Low-dose CT screening linked to reduced lung cancer mortality among current, former smokers

Paul A. Bunn Jr., MD

Lung cancer incidence and mortality rates continue to decline in the United States among both men and women, and the decrease can be attributed to prevention, including lower smoking rates, screening and improved therapy.

Screening for lung cancer saves lives, as the NELSON trial in Europe confirmed findings of the U.S. NLST trial and the magnitude of benefit in women exceeded that in men. However, the bad news is that less than 4% of eligible individuals in the U.S. undergo CT screening, which includes women. In addition, lung cancer remains the leading cause of cancer death in the U.S. among both men and women.

So, what should oncologists and physicians do with this information? For one, we need to educate other physicians, including those in general practice, about the value of CT screening. Second, we need to educate and work with the community, including women’s organizations, to spread the word about the value of CT screening.

Nearly 20% of the adult population still smoke and nicotine addiction through vaping is on the rise. Therefore, we need to continue to work on regulations through the FDA and local and regional governments to raise taxes and restrict certain practices. Finally, we need to educate other physicians and the public about the huge advances in cancer therapy to change the negative stigma surrounding lung cancer so that all patients will have equal access to the latest and best therapies.

Tawee Tanvetyanon, MD, MPH

The positive results from the NELSON trial confirm the efficacy of low-dose CT screening in reducing lung cancer mortality. This is the second-largest lung cancer screening study after the NLST, which enrolled more than 53,000 participants who were randomly assigned to low-dose CT screening or chest X-ray and demonstrated that low-dose CT screening reduced lung cancer death by 20% after approximately 6 years of follow-up.

The NELSON trial, which enrolled 13,000 men in the primary analysis randomly assigned to low-dose CT screening or observation, showed that low-dose CT screening reduced lung cancer death by 24% after about 10 years. Taken together, these results firmly established the benefit of low-dose CT screening among high-risk individuals.

Although the benefits of low-dose CT screening in both studies are comparable, some differences in the eligibility criteria and the conduct of screening are notable. In the NELSON trial, participants with as little as 15 pack-years of smoking history were considered eligible. Conversely the NLST only included those with at least 30 pack-years of smoking history. Further, the NELSON trial allowed participants as young as age 50 years, whereas in the NLST, participants were aged at least 55 years. Given the fact that the benefit of low-dose CT screening is seen in this group of lighter smokers of younger age, consideration should be given to extending the health coverage policy recommending low-dose CT screening in this population group to reflect the findings of the NELSON trial.

Another notable aspect of the eligibility criteria is that the NELSON trial does not require that participants be free of symptoms suggestive of lung cancer. In view of the difficulty determining whether any symptomatology in a patient may be due to lung cancer, it is practical to not exclude those who report any symptoms.

The NELSON trial utilized software to calculate lung nodule volume and used the volume of the nodule as a guide to management. This is in stark contrast to the NLST trial, which used lung nodule diameter. A nodule with volume of 50 mm³ to 500 mm³ (corresponding to nodule diameter of 4.6 mm³ to 12.4 mm³) at first detection is considered indeterminate — requiring repeat low-dose CT screening in 3 months — whereas a larger nodule is considered positive. This is in contrast to our current system, which uses the Lung Imaging Reporting and Data System (Lung-RADS). Patients with Lung-RADS 4A — which corresponds to a nodule 8 mm or larger and is considered a positive screen — will get additional work-up, which may include low-dose CT screening in 3 months, similarly to patients with indeterminate nodules in the NELSON trial. By avoiding a liberal definition of a “positive” test, the NELSON trial can be said to reduce false-positives. Regardless, given the comparable results from the NLST and NELSON trials, either a volume-based or dimension-based technique appears effective for lung cancer screening.

Although the NELSON and NLST trials represent significant medical progress in curbing the lung cancer epidemic using low-dose CT screening, the technology is far from perfect. For example, in the NELSON trial, only about two-thirds of lung cancers were detected by low-dose CT screening. In other words, despite greater than 90% compliance to low-dose CT screening, many lung cancers still went undetected. In addition, despite the reduction in lung cancer-specific mortality, the NELSON study was not able to demonstrate any improvement in overall mortality. Granted, the study may be too small to show significant improvement in overall mortality; however, it would have been encouraging to at least see a trend.

Setting this aside, it is important to address effective smoking cessation along with low-dose CT screening among current smokers or recent quitters. Low-dose CT screening can serve as another opportunity to provide health promotion. Improvement in the health of participants will ultimately bring the greatest public health impact.

Reference:

National Lung Screening Trial Research Team. N Engl J Med. 2011;doi:10.1056/NEJMoa1102873.