January 29, 2020
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Low-dose CT screening linked to reduced lung cancer mortality among current, former smokers
Low-dose, volume-based CT screening appeared associated with reduced lung cancer mortality compared with no screening among individuals at high risk for the disease, according to results of the randomized NELSON trial published in The New England Journal of Medicine.
Additionally, researchers observed low rates of follow-up procedures for results suggestive of lung cancer.
“The NELSON trial showed that volume CT lung cancer screening, with low rates of follow-up procedures for test results suggestive of lung cancer, resulted in substantially lower lung cancer mortality than no screening among high-risk persons,” Harry J. de Koning, MD, PhD, researcher in the department of public health at Erasmus Medical Center in the Netherlands, and colleagues wrote. “Volume CT screening enabled a significant reduction of harms without jeopardizing favorable outcomes.”
Limited data from randomized trials exist on the effect of volume-based, low-dose CT screening on lung cancer mortality among male former and current smokers.
Researchers compared lung cancer mortality between the CT screening group and control group using the intention-to-screen principle
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In the Dutch-Belgian NELSON trial, de Koning and colleagues sought to show a 25% or greater decrease in lung cancer mortality with the use of volume-based, low-dose CT screening among a population-based cohort of men at high risk for lung cancer.
For the primary analysis, researchers randomly assigned 13,195 men (median age, 58 years; median smoking history, 38 pack-years) to CT screening at baseline and intervals of 1, 2 and 2.5 years (n = 6,583) or no screening (n = 6,612). Nearly half (44.9%) of the men were former smokers.
Researchers also analyzed a subgroup of 2,594 women aged 50 to 74 years.
The investigators pooled data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium. A review committee confirmed lung cancer as the cause of death, when possible.
For the primary analysis, researchers compared lung cancer mortality between the CT screening group and control group using the intention-to-screen principle. For the secondary analysis, investigators compared all-cause mortality and incidence of first recorded lung cancer diagnosis, death of lung cancer and death of any cause.
Minimum follow-up was 10 years.
Results of the primary analysis showed that among men, average adherence to CT screening was 90% (95% CI, 76.9-95.8). In addition, 9.2% of screened participants underwent at least one additional CT scan. Overall referral rate for suspicious nodules was 2.1%.
Researchers reported 10-year lung cancer incidence of 5.58 cases per 1,000 person-years in the CT screening group and 4.91 cases per 1,000 person-years in the control group.
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Lung cancer mortality incidence was 2.5 deaths per 1,000 person-years for the CT screening group vs. 3.3 deaths per 1,000 person-years for the control group. Researchers calculated a 10-year cumulative rate-ratio for lung cancer death of 0.76 (95% CI, 0.61-0.94) in the CT screening group compared with the control group.
Results of the subgroup analyses among women showed a cumulative rate ratio for lung cancer death of 0.67 (95% CI, 0.38-1.14) at 10 years, 0.52 (95% CI, 0.28-0.94) at 9 years, 0.41 (95% CI, 0.19-0.84) at 8 years and 0.46 (95% CI, 0.21-0.96) at 7 years.
“In the small subset of women, the effects of screening on lung cancer mortality were consistently more favorable,” the researchers wrote. “More research is required in women, as well as in other subgroups.”
Low-dose CT screening has been adopted as policy in the U.S. following publication of the first mortality results from the National Lung Screening Trial (NLST), which showed the intervention resulted in a 20% reduction in lung cancer mortality among those at high risk.
“Policy decisions are still awaited in many countries, despite the unequivocal nature of the original NLST results,” Stephen W. Duffy, MSc, researcher at Wolfson Institute of Preventive Medicine at Queen Mary University of London, and John K. Field, PhD, FRCP, researcher in the department of molecular and clinical cancer medicine at University of Liverpool, wrote in an accompanying editorial.
“With the NELSON results, the efficacy of low-dose CT screening for lung cancer is confirmed,” they wrote. “Our job is no longer to assess whether low-dose CT screening works — it does. Our job is to identify the target population in which it will be acceptable and cost-effective.” – by Jennifer Southall
Disclosures: De Koning reports research grants from European Research Council, NIH, TRANSCAN and Zorg Onderzoek Nederland. Please see the study for all other authors’ relevant financial disclosures. Duffy reports no relevant financial disclosures. Field reports advisory board roles with AstraZeneca, Epigenomics and NUCLEIX Ltd.; a speakers bureau role with AstraZeneca; and grants from Janssen Research & Development LLC, outside of the submitted work
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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.
Paul A. Bunn Jr., MD
University of Colorado
Disclosures: Bunn reports no relevant financial disclosures.
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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.
Tawee Tanvetyanon, MD, MPH
Moffitt Cancer Center
Disclosures: Tanvetyanon reports no relevant financial disclosures.
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