after 1 or 2 screenings, said Jasleen Pannu, MBBS, interventional pulmonologist at the Ohio State University Wexner Medical Center, Columbus. “It continues to be covered by Medicare until age 77, but to date there was really no evidence,” showing that long-term screening was beneficial — or even at what point it should be discontinued. “It’s not that we were not doing long-extended screening,” she said. “This is just the first time we know that extended screening may make sense.”

“If this was all we had, we probably wouldn’t have enough,” said Alain Tremblay, MD, founder of the Interventional Pulmonary Medicine Centre at the University of Calgary, Alberta. But it makes sense that the benefits of screening would be more pronounced years down the road, he said. “When you screen, it’s early detection,” he pointed out. “The people you diagnose today aren’t people who were going to die next week.”

Still, screening isn’t without risk, so it’s important to demonstrate a benefit before promoting more screening. Harms include high rates of false positives, overdiagnosis, and radiation exposure. In addition, people eligible for the screening may also have heart and lung conditions that make them vulnerable to complications from surgery.

In 2015, Centers for Medicare & Medicaid Services (CMS) began requiring a dedicated counseling visit, incorporating the use of decision aids, for patients considering lung cancer screening.5 “That’s unprecedented,” said Dr Hoffman. “They’ve never said you have to do that, and the reason is because there’s some really important trade-offs.”

Dr Hoffman, who works on decision aids and shared decision making, cautioned against downplaying the harms associated with screening. Even in the context of a clinical trial, where the screening is conducted by highly trained specialists, “there were serious complications from diagnostic procedures and treatments,” he said. “And what we’re seeing in community data is actually that the complication rates are much higher.”

The CMS-mandated counseling visit isn’t necessarily a bad thing, said Dr Tremblay. For any cancer screening, not just lung screening, he said, there are “definite harms and benefits, and things that need to be discussed. That’s part of what offering a medical intervention is [about].” But, he also acknowledged, “Some physicians are better than others at having the discussion.” Indeed, a recent study found that rates of physician-patient discussions about lung cancer screening have declined since 2012.6

When considering harms of screening, though, it is important to recognize that practices have improved in the 2 decades since the NLST began. Improvements in predictive algorithms and clinical practices are reducing the rate of false positives and overdiagnosis.

The MILD trial addressed this as well, by testing active surveillance rather than resection for subsolid nodules. According to Dr Pastorino, “This is the only trial that tried to avoid unnecessary surgery for nonevolving in situ carcinoma.” In most cases, the nodules never evolved, he said, and those that did evolve were successfully resected at stage I even after 8 to 10 years. “We managed to reduce substantially one of the harmful components of screening, which is unnecessary resection for benign lesions or for cancers that don’t evolve,” he said. “In our opinion, this is a very important contribution of our study.”

References

  1. Pastorino U, Silva M, Sestini S, et al. Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy [published online April 1, 2019]. Ann Oncol. doi: 10.1093/annonc/mdz117
  2. National Lung Screening Trial Research Team; Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395–409.
  3. International Association for the Study of Lung Cancer. NELSON study shows CT screening for nodule volume management reduces lung cancer mortality by 26 percent in men [news release]. Presented at: IASLC’s 2018 World Conference on Lung Cancer; September 23-26, 2018; Toronto, Canada.
  4. Pastorino U, Rossi M, Rosato V, et al. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev. 2012;21(3):308-315.
  5. Centers for Medicare & Medicaid Services. Decision memo for screening for lung cancer with low dose computed tomography (LDCT). Published February 5, 2015. Accessed May 10, 2019.
  6. Huo J, Hong Y-R, Bian J, Guo Y, Wilkie DJ, Mainous AG 3rd. Low rates of patient-reported physician–patient discussion about lung cancer screening among current smokers: data from Health Information National Trends Survey. Cancer Epidemiol Biomarkers Prev. 2019;28(5):963-973.